title: 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.
authors.affiliation: Saint Joseph's Translational Research Institute, Atlanta, GA, USA. rsuperko@sjha.org
authors.forename: H Robert
authors.initials: HR
authors.lastname: Superko
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Garrett
authors.forename: Spencer B
authors.initials: SB
authors.lastname: King
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Momary
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Chronos
authors.forename: Peter D
authors.initials: PD
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015248:Gemfibrozil / Q000008:administration & dosage*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D053419:Lipoproteins, IDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001053:Apolipoproteins; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D009525:Niacin; D015248:Gemfibrozil