Genetic Risk Scores Predict Recurrence of Acute Coronary Syndrome

Abstract

Background— Several clinical risk estimation tools have established their role in the prediction of recurrence of acute coronary syndrome (ACS), but the value of genetic risk scores (GRSs) remains unclear. We examined how well 2 different GRSs estimate recurrent ACS and whether clinical factors are associated with GRSs. Methods and Results— A cohort of 2090 consecutive patients with ACS who underwent coronary angiography between July 2006 and March 2008 in a single tertiary center was genotyped and prospectively followed up for a median of 5.5 years. We formed 2 partially overlapping GRSs: GRS47 of 47 single-nucleotide polymorphisms with previously reported significant association with coronary artery disease and GRS153 of 153 single-nucleotide polymorphisms with significant or suggestive association with coronary artery disease. GRS47 showed association with recurrent ACS independent of clinical factors ( P =0.037; hazard ratio, 1.17; 95% confidence interval, 1.01–1.36). GRS153 had no association with either recurrent ACS or composite of recurrent ACS or death. Also, GRS47 was associated inversely with smoking and ST-segment–elevation myocardial infarction ( P =0.004; odds ratio, 0.22; 95% confidence interval, 0.08–0.62 and P =0.041; odds ratio, 0.36; 95% confidence interval, 0.13–0.96, respectively). Conclusions— GRSs combined of 47 known coronary artery disease risk single-nucleotide polymorphisms were associated with recurrent ACS after multivariable adjustments in a heterogenic ACS population for the first time. Smoking and ST-segment–elevation myocardial infarction had an inverse association with the GRSs. The significance of smoking in relation to genetic coronary artery disease predisposition may merit further evaluation in patients with ACS.

Coronary artery disease-associated genetic variants and biomarkers of inflammation

“…Combined into genetic risk scores (GRS), these SNPs predict adverse cardiovascular events in various populations with and without prior cardiovascular disease [7–10]. Although the majority of loci identified seem to act through induction of atherosclerosis, little is known about the underlying mechanisms.…”

Genetic Risk Score for Coronary Heart Disease: Review

“…For GRS-47, a significant association with ACS recurrence was confirmed regardless of clinical factors (HR = 1.17, 95% CI: 1.01-1.36, p = 0.037). For GRS-153, the association with relapses of ACS and/or mortality was not confirmed; however, an association of GRS-32 with a three-vessel lesion was found, and, for GRS-47, an inverse correlation with smoking and MI featuring ST elevation was revealed [53].…”

“…Thus, most authors have reported an improvement in prognostic power when a GRS is added to existing CVD risk calculators; however, some authors have not confirmed (partially or completely) the association between a GRS and CVDs [5,32,39,41,42,53,77]. This lack of associations can be explained by the need for a more thorough functional analysis of the SNPs included in GRSs.…”

“…Antiochos P. et al have evaluated prognostic power of a combination of a family history of diseases and GRSs (38,53, and 153 SNPs) for CHD cases among whites from a prospective study, CoLaus. After adjustment for cardiovascular RFs, both the family history and weighted polygenic GRSs were found to be associated with CHD, both jointly and separately, and provided additional information for predicting coronary events [52].…”

“…Although most studies are focused on identifying genetic factors of CVDs, only a few deal with a GRS to improve the prediction of recurrence in patients with established CVDs; the latter approach may be of therapeutic value in the management of these patients [7,42,53]. Accordingly, the aim of the study by Pereira A. et al was the assessment of long-term cardiovascular mortality in individuals with CHD from Southern Europe by means of a GRS (32 SNPs).…”