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.

Association of polygenic risk scores for coronary artery disease with subsequent events amongst established cases

“…These findings imply that genetic prediction of subsequent coronary disease events is likely to require dedicated GWAS of coronary disease progression. Second, our findings contribute to the existing literature (13, 31, 32, 39, 40) emphasising the caution required when using genetic data to infer causality in the context of disease progression. Genetic associations are generally thought to be causal by analogy with Mendelian randomization (41) because of the reduced possibility of confounding and reverse causation, but the observed protective associations of CAD PRS with mortality and ischemic stroke suggest that this may not hold for case-only studies.…”

“…This may be due to index event bias, although other possibilities need to be explored. Future work, such as dedicated GWAS of disease progression, by initiatives such as the GENIUS-CHD consortium (40) will aim to further explore genetic differences between onset and progression of CAD.…”

The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS): Design and Methodology

“…The vast majority of studies examining the genetic contribution to the risk of secondary events in those with established coronary artery disease have been in European populations, with the largest being the GENIUS-CHD consortium involving over 185,000 participants [37,38]. However, there are far fewer studies of non-European populations who are at particularly high risk [39,40].…”

“Bridging the Gap” Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era

“…Moreover, the Genetics of Subsequent Coronary Heart Disease consortium (GENIUS-CHD) was established to discover and validate genetic variants and biomarkers for the risk assessment of subsequent ischemic events along with novel drug targets for secondary prevention. It is considered a first-class initiative able to generate extraordinary results also in the field of sex-oriented cardiology [53]. Our group has contributed for a long time to the disclosure of the genetics/pharmacogenetics bases of myocardial infarction [54][55][56][57][58][59], and very recently we summarized our previous efforts and patents [US2016363592 (A1); ITTO20130532 (A1)] in a Special Issue belonging to the "Novel Molecular Targets for Cardioprotection: The EU-Cardioprotection Cost Action (CA16225)", which suggest useful sex-oriented prognostic biomarkers [60].…”