Traditional risk factors and a Genetic Risk Score are associated with age of first acute coronary syndrome.
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.
Christopher
C
Labos
Rui Hao Leo
RH
Wang
Louise
L
Pilote
Peter
P
Bogaty
James M
JM
Brophy
James C
JC
Engert
George
G
Thanassoulis
D054058:Acute Coronary Syndrome / Q000453:epidemiology* / Q000235:genetics*; D000367:Age Factors; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors