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  • 1.
    Ahlström, Tommy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rudberg, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women2009In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 71, no 5, p. 673-678Article in journal (Refereed)
    Abstract [en]

    CONTEXT: In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear.

    OBJECTIVE: To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population.

    DESIGN: We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined.

    RESULTS: The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated.

    CONCLUSIONS: We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.

  • 2. Allahyari, Ali
    et al.
    Jernberg, Tomas
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Leosdottir, Margrét
    Lundman, Pia
    Ueda, Peter
    Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study2020In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 41, no 40, p. 3900-3909Article in journal (Refereed)
    Abstract [en]

    AIMS: To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines.

    METHODS AND RESULTS: Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6-10 weeks after an MI event, 2013-17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of <1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target.

    CONCLUSION : Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.

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  • 3. Allahyari, Ali
    et al.
    Jernberg, Tomas
    Lautsch, Dominik
    Lundman, Pia
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Schubert, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Boggs, Robert
    Salomonsson, Stina
    Ueda, Peter
    Low-density lipoprotein-cholesterol target attainment according to the 2011 and 2016 ESC/EAS dyslipidaemia guidelines in patients with a recent myocardial infarction: nationwide cohort study, 2013–17 2021In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 7, no 1, p. 59-67Article in journal (Refereed)
    Abstract [en]

    AIMS: To assess low-density lipoprotein cholesterol (LDL-C) treatment target attainment among myocardial infarction (MI) patients according to the ESC/EAS dyslipidaemia guidelines from 2011 (LDL-C <1.8 mmol/L or ≥ 50% LDL-C reduction) and 2016 (LDL-C <1.8 mmol/L and ≥50% LDL-C reduction).

    METHODS AND RESULTS: Using nationwide registers, we identified 44,890 patients aged 21-74 admitted for MI, 2013-2017. We included those attending follow-up visits at 6-10 weeks (n = 25,466) and 12-14 months (n = 17,117) after the event. Most patients received high-intensity statin monotherapy (84.3% [6-10 weeks] and 69.0% [12-14 months]) or statins with ezetimibe (2.7% and 10.2%). The proportion of patients attaining the 2011 LDL-C target was 63.8% (6-10 weeks) and 63.5% (12-14 months). The corresponding numbers for the 2016 LDL-C target was 31.6% (6-10 weeks) and 31.5% (12-14 months). At the 6-10-week follow-up, 37% of those not attaining the 2011 LDL-C target and 48% of those not attaining the 2016 target had an LDL-C level that was ≥0.5 mmol/L from the target. When comparing LDL-C measurements performed before vs. after the release of the 2016 guidelines, attainment of the 2016 LDL-C target increased from 30.2% to 35.0% (6-10 weeks) and from 27.6% to 37.6% (12-14 months).

    CONCLUSIONS: In a nationwide register, one out of three patients with a recent MI had not attained the LDL-C target of the 2011 ESC/EAS guidelines and two out of three patients had not attained the LDL-C target of the 2016 guidelines.

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  • 4. Alsén, Martin
    et al.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eggers, Kai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    »HEART score« – lösningen på säker handläggning av patienter med misstänkt akut kranskärlsjukdom på akutmottagningen?: ["HEART score"--the solution for secure management of patients with suspected acute coronary syndrome in the emergency department?]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 27-28, p. 1297-Article in journal (Other academic)
  • 5.
    Avis, Suzanne R.
    et al.
    Royal North Shore Hosp, Cardiovasc Discovery Grp, Kolling Inst, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Fac Med & Hlth, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Tasmania, Coll Hlth & Med, Tasmanian Sch Med, Sydney Campus,Glover St, Lilyfield, NSW 2040, Australia..
    Vernon, Stephen T.
    Royal North Shore Hosp, Cardiovasc Discovery Grp, Kolling Inst, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Fac Med & Hlth, Level 12,Bldg 6, St Leonards, NSW 2065, Australia..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Figtree, Gemma A.
    Royal North Shore Hosp, Cardiovasc Discovery Grp, Kolling Inst, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Fac Med & Hlth, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Royal North Shore Hosp, Dept Cardiol, Reserve Rd, St Leonards, NSW 2065, Australia..
    Coronary artery disease in the absence of traditional risk factors: a call for action2021In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 42, no 37, p. 3822-3824Article in journal (Other academic)
  • 6.
    Batra, Gorav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ghukasyan, Tatevik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    White, Harvey D
    Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
    Stewart, Ralph A H
    Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
    Koenig, Wolfgang
    Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
    Cannon, Christopher P
    Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts.
    Budaj, Andrzej
    Department of Cardiology, Centre of Postgraduate Medical Education, Grochowski Hospital, Warsaw, Poland.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome2021In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 6, no 12, p. 1440-1445Article in journal (Refereed)
    Abstract [en]

    Importance: Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease.

    Objective: To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function.

    Design, Setting, and Participants: This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020.

    Exposures: Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs ≥2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [≥90 mL/min/1.73 m2], mildly decreased eGFR level [60-90 mL/min/1.73 m2], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m2]).

    Main Outcomes and Measures: Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke.

    Results: This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (≥2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]).

    Conclusions and Relevance: In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.

  • 7.
    Bergstrom, Goran
    et al.
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Persson, Margaretha
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Adiels, Martin
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Bjornson, Elias
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Bonander, Carl
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alfredsson, Joakim
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Angeras, Oskar
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Cardiol, Gothenburg, Sweden..
    Berglund, Goran
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Brandberg, John
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Borjesson, Mats
    Sahlgrens Acad, Inst Med, Gothenburg, Sweden.;Univ Gothenburg, Ctr Hlth & Performance, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Olov.Duvernoy@radiol.uu.se.
    Ekblom, Orjan
    Swedish Sch Sport & Hlth Sci GIH, Dept Phys Act & Hlth, Stockholm, Sweden..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Engvall, Jan E.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Fagman, Erika
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Eriksson, Mats
    Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Clin Res Ctr, Stockholm, Sweden..
    Erlinge, David
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Fagerberg, Bjorn
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Flinck, Agneta
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Goncalves, Isabel
    Lund Univ, Dept Clin Sci Malmö, Lund, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hjelmgren, Ola
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindqvist, Per
    Umeå Univ, Dept Surg & Perioperat Sci, Umeå, Sweden..
    Ljungberg, Johan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Magnusson, Martin
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;North West Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa..
    Mannila, Maria
    Karolinska Univ Hosp, Dept Cardiol & Clin Genet, Heart & Vasc Theme, Stockholm, Sweden..
    Markstad, Hanna
    Lund Univ, Clin Sci Malmö, Clin Res Ctr, Expt Cardiovasc Res, Malmö, Sweden.;Lund Univ, Ctr Med Imaging & Physiol, Lund, Sweden..
    Mohammad, Moman A.
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Nystrom, Fredrik H.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Ostenfeld, Ellen
    Skane Univ Hosp, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Clin Physiol, Lund, Sweden..
    Persson, Anders
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Rosengren, Annika
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Sandstrom, Anette
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Sjalander, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Skold, Magnus C.
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Resp Med & Allergy, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia..
    Swahn, Eva
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Soderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Toren, Kjell
    Univ Gothenburg, Sch Publ Hlth & Community Med, Occupat & Environm Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Ostgren, Carl Johan
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population2021In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 144, no 12, p. 916-929Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or >= 50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (>= 50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

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  • 8.
    Bergstrom, Goran
    et al.
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Physiol, Gothenburg, Sweden..
    Rosengren, Annika
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrenska Univ Hosp Ostra Hosp, Dept Med Geriatr & Emergency Med, Gothenburg, Sweden..
    Brolin, Elin Bacsovics
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Capio St Goran Hosp, Dept Radiol, Stockholm, Sweden..
    Brandberg, John
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Radiol, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Radiol, Gothenburg, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden..
    Engvall, Jan E.
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Eriksson, Maria J.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Goncalves, Isabel
    Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Dept Clin Sci Malmö, Cardiovasc Res Translat Studies, Malmö, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lilja, Mikael
    Umeå Univ, Östersund Hosp, Dept Publ Hlth & Clin Med, Unit Res Educ & Dev, Umeå, Sweden..
    Magnusson, Martin
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;North West Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa..
    Persson, Anders
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Karolinska Inst, Huddinge Univ Hosp, Dept Clin Sci, Stockholm, Sweden..
    Persson, Margaretha
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Sandstrom, Anette
    Umeå Univ, Heart Ctr, Umeå, Sweden.;Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Schmidt, Caroline
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Larsson, Linn Skoglund
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Univ New South Wales, George Inst Global Hlth, Sydney, Australia..
    Swahn, Eva
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Soderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Toren, Kjell
    Univ Gothenburg, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Inst Med,Sect Occupat & Environm Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Occupat & Environm Med, Gothenburg, Sweden..
    Ostgren, Carl Johan
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS2023In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 373, p. 46-54Article in journal (Refereed)
    Abstract [en]

    Background and aims: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.

    Methods: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomog-raphy angiography (CCTA) and expressed as segment involvement score (SIS).

    Results: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.

    Conclusions: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

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  • 9.
    Bhatt, Deepak L.
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.
    Fox, Kim
    Imperial Coll, Natl Heart & Lung Inst, London, England;Royal Brompton Hosp, London, England.
    Harrington, Robert A.
    Stanford Univ, Dept Med, SCCR, Stanford, CA 94305 USA.
    Leiter, Lawrence A.
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
    Mehta, Shamir R.
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Hamilton, ON, Canada.
    Simon, Tabassome
    Sorbonne Univ Paris, Hop St Antoine, AP HP, Dept Clin Pharmacol URCEST, Paris, France.
    Andersson, Marielle
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Himmelmann, Anders
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Ridderstrale, Wilhelm
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Uppsala Clin Res Ctr, Dept Med Sci, Cardiol, Uppsala, Sweden.
    Steg, Philippe Gabriel
    Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,F CRIN Network,FACT, Paris, France;Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,INSERM,U 1148, Paris, France;Imperial Coll, Royal Brompton Hosp, NHLI, London, England.
    Steg, Gabriel
    Diaz, Rafael
    Amerena, John
    Huber, Kurt
    Sinnaeve, Peter
    Nicolau, Jose Carlos
    Kerr Saraiva, Jose Francisco
    Petrov, Ivo
    Corbalan, Ramon
    Ge, Junbo
    Zhao, Qiang
    Botero, Rodrigo
    Widimsky, Petr
    Kristensen, Steen Dalby
    Hartikainen, Juha
    Danchin, Nicolas
    Darius, Harald
    Fat, Tse Hung
    Kiss, Robert Gabor
    Pais, Prem
    Lev, Eli
    De Luca, Leonardo
    Goto, Shinya
    Ramos Lopez, Gabriel Arturo
    Cornel, Jan Hein
    Kontny, Frederic
    Medina, Felix
    Babilonia, Noe
    Opolski, Grzegorz
    Vinereanu, Dragos
    Zateyshchikov, Dmitry
    Ruda, Mikhail
    Elamin, Omer
    Kovar, Frantisek
    Dalby, Anthony John
    Jeong, Myung Ho
    Bueno, Hector
    James, Stefan
    Chiang, Chern-En
    Tresukosol, Damras
    Ongen, Zeki
    Ray, Kausik
    Parkhomenko, Alexander
    McGuire, Darren
    Kosiborod, Mikhail
    Nguyen, Tuan Quang
    Wallentin, Lars
    Fox, Keith A. A.
    Eikelboom, John W.
    Tuomilehto, Jaakko
    Lee, Kerry L.
    Al-Khalidi, Hussein R.
    Ellis, Stephen J.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmgren, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Heldestad, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hallberg, Theresa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Renlund Grausne, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alm, Cristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svanberg, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Capell, Warren H.
    Nehler, Mark R.
    Hiatt, William R.
    Bonaca, Marc P.
    Houser, Stacey
    Bachler, Susie
    Jaeger, Nicole
    Aunes, Maria
    Brusehed, Asa
    Chen, Jersey
    Dahlof, Bjorn
    Dolezalova, Jitka
    Domzol, Maciej
    Findley, Magdalena
    Holmberg, Niclas
    Jahreskog, Marianne
    Knutsson, Mikael
    Kruszewski, Jakub
    Leonsson-Zachrisson, Maria
    Stark, Maj
    Winder, Elin
    Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study2019In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 5, p. 498-505Article in journal (Refereed)
    Abstract [en]

    In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.

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  • 10.
    Bittner, Vera A.
    et al.
    Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL USA.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Univ Uppsala Hosp, Uppsala, Sweden.
    Ball, Eric
    Walla Walla Clin, Walla Walla, WA USA.
    Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome2020In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 75, no 2, p. 133-144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). METHODS One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. RESULTS Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). CONCLUSIONS Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) 

  • 11. Brinck, Jonas
    et al.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Nåtman, Jonatan
    Franzén, Stefan
    Eeg-Olofsson, Katarina
    Nathanson, David
    Eliasson, Björn
    Cardiovascular Outcomes in Patients With Both Diabetes and Phenotypic Familial Hypercholesterolemia: A Nationwide Register-Based Cohort Study2022In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 45, no 12, p. 3040-3049Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Patients with diabetes or familial hypercholesterolemia (FH) have an increased incidence of cardiovascular diseases compared with the population, but whether this risk is exacerbated in patients with combined traits is unknown.

    RESEARCH DESIGN AND METHODS: In this Swedish nationwide, register-based cohort study, patients with diabetes were included between 2002 and 2020. Adjusted Cox proportional hazards models were used to assess the risk of cardiovascular events in patients with or without phenotypic FH (≥6 points for phenotypic FH according to Dutch Lipid Clinic Network criteria) compared with general population control subjects without diabetes as reference.

    RESULTS: A total of 45,585 patients with type 1 diabetes (227,923 control subjects) and 655,250 patients with type 2 diabetes (655,250 control subjects) were followed for a median of 14.1 and 7.9 years, respectively. Of those, 153 and 7,197, respectively, had phenotypic FH. Compared with control subjects, patients with diabetes and phenotypic FH had higher risk of cardiovascular mortality (type 1: hazard ratio 21.3 [95% CI 14.6-31.0]; type 2: 2.40 [2.19-2.63]) and of a cardiovascular event (type 1: 15.1 [11.1-20.5]; type 2: 2.73 [2.58-2.89]). Further, patients with diabetes and phenotypic FH had higher LDL-cholesterol levels during observation (P < 0.05) and increased risk of all major cardiovascular outcomes (P < 0.0001) than patients with diabetes but without FH. The proportion receiving lipid-lowering treatment was higher in patients with phenotypic FH (P < 0.0001).

    CONCLUSIONS: Patients with both diabetes and phenotypic FH are more at risk for adverse cardiovascular outcomes and have higher LDL-cholesterol levels despite receiving intensified lipid-lowering therapy.

  • 12.
    Bäck, Maria
    et al.
    Linköping Univ, Dept Hlth Med & Caring Sci, Unit Physiotherapy, S-58183 Linköping, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, S-40530 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Physiotherapy, Vita Straket 13, S-41345 Gothenburg, Sweden..
    Leosdottir, Margret
    Lund Univ, Fac Med, Dept Clin Sci Malmö, S-20502 Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Jan Waldenstroms Gata 35, S-21428 Malmö, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Norhammar, Anna
    Karolinska Univ Hosp, Dept Med K2, Unit Cardiol, Karolinska Inst, S-17176 Stockholm, Sweden.;Capio Srt Gorans Hosp, Stockholm, Sweden..
    Hag, Emma
    Cty Hosp Ryhov, Dept Internal Med, S-55111 Jönköping, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, S-18288 Stockholm, Sweden..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Asgatan 41, S-79171 Falun, Sweden..
    The SWEDEHEART secondary prevention and cardiac rehabilitation registry (SWEDEHEART CR registry)2021In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 7, no 5, p. 431-437Article in journal (Refereed)
    Abstract [en]

    Aims

    The quality registry SWEDEHEART covers data across the patient pathway after an acute myocardial infarction (MI), from hospital care to secondary prevention. Although cardiac rehabilitation (CR) is strongly recommended after an MI, there is still heterogeneity regarding standards, uptake, and adherence rates. The aim of the SWEDEHEART-CR registry is to provide continuous information on secondary prevention and CR performance to support the audit and development of evidence-based practice. To facilitate quality improvement and research initiatives, a description of the characteristics and development of the SWEDEHEART-CR registry is needed.

    Methods and results

    The SWEDEHEART-CR registry starts with data obtained during hospital care and then collects data at out-patient visits 2 months and 1-year after discharge, and at start and end of an exercise-based CR programme. The registry data covers comorbidities, biochemistry, blood pressure, anthropometric variables, medication, psychosocial- and lifestyle variables, readmissions, patient-reported outcome measures, attendance in CR-related programmes, and physical fitness variables. Over 100 000 patients with MI have been included in the SWEDEHEART-CR registry since its start in 2005. From initially covering 35 centres (47%) and 2200 patients annually (27%), SWEDEHEART-CR has developed to a nation-wide registry with 75 centres (100%) and 8800 patients annually (80%) in 2020.

    Conclusion

    The SWEDEHEART-CR registry includes a high proportion of the national MI population entering a CR programme and is a powerful tool for quality audit, improvement, and research. The registry provides insights into the characteristics, treatment, and outcomes of evidence-based secondary preventive practice, ultimately leading to better cardiovascular health.

  • 13.
    Cederström, Sofia
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lundman, Pia
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Alfredsson, Joakim
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ravn-Fischer, Annica
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Cardiol,Sahlgrenska Univ Hosp,Dept Mol & Clin, Gothenburg, Sweden..
    Söderberg, Stefan
    Umeå Univ, Heart Ctr, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Yndigegn, Troels
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Tornvall, Per
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden..
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Association between high-sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, article id 12171Article in journal (Refereed)
    Abstract [en]

    Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64 years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (& GE; 2.3 mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07-1.24), coronary diameter stenosis & GE; 50% (OR 1.27, 95% CI 1.09-1.47), & GE; 4 segments involved (OR 1.13, 95% CI 1.01-1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05-1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02-1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.

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  • 14.
    Cedervall, Jessica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Herre, Melanie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rabelo-Melo, F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Svensson, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Thålin, C
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden..
    Rosell, A
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden..
    Hjalmar, V
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden..
    Wallén, H
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden..
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Larsson, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Olsson, A K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress.2022In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 11, no 1, article id 2049487Article in journal (Refereed)
    Abstract [en]

    Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients.

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  • 15. Chiang, Chern-En
    et al.
    Schwartz, Gregory G
    Elbez, Yedid
    Szarek, Michael
    Bhatt, Deepak L
    Bittner, Vera A
    Diaz, Rafael
    Erglis, Andrejs
    Goodman, Shaun G
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Jukema, J Wouter
    Liberopoulos, Evangelos
    Loy, Megan
    Pordy, Robert
    White, Harvey D
    Simon, Tabassome
    Steg, Philippe Gabriel
    Alirocumab and Cardiovascular Outcomes in Patients With Previous Myocardial Infarction: Prespecified Subanalysis From ODYSSEY OUTCOMES2022In: Canadian Journal of Cardiology, ISSN 0828-282X, E-ISSN 1916-7075, Vol. 38, no 10, p. 1542-1549Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: After acute coronary syndrome (ACS), patients with a previous myocardial infarction (MI) may be at particularly high risk for major adverse cardiovascular events (MACE) and death. We studied the effects of the PCSK9 inhibitor alirocumab in patients with recent ACS according to previous history of MI.

    METHODS: The ODYSSEY OUTCOMES trial compared alirocumab with placebo, beginning 1 to 12 months after ACS with median 2.8-year follow-up. The primary MACE outcome comprised death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, and hospitalization for unstable angina. Of 18,924 patients, 3633 (19.2%) had previous MI.

    RESULTS: Patients with previous MI were older, more likely male, with more cardiovascular risk factors and previous events. With placebo, 4-year risks of MACE and death were higher among those with vs without previous MI (20.5% vs 8.9%, P < 0.001; 7.4% vs 3.4%, P < 0.001, respectively). Alirocumab reduced the risk of events regardless of the presence or absence of a history of MI (MACE, adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI], 0.78-1.05 vs 0.82, 0.73-0.92; Pinteraction = 0.34; death, aHR 0.84; 95% CI, 0.64-1.08 vs 0.87, 0.72-1.05; Pinteraction = 0.81). Estimated absolute risk reductions with alirocumab were numerically greater with vs without previous MI (MACE, 1.91% vs 1.42%; death, 1.35% vs 0.41%).

    CONCLUSIONS: A previous history of MI places patients with recent ACS at high risk for recurrent MACE and death. Alirocumab reduced the relative risks of these events consistently in patients with or without previous MI but with numerically greater absolute benefit in the former subgroup. (ODYSSEY OUTCOMES: NCT01663402).

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  • 16. Damask, Amy
    et al.
    Steg, P Gabriel
    Schwartz, Gregory G
    Szarek, Michael
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Badimon, Lina
    Chapman, M John
    Boileau, Catherine
    Tsimikas, Sotirios
    Ginsberg, Henry N
    Banerjee, Poulabi
    Manvelian, Garen
    Pordy, Robert
    Hess, Sibylle
    Overton, John D
    Lotta, Luca A
    Yancopoulos, George D
    Abecasis, Goncalo R
    Baras, Aris
    Paulding, Charles
    Patients with High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit from Alirocumab Treatment in the Odyssey Outcomes Trial2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 8, p. 624-636Article in journal (Refereed)
    Abstract [en]

    Background: Alirocumab, an antibody that blocks proprotein convertase subtilisin/kexin type 9 (PCSK9), was associated with reduced major adverse cardiovascular events (MACE) and death in the ODYSSEY OUTCOMES trial. In this study, higher baseline LDL cholesterol (LDL-C) levels predicted greater benefit from alirocumab treatment. Recent studies indicate high polygenic risk scores (PRS) for coronary artery disease (CAD) identify individuals at higher risk who derive increased benefit from statins. Herein we perform post hoc analyses to determine whether high PRS for CAD identifies higher-risk individuals, independently from baseline LDLC and other known risk factors, who might derive greater benefit from alirocumab treatment. Methods: ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled trial comparing alirocumab or placebo in 18,924 patients with acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin treatment. The primary endpoint (MACE) comprised death from CAD, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. A genome-wide PRS for CAD comprising 6,579,025 genetic variants was evaluated in 11,953 patients with available DNA samples. Analysis of MACE risk was performed in placebo treated patients while treatment benefit analysis was performed in all patients. Results: The incidence of MACE in the placebo group was related to PRS for CAD: 17.0% for high PRS patients (>90th percentile) and 11.4% for lower PRS patients (≤90th percentile) (p<0.001); this PRS relationship was not explained by baseline LDL-C or other established risk factors. Both the absolute and relative reduction of MACE by alirocumab compared to placebo was greater in high versus low PRS patients. There was an absolute reduction by alirocumab in high versus low PRS groups of 6.0% and 1.5%, respectively, and relative risk reduction by alirocumab of 37% in the high PRS group (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.46-0.86; p = 0.004) versus 13% reduction in the low PRS group (HR 0.87; 95% CI 0.78-0.98; p=0.022; interaction p = 0.04). Conclusions: A high PRS for CAD is associated with elevated risk for recurrent MACE after ACS, and larger absolute and relative risk reduction with alirocumab treatment, providing an independent tool for risk stratification and precision medicine.

  • 17.
    Delgado-Vega, Angelica Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Kommata, Varvara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology.
    Wisten, Aase
    Umeå Universitet.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stattin, Evalena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Family History and Warning Symptoms Precede Sudden Cardiac Death in Arrhythmogenic Right Ventricular Cardiomyopathy (From A Nationwide Study in Sweden)2022In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 178, p. 124-130Article in journal (Refereed)
    Abstract [en]

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiacdisease explaining about 4% of sudden cardiac death (SCD) cases among the youngin Sweden. The aim of this study was to describe the circumstances preceding SCDdue to ARVC in all victims <35 years of age who received an autopsy-confirmeddiagnosis of ARVC from January 1st, 2000 to December 31st, 2010 in Sweden (n=22).Data on demographics, medical and family history, circumstances of death, andanatomopathological findings were collected from several compulsory national healthregistries, clinical records, family interviews, and autopsy reports. Registry-based datawas compared with age-, sex- and geographically-matched population controls. Duringthe 6 months preceding SCD, 15 cases (68%) had experienced symptoms of cardiacorigin, mainly syncope or presyncope (54%), and chest discomfort (27%). Eight cases(36%) had sought medical care due to cardiac symptoms. The occurrence of hospitalvisits was significantly increased in cases compared with controls (OR 4.62 [1.35-15.8]). Ten cases (45%) had a family history of SCD. The most common activity at thetime of death was exercise (41%). Complete cardiac investigation was seldomperformed, only one case was diagnosed with ARVC before death. In conclusion, inthis nationwide study we observed a high prevalence of symptoms of cardiac origin,health-care utilization, and family history of SCD preceding SCD due to ARVC amongthe young. Increased awareness of these warning signals in the young is critical toimprove risk stratification and early disease detection.

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  • 18.
    Ekblom‐Bak, Elin
    et al.
    Department of Physical Activity and Health The Swedish School of Sport and Health Sciences Stockholm Sweden.
    Börjesson, Mats
    Center for Health and Performance Department of Molecular and Clinical Medicine Sahlgrenska Academy Gothenburg University Sweden;Dept MGA Sahlgrenska University Hospital Region Västra Götaland Gothenburg Sweden.
    Bergman, Frida
    Department of Public Health and Clinical Medicine Umeå University Umeå Sweden.
    Bergström, Göran
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Physiology Sahlgrenska University Hospital Gothenburg Sweden.
    Dahlin‐Almevall, Albin
    Department of Health, Learning and Technology Luleå University of Technology Luleå Sweden.
    Drake, Isabel
    Department of Clinical Sciences in Malmö Lund University, Malmö Sweden.
    Engström, Gunnar
    Department of Clinical Sciences in Malmö Lund University, Malmö Sweden.
    Engvall, Jan E.
    CMIV, Centre of Medical Image Science and Visualization Linköping University Linköping Sweden;Department of Clinical Physiology, and Department of Medical and Health Sciences Linköping University Linköping Sweden.
    Gummesson, Anders
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Genetics and Genomics Sahlgrenska University Hospital Gothenburg Sweden.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hjelmgren, Ola
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Physiology Sahlgrenska University Hospital Gothenburg Sweden.
    Jernberg, Tomas
    Department of Clinical Sciences Danderyd University Hospital Karolinska Institutet Stockholm Sweden.
    Johansson, Peter J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Mannila, Maria
    Heart and Vascular Theme Karolinska University Hospital Stockholm Sweden.
    Nyberg, André
    Department of Community Medicine and Rehabilitation Umeå University Umeå Sweden.
    Persson, Margaretha
    Department of Clinical Sciences in Malmö Lund University Malmö Sweden.
    Reitan, Christian
    Department of Clinical Sciences Danderyd University Hospital Karolinska Institutet Stockholm Sweden.
    Rosengren, Annika
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Physiology Sahlgrenska University Hospital Gothenburg Sweden.
    Rådholm, Karin
    Department of Health, Medicine and Caring Sciences Linköping University Linköping Sweden.
    Schmidt, Caroline
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg.
    Sköld, Magnus C.
    Department of Respiratory Medicine and Allergy Karolinska University Hospital Solna Stockholm Sweden;Respiratory Medicine Unit Department of Medicine Solna and Center for Molecular Medicine Karolinska Institutet Stockholm Sweden.
    Sonestedt, Emily
    Department of Clinical Sciences in Malmö Lund University Malmö Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. The George Institute for Global Health, University of New South Wales, Sydney, Australia.
    Swahn, Eva
    Department of Health, Medicine and Caring Sciences Linköping University Linköping Sweden;Department of Cardiology Linköping University Linköping Sweden.
    Öhlin, Jerry
    Department of Community Medicine and Rehabilitation Umeå University Umeå Sweden.
    Östgren, Carl Johan
    Department of Health, Medicine and Caring Sciences Linköping University Linköping Sweden.
    Ekblom, Örjan
    Department of Physical Activity and Health The Swedish School of Sport and Health Sciences Stockholm Sweden.
    Accelerometer derived physical activity patterns in 27.890 middle‐aged adults: The SCAPIS cohort study2022In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 32, no 5, p. 866-880Article in journal (Refereed)
    Abstract [en]

    The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.

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  • 19. Engström, G.
    et al.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Dekkers, Koen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lin, Yi-Ting
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ahlm, K.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alfredsson, J.
    Bergström, G.
    Blomberg, A.
    Brandberg, J.
    Caidahl, K.
    Cederlund, K.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engvall, J. E.
    Eriksson, M. J.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Gigante, B.
    Gummesson, A.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hamrefors, V.
    Hedner, J.
    Janzon, M.
    Jernberg, T.
    Johnson, L.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Mannila, M.
    Nilsson, U.
    Persson, A.
    Persson, H. L.
    Persson, M.
    Ramnemark, A.
    Rosengren, A.
    Schmidt, C.
    Skoglund Larsson, L.
    Sköld, C. M.
    Swahn, E.
    Söderberg, S.
    Torén, K.
    Waldenström, A.
    Wollmer, P.
    Zaigham, Suneela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Östgren, C. J.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications2024In: Eur J Epidemiol, ISSN 1573-7284 Electronic 0393-2990 LinkingArticle in journal (Refereed)
    Abstract [en]

    Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

  • 20.
    Figtree, Gemma A.
    et al.
    Royal North Shore Hosp, Kolling Inst, Sydney, NSW, Australia.;Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia.;Royal North Shore Hosp, Dept Cardiol, Sydney, NSW, Australia.
    Vernon, Stephen T.
    Royal North Shore Hosp, Kolling Inst, Sydney, NSW, Australia.;Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia.;Royal North Shore Hosp, Dept Cardiol, Sydney, NSW, Australia.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. UNSW Sydney, George Inst Global Hlth, Sydney, NSW, Australia.
    Alfredsson, Joakim
    Linköping Univ, Fac Med & Hlth Sci, Linköping, Sweden.
    Arnott, Clare
    UNSW Sydney, George Inst Global Hlth, Sydney, NSW, Australia.;Royal Prince Alfred Hosp, Dept Cardiol, Sydney, NSW, Australia.
    Delatour, Vincent
    Lab Natl Metrol & Essais, Paris, France.
    Leosdottir, Margret
    Lund Univ, Dept Clin Sci, Fac Med, Malmö, Sweden.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data2021In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 397, no 10279, p. 1085-1094Article in journal (Refereed)
    Abstract [en]

    Background In cardiovascular disease, prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes, hypercholesterolaemia, and smoking) are crucial; however, myocardial infarction in the absence of SMuRFs is not infrequent. The outcomes of individuals without SMuRFs are not well known.

    Methods We retrospectively analysed adult patients with first-presentation ST-elevation myocardial infarction (STEMI) using data from the Swedish myocardial infarction registry SWEDEHEART. Clinical characteristics and outcomes of adult patients (age >= 18 years) with and without SMuRFs were examined overall and by sex. Patients with a known history of coronary artery disease were excluded. The primary outcome was all-cause mortality at 30 days after STEMI presentation. Secondary outcomes included cardiovascular mortality, heart failure, and myocardial infarction at 30 days. Endpoints were also examined up to discharge, and to the end of a 12-year follow-up. Multivariable logistic regression models were used to compare in-hospital mortality, and Cox-proportional hazard models and Kaplan-Meier analysis for long-term outcomes.

    Findings Between Jan 1, 2005, and May 25, 2018, 9228 (14.9%) of 62 048 patients with STEMI had no SMuRFs reaching diagnostic thresholds. Median age was similar between patients with SMuRFs and patients without SMuRFs (68 years [IQR 59-78]) vs 69 years [60-78], p<0.0001). SMuRF-less patients had a similar rate of percutaneous coronary intervention to those with at least one modifiable risk factor, but were significantly less likely to receive statins, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockade (ARB), or beta-blockers at discharge. By 30 days after presentation, all-cause mortality was significantly higher in SMuRF-less patients (hazard ratio 1.47 [95% CI 1.37-1.57], p<0.0001). SMuRF-less women had the highest 30-day mortality (381 [17.6%] of 2164), followed by women with SMuRFs (2032 [11.1%] of 18 220), SMuRF-less men (660 [9.3%] of 7064), and men with SMuRFs (2117 [6.1%] of 34 600). The increased risk of 30-day all-cause mortality in SMuRF-less patients remained significant after adjusting for age, sex, left ventricular ejection fraction, creatinine, and blood pressure, but was attenuated on inclusion of pharmacotherapy prescription (ACEI or ARB, beta-blocker, or statin) at discharge. Additionally, SMuRF-less patients had a significantly higher rate of in-hospital all-cause mortality than patients with one or more SMuRF (883 [9.6%] vs 3411 [6.5%], p<0.0001). Myocardial infarction and heart failure at 30 days were lower in SMuRF-less patients. All-cause mortality remained increased in the SMuRF-less group for more than 8 years in men and up to the 12-year endpoint in women.

    Interpretation Individuals who present with STEMI in the absence of SMuRFs have a significantly increased risk of all-cause mortality, compared with those with at least one SMuRF, which was particularly evident in women. The increased early mortality rates are attenuated after adjustment for use of guideline-indicated treatments, highlighting the need for evidence-based pharmacotherapy during the immediate post-infarct period irrespective of perceived low risk. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

  • 21.
    Figtree, Gemma A.
    et al.
    Royal North Shore Hosp, Kolling Inst, Sydney, NSW, Australia.;Univ Sydney, Sydney, NSW, Australia.;Royal North Shore Hosp, Dept Cardiol, Sydney, NSW, Australia.
    Vernon, Stephen T.
    Royal North Shore Hosp, Kolling Inst, Sydney, NSW, Australia.;Univ Sydney, Sydney, NSW, Australia.;Royal North Shore Hosp, Dept Cardiol, Sydney, NSW, Australia.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. UNSW Sydney, George Inst Global Hlth, Sydney, NSW, Australia.
    Alfredsson, Joakim
    Linköping Univ, Fac Med & Hlth Sci, Linköping, Sweden.
    Nicholls, Stephen J.
    Monash Univ, Monash Cardiovasc Res Ctr, Victorian Heart Inst, Clayton, Vic, Australia.
    Chow, Clara K.
    Univ Sydney, Westmead Appl Res Ctr, Fac Med & Hlth, Sydney, NSW, Australia.;Westmead Hosp, Dept Cardiol, Sydney, NSW, Australia.
    Psaltis, Peter
    Univ Adelaide, Vasc Res Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.;Univ Adelaide, Adelaide Med Sch, Adelaide, SA, Australia.
    Røsjø, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Akershus Univ Hosp, Lorenskog, Norway; Univ Oslo, Oslo, Norway.
    Leósdóttir, Margrét
    Lund Univ, Dept Clin Sci, Fac Med, Malmö, Sweden.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Royal North Shore Hosp, Dept Cardiol, Sydney, NSW, Australia.
    Mortality and Cardiovascular Outcomes in Patients Presenting With Non-ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART Registry2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 15, article id 024818Article in journal (Refereed)
    Abstract [en]

    Background A significant proportion of patients with ST-segment-elevation myocardial infarction (MI) have no standard modifiable cardiovascular risk factors (SMuRFs) and have unexpected worse 30-day outcomes compared with those with SMuRFs. The aim of this article is to examine outcomes of patients with non-ST-segment-elevation MI in the absence of SMuRFs.

    Methods and Results Presenting features, management, and outcomes of patients with non-ST-segment-elevation MI without SmuRFs (hypertension, diabetes, hypercholesterolemia, smoking) were compared with those with SmuRFs in the Swedish MI registry SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies; 2005-2018). Cox proportional hazard models were used. Out of 99 718 patients with non-ST-segment-elevation MI, 11 131 (11.2%) had no SMuRFs. Patients without SMuRFs had higher all-cause and cardiovascular mortality at 30 days (hazard ratio [HR], 1.20 [95% CI, 1.10-1.30], P<0.0001; and HR, 1.25 [95% CI, 1.13-1.38]), a difference that remained after adjustment for age and sex. SMuRF-less patients were less likely to receive secondary prevention statins (76% versus 82%); angiotensin-converting enzyme inhibitors/angiotensin receptor blockade (54% versus 72%); or beta-blockers (81% versus 87%, P for all <0.0001), with lowest rates observed in women without SMuRFs. In patients who survived to 30 days, rates of all-cause and cardiovascular death were lower in patients without SMuRFs compared with those with risk factors, over 12 years.

    Conclusions One in 10 patients presenting with non-ST-segment-elevation MI present without traditional risk factors. The excess 30-day mortality rate in this group emphasizes the need for both improved population-based strategies for prevention of MI, as well as the need for equitable evidence-based treatment at the time of an MI.

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  • 22.
    Forbes, C. A.
    et al.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England..
    Deshpande, S.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England..
    Sorio-Vilela, F.
    Amgen Europe, Zug, Switzerland.;EEMEA, Zug, Switzerland..
    Kutikova, L.
    Amgen Europe GmbH, Zug, Switzerland..
    Duffy, S.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England..
    Gouni-Berthold, I
    Univ Cologne, Cologne, Germany..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Comparison Of Methods To Measure Patient Adherence And Persistence With Pharmacological Therapy: A Systematic Review2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A620-A620Article in journal (Other academic)
  • 23.
    Forbes, Carol A.
    et al.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England.
    Deshpande, Sohan
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England.
    Sorio-Vilela, Francesc
    Amgen Europe GmbH, Global Hlth Econ, Zug, Switzerland.
    Kutikova, Lucie
    Amgen Europe GmbH, Global Hlth Econ, Zug, Switzerland.
    Duffy, Steven
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England.
    Gouni-Berthold, Ioanna
    Univ Cologne, Polyclin Endocrinol Diabet & Prevent Med, Cologne, Germany.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    A systematic literature review comparing methods for the measurement of patient persistence and adherence2018In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 34, no 9, p. 1613-1625Article, review/survey (Refereed)
    Abstract [en]

    Objectives: A systematic literature review was conducted comparing different approaches estimating persistence and adherence in chronic diseases with polypharmacy of oral and subcutaneous treatments. Methods: This work followed published guidance on performing systematic reviews. Twelve electronic databases and grey literature sources were used to identify studies and guidelines for persistence and adherence of oral and subcutaneous therapies in hypercholesterolemia, type 2 diabetes, hypertension, osteoporosis and rheumatoid arthritis. Outcomes of interest of each persistence and adherence data collection and calculation method included pros: accurate, easy to use, inexpensive; and cons: inaccurate, difficult to use, expensive. Results: A total of 4158 records were retrieved up to March 2017. We included 16 observational studies, 5 systematic reviews and 7 guidelines, in patients with hypercholesterolemia (n=8), type 2 diabetes (n=4), hypertension (n=2), rheumatoid arthritis (n=1) and mixed patient populations (n=13). Pharmacy and medical records offer an accurate, easy and inexpensive data collection method. Pill count, medication event monitoring systems (MEMs), self-report questionnaires and observer report are easy to use. MEMS and biochemical monitoring tests can be expensive. Proportion of days covered (PDC) was recommended as a gold standard calculation method for long-term treatments. PDC avoids use of days' supply in calculation, hence is more accurate compared to medication possession ratio (MPR) to assess adherence to treatments in chronic diseases. Conclusions: Decisions on what method to use should be based on considerations of the route of medication administration, the resources available, setting and aim of the assessment. Combining different methods may provide wider insights into adherence and persistence, including patient behavior.

  • 24.
    Goodman, Shaun G.
    et al.
    Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada;Univ Toronto, St Michaels Hosp, Toronto, ON, Canada.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Ball, Eric
    Walla Walla Clin, Walla Walla, WA USA.
    Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 74, no 9, p. 1177-1186Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. The primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS In each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation.

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  • 25.
    Guimaraes, Patricia Oliveira
    et al.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Granger, Christopher B.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stebbins, Amanda
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hochman, Judith S.
    NYU, Dept Med, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA..
    Krug-Gourley, Susan
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, Collegeville, PA USA..
    Lonn, Eva
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Lopes, Renato D.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stewart, Ralph A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Danchin, Nicolas
    Hop Europeen Georges Pompidou, AP HP, INSERM U970, Paris, France.;Univ Paris 05, Paris, France..
    Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 9, article id e006695Article in journal (Refereed)
    Abstract [en]

    Background-Greater understanding of differences between men and women with coronary heart disease is needed. Methods and Results-In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P<0.0001). The median duration of follow-up was 3.7 years (25th-75th percentiles: 3.5-3.8 years). Use of evidence-based medications for coronary heart disease at baseline and 24 months was similar between sexes, as were event rates for all outcomes analyzed. In the multivariable model including psychosocial measures, female sex was associated with lower cardiovascular risk. There was a statistically significant interaction (P=0.03) such that the lower risk in women varied by depressive symptom frequency, whereby women who were more depressed had a risk similar to men. Conclusions-Female sex was independently associated with better long-term clinical outcomes, although this was modified by frequency of depressive symptoms. This suggests that emotional state may be an important target for improving outcomes in patients with coronary heart disease, specifically in women.

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  • 26.
    Hageman, Steven H. J.
    et al.
    Univ Med Ctr Utrecht, Dept Vasc Med, POB 85500, NL-3508 GA Utrecht, Netherlands.
    McKay, Ailsa J.
    Imperial Coll London, Dept Primary Care & Publ Hlth, London, England.
    Ueda, Peter
    Karolinska Inst, Dept Med, Clin Epidemiol Div, Stockholm, Sweden.
    Gunn, Laura H.
    Imperial Coll London, Dept Primary Care & Publ Hlth, London, England.;Univ North Carolina Charlotte, Dept Publ Hlth Sci, Charlotte, NC USA.;Univ North Carolina Charlotte, Sch Data Sci, Charlotte, NC USA.
    Jernberg, Tomas
    Karolinska Inst, Dept Clin Sci, Danderyd Hosp, Stockholm, Sweden.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Bhatt, Deepak L.
    Harvard Med Sch, Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA.
    Steg, Ph Gabriel
    Univ Paris, Hop Bichat, AP HP, INSERM Unite,French Alliance Cardiovasc Trials, F-1148 Paris, France.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Gynnild, Mari Nordbo
    NTNU Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, Dept Neuromed & Movement Sci, Trondheim, Norway.;Trondheim Reg & Univ Hosp, Dept Stroke, Clin Med, St Olavs Hosp, Trondheim, Norway.
    Ellekjaer, Hanne
    NTNU Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, Dept Neuromed & Movement Sci, Trondheim, Norway.;Trondheim Reg & Univ Hosp, Dept Stroke, Clin Med, St Olavs Hosp, Trondheim, Norway.
    Saltvedt, Ingvild
    NTNU Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, Dept Neuromed & Movement Sci, Trondheim, Norway.;Trondheim Reg & Univ Hosp, Dept Geriatr, Clin Med, St Olavs Hosp, Trondheim, Norway.
    Tunon, Jose
    Univ Autonoma Madrid, Fdn Jimenez Diaz, Dept Cardiol, Madrid, Spain.;CIBERCV, Madrid, Spain.
    Mahillo, Ignacio
    Fdn Jimenez Diaz, Dept Epidemiol, Madrid, Spain.
    Acena, Alvaro
    Univ Autonoma Madrid, Fdn Jimenez Diaz, Dept Cardiol, Madrid, Spain.
    Kaminski, Karol
    Med Univ Bialystok, Dept Populat Med & Lifestyle Dis Prevent, Bialystok, Poland.
    Chlabicz, Malgorzata
    Med Univ Bialystok, Dept Populat Med & Lifestyle Dis Prevent, Bialystok, Poland.;Med Univ Bialystok, Dept Invas Cardiol, Bialystok, Poland.
    Sawicka, Emilia
    Med Univ Bialystok, Dept Populat Med & Lifestyle Dis Prevent, Bialystok, Poland.;Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    Tillman, Taavi
    UCL, Ctr Noncommunicable Dis, Inst Global Hlth, London, England.
    McEvoy, John W.
    Natl Inst Prevent & Cardiovasc Hlth, Galway, Ireland.;Natl Univ Ireland Galway, Galway Campus, Galway, Ireland.
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England.
    Graham, Ian
    Univ Dublin, Trinity Coll Dublin, Sch Med, Dublin, Ireland.
    De Bacquer, Dirk
    Univ Ghent, Dept Publ Hlth & Primary Care, Ghent, Belgium.
    Ray, Kausik K.
    Imperial Coll London, Dept Primary Care & Publ Hlth, London, England.
    Dorresteijn, Jannick A. N.
    Univ Med Ctr Utrecht, Dept Vasc Med, POB 85500, NL-3508 GA Utrecht, Netherlands.
    Visseren, Frank L. J.
    Univ Med Ctr Utrecht, Dept Vasc Med, POB 85500, NL-3508 GA Utrecht, Netherlands.
    Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm2022In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 43, no 18, p. 1715-1727Article in journal (Refereed)
    Abstract [en]

    Aims The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations.

    Methods and results Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options.

    Conclusion The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

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  • 27.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 238, no 2, p. 420-426Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Diseases with abnormal levels of parathyroid hormone (PTH) and calcium, such as primary and secondary hyperparathyroidism, are associated with an increased risk of cardiovascular morbidity and mortality. However, there is paucity on the association between calcium, PTH and abnormalities in the vascular system in the general population.

    METHODS:

    In the PIVUS study (Prospective Investigation of the Vasculature in Uppsala Seniors), a community based cohort of 70-year old men and women (n = 1016), the associations between s-calcium, p-PTH and endothelial function, arterial stiffness and blood pressures were investigated, adjusting for cardiovascular risk factors and mineral metabolism.

    RESULTS:

    In multivariable linear regression models 1 SD increase in calcium was associated with 1.1 units decrease in the stroke volume/pulse pressure ratio and 0.06 decrease in common carotid artery distensibility (p < 0.001) indicative of increased arterial stiffness. Further, calcium was associated with increasing calculated central pulse pressure with 1.3 mmHg elevation per 1 SD increase in calcium (p < 0.05). 1 SD increase in PTH was associated with 1.9 and 1.0 mmHg increase in intra-arterially measured brachial artery systolic and diastolic blood pressures, respectively (p < 0.01), as well as 1.6 and 0.9 mmHg increase in calculated central systolic and diastolic blood pressures (p < 0.05). PTH was not associated with arterial stiffness, endothelial function or pulse pressure.

    CONCLUSION:

    In a large community-based sample of elderly, calcium was independently associated with increased arterial stiffness, and PTH independently to intra-arterial peripheral and calculated central blood pressures. The findings indicate a possible link between the vasculature and mineral metabolism.

  • 28.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barratt, Bryan J.
    Becker, Richard C.
    Himmelmann, Anders
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Katus, Hugo A.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Steg, Philippe G.
    Storey, Robert F.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Are There Any Causal Relations Between Growth Differentiation Factor 15 and Outcomes in Patients With Acute Coronary Syndrome?: - A Report From the Plato Gwas Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 29.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Response to Letter: 'Sorrow and cardiovascular events'2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 415-415Article in journal (Other academic)
  • 30.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Stewart, Ralph A H
    Aylward, Philip E
    Budaj, Andrzej
    Cannon, Christopher P
    Koenig, Wolfgang
    Krug-Gourley, Sue
    Mohler, Emile R
    Steg, Philippe Gabriel
    Tarka, Elizabeth
    Östlund, Ollie
    White, Harvey D
    Siegbahn, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 1, p. 325-333Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited.

    METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed.

    RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI.

    CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.

  • 31.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Tobias E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and the risk of cardiovascular mortality in the community2009In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, no 21, p. 2765-2771Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

  • 32.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 2, p. 317-324Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretion-in the normocalcaemic general population. MATERIALS AND METHODS: We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n = 961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT. RESULTS: In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg(-1) min(-1) (mU/l)(-1) x 100 (0.024 mg kg(-1) min(-1) [pmol/l](-1) x 100) decrease in M/I (p = 0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n = 413, regression coefficient for 1 SD increase -0.45, p = 0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR. CONCLUSION/INTERPRETATION: Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.

  • 33.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Tobias E.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and risk of congestive heart failure in the community2010In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, no 11, p. 1186-1192Article in journal (Refereed)
    Abstract [en]

    In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.

  • 34.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Becker, Richard C
    Himmelmann, Anders
    Husted, Steen
    Katus, Hugo A
    Steg, Philippe Gabriel
    Storey, Robert F
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Growth differentiation factor-15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes: results from the PLATO study2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 16, p. 1325-1333Article in journal (Refereed)
    Abstract [en]

    Aims Growth differentiation factor-15 (GDF-15) predicts death and composite cardiovascular (CV) events in patients with acute coronary syndrome (ACS). We investigated the independent associations between GDF-15 levels and major bleeding, the extent of coronary lesions and individual CV events in patients with ACS. Methods and results Growth differentiation factor-15 was analysed at baseline (n = 16 876) in patients with ACS randomized to ticagrelor or clopidogrel in the PLATO (PLATelet inhibition and patient Outcomes) trial. Growth differentiation factor-15 levels were related to extent of coronary artery disease (CAD) and to all types of non-coronary artery bypass grafting (CABG)-related major bleeding, spontaneous myocardial infarction (MI), stroke, and death during 12-month follow-up. In Cox proportional hazards models adjusting for established risk factors for CV disease and prognostic biomarkers (N-terminal pro B-type natriuretic peptide, cystatin C, high-sensitive C-reactive protein, and high-sensitive troponin T), 1 SD increase in ln GDF-15 was associated with increased risk of major bleeding with a hazard ratio (HR) 1.37 (95% confidence interval: 1.25-1.51) and with a similar increase in risk across different bleeding locations. For the same increase in ln GDF-15, the HR for the composite of CV death, spontaneous MI, and stroke was 1.29 (1.21-1.37), CV death 1.41 (1.30-1.53), all-cause death 1.41 (1.31-1.53), spontaneous MI 1.15 (1.05-1.26), and stroke 1.19 (1.01-1.42). The C-statistic improved for the prediction of CV death and non-CABG-related major bleeding when adding GDF-15 to established risk factors. Conclusions In patients with ACS, higher levels of GDF-15 are associated with raised risks of all types of major non-CABG-related bleeding, spontaneous MI, and stroke as well as CV and total mortality and seem to improve risk stratification for CV-mortality and major bleeding beyond established risk factors.

  • 35.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Plasma Parathyroid Hormone Is Associated with Vascular Dementia and Cerebral Hyperintensities in Two Community-Based Cohorts2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 11, p. 4181-4189Article in journal (Refereed)
    Abstract [en]

    Context:

    In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

    Objective:

    We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease.

    Setting and Design:

    The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

    Participants and Main Outcome Measure:

    In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

    Results:

    During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

    Conclusions:

    In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

  • 36.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lundgren, Ewa
    Hellman, Per
    Primary Hyperparathyroidism is associated with low insulin sensitivity and impaired glucose metabolismManuscript (Other academic)
  • 37.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Lithell, Hans
    Berglund, Lars
    Ljunghall, Sverker
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years2002In: Clinical Endocrinology (Oxf), ISSN 0300-0664, Vol. 56, no 2, p. 253-260Article in journal (Refereed)
  • 38.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism2006In: Journal of Internal Medicine, ISSN 0954-6820, Vol. 259, no 2, p. 191-198Article in journal (Refereed)
  • 39.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening2006In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 155, no 1, p. 33-39Article in journal (Refereed)
    Abstract [en]

    Objective: Dyslipidemia, hypertension, diabetes mellitus and also primary hyperparathyroidism (pHPT)are associated with an increased risk of cardiovascular diseases. Metabolic abnormalities in mild pHPThave been reported, but never in cases with normal calcium and high parathyroid hormone (PTH)levels, i.e. suffering from ‘normocalcemic pHPT’. Our aim was to explore the occurrence of thesemetabolic abnormalities in individuals with normocalcemic pHPT identified in a population-basedscreening, and the effects of parathyroidectomy vs conservative treatment on metabolic variables.Design and methods: A population-based screening of 5202 post-menopausal women identified 30patients with normal calcium, inappropriately high PTH and normal creatinine. A 5-year follow-upincluded 15 parathyroidectomized (PTx) and nine conservatively followed cases, in a non-randomizedsetting, together with age-matched controls. Biochemical variables and body mass index (BMI) wereinvestigated.Results: At study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein (LDL)/highdensitylipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, total triglycerides,and BMI compared to controls (PZ!0.0001–0.035). The cases had a lower HDL-cholesterolvalue (PZ0.013) and one third of the cases had hypertriglyceridemia. During follow-up, the PTx casesdecreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (PZ0.0076–0.022).Investigated biochemical variables remained adverse in conservatively followed cases during follow-upexcept a decreased LDL-cholesterol value. All surgically treated patients had parathyroid adenoma.Conclusions: Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels, BMIand glucose levels compared to age-matched controls. Parathyroidectomy has positive effects on someof these variables and reverses them to the same level as the controls, while conservative treatmentfails to normalize the investigated metabolic variables.

  • 40.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Plasma-Parathyroid Hormone Is Associated With Subclinical and Clinical Atherosclerotic Disease in 2 Community-Based Cohorts2014In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 34, no 7, p. 1567-73Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.

    APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.

    CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.

  • 41.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala Univ, Dept Publ Hlth, Uppsala, Sweden.;Uppsala Univ, Caring Sci, Clin Psychol Healthcare, Uppsala, Sweden..
    Harrington, R. A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Lopez-Sendon, J.
    Hosp Univ La Paz, Dept Cardiol, IdiPaz, Madrid, Spain..
    Soffer, J.
    GlaxoSmithKline, Metabol Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA..
    Stebbins, A.
    Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA..
    Stewart, R. A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, H. D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Living alone and depressive symptoms are associated with major cardiovascular events in patients with chronic coronary heart disease2015Conference paper (Refereed)
  • 42.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Stebbins, Amanda
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    Armstrong, P W
    University of Alberta, Edmonton, Canada..
    Chiswell, K
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    Granger, C B
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    López-Sendón, J
    Hospital Universitario La Paz, Instituto de investigacion IdiPaz, Paseo de la Castellana, Madrid, Spain..
    Pella, D
    Department of Medicine, PJ Safarik University, Kosice, Slovakia..
    Soffer, J
    Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Collegeville, PA, USA..
    Sy, R
    Department of Internal Medicine, College of Medicine, University of the Philippines-Manila, Manila, Philippines..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    White, H D
    Green Lane Cardiovascular Service, Auckland, New Zealand.; University of Auckland, Auckland, New Zealand..
    Stewart, R A H
    Green Lane Cardiovascular Service, Auckland, New Zealand.; University of Auckland, Auckland, New Zealand..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 1, p. 83-92Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD).

    METHODS: Psychosocial stress was assessed by a questionnaire in 14 577 patients (median age 65.0, IQR 59, 71; 81.6% males) with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial. Adjusted Cox regression models were used to assess associations between individual stressors, baseline cardiovascular risk factors and outcomes.

    RESULTS: After 3.7 years of follow-up, depressive symptoms, loss of interest and financial stress were associated with increased risk (hazard ratio, 95% confidence interval) of CV death (1.21, 1.09-1.34; 1.15, 1.05-1.27; and 1.19, 1.08-1.30, respectively) and the primary composite end-point of CV death, nonfatal MI or nonfatal stroke (1.21, 1.13-1.30; 1.19, 1.11-1.27; and 1.17, 1.10-1.24, respectively). Living alone was related to higher risk of CV death (1.68, 1.38-2.05) and the primary composite end-point (1.28, 1.11-1.48), whereas being married as compared with being widowed, was associated with lower risk of CV death (0.64, 0.49-0.82) and the primary composite end-point (0.81, 0.67-0.97).

    CONCLUSIONS: Psychosocial stress, such as depressive symptoms, loss of interest, living alone and financial stress, were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment. Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials.

  • 43.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Roe, Matthew T.
    Duke Univ, Sch Med, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA..
    Hafley, Gail
    Duke Univ, Sch Med, Duke Clin Res Inst, Dept Stat, Durham, NC USA..
    Neely, Megan L.
    Duke Univ, Sch Med, Duke Clin Res Inst, Dept Stat, Durham, NC USA..
    Sidhu, Mandeep S.
    Albany Stratton VA Med Ctr, Dept Med, Albany, NY USA. Albany Med Coll, Albany Med Ctr, Albany, NY 12208 USA..
    Winters, Kenneth J.
    Eli Lilly & Co, Indianapolis, IN 46285 USA..
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control & Publ Hlth Fdn India, New Delhi, India..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Armstrong, Paul W.
    Univ Alberta, Canadian VIGOUR Ctr, Dept Med, Div Cardiol, Edmonton, AB, Canada..
    Fox, Keith A. A.
    Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland..
    Ohman, Magnus
    Duke Univ, Sch Med, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA..
    Boden, William E.
    Albany Stratton VA Med Ctr, Dept Med, Albany, NY USA. Albany Med Coll, Albany Med Ctr, Albany, NY 12208 USA..
    Association Between Very Low Levels of High-Density Lipoprotein Cholesterol and Long-term Outcomes of Patients With Acute Coronary Syndrome Treated Without Revascularization: Insights From the TRILOGY ACS Trial2016In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 39, no 6, p. 329-337Article in journal (Refereed)
    Abstract [en]

    Background: Low levels of high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL) are associated with increased risk of cardiovascular events, but it is unclear whether lower thresholds (< 30 mg/dL) are associated with increased hazard.

    Hypothesis: Very low levels of HDL-C may provide prognostic information in acute coronary syndrome (ACS) patients treated medically without revascularization.

    Methods: We examined data from 9064/9326 ACS patients enrolled in the TRILOGY ACS trial. Participants were randomized to clopidogrel or prasugrel plus aspirin. Study treatments continued for 6 to 30 months. Relationships between baseline HDL-C and the composite of cardiovascular death, myocardial infarction (MI), or stroke, and individual endpoints of death (cardiovascular and all-cause), MI, and stroke, adjusted for baseline characteristics through 30 months, were analyzed. The HDL-C was evaluated as a dichotomous variable-very low (< 30 mg/dL) vs higher (>= 30 mg/dL)-and continuously.

    Results: Median baseline HDL-C was 42mg/dL (interquartile range, 34-49mg/dL) with little variation over time. Frequency of the composite endpoint was similar for very low vs higher baseline HDL-C, with no risk difference between groups (hazard ratio [ HR]: 1.13, 95% confidence interval [ CI]: 0.95-1.34). Similar findings were seen for MI and stroke. However, risks for cardiovascular (HR: 1.42, 95% CI: 1.13-1.78) and all-cause death (HR: 1.36, 95% CI: 1.11-1.67) were higher in patients with very low baseline HDL-C.

    Conclusions: Medically managed ACS patients with very low baseline HDL-C levels have higher risk of long-term cardiovascular and all-cause death but similar risks for nonfatal ischemic outcomes vs patients with higher baseline HDL-C.

  • 44.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Sorio Vilela, Francesc
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Amgen AB, Gustav III:s Boulevard 54, 169 74, Solna Municipality, Sweden.
    Hallberg, Sara
    Söreskog, Emma
    Villa, Guillermo
    Cardiovascular Event Rates After Myocardial Infarction or Ischaemic Stroke in Patients with Additional Risk Factors: A Retrospective Population-Based Cohort Study2021In: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 38, no 9, p. 4695-4708Article in journal (Refereed)
    Abstract [en]

    Introduction: The impact of additional risk factors on major cardiovascular event (MACE) rates in patients with a history of myocardial infarction (MI) or ischaemic stroke (IS) treated with statins is not well defined.

    Methods: In this retrospective population-based cohort study, patients with a history of MI or IS treated with moderate- or high-intensity statins were identified using Swedish national register data. Patients were incident (index event between July 2006 and December 2014 and followed from diagnosis) or prevalent (MI or IS before July 2006 and followed thereafter). Four subgroups were defined on the basis of additional risk factors associated with increased cardiovascular risk: diabetes mellitus with target organ damage; chronic kidney disease stages 3-4; index event within 2 years after prior MI or IS; and polyvascular disease. First and total MACE rates (i.e. MI, IS, or cardiovascular death) were calculated, and first MACE 10-year risks (prevalent cohort only) were predicted.

    Results: Numerically, MACE rates in subgroups were 1.5-3 times higher than in overall populations, and were highest in the 2 years after the index event. First MACE rates in the additional risk factor subgroups were 17.2-33.5 per 100 person-years for the incident cohorts and 9.9-13.2 per 100 person-years for the prevalent cohorts. Total MACE rates per 100 person-years were 20.1-39.8 per 100 person-years and 12.4-17.6 per 100 person-years, respectively.

    Conclusion: Despite previous use of moderate- or high-intensity statins, patients with a history of MI or IS, and additional risk factors remain at very high cardiovascular risk.

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  • 45.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Steg, P. Gabriel
    Univ Paris, Hop Bichat, AP HP, Dept Cardiol,FACT French Alliance Cardiovasc Tria, Paris, France.;INSERM U1148, Paris, France.;Imperial Coll, Royal Brompton Hosp, London, England..
    Szarek, Michael
    Univ Colorado, Sch Med, CPC Clin Res, Aurora, CO USA.;Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA.;SUNY Downstate Hlth Sci Univ, Brooklyn, NY USA..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Heart & Vasc Ctr, Dept Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Bittner, Vera A.
    Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA..
    Danchin, Nicolas
    Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France.;Univ Paris 05, Paris, France..
    Diaz, Rafael
    Inst Cardiovasc Rosario, Estudios Cardiol Latino Amer, Rosario, Argentina..
    Goodman, Shaun G.
    Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada.;Univ Toronto, St Michaels Hosp, Toronto, ON, Canada..
    Harrington, Robert A.
    Stanford Univ, Stanford Ctr Clin Res, Dept Med, Stanford, CA 94305 USA..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Netherlands Heart Inst, Utrecht, Netherlands..
    Liberopoulos, Evangelos
    Natl & Kapodistrian Univ Athens, Sch Med, Athens, Greece..
    Marx, Nikolaus
    Rhein Westfal TH Aachen, Univ Hosp, Aachen, Germany..
    McGinniss, Jennifer
    Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA..
    Manvelian, Garen
    Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA..
    Pordy, Robert
    Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA..
    Scemama, Michel
    Sanofi, Paris, France..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Auckland Univ, Auckland, New Zealand..
    Zeiher, Andreas M.
    Goethe Univ, Dept Med 3, Frankfurt, Germany..
    Schwartz, Gregory G.
    Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA..
    Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab2022In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 146, no 9, p. 657-672Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score-matched models. RESULTS: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9-3.6], 4.0 [95% CI, 3.6-4.5], and 5.5 [95% CI, 5.0-6.1] events per 100 patient-years in strata <75, 75-<90, >= 90 mg/dL, respectively; P-trend<0.0001) and after adjustment for low-density lipoprotein cholesterol (P-trend=0.035). Higher baseline apoB stratum was associated with greater relative (P-trend<0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78-4.79], 3.09 [95% CI, 2.69-3.54], and 2.41 [95% CI, 2.11-2.76] events per 100 patient-years in strata >= 50, >35-<50, and <= 35 mg/dL, respectively). Compared with propensity score-matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol but not vice versa. CONCLUSIONS: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as <= 35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome.

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  • 46.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wojdyla, D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Neely, M. L.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Stevens, S. R.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Harrington, R. A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Alexander, J. H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Goodman, S. G.
    Univ Toronto, St Michaels Hosp, Canadian Heart Res Ctr, Terrence Donnelly Heart Ctr, Toronto, ON, Canada..
    Lopes, R. D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Management and clinical consequences of major bleeding in high-risk patients following an acute coronary syndrome. Is aspirin the problem?: Insights from the APPRAISE-2 trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 861-862Article in journal (Other academic)
  • 47.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and the risk of cerebrovascular diseases in the community2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 236-236Article in journal (Other academic)
  • 48.
    Held, Claes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Aylward, Philip E.
    Flinders Univ S Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.;Med Ctr, Adelaide, SA, Australia..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hochman, Judith S.
    NYU, Langone Med Ctr, Dept Med, New York, NY USA..
    Stewart, Ralph A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala Univ, Cardiol, Dept Med Sci, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Body Mass Index and Association With Cardiovascular Outcomes in Patients With Stable Coronary Heart Disease - A STABILITY Substudy2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 3, article id e023667Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The obesity paradox states that patients with higher body mass index (BMI) and cardiovascular disease may experience better prognosis. However, this is less clear in patients with coronary heart disease. METHODS AND RESULTS: The prospective STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial included 15 828 patients with stable coronary heart disease with 3 to 5 years' follow-up on optimal secondary preventive treatment. BMI was measured at baseline (n=15 785). Associations between BMI and cardiovascular outcomes were evaluated by Cox regression analyses with multivariable adjustments. Mean age was 64 +/- 9 years and 19% women. Most risk markers (diabetes, hypertension, inflammatory biomarkers, triglycerides) showed a graded association with higher BMI. The frequency of smoking, levels of high-density lipoprotein, growth differentiation factor 15, and NT-proBNP (N-terminal pro-Btype natriuretic peptide) were higher at lower BMI. Low BMI (<20 kg/m(2); n=244 [1.5%]) was associated with doubled risk of total death (hazard ratio [HR], 2.27; 95% CI, 1.60-3.22), cardiovascular death (HR, 2.26; 95% CI, 1.46-3.49), and heart failure (HR, 2.51; 95% CI, 1.35-4.68) compared with BMI of 25 to <30 kg/m(2) (n=6752 [42.8%]) as reference. Similarly, high BMI of >= 35 kg/m(2) (n=1768 [11.2%]) was associated with increased risk of the same outcomes. A BMI between 20 and <25 kg/m(2) was associated with increased risk of cardiovascular death (HR, 1.26; 95% CI, 1.03-1.54) and total death (HR, 1.21; 95% CI, 1.03-1.42). CONCLUSIONS: Patients with stable coronary heart disease showed a graded increase in cardiometabolic and inflammatory risk factors with increasing BMI category >25 kg/m(2). All-cause and cardiovascular mortality were lowest at BMI of 25 to 35 kg/m(2). Underweight with BMI of <20 kg/m(2) and very high BMI of >= 35 kg/m(2) were strong risk markers for poor prognosis.

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  • 49.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Low-renin hypertension2014In: Primary aldosteronism: Molocular Genetics, Endocrinology and Translational Medicine / [ed] Hellman, Per, New York: Springer , 2014, p. 39-44Chapter in book (Refereed)
  • 50.
    Hess, Connie N.
    et al.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Roe, Matthew T.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Clare, Robert M.
    Duke Clin Res Inst, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Clin Res Inst, Durham, NC 27705 USA..
    Kelly, Joseph
    Duke Clin Res Inst, Durham, NC 27705 USA.;Duke Clin Res Inst, Ctr Learning Healthcare, Durham, NC 27705 USA..
    Tcheng, James E.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Dept Med Sci Cardiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Khouri, Michel G.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA..
    Hirsch, Bradford R.
    Duke Clin Res Inst, Durham, NC 27705 USA.;Duke Canc Inst, Durham, NC USA..
    Kong, David F.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Abernethy, Amy P.
    Duke Univ, Div Med Oncol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Ctr Learning Healthcare, Durham, NC 27705 USA.;Duke Canc Inst, Durham, NC USA..
    Krucoff, Mitchell W.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Relationship Between Cancer and Cardiovascular Outcomes Following Percutaneous Coronary Intervention2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 7, article id e001779Article in journal (Refereed)
    Abstract [en]

    Background-Cardiovascular disease and cancer increasingly coexist, yet relationships between cancer and long-term cardiovascular outcomes post-percutaneous coronary intervention (PCI) are not well studied. Methods and Results-We examined stented PCI patients at Duke (1996-2010) using linked data from the Duke Information Systems for Cardiovascular Care and the Duke Tumor Registry (a cancer treatment registry). Our primary outcome was cardiovascular mortality. Secondary outcomes included composite cardiovascular mortality, myocardial infarction, or repeat revascularization and all-cause mortality. We used adjusted cause-specific hazard models to examine outcomes among cancer patients (cancer treatment pre-PCI) versus controls (no cancer treatment pre-PCI). Cardiovascular mortality was explored in a cancer subgroup with recent (within 1 year pre-PCI) cancer and in post-PCI cancer patients using post-PCI cancer as a time-dependent variable. Among 15 008 patients, 3.3% (n=496) were cancer patients. Observed rates of 14-year cardiovascular mortality (31.4% versus 27.7%, P=0.31) and composite cardiovascular death, myocardial infarction, or revascularization (51.1% versus 55.8%, P=0.37) were similar for cancer versus control groups; all-cause mortality rates were higher (79.7% versus 49.3%, P<0.01). Adjusted risk of cardiovascular mortality was similar for cancer patients versus controls (hazard ratio 0.95; 95% CI 0.76 to 1.20) and for patients with versus without recent cancer (hazard ratio 1.46; 95% CI 0.92 to 2.33). Post-PCI cancer, present in 4.3% (n=647) of patients, was associated with cardiovascular mortality (adjusted hazard ratio 1.51; 95% CI 1.11 to 2.03). Conclusions-Cancer history was present in a minority of PCI patients but was not associated with worse long-term cardiovascular outcomes. Further investigation into PCI outcomes in this population is warranted.

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