Heterozygous Familial Hypercholesterolemia Increases Risk for Aortic Valve Calcification

Aortic valve calcification appears to be more prevalent in patients with heterozygous familial hypercholesterolemia, especially those with low-density lipoprotein receptor-negative mutations.

Patients with heterozygous familial hypercholesterolemia (he-FH), particularly those with low-density lipoprotein receptor (LDLR)-negative mutations, experienced a significantly higher incidence of aortic valve calcification (AoVC) when compared with controls, according to new research published in the Journal of the American College of Cardiology.

This association, the researchers wrote, highlights “the critical role of [low-density lipoprotein cholesterol (LDL-C)] metabolism in AoVC etiology.”

For patients with homozygous familial hypercholesterolemia, the prevalence of AoVC reaches 100% and is often symptomatic. The goal of the present study was to examine the currently unknown prevalence, extent, and risk modifiers of AoVC in patients with he-FH.

In all, 145 asymptomatic patients with he-FH (mean age, 52 ± 8 years; 64% men) and 131 non-familial hypercholesterolemia controls (mean age, 56 ± 9; 60% men) were enrolled in the study. Researchers performed computed tomography calcium scoring and defined AoVC as the presence of calcium at the aortic valve leaflets.

Baseline characteristics indicated that age, systolic blood pressure, and prevalence of hypertension and diabetes were higher in the control group, whereas patients with he-FH had higher untreated maximum LDL-C levels, more frequently used statins, and were more likely to have a positive family history of coronary artery disease.

Compared with controls, there was a significantly higher prevalence of AoVC (41% vs 21%; P<.001) and higher AoVC score (51 vs 21; P=.007) in patients with he-FH.

Risk factors for AoVC score included age (OR=1.12; P<.001), untreated maximum LDL-C (OR=1.18; P=.01), and diastolic blood pressure (OR=1.04; P=.01), with LDLR-negative mutational he-FH being the strongest predictor of AoVC score (OR=4.81; P<.001).

“The high prevalence and large extent of aortic valve calcification in treated [he-FH] patients suggest that aortic valve pathology will be a common problem among the aging statin-treated [he-]FH patients,” the researchers wrote. “Future research should be directed toward developing more accurate cardiovascular risk prediction tools.”


ten Kate GR, Bos S, Dedic A, et al. Increased aortic valve calcification in familial hypercholesterolemia: Prevalence, extent, and associated risk factors. J Am Coll Cardiol. 2015;66:2687-2695.