Effect of Lipid-Lowering Treatment on Natural History of Heterozygous Familial Hypercholesterolemia in Past Three Decades

Long-term data on the effects of cholesterol-lowering regimens on low-density lipoprotein cholesterol levels and cardiovascular events in patients with familial hypercholesterolemia (FH) are lacking. The present study evaluated the effectiveness of long-term intensive lipid-lowering therapy on the natural history of FH. Of approximately 1,000 adult patients with heterozygous FH treated from 1974 to 2008, the charts of 327 were randomly selected for review. FH was defined according to the Simon Broome Registry Group criteria. The recorded data included age; gender; lipid levels with diet only, with each lipid-lowering regimen, and at the most recent visit during treatment; the length of follow-up; cardiovascular events; and revascularization procedures. The lipid assay calibrations and standardization were unchanged throughout the study period. Of the 327 patients, 60% were men, the mean age at diagnosis was 38 ± 14 years, and the mean follow-up was 15 ± 8 years. The baseline and most recent low-density lipoprotein cholesterol levels during treatment were 256 ± 60 mg/dl and 116 ± 46 mg/dl, respectively, for a mean reduction of 55% from baseline (p <0.0001). At their most recent visit, 24% of all subjects were treated with statin monotherapy, 55% with a statin plus another agent, and 21% with triple therapy; 44% received a statin-ezetimibe combination. The interval between recurrent cardiovascular events tended to increase from 5.3 ± 4.8 years before treatment to 7.4 ± 6.7 years after referral (p = 0.1303). In conclusion, advances in drug therapy during the past 3 decades has led to substantial reductions in low-density lipoprotein cholesterol levels and appears to diminish the cardiovascular risk in patients with FH.