Background: Despite lipid-lowering therapy (LLT), some patients with familial hypercholesterolemia (FH) still develop cardiovascular events. Data about the quantification and factors contributing to this residual risk are lacking.
Objective: This study assessed how many patients with FH developed a cardiovascular event despite LLT and which factors contribute to this risk.
Methods: We performed a time-dependent analysis in a cohort of consecutive heterozygous FH patients using stable LLT to evaluate first and subsequent cardiovascular events. Univariate and multivariate regression analyses were conducted to study the association between clinical characteristics and cardiovascular events.
Results: Of 821 FH patients (median age 47.4 [interquartile range (IQR) 35.3-58.3] years) treated with LLT for a median period of 9.5 (IQR 5.1-14.2) years, 102 patients (12%) developed cardiovascular disease (CVD) in 8538 statin-treated person-years. Patients who developed a cardiovascular event had a median age of 52.0 (IQR 43.8-59.3) years. These patients more often had previous cardiovascular events (32% vs 9%, P < .001), a family history of premature CVD (58% vs 40%, P = .001), hypertension (70% vs 22%, P < .001), higher on-treatment low-density lipoprotein cholesterol (162 ± 54 vs 135 ± 58 mg/dL, P < .001), lower on-treatment high-density lipoprotein cholesterol (50 ± 15 vs 54 ± 15 mg/dL, P < .001), and were smokers (32% vs 14%, P < .001), compared to patients without cardiovascular events. In 31 patients (30%), a subsequent cardiovascular event occurred with a median interval of 5.7 (IQR 2.4-9.3) years between events. They were more often smokers (32% vs 10%, P = .01) compared to patients with a single cardiovascular event.
Conclusions: Despite LLT, FH patients still develop cardiovascular events and especially subsequent events. Classical risk factors such as smoking and hypertension are driving factors for this risk, indicating the high priority of optimizing risk factor reduction in addition to maximum LLT.
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