Effect of gemfibrozil on levels of lipoprotein[a] in type II hyperlipoproteinemic subjects.

P H Jones,H J Pownall,W Patsch,J A Herd,J A Farmer,C Payton-Ross,K T Kimball,A M Gotto,J D Morrisett

doi:10.1016/s0022-2275(20)39159-8

Abstract

Plasma lipoprotein[a] (Lp[a]) levels are highly correlated with angiographically demonstrable coronary heart disease, and elevated Lp[a] is an independent risk factor for atherosclerosis. Previous studies have provided evidence that the levels of Lp[a] and triglyceride are related, suggesting that Lp[a] might be altered by gemfibrozil, a drug well known for its efficacy in reducing plasma triglycerides. Accordingly, 18 type IIa and 16 type IIb hyperlipoproteinemic males aged 35-58 were treated for 3 months with 600 mg of gemfibrozil twice daily. The efficacy of the drug in altering lipid and lipoprotein levels was different in the two type groups. In type IIa and IIb subjects the respective changes in median levels were: total cholesterol, -7.5 and -8.5% triglycerides, -35.6 and -54.4%; HDL-cholesterol, +9.0 and +11.0%; and Lp[a], -17.2 and +6.1%. Before and after gemfibrozil treatment, 7 type IIa and 10 type IIB subjects were given a 100 g/2 m2 oral-fat load; triglycerides and Lp[a] were measured post-prandially at 0, 2, 4, 6, 8, and 10 h. The differences between before- and after-gemfibrozil post-prandial curve integrated areas (PPCIA) were compared for triglycerides and Lp[a]. The changes in median PPCIA for triglycerides in types IIa and IIB were -54% and -53%, and for Lp[a] were -8% and +8%, respectively. These results indicate i) that the levels of Lp[a] are about 2 times higher in type IIa than IIb subjects, and ii) that although gemfibrozil elicits a rather uniform decrease in fasting and post-prandial triglyceride levels in type IIa and IIb patients, the drug causes heterogeneous changes in Lp[a], suggesting that different metabolic mechanisms may be dominant in subjects showing opposing effects.

Highlights

Plasma lipoprotein[a](Lp[a])levels are highly correlated with angiographically demonstrable coronary heart disease, and elevated Lp[a] is an independent risk factor for atherosclerosis
High density lipoprotein cholesterol (HDL-C)was determined by measuring cholesterol in the supernatant liquid after precipitation of the plasma with MgC12 and dextran sulfate [28].Low density lipoprotein cholesterol (LDL-C) levels were calculated according to Friedewald, Levy, and Fredrickson [29] with correction for Lp[a] cholesterol determined by multiplying Lp[a] protein by 1.05
To determine whether triglyceride levels have a significant effect on immunoassayable Lp[a] in hypertriglyceridemic plasma, samples from two individuals were subjected to in vitro lipolysis stimulated by the addition of exogenous bovine milk lipase and human apoC-11.Sixty-ninepercent lipolysisof plasma sample # 1 was attended by a 12% increase in immunoassayable Lp[a], and a second sample that had undergone 48% lipolysisdisplayedan 8%increase in Lp[a] immunoreactivity (Table 3)

Summary

Introduction

Plasma lipoprotein[a](Lp[a])levels are highly correlated with angiographically demonstrable coronary heart disease, and elevated Lp[a] is an independent risk factor for atherosclerosis. I These results indicate i) that the levels of Lp[a] are about 2 times higher in type IIa than IIb subjects, and ii) that gemfibrozil elicits a rather uniform decrease in fasting and post-prandial triglyceride levels in type IIa and IIb patients, the drug causes heterogeneous changes in Lp[a], suggesting that different metabolic mechanisms may be dominant in subjects showing opposing effects.-Jones, P. When neomycin (2 g/day) was administered with niacin (3g/day), Lp[a] was reduced by 45%.Significantly, those patients with the initially highest Lp[a] levels experienced the greatest reduction in Lp[a] with this combination therapy. In patients with primary hypercholesterolemia receiving niceritrol, a derivative of nicotinic acid, (1.5 g/day) for 12 weeks, the drug was not effective in lowering Lp[a] if those subjects had an initial mean level of 10.6 mg/dl, but the drug produced a 34% decrease in a subgroup. When the drug was administered at dosages of 5, 20, and 80 mg/day, LDL-cholesterol was markedly reduced by 29, 44, and 61%, but much less

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