Chromosome 9p21 variants increased the risk of first CHD events (HR 1.19; 95% CI 1.17-1.22) but not subsequent events (HR 1.01; 95% CI 0.97-1.06), with significant heterogeneity (P=5.6x10^-11).
Meta-Analysis (n=193,372)
Yes
Do genetic variants at chromosome 9p21 increase the risk of first versus subsequent coronary heart disease events?
The Ch9p21 locus is a strong risk factor for first CHD events but does not predict subsequent events in patients with established CHD, impacting genetic risk prediction strategies.
Effect estimate: HR 1.19 (first event); HR 1.01 (subsequent event) (95% CI 1.17-1.22 (first event); 0.97-1.06 (subsequent event))
p-value: p=5.6 × 10(-11) for heterogeneity
OBJECTIVES: The purpose of this analysis was to compare the association between variants at the chromosome 9p21 locus (Ch9p21) and risk of first versus subsequent coronary heart disease (CHD) events through systematic review and meta-analysis. BACKGROUND: Ch9p21 is a recognized risk factor for a first CHD event. However, its association with risk of subsequent events in patients with established CHD is less clear. METHODS: We searched PubMed and EMBASE for prospective studies reporting association of Ch9p21 with incident CHD events and extracted information on cohort type (individuals without prior CHD or individuals with established CHD) and effect estimates for risk of events. RESULTS: We identified 31 cohorts reporting on 193,372 individuals. Among the 16 cohorts of individuals without prior CHD (n = 168,209), there were 15,664 first CHD events. Ch9p21 was associated with a pooled hazard ratio (HR) of a first event of 1.19 (95% confidence interval: 1.17 to 1.22) per risk allele. In individuals with established CHD (n = 25,163), there were 4,436 subsequent events providing >99% and 91% power to detect a per-allele HR of 1.19 or 1.10, respectively. The pooled HR for subsequent events was 1.01 (95% confidence interval: 0.97 to 1.06) per risk allele. There was strong evidence of heterogeneity between the effect estimates for first and subsequent events (p value for heterogeneity = 5.6 × 10(-11)). We found no evidence for biases to account for these findings. CONCLUSIONS: Ch9p21 shows differential association with risk of first versus subsequent CHD events. This has implications for genetic risk prediction in patients with established CHD and for mechanistic understanding of how Ch9p21 influences risk of CHD.
Patel et al. (Sun,) conducted a meta-analysis in Coronary Heart Disease (n=193,372). Chromosome 9p21 (Ch9p21) genetic variants vs. Individuals without prior CHD versus individuals with established CHD was evaluated on First versus subsequent coronary heart disease (CHD) events (HR 1.19 (first event); HR 1.01 (subsequent event), 95% CI 1.17-1.22 (first event); 0.97-1.06 (subsequent event), p=5.6 × 10(-11) for heterogeneity). Chromosome 9p21 variants increased the risk of first CHD events (HR 1.19; 95% CI 1.17-1.22) but not subsequent events (HR 1.01; 95% CI 0.97-1.06), with significant heterogeneity (P=5.6x10^-11).
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