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Hagström, Emil
Publications (10 of 59) Show all publications
Ridefelt, P., Hagström, E., Svensson, M. K., Åkerfeldt, T. & Larsson, A. (2019). Age- and sex-specific reference values for non-HDL cholesterol and remnant cholesterol derived from the Nordic Reference Interval Project (NORIP).. Scandinavian Journal of Clinical and Laboratory Investigation
Open this publication in new window or tab >>Age- and sex-specific reference values for non-HDL cholesterol and remnant cholesterol derived from the Nordic Reference Interval Project (NORIP).
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2019 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVES: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP).

METHODS: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.

RESULTS: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata.

CONCLUSIONS: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories.

Keywords
HDL-cholesterol, Reference values, non-HDL-cholesterol, remnant cholesterol, triglyceride-rich particles
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-373651 (URN)10.1080/00365513.2018.1550809 (DOI)30638091 (PubMedID)
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-04-02Bibliographically approved
Patel, R. S., Schmidt, A. F., Tragante, V., McCubrey, R. O., Holmes, M. V., Howe, L. J., . . . Asselbergs, F. W. (2019). Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data. Circulation: Genomic and Precision Medicine, 12(4), Article ID e002471.
Open this publication in new window or tab >>Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data
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2019 (English)In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002471Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.

METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.

RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).

CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Keywords
chromosome, genetic, variation, myocardial infarction, risk factor, secondary prevention
National Category
Cardiac and Cardiovascular Systems Medical Genetics
Identifiers
urn:nbn:se:uu:diva-383874 (URN)10.1161/CIRCGEN.119.002471 (DOI)000466741600005 ()30897348 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 201668EU, European Research Council, 294609EU, Horizon 2020, 01KL1802NIH (National Institute of Health)EU, Horizon 2020, 692145Wellcome trustEU, FP7, Seventh Framework Programme, 223004Forte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2019-06-14 Created: 2019-06-14 Last updated: 2019-06-14Bibliographically approved
Bhatt, D. L., Fox, K., Harrington, R. A., Leiter, L. A., Mehta, S. R., Simon, T., . . . Winder, E. (2019). Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study. Clinical Cardiology, 42(5), 498-505
Open this publication in new window or tab >>Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
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2019 (English)In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 5, p. 498-505Article in journal (Refereed) Published
Abstract [en]

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

Keywords
antiplatelet therapy, clinical trials, diabetes mellitus, general clinical cardiology, adult, ischemic heart disease
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-387294 (URN)10.1002/clc.23164 (DOI)000468080800001 ()30788847 (PubMedID)
Funder
AstraZeneca
Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved
Patel, R. S., Tragante, V., Schmidt, A. F., McCubrey, R. O., Holmes, M. V., Howe, L. J., . . . Asselbergs, F. W. (2019). Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium. Circulation: Genomic and Precision Medicine, 12(4), Article ID e002470.
Open this publication in new window or tab >>Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium
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2019 (English)In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002470Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.

METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.

RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.

CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Keywords
coronary artery disease, genetics, myocardial infarction, prognosis, secondary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-383875 (URN)10.1161/CIRCGEN.119.002470 (DOI)000466741600004 ()30896328 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 201668EU, FP7, Seventh Framework Programme, 305739EU, European Research Council, 294609Swedish Research CouncilSwedish Foundation for Strategic Research EU, European Research Council, 294609EU, Horizon 2020, 01KL1802NIH (National Institute of Health), R0133169NIH (National Institute of Health), R01ES021801NIH (National Institute of Health), R01MD010358NIH (National Institute of Health), R01ES025786NIH (National Institute of Health), R01HL103866NIH (National Institute of Health), R01DK106000NIH (National Institute of Health), R01HL126827NIH (National Institute of Health), P20HL113452NIH (National Institute of Health), P01HL098055NIH (National Institute of Health), P01HL076491NIH (National Institute of Health), R01HL103931NIH (National Institute of Health), AG051633NIH (National Institute of Health), 5P01HL101398-02NIH (National Institute of Health), 1P20HL113451-01NIH (National Institute of Health), 1R56HL126558-01NIH (National Institute of Health), 1RF-1AG051633-01NIH (National Institute of Health), R01 NS064162-01NIH (National Institute of Health), R01 HL89650-01NIH (National Institute of Health), HL095479-01NIH (National Institute of Health), 1U10HL110302-01NIH (National Institute of Health), 1DP3DK094346-01NIH (National Institute of Health), 2P01HL086773-06A1EU, Horizon 2020, 692145Wellcome trust, 072960/Z/03/ZWellcome trust, 084726/Z/08/ZWellcome trust, 084727/Z/08/ZWellcome trust, 085475/Z/08/ZWellcome trust, 085475/B/08/ZSwedish Heart Lung FoundationThe Crafoord FoundationKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework Programme, 223004Forte, Swedish Research Council for Health, Working Life and WelfareNIH (National Institute of Health), R01 NR013396
Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-06-12Bibliographically approved
Forbes, C. A., Deshpande, S., Sorio-Vilela, F., Kutikova, L., Duffy, S., Gouni-Berthold, I. & Hagström, E. (2018). A systematic literature review comparing methods for the measurement of patient persistence and adherence. Current Medical Research and Opinion, 34(9), 1613-1625
Open this publication in new window or tab >>A systematic literature review comparing methods for the measurement of patient persistence and adherence
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2018 (English)In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 34, no 9, p. 1613-1625Article, review/survey (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
Keywords
Cardiovascular diseases, chronic disease, adherence, persistence, methodology, systematic review
National Category
Social and Clinical Pharmacy Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-365685 (URN)10.1080/03007995.2018.1477747 (DOI)000441048500010 ()29770718 (PubMedID)
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Hagström, E., Norlund, F., Stebbins, A., Armstrong, P. W., Chiswell, K., Granger, C. B., . . . Held, C. (2018). Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease. Journal of Internal Medicine, 283(1), 83-92
Open this publication in new window or tab >>Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease
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2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 1, p. 83-92Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

Keywords
death, depression, psychosocial stress, stable coronary heart disease
National Category
Cardiac and Cardiovascular Systems Psychology
Identifiers
urn:nbn:se:uu:diva-333087 (URN)10.1111/joim.12692 (DOI)000418411100006 ()28960596 (PubMedID)
Funder
GlaxoSmithKline (GSK)
Available from: 2017-11-06 Created: 2017-11-06 Last updated: 2018-01-29Bibliographically approved
Hagström, E. & Held, C. (2018). Response to Letter: 'Sorrow and cardiovascular events' [Letter to the editor]. Journal of Internal Medicine, 283(4), 415-415
Open this publication in new window or tab >>Response to Letter: 'Sorrow and cardiovascular events'
2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 415-415Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-356890 (URN)10.1111/joim.12731 (DOI)000428438600011 ()29356160 (PubMedID)
Available from: 2018-08-10 Created: 2018-08-10 Last updated: 2018-08-10Bibliographically approved
Larsson, A., Hagström, E., Nilsson, L. & Svensson, M. K. (2018). Treatment target re-classification of subjects comparing estimation of low-density lipoprotein cholesterol by the Friedewald equation and direct measurement of LDL-cholesterol. Upsala Journal of Medical Sciences, 123(2), 94-99
Open this publication in new window or tab >>Treatment target re-classification of subjects comparing estimation of low-density lipoprotein cholesterol by the Friedewald equation and direct measurement of LDL-cholesterol
2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 2, p. 94-99Article in journal (Refereed) Published
Abstract [en]

AIMS: To compare low-density lipoprotein cholesterol (LDL-C) values calculated by the Friedewald equation with direct LDL-C in patient samples and assess the possible impact on re-classification of LDL-C target values for primary prevention or high cardiovascular disease (CVD) risk (<2.5 mmol/L) and secondary prevention or very high CVD risk (<1.8 mmol/L). LDL-C is an important CVD risk factor. Over the last decade, there has been a change in laboratory methodology from indirectly calculated LDL-C with the Friedewald equation to direct LDL-C measurements (dLDL-C).

METHODS: Reported results for plasma triglycerides, total cholesterol, high-density lipoprotein-cholesterol, and dLDL-C from 34,981 samples analyzed in year 2014 were extracted from the laboratory information system, Uppsala University Hospital, Uppsala, Sweden.

RESULTS: dLDL-C was approximately 10% lower than the corresponding LDL-C results calculated by the Friedewald equation in both men and women. In subjects with triglyceride concentrations above 4 mmol/L (n = 1250) the same discordant pattern was seen as for the entire study population. Altogether 5469 out of 18,051 men (30.3%) and 4604 out of 16,928 women (27.2%) were down-classified at least one CVD risk category. A very small number of subject was up-classified, in total 37 out of 18,051 men (0.2%) and 28 out of 16,928 women (0.2%).

CONCLUSIONS: The two LDL-C methods had a high concordance, but the direct LDL-C measurement consistently gave approx. 10% lower values, and this caused one-third of subjects to be re-classified as having a lower cardiovascular disease risk in relation to recommended LDL-C target values and decision limits.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
Keywords
Direct LDL-C measurement, Friedewald equation, LDL-cholesterol, primary prevention, re-classification, secondary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-353344 (URN)10.1080/03009734.2018.1465496 (DOI)000438159000004 ()29745278 (PubMedID)
Available from: 2018-06-12 Created: 2018-06-12 Last updated: 2019-06-27Bibliographically approved
Vedin, O., Hagström, E., Östlund, O., Avezum, A., Budaj, A., Flather, M. D., . . . Held, C. (2017). Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease. International Journal of Cardiology, 245, 271-276
Open this publication in new window or tab >>Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease
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2017 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 245, p. 271-276Article in journal (Refereed) Published
Abstract [en]

Background:

Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss-a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial.

Methods and results:

Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively.

After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14-1.29), interleukin 6 1.14 (1.10-1.18), lipoprotein-associated phospholipase A(2) activity 1.05 (1.03-1.06), growth differentiation factor 15 1.11 (1.08-1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11-1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98-1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact.

Conclusions:

A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers.

Keywords
Tooth loss, Periodontal disease, Stable coronary heart disease, Biomarkers, Risk factors
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-336290 (URN)10.1016/j.ijcard.2017.07.036 (DOI)000411288700055 ()28735759 (PubMedID)
Available from: 2018-01-23 Created: 2018-01-23 Last updated: 2018-01-23Bibliographically approved
Lindholm, D., Lindbäck, J., Armstrong, P. W., Budaj, A., Cannon, C. P., Granger, C. B., . . . Wallentin, L. (2017). Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease. Journal of the American College of Cardiology, 70(7), 813-826
Open this publication in new window or tab >>Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease
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2017 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 70, no 7, p. 813-826Article in journal (Refereed) Published
Abstract [en]

Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
cardiac troponin, low-density lipoprotein cholesterol, N-terminal pro-B-type natriuretic peptide, risk prediction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-327281 (URN)10.1016/j.jacc.2017.06.030 (DOI)000407028500001 ()28797349 (PubMedID)
Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-11-23Bibliographically approved
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