Effect of Combination Nicotinic Acid and Gemfibrozil Treatment on Intermediate Density Lipoprotein, and Subclasses of Low Density Lipoprotein and High Density Lipoprotein in Patients With Combined Hyperlipidemia

Abstract

The goal of this study was to determine, using analytic ultracentrifugation, the effect of nicotinic acid alone or nicotinic acid added to gemfibrozil on lipoprotein subclass distribution, including intermediate-density lipoprotein (IDL; low-density to very low density flotation rate [S(f)] 12 to 20); low-density lipoprotein (LDL) subfractions LDL-I (S(f) 7 to 12), LDL-II (S(f) 5 to 7), LDL-III (S(f) 3 to 5), and LDL-IV (S(f) 0 to 3); and high-density lipoprotein (HDL) subfractions HDL(2) (high-density flotation rate 3.5 to 9.0) and HDL(3) (high-density flotation rate 0 to 3.5). Patients with combined hyperlipidemia were randomized to nicotinic acid (1,500 mg/day) plus placebo or nicotinic acid plus gemfibrozil (1,200 mg/d) for 12 weeks. Baseline characteristics were similar between the 2 groups, and mean LDL cholesterol (180 +/- 33 mg/dl) and triglycerides (310 +/- 126 mg/dl) were typical for patients with combined hyperlipidemia. Treatment with nicotinic acid resulted in a reduction in dense LDL (S(f) 5 to 7; p = 0.02), which was counterbalanced by an increase in buoyant LDL (S(f) 7 to 12; p = 0.03) that resulted in no significant LDL mass or LDL cholesterol change. IDL was reduced (p = 0.005) and HDL(2) increased by 143% (p = 0.004). The combination of nicotinic acid and gemfibrozil resulted in a further 17.8% reduction in apolipoprotein B (p = 0.06), a further 33.8% reduction in IDL (p = 0.06), and a greater reduction in the apolipoprotein B/apolipoprotein A-I ratio (p = 0.02). The combination of nicotinic acid and gemfibrozil reduced atherogenic by IDL 71%, dense LDL-III by 52%, and apolipoprotein B by 37% and increased protective HDL(2) by 90%. In conclusion, this investigation revealed that a combination of a fibric acid derivative and nicotinic acid offers greater improvement in detailed lipoprotein subclass distribution and apolipoprotein ratios than monotherapy.