Association of a Genetic Risk Score With Prevalent and Incident Myocardial Infarction in Subjects Undergoing Coronary Angiography

作者：Patel Riyaz S; Sun Yan V; Hartiala Jaana; Veledar Emir; Su Shaoyong; Sher Salman; Liu Ying X; Rahman Ayaz; Patel Ronak; Rab S Tanveer; Vaccarino Viola; Zafari A Maziar; Samady Habib; Tang W H Wilson; Allayee Hooman; Hazen Stanley L; Quyyumi Arshed A^*

来源：Circulation-Cardiovascular Genetics, 2012, 5(4): 441-449.

DOI：10.1161/CIRCGENETICS.111.960229

• cardiovascular disease risk factors
• coronary artery disease
• myocardial infarction
• genetic risk score

Background-Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established. %26lt;br%26gt;Methods and Results-In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age %26lt;70 years and controls %26gt;= 70 years without prior MI and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants, and a GRS was calculated based on average number of risk alleles carried at each locus weighted by effect size. Replication of association findings was sought in an independent angiographic cohort (n=2702). The GRS was significantly associated with prevalent MI, occurring before age 70, compared with older controls (%26gt;= 70 years of age) with no history of MI (P%26lt;0.001). This association was successfully replicated in a second cohort, yielding a pooled P value of %26lt;0.001. The GRS modestly improved the area-under-the-curve statistic in models of prevalent MI with traditional risk factors; however, the association was not statistically significant when elderly controls without MI but with stable angiographic CAD were examined (pooled P=0.11). Finally, during a median 2.5-year follow-up, only a nonsignificant trend was noted between the GRS and incident events, which was also not significant in the replication cohort. %26lt;br%26gt;Conclusions-A GRS of 11 CAD/MI variants is associated with prevalent MI but not near-term incident adverse events in 2 independent angiographic cohorts. These findings have implications for understanding the clinical use of genetic risk scores for secondary as opposed to primary risk prediction. (Circ Cardiovasc Genet. 2012;5:441-449.)

• 出版日期2012-8
• 单位河北医科大学