Dataset Information

Subsequent Event Risk in Individuals With Established Coronary Heart Disease.

ABSTRACT: 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.

SUBMITTER: Patel RS

PROVIDER: S-EPMC6629546 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Subsequent Event Risk in Individuals With Established Coronary Heart Disease.

Patel Riyaz S RS Tragante Vinicius V Schmidt Amand F AF McCubrey Raymond O RO Holmes Michael V MV Howe Laurence J LJ Direk Kenan K Åkerblom Axel A Leander Karin K Virani Salim S SS Kaminski Karol A KA Muehlschlegel Jochen D JD Allayee Hooman H Almgren Peter P Alver Maris M Baranova Ekaterina V EV Behloui Hassan H Boeckx Bram B Braund Peter S PS Breitling Lutz P LP Delgado Graciela G Duarte Nubia E NE Dubé Marie-Pierre MP Dufresne Line L Eriksson Niclas N Foco Luisa L Scholz Markus M Gijsberts Crystel M CM Glinge Charlotte C Gong Yan Y Hartiala Jaana J Heydarpour Mahyar M Hubacek Jaroslav A JA Kleber Marcus M Kofink Daniel D Kotti Salma S Kuukasjärvi Pekka P Lee Vei-Vei VV Leiherer Andreas A Lenzini Petra A PA Levin Daniel D Lyytikäinen Leo-Pekka LP Martinelli Nicola N Mons Ute U Nelson Christopher P CP Nikus Kjell K Pilbrow Anna P AP Ploski Rafal R Sun Yan V YV Tanck Michael W T MWT Tang W H Wilson WHW Trompet Stella S van der Laan Sander W SW Van Setten Jessica J Vilmundarson Ragnar O RO Viviani Anselmi Chiara C Vlachopoulou Efthymia E Al Ali Lawien L Boerwinkle Eric E Briguori Carlo C Carlquist John F JF Carruthers Kathryn F KF Casu Gavino G Deanfield John J Deloukas Panos P Dudbridge Frank F Engstrøm Thomas T Fitzpatrick Natalie N Fox Kim K Gigante Bruna B James Stefan S Lokki Marja-Liisa ML Lotufo Paulo A PA Marziliano Nicola N Mordi Ify R IR Muhlestein Joseph B JB Newton-Cheh Christopher C Pitha Jan J Saely Christoph H CH Samman-Tahhan Ayman A Sandesara Pratik B PB Teren Andrej A Timmis Adam A Van de Werf Frans F Wauters Els E Wilde Arthur A M AAM Ford Ian I Stott David J DJ Algra Ale A Andreassi Maria G MG Ardissino Diego D Arsenault Benoit J BJ Ballantyne Christie M CM Bergmeijer Thomas O TO Bezzina Connie R CR Body Simon C SC Boersma Eric H EH Bogaty Peter P Bots Michiel L ML Brenner Hermann H Brugts Jasper J JJ Burkhardt Ralph R Carpeggiani Clara C Condorelli Gianluigi G Cooper-DeHoff Rhonda M RM Cresci Sharon S Danchin Nicolas N de Faire Ulf U Doughty Robert N RN Drexel Heinz H Engert James C JC Fox Keith A A KAA Girelli Domenico D Grobbee Diederick E DE Hagström Emil E Hazen Stanley L SL Held Claes C Hemingway Harry H Hoefer Imo E IE Hovingh G Kees GK Jabbari Reza R Johnson Julie A JA Jukema J Wouter JW Kaczor Marcin P MP Kähönen Mika M Kettner Jiri J Kiliszek Marek M Klungel Olaf H OH Lagerqvist Bo B Lambrechts Diether D Laurikka Jari O JO Lehtimäki Terho T Lindholm Daniel D Mahmoodi B K BK Maitland-van der Zee Anke H AH McPherson Ruth R Melander Olle O Metspalu Andres A Niemcunowicz-Janica Anna A Olivieri Oliviero O Opolski Grzegorz G Palmer Colin N CN Pasterkamp Gerard G Pepine Carl J CJ Pereira Alexandre C AC Pilote Louise L Quyyumi Arshed A AA Richards A Mark AM Sanak Marek M Siegbahn Agneta A Simon Tabassome T Sinisalo Juha J Smith J Gustav JG Spertus John A JA Stender Steen S Stewart Alexandre F R AFR Szczeklik Wojciech W Szpakowicz Anna A Tardif Jean-Claude JC Ten Berg Jurriën M JM Tfelt-Hansen Jacob J Thanassoulis George G Thiery Joachim J Torp-Pedersen Christian C van der Graaf Yolanda Y Visseren Frank L J FLJ Waltenberger Johannes J Weeke Peter E PE Van der Harst Pim P Lang Chim C CC Sattar Naveed N Cameron Vicky A VA Anderson Jeffrey L JL Brophy James M JM Pare Guillaume G Horne Benjamin D BD März Winfried W Wallentin Lars L Samani Nilesh J NJ Hingorani Aroon D AD Asselbergs Folkert W FW

Circulation. Genomic and precision medicine 20190321 4

<h4>Background</h4>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.<h4>Methods</h4>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 follow ...[more]

PMID: 30896328

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Project description:BackgroundGenetic 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.MethodsA 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.ResultsMeta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD 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).ConclusionsIn 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.

Project description:IMPORTANCE:High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiovascular risk and could be approved in the United States for clinical use soon. However, data linking long-term temporal change in hs-cTnT to outcomes are limited, particularly in primary prevention settings. OBJECTIVE:To examine the association of 6-year change in hs-cTnT with incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS:This prospective observational cohort study, performed from January 1, 1990, to December 31, 2011, included 8838 participants with biracial representation from the Atherosclerosis Risk in Communities Study who were initially free of CHD and HF and who had hs-cTnT measured twice, 6 years apart. Data analysis was performed from October 28, 2014, to March 9, 2016. MAIN OUTCOME AND MEASURES:Risk factor and temporal hs-cTnT data were collected. Using Cox proportional hazards regression, we examined the association of hs-cTnT change with subsequent CHD, HF, and death during a maximum of 16 years. Improvement in discrimination was determined by the Harrell C statistic. RESULTS:Of the 8838 participants (mean age, 56 years; 5215 female [59.0%]; 1891 black [21.4%]) there were 1157 CHD events, 965 HF events, and 1813 deaths overall. Incident detectable hs-cTnT (baseline, <0.005 ng/mL; follow-up, ?0.005 ng/mL) was independently associated with subsequent CHD (hazard ratio [HR], 1.4; 95% CI, 1.2-1.6), HF (HR, 2.0; 95% CI, 1.6-2.4), and death (HR, 1.5; 95% CI, 1.3-1.7), relative to an hs-cTnT level less than 0.005 ng/mL at both visits. In addition, HRs as high as 4 for CHD and death and 8 for HF were recorded among individuals with the most marked hs-cTnT increases (eg, baseline, < 0.005 ng/mL; follow-up, ?0.014 ng/mL). Risk for subsequent outcomes was lower among those with relative hs-cTnT reductions greater than 50% from baseline. Furthermore, information on hs-cTnT change improved discrimination for HF and death when added to a model that included traditional risk factors, N-terminal pro-brain natriuretic peptide, and baseline hs-cTnT level. Among individuals with adjudicated HF hospitalizations, hs-cTnT change appeared to be similarly associated with HF with reduced and preserved ejection fraction. CONCLUSIONS AND RELEVANCE:Temporal increases in hs-cTnT, suggestive of progressive myocardial damage, are independently associated with incident CHD, death, and, above all, HF. Serial determination of hs-cTnT trajectory adds clinically relevant information to baseline testing and may be useful in prognostic assessments and the targeting of prevention strategies to high-risk individuals, especially among persons with stage A or B HF.

Project description:Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death. Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models. Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04-1.25) and 1.28 (95% CI, 1.10-1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96-1.37) and CHD (HR, 1.33; 95% CI, 0.99-1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08-1.43; CHD: HR, 1.65; 95% CI 1.30-2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12-1.44; CHD: HR, 1.53; 95% CI, 1.23-1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30-1.71; CHD: HR, 1.87; 95% CI, 1.48-2.37). Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.

Project description:BACKGROUND: Certain immune-mediated diseases (IMDs), such as rheumatoid arthritis and systemic lupus erythematosus, have been linked to cardiovascular disorders. We examined whether there is an association between 32 different IMDs and risk of subsequent hospitalization for coronary heart disease (CHD) related to coronary atherosclerosis in a nationwide follow up study in Sweden. METHODS AND FINDINGS: All individuals in Sweden hospitalized with a main diagnosis of an IMD (n = 336,479) without previous or coexisting CHD, between January 1, 1964 and December 31 2008, were followed for first hospitalization for CHD. The reference population was the total population of Sweden. Standardized incidence ratios (SIRs) for CHD were calculated. Overall risk of CHD during the first year after hospitalization for an IMD was 2.92 (95% CI 2.84-2.99). Twenty-seven of the 32 IMDs studied were associated with an increased risk of CHD during the first year after hospitalization. The overall risk of CHD decreased over time, from 1.75 after 1-5 years (95% CI 1.73-1.78), to 1.43 after 5-10 years (95% CI 1.41-1.46) and 1.28 after 10+ years (95% CI 1.26-1.30). Females generally had higher SIRs than males. The IMDs for which the SIRs of CDH were highest during the first year after hospitalization included chorea minor 6.98 (95% CI 1.32-20.65), systemic lupus erythematosus 4.94 (95% CI 4.15-5.83), rheumatic fever 4.65 (95% CI 3.53-6.01), Hashimoto's thyroiditis 4.30 (95% CI 3.87-4.75), polymyositis/dermatomyositis 3.81 (95% CI 2.62-5.35), polyarteritis nodosa 3.81 (95% CI 2.72-5.19), rheumatoid arthritis 3.72 (95% CI 3.56-3.88), systemic sclerosis 3.44 (95% CI 2.86-4.09), primary biliary cirrhosis 3.32 (95% CI 2.34-4.58), and autoimmune hemolytic anemia 3.17 (95% CI 2.16-4.47). CONCLUSIONS: Most IMDs are associated with increased risk of CHD in the first year after hospital admission. Our findings suggest that many hospitalized IMDs are tightly linked to coronary atherosclerosis.

Project description:BackgroundThe relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.Methods and findingsMeasurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual") IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels).ConclusionsLong-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CHD.

Dataset Information

Subsequent Event Risk in Individuals With Established Coronary Heart Disease.

Publications

Subsequent Event Risk in Individuals With Established Coronary Heart Disease.

Similar Datasets

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