uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 188) Show all publications
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
Show others...
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
Hochman, J. S., Held, C. & Jeffries, N. (2019). Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial. JAMA cardiology, 4(3), 273-286
Open this publication in new window or tab >>Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial
2019 (English)In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 4, no 3, p. 273-286Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE

It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia.

OBJECTIVE

To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles.

DESIGN, SETTING, AND PARTICIPANTS

The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (< 50% for imaging stress test and < 70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018.

MAIN OUTCOMES AND MEASURES

Enrolled, excluded, and randomized participants' baseline characteristics. No clinical outcomes are reported.

RESULTS

A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n = 2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n = 3190 of 3677) (proximal in 46.8% [ n = 1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging.

CONCLUSIONS AND RELEVANCE

The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-381092 (URN)10.1001/jamacardio.2019.0014 (DOI)000461901600018 ()30810700 (PubMedID)
Note

For complete list of authors see http://dx.doi.org/10.1001/jamacardio.2019.0014

Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved
Wallert, J., Mitchell, A., Held, C., Hagström, E., Leosdottir, M. & Olsson, E. (2019). Cardiac rehabilitation goal attainment after myocardial infarction with versus without diabetes: A nationwide registry study. International Journal of Cardiology, 292, 19-24
Open this publication in new window or tab >>Cardiac rehabilitation goal attainment after myocardial infarction with versus without diabetes: A nationwide registry study
Show others...
2019 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 292, p. 19-24Article in journal (Refereed) Published
Abstract [en]

Background: Patients with first-time myocardial infarction (MI) and diabetes mellitus (DM) constitute a vulnerable subgroup of cardiovascular (CV) patients for which secondary prevention is particularly important. We investigated if patients with versus without DM differ in attaining four main lifestyle-related cardiac rehabilitation (CR) targets, one-year post-MI.

Methods: This national cohort study (2006-2015) identified individuals with and without DM at hospital admission in the Swedish cardiac registry, SWEDEHEART. CR goal attainment was assessed one year later. The study population included 47,907 unique patients with first-time MI <75 years at baseline (61.8 mean age, 26.7% women, 14.6% with DM). After imputation, propensity score matching was performed. Analyses were conducted with logistic regression.

Results: In the matched population, having DM was associated (OR [95% CI]) with lower odds of attaining the one-year post-MI CR goal for both smoking cessation (0.90 [0.81, 0.99]) and attendance in exercise training (0.88 [0.83, 0.95]), yet with higher odds of the <1.8 mmol LDL-C target (1.28 [1.19, 1.36]), and similar odds for the <140 mm Hg systolic blood pressure target (0.97 [0.91, 1.04]). In addition, women with DM were particularly unlikely to attend exercise training.

Conclusions: Patients with first-time MI and DM are less likely to attain two of four selected CR goals compared to those without DM. The particularly low exercise training attendance by women with DM is of concern. Possibilities for tailored interventions targeting behavioural change for this high-risk group, including focused efforts to increase exercise training attendance in women with DM, should be investigated. 

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2019
Keywords
Behavioural risk factors, Coronary artery disease, Diabetes mellitus, Exercise training, Secondary prevention, Smoking cessation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-391274 (URN)10.1016/j.ijcard.2019.04.049 (DOI)000476878000003 ()31031079 (PubMedID)
Available from: 2019-08-27 Created: 2019-08-27 Last updated: 2019-08-27Bibliographically approved
Spitzer, E., McFadden, E., Vranckx, P., Garcia-Garcia, H. M., Seltzer, J. H., Held, C., . . . Serruys, P. W. (2019). Critical Appraisal of Contemporary Clinical Endpoint Definitions in Coronary Intervention Trials A Guidance Document. JACC: Cardiovascular Interventions, 12(9), 805-819
Open this publication in new window or tab >>Critical Appraisal of Contemporary Clinical Endpoint Definitions in Coronary Intervention Trials A Guidance Document
Show others...
2019 (English)In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 12, no 9, p. 805-819Article, review/survey (Refereed) Published
Abstract [en]

The Academic Research Consortium (ARC) and the Standardized Data Collection for Cardiovascular Trials Initiative have recently published updated clinical and angiographic endpoint definitions for percutaneous coronary intervention trials. The aim of this document is to provide practical guidance to facilitate and harmonize the implementation of those definitions in randomized trials or registries, as well as to foster consistency among independent adjudication committees. The authors compared the ARC-2 and Standardized Data Collection for Cardiovascular Trials Initiative definitions to identify areas of consistency, complex scenarios, and definitions in need of further standardization. Furthermore, the authors compared the fourth universal definition of myocardial infarction with the ARC-2 definition of myocardial infarction. The Society for Cardiovascular Angiography and Interventions definition of periprocedural myocardial infarction was also compared with the ARC-2 definition and the fourth universal definition of myocardial infarction. An in-depth assessment was done for each individual clinical endpoint to guide clinical investigators on reporting and classifying clinical adverse events. Finally, the authors propose standard streamlined data capture templates for reporting and adjudicating death, myocardial infarction, stroke, revascularization, stent or scaffold thrombosis, and bleeding. (c) 2019 by the American College of Cardiology Foundation.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
bleeding, clinical endpoint adjudication, clinical endpoint definition, death, myocardial infarction, revascularization, scaffold thrombosis, stent thrombosis, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-384078 (URN)10.1016/j.jcin.2018.12.031 (DOI)000466940300004 ()31072504 (PubMedID)
Available from: 2019-06-18 Created: 2019-06-18 Last updated: 2019-06-18Bibliographically approved
Bosch, J., O'Donnell, M., Swaminathan, B., Lonn, E. M., Sharma, M., Dagenais, G., . . . Yusuf, S. (2019). Effects of blood pressure and lipid lowering on cognition Results from the HOPE-3 study. Neurology, 92(13), E1435-E1446
Open this publication in new window or tab >>Effects of blood pressure and lipid lowering on cognition Results from the HOPE-3 study
Show others...
2019 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 13, p. E1435-E1446Article in journal (Refereed) Published
Abstract [en]

Objective: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.

Methods: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 x 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were >= 70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.

Results: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD +/- 3.5 years); 59% were women; 45% had hypertension; and 24% had >= 12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.

Conclusions: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. ClinicalTrials.gov identifier: NCT00468923. Classification of evidence: This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-382528 (URN)10.1212/WNL.0000000000007174 (DOI)000463260800017 ()30814321 (PubMedID)
Funder
AstraZeneca
Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-04-26Bibliographically approved
Fanaroff, A. C., Clare, R., Pieper, K. S., Mahaffey, K. W., Melloni, C., Green, J. B., . . . Lopes, R. D. (2019). Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials. Circulation, 139(7), 863-873
Open this publication in new window or tab >>Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials
Show others...
2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 7, p. 863-873Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient-and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term followup, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.

Keywords
clinical trial, cause of death, death, follow-up studies, quality control
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-378677 (URN)10.1161/CIRCULATIONAHA.118.037202 (DOI)000458410000008 ()30586739 (PubMedID)
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-03-12Bibliographically approved
Lissåker, C., Norlund, F., Wallert, J., Held, C. & Olsson, E. (2019). Persistent emotional distress after a first-time myocardial infarction and its assocation to late cardiovascular and non-cardiovascular mortality. European Journal of Preventive Cardiology
Open this publication in new window or tab >>Persistent emotional distress after a first-time myocardial infarction and its assocation to late cardiovascular and non-cardiovascular mortality
Show others...
2019 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND:

Patients with symptoms of depression and/or anxiety - emotional distress - after a myocardial infarction (MI) have been shown to have worse prognosis and increased healthcare costs. However, whether specific subgroups of patients with emotional distress are more vulnerable is less well established. The purpose of this study was to identify the association between different patterns of emotional distress over time with late cardiovascular and non-cardiovascular mortality among first-MI patients aged <75 years in Sweden.

METHODS:

We utilized data on 57,602 consecutive patients with a first-time MI from the national SWEDEHEART registers. Emotional distress was assessed using the anxiety/depression dimension of the European Quality of Life Five Dimensions questionnaire two and 12 months after the MI, combined into persistent (emotional distress at both time-points), remittent (emotional distress at the first follow-up only), new (emotional distress at the second-follow up only) or no distress. Data on cardiovascular and non-cardiovascular mortality were obtained until the study end-time. We used multiple imputation to create complete datasets and adjusted Cox proportional hazards models to estimate hazard ratios.

RESULTS:

Patients with persistent emotional distress were more likely to die from cardiovascular (hazard ratio: 1.46, 95% confidence interval: 1.16, 1.84) and non-cardiovascular causes (hazard ratio: 1.54, 95% confidence interval: 1.30, 1.82) than those with no distress. Those with remittent emotional distress were not statistically significantly more likely to die from any cause than those without emotional distress.

DISCUSSION:

Among patients who survive 12 months, persistent, but not remittent, emotional distress was associated with increased cardiovascular and non-cardiovascular mortality. This indicates a need to identify subgroups of individuals with emotional distress who may benefit from further assessment and specific treatment.

Keywords
Anxiety, depression, mortality, myocardial infarction
National Category
Cardiac and Cardiovascular Systems Psychology
Research subject
Cardiology; Psychology
Identifiers
urn:nbn:se:uu:diva-385248 (URN)10.1177/2047487319841475 (DOI)
Funder
Swedish Heart Lung Foundation, 2016-0463
Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-06-12
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
Show others...
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
Khunti, K., Jung, H., Dans, A. L., Held, C., Dagenais, G. R., Yusuf, S. & Lonn, E. (2019). Statin Use in Primary Prevention: A Simple Trial-Based Approach Compared With Guideline-Recommended Risk Algorithms for Selection of Eligible Patients. Canadian Journal of Cardiology, 35(5), 644-652
Open this publication in new window or tab >>Statin Use in Primary Prevention: A Simple Trial-Based Approach Compared With Guideline-Recommended Risk Algorithms for Selection of Eligible Patients
Show others...
2019 (English)In: Canadian Journal of Cardiology, ISSN 0828-282X, E-ISSN 1916-7075, Vol. 35, no 5, p. 644-652Article in journal (Refereed) Published
Abstract [en]

Background: Cardiovascular disease risk assessment tools help identify individuals likely to benefit from preventative therapies. In this study we compared outcomes using the American College of Cardiology/American Heart Association (ACC/AHA) risk algorithm and the Framingham Risk Score (FRS) tool in the Heart Outcomes Prevention Evaluation (HOPE)-3 study.

Methods: We compared outcomes using the ACC/AHA algorithm and the FRS with those seen in HOPE-3, which randomized participants to 10 mg rosuvastatin or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second coprimary outcome additionally included heart failure, cardiac arrest, and revascularization.

Results: Relative risks using risk scores were similar to those observed in the HOPE-3. Hazards ratios for the first coprimary outcome according to risk categories of <= 10%, 10%-20%, and <= 20% using the ACC/AHA algorithm were 0.82 (95% confidence interval [CI], 0.53-1.28), 0.72 (95% CI, 0.53-0.96), and 0.72 (95% CI, 0.55-0.93), and absolute risk reduction (ARR) of 0.18%, 1.33%, and 1.85%, respectively, over a median of 5.6 years. Corresponding results using the FRS were 0.69 (95% CI, 0.36-1.35), 0.73 (95% CI, 0.52-1.01), and 0.75 (95% CI, 0.60-0.94); and ARR of 1.32%, 0.61%, and 1.43%. Hazard ratios for the second coprimary outcome were 0.77 (95% CI, 0.51-1.14), 0.73 (95% CI, 0.56-0.95), and 0.74 (95% CI, 0.58-0.94); and ARR of 0.36%, 1.49%, and 1.85%, using the ACC/AHA algorithm and 0.76 (95% CI, 0.41-1.41), 0.70 (95% CI, 0.52-0.95), and 0.76 (95% CI, 0.62-0.94); and ARR of 1.08%, 0.83%, and 1.56% using the FRS.

Conclusions: The pragmatic HOPE-3 trial approach identifies in an ethnically diverse primary prevention population individuals at intermediate risk who benefit from statin therapy using simple clinical characteristics without the need for complex, currently used risk assessment tools.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-383150 (URN)10.1016/j.cjca.2019.03.002 (DOI)000465556800015 ()31030865 (PubMedID)
Funder
AstraZeneca
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-10Bibliographically 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
Show others...
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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9402-7404

Search in DiVA

Show all publications