In patients with familial hypercholesterolemia (FH), a monogenic cause significantly increases the risk for premature cardiovascular disease (CVD), according to study results published in the Journal of the American College of Cardiology.
The results also indicated that in patients with monogenic FH, having elevated low-density lipoprotein cholesterol further increases CVD risk.
The study included patients with clinically diagnosed FH (N=626). The researchers performed targeted sequencing of genes known to cause FH and common genetic variants in order to calculate polygenic scores in patients with possible, probable, or definite FH according to Dutch Lipid Clinic Network Criteria. Patients who had a polygenic score ≥80th percentile were classified as having polygenic FH. The researchers examined the risk for unstable angina, myocardial infarction, coronary revascularization, or stroke.
The results indicated that a monogenic cause of FH was associated with a significantly higher risk for CVD compared with patients with no genetic cause of FH (adjusted hazard ratio 1.96; 95% CI, 1.24-3.12; P =.004).
In patients whose FH had a polygenic cause, there was no significant difference in CVD risk compared with patients with no genetic cause of FH.
In patients with a monogenic cause of FH, patients with an elevated low-density lipoprotein cholesterol had a further increase in CVD risk (adjusted hazard ratio 3.06; 95% CI, 1.56-5.99; P =.001).
“Our results demonstrate the utility of genetic testing, including the identification of both monogenic and polygenic variants, to improve the diagnosis and risk stratification of patients with clinically diagnosed FH,” the researchers wrote.
Trinder M, Li X, DeCastro ML, et al. Risk of premature atherosclerotic disease in patients with monogenic versus polygenic familial hypercholesterolemia. J Am Coll Cardiol. 2019;74(4):512-522.