Genetic factors increasing the risk for coronary disease are associated with multiple cardiovascular (CV) conditions and premature death, but further studies are needed to elucidate the mechanisms linking these genetic variants and how they contribute to the risk for other diseases, according to study results published in the Journal of the American College of Cardiology.
This large prospective cohort study investigated coronary artery disease (CAD) risk factors and their genetic relationship to cardiovascular disease (CVD) and non-CVD to determine potential common genetic roots for patients with comorbid conditions.
Data on 425,196 participants in the UK Biobank were analyzed to determine a genetic risk score (GRS) according to 300 CAD-associated variants. This CAD-GRS was associated with 22 traits, including diseases secondary to CAD, comorbid and non-CV conditions, and risk factors. Sensitivity analyses were performed using data on individuals free from CAD or stable angina diagnosis.
Strong associations were found between hypercholesterolemia (odds ratio [OR] 1.27; 95% CI, 1.26-1.29) and hypertension (OR 1.11; 95% CI, 1.1-1.12) and the CAD-GRS, indicating that the score contained variants predisposing individuals to these conditions. The CAD-GRS was also significant in participants with CAD who were free of CAD risk factors (OR 1.37; 95% CI, 1.3-1.44).
Significant associations were seen between the CAD-GRS and peripheral arterial disease (OR 1.28; 95% CI, 1.23-1.32), abdominal aortic aneurysms (OR 1.28; 95% CI, 1.2-1.37), and stroke (OR 1.08; 95% CI, 1.05-1.1), and these remained significant in sensitivity analyses, suggesting a shared genetic predisposition.
CAD-GRS scores were also associated with heart failure (OR 1.25; 95% CI, 1.22-1.29), atrial fibrillation (OR 1.07; 95% CI, 1.05-1.08), and premature death (OR 1.04; 95% CI, 1.02-1.06), but these associations did not persist in sensitivity analyses, suggesting that they were secondary to prevalent CAD. An inverse association was observed between CAD-GRS scores and migraine headaches (OR 0.94; 95% CI, 0.93-0.96).
Study investigators concluded, “Our results suggested that genetic predisposition to CAD also affected the prevalence of other [CVDs], including premature death. Genetic variants associated with increased risk of CAD were also associated with increased risk of other atherogenic diseases, whereas for conditions like heart failure, our findings indicated that a large proportion of clinically appearing manifestations of the disease were secondary to CAD. Finally, the genetic overlap between CAD and migraine was based on a range of genetic loci with opposing effects to the 2 diseases.”
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Ntalla I, Kanoni S, Zeng L, et al.; UK Biobank CardioMetabolic Consortium CHD Working Group. Genetic risk score for coronary disease identifies predispositions to cardiovascular and noncardiovascular diseases. J Am Coll Cardiol. 2019;73(23):2932-2942.