Effects of HMG Co-A Reductase Inhibitors on Lipids and Lipoprotein(a) in Hypercholesterolaemia

Summary

Lipoprotein(a) combines structural elements of low. density lipoprotein (LDL) and plasminogen and is a strong independent risk factor for development of coronary heart disease (CHD). In 46 patients with primary hypercholesterolaemia, plasma lipoprotein(a) levels were highest in patients who had a history of coronary artery bypass graft surgery (700 ± 110 mg/L mean ±SEM), intermediate in those with CHD without bypass surgery (480 ± 80 mg/L) and lowest in those without CHD (350 ± 90 mg/L). 12 weeks’ treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG Co-A) reductase inhibitors, either pravastatin (20 to 40 mg/day; n = 22) or simvastatin (10 to 40 mg/day; n = 24), produced a 30% reduction in total plasma cholesterol (from 8.2 ± 1.1 to 5.7 ± 0.5 mmol/L, p < 0.01) and a 37% (p < 0.01) reduction in low density lipoprotein. Levels of apolipoprotein B and triglycerides also fell significantly (p < 0.01) and there was a significant rise (p < 0.05) in both HDL cholesterol and apolipoprotein A1. None of these variables changed in 6 patients randomised to receive placebo for 12 weeks. Lipoprotein(a) concentrations (475 ± 100 vs 490 ± 90 mg/L) did not change during treatment with pravastatin or simvastatin. The results of this study and other large scale clinical trials suggest that reduction of plasma LDL cholesterol by HMG Co-A reductase inhibitors, which act by upregulating LDL receptors, does not reduce this important risk factor in hyperlipidaemic patients.