Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Genetic variants at chromosome 9p21 and risk of first versus subsequent coronary heart disease events
T2 - a systematic review and meta-analysis
AU - Patel, Riyaz S.
AU - Asselbergs, Folkert W.
AU - Quyyumi, Arshed A.
AU - Palmer, Tom M.
AU - Finan, Chris I.
AU - Tragante, Vinicius
AU - Deanfield, John
AU - Hemingway, Harry
AU - Hingorani, Aroon D.
AU - Holmes, Michael V.
N1 - Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PY - 2014/6/3
Y1 - 2014/6/3
N2 - 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.
AB - 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.
KW - Animals
KW - Chromosomes, Human, Pair 9
KW - Coronary Disease
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
U2 - 10.1016/j.jacc.2014.01.065
DO - 10.1016/j.jacc.2014.01.065
M3 - Journal article
C2 - 24607648
VL - 63
SP - 2234
EP - 2245
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 1558-3597
IS - 21
ER -