PRAVASTATIN EFFECTIVELY LOWERS LDL CHOLESTEROL IN FAMILIAL COMBINED HYPERLIPIDEMIA WITHOUT CHANGING LDL SUBCLASS PATTERN

Familial combined hyperlipidemia (FCHL) is the most common genetic lip id disorder among young survivors of myocardial infarction. Elevations of plasma total and low-density lipoprotein (LDL) cholesterol and the prevalence of small, dense LDL particles are both involved in the hig h coronary risk of FCHL patients. We investigated the ability of prava statin to favorably correct plasma lipid and lipoprotein levels and LD L structure in FCHL patients. Twelve patients with FCHL, documented by studies of first-degree relatives, received pravastatin (40 mg/d) for 12 weeks. Pravastatin significantly lowered plasma total and LDL chol esterol levels by 21% and 32%, respectively. Triglyceride levels did n ot change, and apolipoprotein B (apoB) concentrations decreased by 9% (P = NS). High-density lipoprotein (HDL) cholesterol increased by 6% b ecause of a significant 73% rise of HDL(2) cholesterol. LDL were small er (diameter, 24.5 +/- 0.5 nm), less buoyant, and apoB-rich (cholester yl ester-apoB ratio, 1.64 +/- 0.46) in the selected patients compared with patients with familial hypercholesterolemia or healthy control su bjects. LDL became even smaller (23.8 +/- 0.6 nm) and richer in apoB ( cholesteryl ester-apoB ratio, 1.27 +/- 0.52) after pravastatin treatme nt. Although pravastatin favorably altered plasma lipid and lipoprotei n levels in FCHL patients, the abnormal LDL particle distribution and composition were not affected. Because of the apparent resistance of t he small, dense LDL to drug-induced modifications, a maximal lipid-low ering effect is needed to reduce coronary risk in FCHL patients.