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Original article
Traditional risk factors and a Genetic Risk Score are associated with age of first acute coronary syndrome
  1. Christopher Labos1,
  2. Rui Hao Leo Wang2,
  3. Louise Pilote2,
  4. Peter Bogaty3,
  5. James M Brophy1,2,
  6. James C Engert4,
  7. George Thanassoulis2
  1. 1Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  2. 2Department of Medicine, McGill University, and the Research Institute of the McGill University Health Center Montreal, Quebec, Canada
  3. 3Institut Universitaire de Cardiologie et de Pneumologie, Laval University, Quebec City, Quebec, Canada
  4. 4Department of Human Genetics, McGill University, Montreal, Quebec, Canada
  1. Correspondence to Dr George Thanassoulis, Preventive and Genomic Cardiology, McGill University Health Center, 687 Pine Ave W. H4.55, Montreal, Quebec, Canada H3A 1A1; george.thanassoulis{at}mcgill.ca

Abstract

Objective To examine the association between traditional risk factors (TRF) and a Genetic Risk Score (GRS) with age of first acute coronary syndrome (ACS). Early onset ACS may occur due to a high burden of TRFs or to genetic factors that accelerate atherosclerosis. Whether recently discovered genetic variants for ACS are more prevalent at earlier age of first ACS remains unknown.

Methods To construct a multilocus GRS, participants were genotyped for 30 single nucleotide polymorphisms (SNP) identified from prior genome-wide association studies. Linear regression models were fit to estimate the association between TRFs and GRS with age of first ACS.

Results We included 460 participants with a first ACS enrolled in the Recurrence and Inflammation in the Acute Coronary Syndromes (RISCA) cohort. Several TRFs were associated (all p<0.05) with earlier age of first ACS: male sex (6.9 years earlier (95% CI 4.1 to 9.7)), current cigarette smoking (8.1 years (95% CI 6.1 to 10.0)), overweight (Body Mass Index, BMI >25) and obesity (BMI>30) (5.2 years (95% CI 2.6 to 7.9)). In women, hormone replacement therapy was also associated with earlier age of first ACS (4.8 years earlier (95% CI 0.3 to 8.4)). After multivariable adjustment for TRFs, a 1 SD increment in the GRS was associated with a 1.0 (95% CI 0.1 to 2.0) year earlier age of first ACS.

Conclusions Among individuals with a first ACS, a GRS composed of 30 SNPs is associated with younger age of presentation. Although genetic predisposition modestly contributes to earlier ACS, a heavy burden of TRF is associated with markedly earlier ACS.

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