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  • 51.
    Alehagen, Urban
    et al.
    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85, Linköping, Sweden..
    Alexander, Jan
    Norwegian Institute of Public Health, Oslo, Norway..
    Aaseth, Jan O
    Department of Research, Innlandet Hospital Trust, Brumunddal, Norway..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Opstad, Trine B
    Center for Clinical Heart Research - Laboratory, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway..
    Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium - positive effects on thyroid hormones, cardiovascular mortality, and quality of life2024In: BMC Medicine, E-ISSN 1741-7015, Vol. 22, no 1, article id 191Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL).

    METHODS: Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses.

    RESULTS: In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group.

    CONCLUSIONS: Supplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency.

    TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.

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  • 52.
    Alehagen, Urban
    et al.
    Linköping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Cardiovasc Med, SE-58185 Linköping, Sweden..
    Shamoun, Levar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Dept Lab Med, Div Med Diagnost, SE-55305 Jönköping, Sweden..
    Dimberg, Jan Ingvar
    Jönköping Univ, Sch Hlth & Welf, Dept Nat Sci & Biomed, SE-55318 Jönköping, Sweden..
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 322021In: Experimental and Therapeutic Medicine, ISSN 1792-0981, E-ISSN 1792-1015, Vol. 21, no 2, article id 127Article in journal (Refereed)
    Abstract [en]

    One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin-32 (IL-32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL-32 and plasma expression, and their associations with mortality. A population of 486 elderly community-living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL-32 rs28372698 using allelic discrimination and plasma measurement of IL-32, using ELISA, were performed. During the follow-up period, 140 (28.8%) all-cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL-32 was observed. The A/A genotype group exhibited significantly higher all-cause mortality (P=0.036), and an almost two-fold increased risk in a multivariate Cox regression model for all-cause and cardiovascular mortality. A highly significant difference in all-cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL-32 was demonstrated to have prognostic information, with an increased risk of all-cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL-32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis-generating.

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  • 53.
    Alehagen, Urban
    et al.
    Linköping Univ, Fac Med, Dept Hlth Med & Caring Sci, Div Cardiovasc Med, SE-58185 Linköping, Sweden.
    Shamoun, Levar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Jönköping Cty, Div Med Diagnost, Dept Lab Med, SE-55305 Jönköping, Sweden.
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality: Results from a 6.7-year follow-up of a healthy community-living elderly population2020In: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 22, no 6, p. 4629-4636Article in journal (Refereed)
    Abstract [en]

    Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.

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  • 54.
    Alehagen, Urban
    et al.
    Linköping Univ, Inst Med & Hlth Sci, Div Cardiovasc Med, Dept Med & Hlth Sci, Fac Hlth Sci, SE-58185 Linköping, Sweden.
    Shamoun, Levar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Jönköping Cty, Div Med Diagnost, Dept Lab Med, Jönköping, Sweden.
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Increased cardiovascular mortality in females with the a/a genotype of the SNPs rs1478604 and rs2228262 of thrombospondin-12020In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 21, no 1, article id 179Article in journal (Refereed)
    Abstract [en]

    Background

    Cardiovascular diseases are still the major cause of death in the Western world, with different outcomes between the two genders. Efforts to identify those at risk are therefore given priority in the handling of health resources. Thrombospondins (TSP) are extracellular matrix proteins associated with cardiovascular diseases. The aim of this study was to investigate variations in single nucleotide polymorphisms (SNPs) of TSP-1 and plasma expression, and associations with mortality from a gender perspective.

    Methods

    A population of 470 community-living persons were invited to participate. The participants were followed for 7.9 years and underwent a clinical examination and blood sampling. SNP analyses of TSP-1 rs1478604 and rs2228262 using allelic discrimination and plasma measurement of TSP-1 using ELISA were performed,

    Results

    During the follow-up period, 135 (28.7%) all-cause and 83 (17.7%) cardiovascular deaths were registered.

    In the female population, the A/A genotype of rs2228262 and the T/T genotype of rs1478604 exhibited significantly more cardiovascular deaths compared with the A/G and G/G, or the T/C and C/C genotypes amalgamated (rs2228262: 13.7% vs 2.0%; Χ2:5.29; P = 0.02; rs1478604:17.7% vs 4.7%; Χ2:9.50; P = 0.002). Applied in a risk evaluation, the A/A, or T/T genotypes exhibited an increased risk of cardiovascular mortality (rs2228262: HR: 7.1; 95%CI 1.11–45.8; P = 0.04; rs1478604: HR: 3.18; 95%CI 1.35–7.50; p = 0.008). No differences among the three genotypes could be seen in the male group.

    Conclusion

    In this study the female group having the A/A genotype of rs2228262, or the T/T genotype of rs1478604 of TSP-1 exhibited higher cardiovascular mortality after a follow-up of almost 8 years. No corresponding genotype differences could be found in the male group. Genotype evaluations should be considered as one of the options to identify individuals at risk. However, this study should be regarded as hypothesis-generating, and more research in the field is needed.

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  • 55.
    Alehagen, Urban
    et al.
    Linkoping Univ, Div Cardiovasc Med, Fac Med & Hlth Sci, SE-58185 Linkoping, Sweden.
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gender difference and genetic variance in lipoprotein receptor-related protein 1 is associated with mortality2019In: BIOMEDICAL REPORTS, ISSN 2049-9434, Vol. 11, no 1, p. 3-10Article in journal (Refereed)
    Abstract [en]

    Cardiovascular diseases are an important health resource problem and studies have shown a genetic association between single nucleotide polymorphisms (SNPs) and cardiovascular diseases. According to the literature, lipoprotein receptor-related protein 1 (LRP1) is associated with coronary artery disease. The aim of the present study was to evaluate a possible association between different genotypes of LRP1 and all-cause and cardiovascular mortality from a gender perspective. In the present study, 489 elderly community-living people were invited to participate. Clinical examination, echocardiography and blood sampling including SNP analyses of LRP1 (rs1466535) were performed, including the T/T, C/T and C/C genotypes, and the participants were followed for 6.7 years. During the follow-up period, 116 (24%) all-cause and 75 (15%) cardiovascular deaths were registered. In the female population, the LRP1 of the T/T or C/T genotype exhibited a 5.6-fold increased risk of cardiovascular mortality and a 2.8-fold increased risk of all-cause mortality compared with the C/C genotype. No such genotype differences could be seen in the male population. Gender differences could be seen regarding the risk of mortality in the different genotypes. Females with the LRP1 T/T or C/T genotypes exhibited a significantly increased risk of both all-cause and cardiovascular mortality compared with the C/C genotypes. Therefore, more individualized cardiovascular prevention and treatment should be prioritized. However, since this was a small study, the observations should only be regarded as hypothesis-generating.

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  • 56.
    Alexander, J.
    et al.
    Duke Clin Res Inst, Durham, NC USA..
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, R. D.
    Duke Clin Res Inst, Durham, NC USA..
    Hijazi, Ziad
    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, Dept Med Sci, Cardiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Hohnloser, S. H.
    Goethe Univ Frankfurt, Div Cardiac Electrophysiol, D-60054 Frankfurt, Germany..
    Ezekowitz, J.
    Univ Alberta, Edmonton, AB, Canada..
    Halvorsen, S.
    Oslo Univ Hosp, Dept Cardiol, Oslo, Norway..
    Hanna, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Granger, C. B.
    Duke Clin Res Inst, Durham, NC USA..
    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.
    Stroke and bleeding outcomes with apixaban versus warfarin in patients with high creatinine, low body weight or high age receiving standard dose apixaban for stroke prevention in atrial fibrillation2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 345-345Article in journal (Other academic)
  • 57. Alexander, John H
    et al.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, Renato D
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hohnloser, Stefan H
    Ezekowitz, Justin A
    Halvorsen, Sigrun
    Hanna, Michael
    Commerford, Patrick
    Ruzyllo, Witold
    Huber, Kurt
    Al-Khatib, Sana M
    Granger, Christopher B
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine: A Secondary Analysis of a Randomized Clinical Trial2016In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 1, no 6, p. 673-681Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: In the Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) trial, the standard dose of apixaban was 5 mg twice daily; patients with at least 2 dose-reduction criteria-80 years or older, weight 60 kg or less, and creatinine level 1.5 mg/dL or higher-received a reduced dose of apixaban of 2.5 mg twice daily. Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban.

    OBJECTIVE: To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5 mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria.

    DESIGN, SETTING, AND PARTICIPANTS: Among 18 201 patients in the ARISTOTLE trial, 17 322 were included in this analysis. Annualized event rates of stroke or systemic embolism and major bleeding and hazard ratios (HRs) and 95% CIs were evaluated. Interactions between the effects of apixaban vs warfarin and the presence of 1 or no dose-reduction criteria were assessed. The first patient was enrolled in the ARISTOTLE trial on December 19, 2006, and follow-up was completed on January 30, 2011. Data were analyzed from January 2015 to May 30, 2016.

    MAIN OUTCOMES AND MEASURES: Analysis of major bleeding included events during study drug treatment. Analysis of stroke or systemic embolism was based on intention to treat.

    RESULTS: Of the patients with 1 or no dose-reduction criteria assigned to receive the 5 mg twice daily dose of apixaban or warfarin, 3966 had 1 dose-reduction criterion; these patients had higher rates of stroke or systemic embolism (HR, 1.47; 95% CI, 1.20-1.81) and major bleeding (HR, 1.89; 95% CI, 1.62-2.20) compared with those with no dose-reduction criteria (n = 13 356). The benefit of the 5 mg twice daily dose of apixaban (n = 8665) compared with warfarin (n = 8657) on stroke or systemic embolism in patients with 1 dose-reduction criterion (HR, 0.94; 95% CI, 0.66-1.32) and no dose-reduction criterion (HR, 0.77; 95% CI, 0.62-0.97) were similar (P for interaction = .36). Similarly, the benefit of 5 mg twice daily dose of apixaban compared with warfarin on major bleeding in patients with 1 dose-reduction criterion (HR, 0.68; 95% CI, 0.53-0.87) and no dose-reduction criterion (HR, 0.72; 95% CI, 0.60-0.86) were similar (P for interaction = .71). Similar patterns were seen for each dose-reduction criterion and across the spectrum of age, body weight, creatinine level, and creatinine clearance.

    CONCLUSIONS AND RELEVANCE: Patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5 mg twice daily dose of apixaban vs warfarin compared with patients without these characteristics. The 5 mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion.

    TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00412984.

  • 58. Alexander, Karen P
    et al.
    Brouwer, Marc A
    Mulder, Hillary
    Vinereanu, Dragos
    Lopes, Renato D
    Proietti, Marco
    Al-Khatib, Sana M
    Hijazi, Ziad
    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.
    Halvorsen, Sigrun
    Hylek, Elaine M
    Verheugt, Freek W A
    Alexander, John H
    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.
    Granger, Christopher B
    Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial2019In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 208, p. 123-131, article id S0002-8703(18)30296-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.

    METHODS: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.

    RESULTS: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban.

    CONCLUSIONS: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.

  • 59.
    Alexander, Karen P.
    et al.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Weisz, Giora
    Shaare Zedek Med Ctr, Jerusalem, Israel.;Cardiovasc Res Fdn, New York, NY USA..
    Prather, Kristi
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mark, Daniel B.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Anstrom, Kevin J.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Davidson-Ray, Linda
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Witkowski, Adam
    Inst Cardiol, Dept Intervent Cardiol & Angiol, Warsaw, Poland..
    Mulkay, Angel J.
    Holy Name Med Ctr, Hackensack, NJ USA..
    Osmukhina, Anna
    Gilead Sci Inc, Foster City, CA 94404 USA..
    Farzaneh-Far, Ramin
    Gilead Sci Inc, Foster City, CA 94404 USA..
    Ben-Yehuda, Ori
    Cardiovasc Res Fdn, New York, NY USA.;Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10027 USA..
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10027 USA..
    Ohman, E. Magnus
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 133, no 1, p. 39-47Article in journal (Refereed)
    Abstract [en]

    Background Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. Methods and Results In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.324.5 versus 69.724.0, P=0.01) to month 1 (86.6 +/- 18.1 versus 85.8 +/- 18.5, P=0.27) and month 12 (88.4 +/- 17.8 versus 88.5 +/- 17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency 60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. Conclusions Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.

  • 60. Alfonso, Fernando
    et al.
    Zelveian, Parounak
    Monsuez, Jean Jacques
    Aschermann, Michael
    Boehm, Michael
    Hernandez, Alfonso Buendia
    Wang, Tzung Dau
    Cohen, Ariel
    Izetbegovic, Sebija
    Doubell, Anton
    Echeverri, Dario
    Enç, Nuray
    Ferreira-González, Ignacio
    Undas, Anetta
    Fortmüller, Ulrike
    Gatzov, Plamen
    Ginghina, Carmen
    Goncalves, Lino
    Faouzi, Addad
    Hassanein, Mahmoud
    Heusch, Gerd
    Huber, Kurt
    Hatala, Robert
    Ivanusa, Mario
    Lau, Chu Pak
    Marinskis, Germanas
    Cas, Livio Dei
    Rochitte, Carlos Eduardo
    Nikus, Kjell
    Fleck, Eckart
    Pierard, Luc
    Obradović, Slobodan
    Del Pilar Aguilar Passano, María
    Jang, Yangsoo
    Rødevand, Olaf
    Sander, Mikael
    Shlyakhto, Evgeny
    Erol, Çetin
    Tousoulis, Dimitris
    Ural, Dilek
    Piek, Jan J
    Varga, Albert
    Flammer, Andreas J
    Mach, François
    Dibra, Alban
    Guliyev, Faiq
    Mrochek, Alexander
    Rogava, Mamanti
    Melgar, Ismael Guzman
    Di Pasquale, Giuseppe
    Kabdrakhmanov, Kanat
    Haddour, Laila
    Fras, Zlatko
    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.
    Shumakov, Valentyn
    Authorship: From Credit to Accountability Reflections From the Editors´ Network.2019In: Anatolian journal of cardiology, ISSN 2149-2263, Vol. 21, no 5, p. 281-286Article in journal (Refereed)
    Abstract [en]

    The Editors´ Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

  • 61. Alfonso, Fernando
    et al.
    Zelveian, Parounak
    Monsuez, Jean-Jacques
    Aschermann, Michael
    Boehm, Michael
    Buendía-Hernández, Alfonso
    Wang, Tzung-Dau
    Cohen, Ariel
    Izetbegovic, Sebija
    Doubell, Anton
    Echeverri, Dario
    Enç, Nuray
    Ferreira-González, Ignacio
    Undas, Anetta
    Fortmüller, Ulrike
    Gatzov, Plamen
    Ginghina, Carmen
    Goncalves, Lino
    Addad, Faouzi
    Hassanein, Mahmoud
    Heusch, Gerd
    Huber, Kurt
    Hatala, Robert
    Ivanusa, Mario
    Lau, Chu-Pak
    Marinskis, Germanas
    Dei-Cas, Livio
    Rochitte, Carlos E
    Nikus, Kjell
    Fleck, Eckart
    Pierard, Luc
    Obradović, Slobodan
    Aguilar-Passano, María Del P
    Jang, Yangsoo
    Rødevand, Olaf
    Sander, Mikael
    Shlyakhto, Evgeny
    Erol, Çetin
    Tousoulis, Dimitris
    Ural, Dilek
    Piek, Jan J
    Varga, Albert
    Mach, Andreas J Flammer/François
    Dibra, Alban
    Guliyev, Faiq
    Mrochek, Alexander
    Rogava, Mamanti
    Guzmán-Melgar, Ismael
    Pasquale, Giuseppe Di
    Kabdrakhmanov, Kanat
    Haddour, Laila
    Fras, Zlatko
    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.
    Shumakov, Valentyn
    Authorship: From credit to accountability - Reflections from the Editors' network.2019In: Archivos de cardiologia de Mexico, ISSN 1665-1731, Vol. 89, no 1, p. 93-99Article in journal (Refereed)
    Abstract [en]

    The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new -(fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

  • 62. Alfonso, Fernando
    et al.
    Zelveian, Parounak
    Monsuez, Jean-Jacques
    Aschermann, Michael
    Boehm, Michael
    Buendía-Hernández, Alfonso
    Wang, Tzung-Dau
    Cohen, Ariel
    Izetbegovic, Sebija
    Doubell, Anton
    Echeverri, Dario
    Enç, Nuray
    Ferreira-González, Ignacio
    Undas, Anetta
    Fortmüller, Ulrike
    Gatzov, Plamen
    Ginghina, Carmen
    Goncalves, Lino
    Addad, Faouzi
    Hassanein, Mahmoud
    Heusch, Gerd
    Huber, Kurt
    Hatala, Robert
    Ivanusa, Mario
    Lau, Chu-Pak
    Marinskis, Germanas
    Dei-Cas, Livio
    Rochitte, Carlos E
    Nikus, Kjell
    Fleck, Eckart
    Pierard, Luc
    Obradović, Slobodan
    Aguilar-Passano, María Del P
    Jang, Yangsoo
    Rødevand, Olaf
    Sander, Mikael
    Shlyakhto, Evgeny
    Erol, Çetin
    Tousoulis, Dimitris
    Ural, Dilek
    Piek, Jan J
    Varga, Albert
    Mach, Andreas J Flammer/François
    Dibra, Alban
    Guliyev, Faiq
    Mrochek, Alexander
    Rogava, Mamanti
    Guzmán-Melgar, Ismael
    Pasquale, Giuseppe Di
    Kabdrakhmanov, Kanat
    Haddour, Laila
    Fras, Zlatko
    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.
    Shumakov, Valentyn
    Authorship: From credit to accountability - Reflections from the Editors' network.2019In: Archivos de cardiologia de Mexico, ISSN 1665-1731, Vol. 89, no 2, p. 105-111Article in journal (Refereed)
    Abstract [en]

    The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new -(fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

  • 63. Alfonso, Fernando
    et al.
    Zelveian, Parounak
    Monsuez, Jean-Jacques
    Aschermann, Michael
    Boehm, Michael
    Hernandez, Alfonso Buendia
    Wang, Tzung-Dau
    Cohen, Ariel
    Izetbegovic, Sebija
    Doubell, Anton
    Echeverri, Dario
    Enç, Nuray
    Ferreira-González, Ignacio
    Undas, Anetta
    Fortmüller, Ulrike
    Gatzov, Plamen
    Ginghina, Carmen
    Goncalves, Lino
    Addad, Faouzi
    Hassanein, Mahmoud
    Heusch, Gerd
    Huber, Kurt
    Hatala, Robert
    Ivanusa, Mario
    Lau, Chu-Pak
    Marinskis, Germanas
    Cas, Livio Dei
    Rochitte, Carlos Eduardo
    Nikus, Kjell
    Fleck, Eckart
    Pierard, Luc
    Obradović, Slobodan
    Passano, María Del Pilar Aguilar
    Jang, Yangsoo
    Rødevand, Olaf
    Sander, Mikael
    Shlyakhto, Evgeny
    Erol, Çetin
    Tousoulis, Dimitris
    Ural, Dilek
    Piek, Jan J
    Varga, Albert
    Flammer, Andreas J
    Mach, François
    Dibra, Alban
    Guliyev, Faiq
    Mrochek, Alexander
    Rogava, Mamanti
    Melgar, Ismael Guzman
    Di Pasquale, Giuseppe
    Kabdrakhmanov, Kanat
    Haddour, Laila
    Fras, Zlatko
    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.
    Shumakov, Valentyn
    Authorship: From credit to accountability. Reflections from the Editors' Network.2019In: Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology, ISSN 2174-2030, Vol. 38, no 7, p. 519-525, article id S0870-2551(19)30450-0Article in journal (Refereed)
    Abstract [en]

    The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

  • 64. Alfonso, Fernando
    et al.
    Zelveian, Parounak
    Monsuez, Jean-Jacques
    Aschermann, Michael
    Böhm, Michael
    Hernandez, Alfonso Buendia
    Wang, Tzung-Dau
    Cohen, Ariel
    Izetbegovic, Sebija
    Doubell, Anton
    Echeverri, Dario
    Enç, Nuray
    Ferreira-González, Ignacio
    Undas, Anetta
    Fortmüller, Ulrike
    Gatzov, Plamen
    Ginghina, Carmen
    Goncalves, Lino
    Addad, Faouzi
    Hassanein, Mahmoud
    Heusch, Gerd
    Huber, Kurt
    Hatala, Robert
    Ivanusa, Mario
    Lau, Chu-Pak
    Marinskis, Germanas
    Cas, Livio Dei
    Rochitte, Carlos Eduardo
    Nikus, Kjell
    Fleck, Eckart
    Pierard, Luc
    Obradović, Slobodan
    Del Pilar Aguilar Passano, María
    Jang, Yangsoo
    Rødevand, Olaf
    Sander, Mikael
    Shlyakhto, Evgeny
    Erol, Çetin
    Tousoulis, Dimitris
    Ural, Dilek
    Piek, Jan J
    Varga, Albert
    Flammer, Andreas J
    Mach, François
    Dibra, Alban
    Guliyev, Faiq
    Mrochek, Alexander
    Rogava, Mamanti
    Guzman Melgar, Ismael
    Di Pasquale, Giuseppe
    Kabdrakhmanov, Kanat
    Haddour, Laila
    Fras, Zlatko
    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.
    Shumakov, Valentyn
    Authorship: from credit to accountability. Reflections from the Editors' Network.2019In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 108, no 7, p. 723-729Article in journal (Refereed)
    Abstract [en]

    The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

  • 65. Alfonso, Fernando
    et al.
    Zelveian, Parounak
    Monsuez, Jean-Jacques
    Aschermann, Michael
    Böhm, Michael
    Hernandez, Alfonso Buendia
    Wang, Tzung-Dau
    Cohen, Ariel
    Izetbegovic, Sebija
    Doubell, Anton
    Echeverri, Dario
    Enç, Nuray
    Ferreira-González, Ignacio
    Undas, Anetta
    Fortmüller, Ulrike
    Gatzov, Plamen
    Ginghina, Carmen
    Goncalves, Lino
    Addad, Faouzi
    Hassanein, Mahmoud
    Heusch, Gerd
    Huber, Kurt
    Hatala, Robert
    Ivanusa, Mario
    Lau, Chu-Pak
    Marinskis, Germanas
    Cas, Livio Dei
    Rochitte, Carlos Eduardo
    Nikus, Kjell
    Fleck, Eckart
    Pierard, Luc
    Obradović, Slobodan
    Del Pilar Aguilar Passano, María
    Jang, Yangsoo
    Rødevand, Olaf
    Sander, Mikael
    Shlyakhto, Evgeny
    Erol, Çetin
    Tousoulis, Dimitris
    Ural, Dilek
    Piek, Jan J
    Varga, Albert
    Flammer, Andreas J
    Mach, François
    Dibra, Alban
    Guliyev, Faiq
    Mrochek, Alexander
    Rogava, Mamanti
    Guzman Melgar, Ismael
    Di Pasquale, Giuseppe
    Kabdrakhmanov, Kanat
    Haddour, Laila
    Fras, Zlatko
    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.
    Shumakov, Valentyn
    Authorship: from credit to accountability. Reflections from the Editors' Network.2019In: Basic Research in Cardiology, ISSN 0300-8428, E-ISSN 1435-1803, Vol. 114, no 3, article id 23Article in journal (Refereed)
    Abstract [en]

    The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

  • 66. Alfredsson, Joakim
    et al.
    Clayton, Tim
    Damman, Peter
    Fox, Keith A. A.
    Fredriksson, Mats
    Lagerqvist, Bo
    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, 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.
    de Winter, Robbert J.
    Swahn, Eva
    Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 4, p. 522-529Article in journal (Refereed)
    Abstract [en]

    Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.

  • 67.
    Alfredsson, Joakim
    et al.
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    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). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Erlinge, David
    Lund Univ, Dept Clin Sci, Cardiol, Lund, Sweden..
    Herlitz, Johan
    Univ Borås, Dept Hlth Sci, Borås, Sweden..
    Frobert, Ole
    Örebro Univ, Fac Med & Hlth, Dept Cardiol, Örebro, Sweden..
    Dworeck, Christian
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Dept Cardiol, Sahlgrenska Univ Hosp, Gothenburg, Sweden..
    Redfors, Bjorn
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Dept Cardiol, Sahlgrenska Univ Hosp, Gothenburg, Sweden..
    Arefalk, Gabriel
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Cardiol, Stockholm, Sweden..
    Mars, Katarina
    Karolinska Inst, Sodersjukhuset, Div Cardiol, Dept Clin Sci & Educ, Sjukhusbacken 10, S-11883 Stockholm, Sweden..
    Haaga, Urban
    Karlstad Cent Hosp, Dept Cardiol, Karlstad, Sweden..
    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).
    Swahn, Eva
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Lawesson, Sofia Sederholm
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Hofmann, Robin
    Karolinska Inst, Sodersjukhuset, Div Cardiol, Dept Clin Sci & Educ, Sjukhusbacken 10, S-11883 Stockholm, Sweden..
    Randomized comparison of early supplemental oxygen versus ambient air in patients with confirmed myocardial infarction: Sex-related outcomes from DETO2X-AMI2021In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 237, p. 13-24Article in journal (Refereed)
    Abstract [en]

    Background The purpose of this study is to investigate the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI). Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis including 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure at long-term follow-up, stratified according to sex. Results Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found ( P = .16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone, there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment. Conclusion Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or heart failure in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age. (Am Heart J 2021;237:13 & ndash;24.)

  • 68. Alfredsson, Joakim
    et al.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Swahn, Eva
    Similar outcome with an invasive strategy in men and women with non-ST-elevation acute coronary syndromes: From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 24, p. 3128-3136Article in journal (Refereed)
    Abstract [en]

    Aims

    To assess gender differences in outcome with an early invasive or non-invasive strategy in patients with non-ST-elevation acute coronary syndromes (NSTE ACS).

    Methods and results

    We included 46 455 patients [14 819 women (32%) and 31 636 men (68%)] from the SWEDEHEART register, with NSTE ACS, between 2000 and 2006, and followed them for 1 year. In the non-invasive strategy arm, the relative risk (RR) of death was (women vs. men) 1.02 [95% confidence interval (CI), 0.94-1.11] and in the invasive strategy arm 1.12 (95% CI, 0.96-1.29). After adjustment for baseline differences between the genders, with propensity score and discharge medication, there was a similar trend towards better outcome among women in both the early non-invasive cohort [RR 0.90 (95% CI, 0.82-0.99)] and the early invasive cohort [RR 0.90 (95% CI, 0.76-1.06)], although it did not reach statistical significance in the early invasive cohort. Results were similar with the combined endpoint death/myocardial infarction. An early invasive treatment was associated with a marked, and similar, mortality reduction in women [RR 0.46 (95% CI, 0.38-0.55)] and men [RR 0.45 (95% CI, 0.40-0.52)], without interaction with gender.

    Conclusion

    In this large cohort of patients with NSTE ACS, reflecting real-life management, women and men had similar and better outcome associated with an invasive strategy.

  • 69.
    Al-Khatib, Sana M.
    et al.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Mulder, Hillary
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 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).
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan..
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Left Ventricular Hypertrophy: Insights From the ARISTOTLE Trial2021In: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 14, no 3, p. 359-361, article id e009614Article in journal (Other academic)
  • 70.
    Al-Khatib, Sana M.
    et al.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Granger, Christopher B.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    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).
    Garcia, David A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Univ Washington, Div Hematol, Seattle, WA 98195 USA..
    Hijazi, Ziad
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Univ & Emergency Hosp, Bucharest, Romania..
    Flaker, Gregory C.
    Univ Missouri, Div Cardiol, Columbia, MO USA..
    Hylek, Elaine M.
    Boston Univ, Sch Med, Boston, MA USA..
    Lopes, Renato D.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Duration of Anticoagulation Interruption Before Invasive Procedures and Outcomes in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial2022In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 146, no 12, p. 958-960Article in journal (Refereed)
  • 71. 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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  • 72. 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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  • 73. Allara, Elias
    et al.
    Lee, Wei-Hsuan
    Burgess, Stephen
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Genetically predicted cortisol levels and risk of venous thromboembolism2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 8, article id e0272807Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: In observational studies, venous thromboembolism (VTE) has been associated with Cushing's syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization.

    METHODS: Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed.

    RESULTS: Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62-0.87, p<0.001). The association was stronger for deep vein thrombosis (OR 0.69, 95% CI 0.55-0.88, p = 0.003) than for pulmonary embolism which did not achieve statistical significance (OR 0.83, 95% CI 0.63-1.09, p = 0.184). Adjusting for genetically predicted systolic blood pressure inverted the direction of the point estimate for VTE, although the resulting CI was wide (OR 1.06, 95% CI 0.70-1.61, p = 0.780).

    CONCLUSIONS: This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for.

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  • 74.
    Allemann, H.
    et al.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Liljeroos, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Thylen, I.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Stromberg, A.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Information and Communication Technology (ICT) as a supportive aid; perceptions amongst family caregivers to persons with heart failure2018In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 17, no suppl 1, p. 100-100Article in journal (Other academic)
  • 75.
    Almeida, Ana G.
    et al.
    Lisbon Univ, Univ Hosp Santa Maria CHLN, Fac Med, Lisbon, Portugal..
    Carpenter, John-Paul
    NHS Fdn Trust, Poole Hosp, Univ Hosp Dorset, Cardiol Dept, Longfleet Rd, Poole BH15 2JB, Dorset, England..
    Cameli, Matteo
    Univ Siena, Dept Med Biotechnol, Div Cardiol, Viale Bracci 16, Siena, Italy..
    Donal, Erwan
    CHU Rennes, INSERM, Dept Cardiol, LTSI UMR 1099, F-35000 Rennes, France..
    Dweck, Marc R.
    Univ Edinburgh, BHF Ctr Cardiovasc Sci, Chancellors Bldg Little France Crescent, Edinburgh EH16 4SB, Midlothian, Scotland.;Edinburgh Heart Ctr, Chancellors Bldg Little France Crescent, Edinburgh EH16 4SB, Midlothian, Scotland..
    Flachskampf, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Maceira, Alicia M.
    Ascires Biomed Grp, Cardiovasc Imaging Unit, Colon St 1, Valencia 46004, Spain.;CEU Cardenal Herrera Univ, Hlth Sci Sch, Dept Med, Lluis Vives St 1, Valencia 46115, Spain..
    Muraru, Denisa
    Univ Milano Bicocca, Dept Med & Surg, Via Cadore 48, I-20900 Monza, Italy.;IRCCS, Dept Cardiovasc Neural & Metab Sci, Ist Auxol Italiano, Piazzale Brescia 20, I-20149 Milan, Italy..
    Neglia, Danilo
    Fdn Toscana G Monasterio, Via G Moruzzi 1, Pisa, Italy..
    Pasquet, Agnes
    Clin Univ St Luc, Dept Cardiovasc, Serv Cardiol, Av Hippocrate 10, B-1200 Brussels, Belgium.;UCLouvain, Div CARD, Inst Rech Expt & Clin IREC, Av Hippocrate 10, B-1200 Brussels, Belgium..
    Plein, Sven
    Univ Leeds, Inst Cardiovasc & Metab Med, Dept Biomed Imaging Sci, Clarendon Way, Leeds LS2 9JT, W Yorkshire, England..
    Gerber, Bernhard L.
    Univ Leeds, Inst Cardiovasc & Metab Med, Dept Biomed Imaging Sci, Clarendon Way, Leeds LS2 9JT, W Yorkshire, England..
    Multimodality imaging of myocardial viability: an expert consensus document from the European Association of Cardiovascular Imaging (EACVI)2021In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 22, no 8, p. E97-E125Article in journal (Refereed)
    Abstract [en]

    In clinical decision making, myocardial viability is defined as myocardium in acute or chronic coronary artery disease and other conditions with contractile dysfunction but maintained metabolic and electrical function, having the potential to improve dysfunction upon revascularization or other therapy. Several pathophysiological conditions may coexist to explain this phenomenon. Cardiac imaging may allow identification of myocardial viability through different principles, with the purpose of prediction of therapeutic response and selection for treatment. This expert consensus document reviews current insight into the underlying pathophysiology and available methods for assessing viability. In particular the document reviews contemporary viability imaging techniques, including stress echocardiography, single photon emission computed tomography, positron emission tomography, cardiovascular magnetic resonance, and computed tomography and provides clinical recommendations for how to standardize these methods in terms of acquisition and interpretation. Finally, it presents clinical scenarios where viability assessment is clinically useful.

  • 76.
    Almeida, Joao G.
    et al.
    Ctr Hosp Gaia Espinho, Dept Cardiol, R Conceicao Fernandes 1079, Vila Nova De Gaia, Portugal.
    Fontes-Carvalho, Ricardo
    Ctr Hosp Gaia Espinho, Dept Cardiol, R Conceicao Fernandes 1079, Vila Nova De Gaia, Portugal; Univ Porto, Dept Surg & Physiol, Fac Med, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal.
    Sampaio, Francisco
    Ctr Hosp Gaia Espinho, Dept Cardiol, R Conceicao Fernandes 1079, Vila Nova De Gaia, Portugal.
    Ribeiro, Jose
    Ctr Hosp Gaia Espinho, Dept Cardiol, R Conceicao Fernandes 1079, Vila Nova De Gaia, Portugal.
    Bettencourt, Paulo
    Univ Porto, Dept Med, Fac Med, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal.
    Flachskampf, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Leite-Moreira, Adelino
    Univ Porto, Dept Surg & Physiol, Fac Med, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal; Sao Joao Hosp Ctr, Dept Cardiothorac Surg, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal.
    Azevedo, Ana
    Univ Porto, Dept Clin Epidemiol, Predict Med & Publ Hlth, Fac Med, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal; Univ Porto ISPUP, Inst Publ Hlth, Epidemiol Res Unit, EPIUnit, Rua Taipas 135, P-4050600 Porto, Portugal.
    Impact of the 2016 ASE/EACVI recommendations on the prevalence of diastolic dysfunction in the general population2018In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 19, no 4, p. 380-386Article in journal (Refereed)
    Abstract [en]

    Aims: Diastolic dysfunction (DD) is frequent in the general population; however, the assessment of diastolic function remains challenging. We aimed to evaluate the impact of the recent 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) recommendations in the prevalence and grades of DD compared with the 2009 guidelines and the Canberra Study Criteria (CSC).

    Methods and results: Within a population-based cohort, a total of 1000 individuals, aged ≥45 years, were evaluated retrospectively. Patients with previously known cardiac disease or ejection fraction <50% were excluded. Diastolic function was assessed by transthoracic echocardiography. DD prevalence and grades were determined according to the three classifications. The mean age was 62.0 ± 10.5 years and 37% were men. The prevalence of DD was 1.4% (n = 14) with the 2016 recommendations, 38.1% (n = 381) with the 2009 recommendations, and 30.4% (n = 304) using the CSC. The concordance between the updated recommendations and the other two was poor (from k = 0.13 to k = 0.18, P < 0.001). Regarding the categorization in DD grades, none of the 14 individuals with DD by the 2016 guidelines were assigned to Grade 1 DD, 64% were classified as Grade 2, 7% had Grade 3, and 29% had indeterminate grade.

    Conclusion: The application of the new 2016 ASE/EACVI recommendations resulted in a much lower prevalence of DD. The concordance between the classifications was poor. The updated algorithm seems to be able to diagnose only the most advanced cases.

  • 77.
    Al-Saadi, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Stockholm, Sweden.
    Mattsson, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Kader, Rozh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Med Univ Gdansk, Gdansk, Poland.
    Magnusson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Dept Med, Cardiol Res Unit, Stockholm, Sweden.
    Apical hypertrophic cardiomyopathy with preexcitation presenting as a myocardial infarction and ischemic stroke with a history of recurrent syncope: A case report2019In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 7, no 4, p. 816-820Article in journal (Refereed)
    Abstract [en]

    Key Clinical Message Contrast-enhanced echocardiography or cardiac magnetic resonance imaging is of value in the diagnosis of apical hypertrophic cardiomyopathy. Apical hypertrophic cardiomyopathy is rare in Caucasians, and gene negativity does not rule out the diagnosis. Risk stratification for sudden cardiac death and decisions about anticoagulation in cases with atrial fibrillation should be based on guidelines.

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  • 78. 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)
  • 79.
    Altreuther, Martin
    et al.
    St Olavs Hosp, Dept Vasc Surg, Trondheim, Norway.;NTNU, Inst Circulat & Med Imaging, Trondheim, Norway..
    Grima, Matthew J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Mater Dei Hosp, Dept Surg, Vasc Unit, Msida, Malta; Univ Malta, Fac Med & Surg, Msida, Malta.
    Lattmann, Thomas
    Kantonsspital Winterthur, Dept Vasc Surg, Winterthur, Switzerland.;Swiss Soc Vasc Surg, Lausanne, Switzerland..
    International Validation Of Vascular Registries: The VASCUNET Validation Template2023In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 66, no 3, p. 438-439Article in journal (Other academic)
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  • 80. Amarenco, Pierre
    et al.
    Denison, Hans
    Evans, Scott R
    Himmelmann, Anders
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Knutsson, Mikael
    Ladenvall, Per
    Molina, Carlos A
    Wang, Yongjun
    Johnston, S Claiborne
    Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke: A Randomized Clinical Trial2020In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 78, no 2, p. 177-185Article in journal (Refereed)
    Abstract [en]

    Importance: Reduction of subsequent disabling stroke is the main goal of preventive treatment in the acute setting after transient ischemic attack (TIA) or minor ischemic stroke.

    Objective: To evaluate the superiority of ticagrelor added to aspirin in preventing disabling stroke and to understand the factors associated with recurrent disabling stroke.

    Design, Setting, and Participants: The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) was a randomized clinical trial conducted between January 22, 2018, and December 13, 2019, with a 30-day follow-up, at 414 hospitals in 28 countries. The trial included 11 016 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk TIA, including 10 803 with modified Rankin Scale score (mRS) recorded at 30 days.

    Interventions: Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo within 24 hours of symptom onset. All patients received aspirin, 300 to 325 mg on day 1 followed by 75 to 100 mg daily for days 2 to 30.

    Main Outcomes and Measures: Time to the occurrence of disabling stroke (progression of index event or new stroke) or death within 30 days, as measured by mRS at day 30. Disabling stroke was defined by mRS greater than 1.

    Results: Among participants with 30-day mRS greater than 1, mean age was 68.1 years, 1098 were female (42.6%), and 2670 had an ischemic stroke (95.8%) as a qualifying event. Among 11 016 patients, a primary end point with mRS greater than 1 at 30 days occurred in 221 of 5511 patients (4.0%) randomized to ticagrelor and in 260 of 5478 patients (4.7%) randomized to placebo (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99, P = .04). A primary end point with mRS 0 or 1 at 30 days occurred in 70 of 5511 patients (1.3%) and 87 of 5478 patients (1.6%) (HR, 0.79; 95% CI, 0.57-1.08; P = .14). The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; 95% CI, 0.65-0.91; P = .002). Factors associated with disability were baseline National Institutes of Health Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure, while treatment with ticagrelor was associated with less disability.

    Conclusions and Relevance: In patients with TIA and minor ischemic stroke, ticagrelor added to aspirin was superior to aspirin alone in preventing disabling stroke or death at 30 days and reduced the total burden of disability owing to ischemic stroke recurrence.

    Trial Registration: ClinicalTrials.gov Identifier: NCT03354429.

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  • 81.
    Amarenco, Pierre
    et al.
    Univ Paris, Bichat Univ Hosp, Dept Neurol, Paris, France; Univ Paris, Bichat Univ Hosp, Stroke Ctr, Paris, France.
    Denison, Hans
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    Evans, Scott R.
    George Washington Univ, Biostat Ctr, Washington, DC USA.
    Himmelmann, Anders
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Knutsson, Mikael
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    Ladenvall, Per
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    Molina, Carlos A.
    Hosp Valle De Hebron, Stroke Unit, Barcelona, Spain.
    Wang, Yongjun
    Tiantan Hosp, Dept Neurol, Beijing, Peoples R China.
    Johnston, S. Claiborne
    Univ Texas Austin, Deans Off, Dell Med Sch, Austin, TX 78712 USA.
    Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin2020In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 51, no 12, p. 3504-3513Article in journal (Refereed)
    Abstract [en]

    Background and Purpose:Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events.

    Methods:In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days.

    Results:Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001).

    Conclusions:In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171).

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  • 82.
    Ambavane, Apoorva
    et al.
    Modeling and Simulation, Evidera, London, United Kingdom.
    Lindahl, Bertil
    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.
    Giannitsis, Evangelos
    Medizinische Klinik III, University Heidelberg, Heidelberg, Germany .
    Roiz, Julie
    Modeling and Simulation, Evidera, London, United Kingdom .
    Mendivil, Joan
    Market Access, Roche Diagnostics International Ltd., Rotkreuz, Switzerland .
    Frankenstein, Lutz
    Department of Cardiology, Angiology, Pulmonology, University Hospital of Heidelberg, Heidelberg, Germany .
    Body, Richard
    Emergency Department, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom .
    Christ, Michael
    Department of Emergency and Critical Care Medicine, Paracelsus Medical University, Nuremberg General Hospital, Nuremberg, Germany .
    Bingisser, Roland
    Emergency Department, University of Basel, University Hospital, Basel, Switzerland .
    Alquezar, Aitor
    Servei de Urgencies. Hospital de Sant Pau, Barcelona, Spain .
    Mueller, Christian
    Department of Cardiology and Cardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland .
    Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 11, article id e0187662Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The 1-hour (h) algorithm triages patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED) towards "rule-out," "rule-in," or "observation," depending on baseline and 1-h levels of high-sensitivity cardiac troponin (hs-cTn). The economic consequences of applying the accelerated 1-h algorithm are unknown.

    METHODS AND FINDINGS: We performed a post-hoc economic analysis in a large, diagnostic, multicenter study of hs-cTnT using central adjudication of the final diagnosis by two independent cardiologists. Length of stay (LoS), resource utilization (RU), and predicted diagnostic accuracy of the 1-h algorithm compared to standard of care (SoC) in the ED were estimated. The ED LoS, RU, and accuracy of the 1-h algorithm was compared to that achieved by the SoC at ED discharge. Expert opinion was sought to characterize clinical implementation of the 1-h algorithm, which required blood draws at ED presentation and 1h, after which "rule-in" patients were transferred for coronary angiography, "rule-out" patients underwent outpatient stress testing, and "observation" patients received SoC. Unit costs were for the United Kingdom, Switzerland, and Germany. The sensitivity and specificity for the 1-h algorithm were 87% and 96%, respectively, compared to 69% and 98% for SoC. The mean ED LoS for the 1-h algorithm was 4.3h-it was 6.5h for SoC, which is a reduction of 33%. The 1-h algorithm was associated with reductions in RU, driven largely by the shorter LoS in the ED for patients with a diagnosis other than AMI. The estimated total costs per patient were £2,480 for the 1-h algorithm compared to £4,561 for SoC, a reduction of up to 46%.

    CONCLUSIONS: The analysis shows that the use of 1-h algorithm is associated with reduction in overall AMI diagnostic costs, provided it is carefully implemented in clinical practice. These results need to be prospectively validated in the future.

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  • 83.
    Anan, Intissar
    et al.
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.;Umeå Univ, Wallenberg Ctr Mol Med, Umeå, Sweden..
    Suhr, Ole B.
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Liszewska, Katarzyna
    Pitea Hosp, Dept Med, Pitea, Sweden..
    Baranda, Jorge Mejia
    Pitea Hosp, Dept Med, Pitea, Sweden..
    Pilebro, Bjorn
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Wixner, Jonas
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Ihse, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Amyloid fibril composition type is consistent over time in patients with Val30Met (p.Val50Met) transthyretin amyloidosis2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 3, article id e0266092Article in journal (Refereed)
    Abstract [en]

    Background: We have previously shown that transthyretin (TTR) amyloidosis patients have amyloid fibrils of either of two compositions; type A fibrils consisting of large amounts of C-terminal TTR fragments in addition to full-length TTR, or type B fibrils consisting of only full-length TTR. Since type A fibrils are associated with an older age in ATTRVal30Met (p.Val50Met) amyloidosis patients, it has been discussed if the TTR fragments are derived from degradation of the amyloid deposits as the patients are aging. The present study aimed to investigate if the fibril composition type changes over time, especially if type B fibrils can shift to type A fibrils as the disease progresses.

    Material and method:s Abdominal adipose tissue biopsies from 29 Swedish ATTRVal30Met amyloidosis patients were investigated. The fibril type in the patients initial biopsy taken for diagnostic purposes was compared to a biopsy taken several years later (ranging between 2 and 13 years). The fibril composition type was determined by western blot.

    Results: All 29 patients had the same fibril composition type in both the initial and the follow-up biopsy (8 type A and 21 type B). Even patients with a disease duration of more than 12 years and an age over 75 years at the time of the follow-up biopsy had type B fibrils in both biopsies.

    Discussion: The result clearly shows that the amyloid fibril composition containing large amounts of C-terminal fragments (fibril type A) is a consequence of other factors than a slow degradation process occurring over time.

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  • 84. Andell, P.
    et al.
    Erlinge, D.
    Smith, J. G.
    James, Stefan
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koul, S.
    The effect of beta-blockers on mortality in COPD patients after myocardial infarction: A Swedish nation-wide observational study2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 686-687Article in journal (Refereed)
  • 85.
    Andell, P.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Karlsson, S.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Mohammad, M.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Gotberg, M.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensen, J.
    Capio St Goran Hosp, Stockholm, Sweden..
    Frobert, O.
    Orebro Univ Hosp, Orebro, Sweden..
    Angeras, O.
    Sahlgrens Acad, Gothenburg, Sweden..
    Nilsson, J.
    Umea Univ Hosp, Umea, Sweden..
    Omerovic, E.
    Sahlgrens Acad, Gothenburg, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Persson, J.
    Danderyd Hosp, Stockholm, Sweden..
    Koul, S.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Erlinge, D.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Intravascular ultrasound guidance is associated with lower mortality in patients undergoing stenting for unprotected left main coronary artery lesions compared to angiography-guided stent implantation2016Conference paper (Refereed)
  • 86. Andell, Pontus
    et al.
    Erlinge, David
    Smith, J. Gustav
    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, Cardiology.
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    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.
    Koul, Sasha
    beta-Blocker Use and Mortality in COPD Patients After Myocardial Infarction: A Swedish Nationwide Observational Study2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 4, article id e001611Article in journal (Refereed)
    Abstract [en]

    Background-Patients with myocardial infarction (MI) and concomitant chronic obstructive pulmonary disease (COPD) constitute a high-risk group with increased mortality. beta-Blocker therapy has been shown to reduce mortality, prevent arrhythmias, and delay heart failure development after an MI in broad populations. However, the effect of beta-blockers in COPD patients is less well established and they may also be less treated due to fear of adverse reactions. We investigated beta-blocker prescription at discharge in patients with COPD after MI. ethods and Results-Patients hospitalized for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with COPD who were alive and discharged after an MI were selected as the study population. In this cohort, patients who were discharged with beta-blockers were compared to patients not discharged with beta-blockers. The primary end point was all-cause mortality. A total of 4858 patients were included, of which 4086 (84.1%) were discharged with a beta-blocker while 772 (15.9%) were not. After adjusting for potential confounders including baseline characteristics, comorbidities, and in-hospital characteristics, patients discharged with a beta-blocker had lower all-cause mortality (hazard ratio 0.87, 95% CI 0.78 to 0.98) during the total follow-up time (maximum 7.2 years). In the subgroup of patients with a history of heart failure, the corresponding hazard ratio was 0.77 (95% CI 0.63 to 0.95). Conclusions-Patients with COPD discharged with beta-blockers after an MI had a lower all-cause mortality compared to patients not prescribed beta-blockers. The results indicate that MI patients with COPD may benefit from beta-blockers.

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  • 87.
    Andell, Pontus
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    James, Stefan K.
    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.
    Cannon, Christopher P.
    Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.;Harvard Clin Res Inst, Boston, MA USA..
    Cyr, Derek D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Molndal, Sweden..
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Keltai, Matyas
    Semmelweis Univ, Hungarian Inst Cardiol, H-1085 Budapest, Hungary..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Santoso, Anwar
    Univ Indonesia, Natl Cardiovasc Ctr, Harapan Kita Hosp, Dept Cardiol,Vasc Med,Fac Med, Jakarta, Indonesia. INSERM, U1148, Paris, France. Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France. Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6LY, England..
    Steg, Gabriel
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2TN, S Yorkshire, England..
    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.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and Chronic Obstructive Pulmonary Disease: An Analysis From the Platelet Inhibition and Patient Outcomes (PLATO) Trial2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002490Article in journal (Refereed)
    Abstract [en]

    Background-Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients. Methods and Results-In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1-year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO-defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non-COPD patients (HR=1.85). No COPD status-by-treatment interactions were found, showing consistency with the main trial results. Conclusions-In this post-hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit-risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD.

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  • 88. Andell, Pontus
    et al.
    James, Stefan
    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.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Yndigegn, Troels
    Sparv, David
    Pernow, John
    Jernberg, Tomas
    Lindahl, Bertil
    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.
    Herlitz, Johan
    Erlinge, David
    Hofmann, Robin
    Oxygen therapy in suspected acute myocardial infarction and concurrent normoxemic chronic obstructive pulmonary disease: a prespecified subgroup analysis from the DETO2X-AMI trial2020In: European Heart Journal: Acute Cardiovascular Care, ISSN 2048-8726, E-ISSN 2048-8734, Vol. 9, no 8, p. 984-992Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction. Patients with chronic obstructive pulmonary disease may both benefit and be harmed by supplemental oxygen. Thus we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction.

    METHODS AND RESULTS: A total of 6629 patients with suspected acute myocardial infarction were randomly assigned in the DETO2X-AMI trial to oxygen or ambient air. In the oxygen group ( n=3311) and the ambient air group ( n=3318), 155 and 141 patients, respectively, had chronic obstructive pulmonary disease (prevalence of 4.5%). Patients with chronic obstructive pulmonary disease were older, had more comorbid conditions and experienced a twofold higher risk of death at one year (chronic obstructive pulmonary disease: 32/296 (10.8%) vs. non-chronic obstructive pulmonary disease: 302/6333 (4.8%)). Oxygen therapy compared to ambient air was not associated with improved outcomes at 365 days (chronic obstructive pulmonary disease: all-cause mortality hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.50-1.99, Pinteraction=0.96); cardiovascular death HR 0.80, 95% CI 0.32-2.04, Pinteraction=0.59); rehospitalisation with acute myocardial infarction or death HR 1.27, 95% CI 0.71-2.28, Pinteraction=0.46); hospitalisation for heart failure or death HR 1.08, 95% CI 0.61-1.91, Pinteraction=0.77]); there were no significant treatment-by-chronic obstructive pulmonary disease interactions.

    CONCLUSIONS: Although chronic obstructive pulmonary disease patients had twice the mortality rate compared to non-chronic obstructive pulmonary disease patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction revealed no evidence for benefit of routine oxygen therapy consistent with the main trial's findings.

    CLINICAL TRIALS REGISTRATION: NCT02290080.

  • 89.
    Andell, Pontus
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Karlsson, Sofia
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Mohammad, Moman A.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Gotberg, Matthias
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jensen, Jens
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Capio St Gorans Sjukhus, Unit Med, Stockholm, Sweden..
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Angeras, Oskar
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Nilsson, Johan
    Umea Univ Hosp, Heart Ctr, Dept Cardiol, Umea, Sweden..
    Omerovic, Elmir
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Persson, Jonas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone2017In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 10, no 5, article id e004813Article in journal (Refereed)
    Abstract [en]

    Background: Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study.

    Methods and Results: Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50-0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47-0.82). In 340 propensity score-matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37-0.80).

    Conclusions: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.

  • 90.
    Andell, Pontus
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden.;Skane Univ Hosp, S-22185 Lund, Sweden..
    Sjogren, Johan
    Skane Univ Hosp, S-22185 Lund, Sweden.;Lund Univ, Dept Cardiothorac Surg, Clin Sci, Lund, Sweden..
    Batra, Gorav
    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.
    Szummer, Karolina
    Dept Med, Huddinge, Sweden.;Karolinska Inst, Stockholm, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden.;Skane Univ Hosp, S-22185 Lund, Sweden..
    Outcome of patients with chronic obstructive pulmonary disease and severe coronary artery disease who had a coronary artery bypass graft or a percutaneous coronary intervention2017In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 52, no 5, p. 930-936Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) who also have acute coronary syndromes are a high-risk population with a high mortality rate. Little is known about these patients following coronary artery bypass grafting (CABG). METHODS: Patients presenting with acute coronary syndromes between 2006 and 2014 with an angiogram showing 3-vessel disease or left main coronary artery involvement who were treated with CABG or percutaneous coronary intervention (PCI) only were included from the nationwide SWEDEHEART registry. Patients were stratified according to COPD status and compared with regard to outcome. The primary end-point was the 5-year mortality rate; secondary outcomes were the 30-day mortality rate and in-hospital complications after CABG. RESULTS: We identified 6985 patients in the population who had CABG (COPD prevalence = 8.0%) and 14 209 who had PCI only (COPD = 8.2%). Patients with COPD were older and had more comorbidities than patients without COPD. The 5-year mortality rate was nearly doubled in patients with COPD versus patients without COPD (CABG: 27.2% vs 14.5%, P < 0.001; PCI only: 50.1% vs 29.1%, P < 0.001). After adjusting for age, sex and comorbidities, patients with COPD in both CABG-treated [hazard ratio = 1.52 (1.25-1.86), P < 0.001] and PCI-treated populations still had a significantly higher 5-year mortality rate. COPD was also independently associated with significantly more postoperative infections in need of antibiotics [odds ratio = 1.48 (1.07-2.04), P = 0.017] and pneumonia [odds ratio = 2.21 (1.39-3.52), P = 0.001]. CONCLUSIONS: Patients with COPD presenting with acute coronary syndromes and severe coronary artery disease are a high-risk population following CABG or PCI only, with higher risk of long-term and short-term death and postoperative infections. Preventive measures, including careful monitoring for signs of infection and prompt antibiotic treatment when indicated, should be considered.

  • 91.
    Andersen, Kasper
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Physical Activity and Cardiovascular Disease2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim was to investigate associations of fitness and types and levels of physical activity with subsequent risk of cardiovascular disease.

    Four large-scale longitudinal cohort studies were used. The exposures were different measures related to physical activity and the outcomes were obtained through linkage to the Swedish In-Patient Register. In a cohort of 466 elderly men without pre-existing cardiovascular disease, we found that skeletal muscle morphology was associated with risk of cardiovascular events. A high amount of type I (slow-twitch, oxidative) skeletal muscle fibres was associated with lower risk of cardiovascular events and high amount of type IIx was associated with higher risk of cardiovascular events. This association was only seen among physically active men. Among 39,805 participants in a fundraising event, higher levels of both total and leisure time physical activity were associated with lower risk of heart failure. The associations were strongest for leisure time physical activity. In a cohort of 53,755 participants in the 90 km skiing event Vasaloppet, a higher number of completed races was associated with higher risk of atrial fibrillation and a higher risk of bradyarrhythmias. Further, better relative performance was associated with a higher risk of bradyarrhythmias. Among 1,26 million Swedish 18-year-old men, exercise capacity and muscle strength were independently associated with lower risk of vascular disease. The associations were seen across a range of major vascular disease events (ischemic heart disease, heart failure, stroke and cardiovascular death). Further, high exercise capacity was associated with higher risk of atrial fibrillation and a U-shaped association with bradyarrhythmias was found. Higher muscle strength was associated with lower risk of bradyarrhythmias and lower risk of ventricular arrhythmias.

    These findings suggest a higher rate of atrial fibrillation with higher levels of physical activity. The higher risk of atrial fibrillation does not appear to lead to a higher risk of stroke. In contrast, we found a strong inverse association of higher exercise capacity and muscle strength with vascular disease. Further, high exercise capacity and muscle strength are related to lower risk of cardiovascular death, including arrhythmia deaths. From a population perspective, the total impact of physical activity on cardiovascular disease is positive.

    List of papers
    1. Skeletal muscle morphology and risk of cardiovascular disease in elderly men
    Open this publication in new window or tab >>Skeletal muscle morphology and risk of cardiovascular disease in elderly men
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    2015 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-210441 (URN)10.1177/2047487313506828 (DOI)000348115400014 ()24092874 (PubMedID)
    Available from: 2013-11-08 Created: 2013-11-08 Last updated: 2021-11-30Bibliographically approved
    2. Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study
    Open this publication in new window or tab >>Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study
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    2014 (English)In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed) Published
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

    Publisher
    p. 16
    Keywords
    heart failure, physical exercise, cohort study, primary prevention, epidemiology
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology; Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-216862 (URN)10.1161/CIRCHEARTFAILURE.113.001010 (DOI)000342490900003 ()25185250 (PubMedID)
    Available from: 2014-02-01 Created: 2014-01-27 Last updated: 2017-12-06Bibliographically approved
    3. Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study
    Open this publication in new window or tab >>Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study
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    2013 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 47, p. 3624-3631Article in journal (Refereed) Published
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-205089 (URN)10.1093/eurheartj/eht188 (DOI)000329134300012 ()23756332 (PubMedID)
    Available from: 2013-08-13 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
    4. Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young men
    Open this publication in new window or tab >>Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young men
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background:

    While physical activity and exercise protects against cardiovascular disease, athletes have higher risk of atrial fibrillation and other arrhythmias. Graded independent and joint influences of exercise capacity and muscle strength on these diseases are unknown.

    Methods:

    All 1.26 million Swedish men who participated in mandatory military conscription between 1972 and 1995 (at a median age of 18.2 years) contributed. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations of maximal exercise capacity and muscle strength at conscription to subsequent risk of vascular disease and arrhythmias, as identified in national registries.

    Results:

    During a median follow-up of 26.3 years, about 26,000 hospitalizations for vascular disease events and 17,000 for arrhythmias occurred. Exercise capacity was inversely associated with risk of vascular disease (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.67]; for 5th vs. 1st quintile) and so was muscle strength (HR 0.79; 0.76-0.83; for 5th vs. 1st quintile ). Similar associations were seen across a range of major vascular disease events. Exercise capacity was associated with incidence of arrhythmias in a U-shaped fashion (HR 0.91; 0.86-0.96; for 3rd vs. 1st quintile, and 0.99; 0.94-1.04; for 5th vs. 1st quintile). Higher muscle strength was associated with lower risk of arrhythmias (HR 0.87; 0.83-0.91; for 5th vs. 1st quintile). 

    Conclusion:

    Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long-term risk of vascular disease and arrhythmias. The lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmias.

    National Category
    Medical and Health Sciences Cardiac and Cardiovascular Systems
    Research subject
    Cardiology; Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-217308 (URN)
    Available from: 2014-02-01 Created: 2014-02-01 Last updated: 2016-01-18Bibliographically approved
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  • 92.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Daniela, Mariosa
    Adami, Hans-Olov
    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.
    Ingelsson, Erik
    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, Molecular epidemiology.
    Lagerros, Ylva Trolle
    Nyren, Olof
    Ye, Weimin
    Bellocco, Rino
    Sundström, 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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed)
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

  • 93.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    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.
    Neovius, Martin
    Tynelius, Per
    Rasmussen, Finn
    Sundström, 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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young menManuscript (preprint) (Other academic)
    Abstract [en]

    Background:

    While physical activity and exercise protects against cardiovascular disease, athletes have higher risk of atrial fibrillation and other arrhythmias. Graded independent and joint influences of exercise capacity and muscle strength on these diseases are unknown.

    Methods:

    All 1.26 million Swedish men who participated in mandatory military conscription between 1972 and 1995 (at a median age of 18.2 years) contributed. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations of maximal exercise capacity and muscle strength at conscription to subsequent risk of vascular disease and arrhythmias, as identified in national registries.

    Results:

    During a median follow-up of 26.3 years, about 26,000 hospitalizations for vascular disease events and 17,000 for arrhythmias occurred. Exercise capacity was inversely associated with risk of vascular disease (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.67]; for 5th vs. 1st quintile) and so was muscle strength (HR 0.79; 0.76-0.83; for 5th vs. 1st quintile ). Similar associations were seen across a range of major vascular disease events. Exercise capacity was associated with incidence of arrhythmias in a U-shaped fashion (HR 0.91; 0.86-0.96; for 3rd vs. 1st quintile, and 0.99; 0.94-1.04; for 5th vs. 1st quintile). Higher muscle strength was associated with lower risk of arrhythmias (HR 0.87; 0.83-0.91; for 5th vs. 1st quintile). 

    Conclusion:

    Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long-term risk of vascular disease and arrhythmias. The lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmias.

  • 94.
    Andersen, Kasper
    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.
    Hållmarker, Ulf
    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. Department of Internal Medicine, Mora Hospital, Sweden.
    James, Stefan
    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.
    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, Cardiology.
    Long-Distance Skiing and Incidence of Hypertension: A Cohort Study of 206,889 Participants in a Long-Distance Cross-Country Skiing Event2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 9, p. 743-750Article in journal (Refereed)
    Abstract [en]

    Background: Hypertension is the leading risk factor for death worldwide and high levels of physical activity is associated with lower incidence of hypertension. The associations of excessive levels of exercise and incidence of hypertension is less known. We aim to compare the incidence of hypertension among 206,889 participants in a long-distance cross-country skiing event and 505,542 persons randomly sampled from the general population (matched to the skiers on age sex and place of residence). Methods: Skiers best performance (in per cent of winning time) and number of completed races during the study period were associated to incidence of hypertension after participation in Vasaloppet. Hypertension was defined as prescription of blood pressure-lowering drugs as obtained from the national drug registry. Models were adjusted for sex, age, education and income (total effect). Results: During a median time-of-risk of 8.3 years skiers had lower incidence of hypertension compared to non-skiers (HR 0.59; 95% confidence interval [CI] 0.58-0.60). Among the skiers, better performance (in % of winning time) in Vasaloppet was strongly associated with lower incidence of hypertension (Fastest fifth: HR 0.41; 95% CI 0.39-0.42. Slowest fifth: 0.78 CI 0.75-0.81). The association was near linear and did not differ between sexes. Among the skiers, a weaker association of number of completed races during the study period with incidence of hypertension (1 race: HR 0.63; 95% CI 0.62-0.65.>5 races: HR 0.51; 95% CI 0.50-0.53). A sub-analysis of 10,804 participants including adjustment for lifestyle factors showed similar results. Conclusions: Participation in a long-distance skiing event was associated with 41% lower incidence of hypertension over the next 8 years, compared to non-participation; and the better the performance, the lower the incidence of hypertension. This adds to the list of beneficial effects of intensive training, as hypertension is the leading risk factor of premature death globally.

  • 95.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, 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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 96.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    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, Cardiology.
    Anthropometric measures and risk of atrial fibrillation - a cohort study of 1.2 million young men2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 910-910Article in journal (Other academic)
  • 97.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Lund Univ, Dept Hlth Sci, Lund, Sweden.
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;Stockholm Cty Council, Ctr Epidemiol & Community Med, Stockholm, Sweden.
    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.
    Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 346-355Article in journal (Refereed)
    Abstract [en]

    Background: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation.

    Objectives: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation.

    Methods: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation.

    Results: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures.

    Conclusions: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

  • 98.
    Andersen, Kasper
    et al.
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rasmussen, Finn
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    Held, Claes
    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.
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, Per
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    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.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h4543Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. DESIGN Cohort study. SETTING General population in Sweden. PARTICIPANTS 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. MAIN OUTCOMES Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. RESULTS During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. CONCLUSIONS Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia.

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  • 99.
    Andersen, Thomas
    et al.
    Stavanger Univ Hosp, Dept Anaesthesiol, Stavanger, Norway.
    Ueland, Thor
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway;Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr TREC, Tromso, Norway.
    Ghukasyan Lakic, Tatevik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åkerblom, Axel
    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.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aukrust, Pal
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway;Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr TREC, Tromso, Norway;Natl Hosp Norway, Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, Oslo, Norway.
    Michelsen, Annika E.
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway.
    James, Stefan K.
    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.
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England.
    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.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kontny, Frederic
    Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway;Drammen Heart Ctr, Drammen, Norway.
    C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 11, p. 2402-2410Article in journal (Refereed)
    Abstract [en]

    Objective:

    The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.

    Approach and Results:

    Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.

    Conclusions:

    In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.

  • 100.
    Andersson, Anne
    et al.
    Umeå Univ, Dept Radiat Sci, Oncol, Umeå, Sweden..
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Erlanson, Martin
    Umeå Univ, Dept Radiat Sci, Oncol, Umeå, Sweden..
    Johansson, Ann-Sofie
    Umeå Univ, Dept Radiat Sci, Oncol, Umeå, Sweden..
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tavelin, Björn
    Umeå Univ, Dept Radiat Sci, Oncol, Umeå, Sweden..
    Näslund, Ulf
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Melin, Beatrice
    Umeå Univ, Dept Radiat Sci, Oncol, Umeå, Sweden..
    High risk of cardiovascular side effects after treatment of Hodgkin's lymphoma - is there a need for intervention in long-term survivors?2021In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 126, no 1, article id e6117Article in journal (Refereed)
    Abstract [en]

    Background: Hodgkin lymphoma (HL) patients have a good prognosis after adequate treatment. Previous treatment with mantle field irradiation has been accompanied by an increased long-term risk of cardiovascular disease (CVD). This study identified co-morbidity factors for the development of cardiovascular side effects and initiated an intervention study aimed to decrease morbidity and mortality of CVD in HL survivors. Design: Hodgkin lymphoma patients aged <= 45 years diagnosed between 1965 and 1995 were invited to participate. In total, 453 patients completed a questionnaire that addressed co-morbidity factors and clinical symptoms. Of these, 319 accepted to participate in a structured clinical visit. The statistical analyses compared individuals with CVD with those with no CVD. Results: Cardiovascular disease was reported by 27.9%. Radiotherapy (odds ratio [OR]: 3.27), hypertension and hypercholesterolemia were shown to be independent risk factors for the development of CVD. The OR for CVD and valve disease in patients who received radiotherapy towards mediastinum was 4.48 and 6.07, respectively. At clinical visits, 42% of the patients were referred for further investigation and 24% of these had a cardiac ultrasound performed due to previously unknown heart murmurs. Conclusion: Radiotherapy towards mediastinum was an independent risk factor for CVD as well as hypercholesterolemia and hypertension. A reasonable approach as intervention for this cohort of patients is regular monitoring of hypertension and hypercholesterolemia and referral to adequate investigation when cardiac symptoms appear. Broad knowledge about the side effects from radiotherapy in the medical community and well-structured information regarding late side effects to the patients are all reasonable approaches as late effects can occur even 40 years after cancer treatment.

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