Abstract 18003: 9p21 is Associated With Risk of First but Not Recurrent Major Adverse Cardiovascular Events
Background: The chromosome 9p21 locus is a recognized risk factor for coronary heart disease (CHD). Emerging data suggest that it may not confer additional risk in patients with established CHD. We sought to examine the association of 9p21 with first and recurrent major adverse cardiovascular events (MACE) through systematic review and meta-analysis.
Methods: We searched PubMed and EMBASE from inception to May 2013. All prospective studies reporting association for 9p21 and MACE (comprising any combination of death, fatal/nonfatal MI, revascularisation) were included. We supplemented identified studies with two unpublished cohorts. Data on clinical setting (healthy/established CHD), outcomes assessed and per-allele effect size and confidence limits were extracted. In 6 studies reporting data separately by 9p21 genotype, we estimated the per-allele effect using meta-regression. We performed a meta-analysis, stratified by clinical setting, and compared estimates using the Altman & Bland test for interaction.
Results: We identified 32 cohorts of which 3 were excluded as reported estimates could not be incorporated into meta-analysis. In 15 studies, of 161,043 individuals predominantly free of CHD and with 14,827 events, 9p21 associated with a pooled HR for a first event of 1.19 (95% CI: 1.17, 1.22). In contrast, in 14 studies of 25,059 patients with established CHD, reporting 4,628 events, the pooled HR of 9p21 for recurrent MACE was 1.02 (95% CI: 0.98, 1.06). There was strong evidence of heterogeneity between the estimates for first and recurrent MACE (P=1.1x10-11 for heterogeneity).
Conclusions: In contrast to association with first MACE, 9p21 may not associate with recurrent MACE in patients with established CHD. This may reflect mechanistic differences in disease onset versus progression or attenuation of effect by CHD therapies. With implications for genetic risk prediction, further studies are needed to precisely define the role of 9p21 in those with CHD.
- © 2013 by American Heart Association, Inc.