Lipoprotein(a) levels and risk of coronary heart disease in men. The Lipid Research Clinics Coronary Primary Prevention Trial

OBJECTIVE--To examine the relationship between elevated levels of lipoprotein(a) [Lp(a)] and coronary heart disease (CHD) risk in a prospective study. DESIGN--Nested case-control study. The cohort consisted of participants in the Lipid Research Clinics Coronary Primary Prevention Trial. SETTING--Lipid research clinics. PARTICIPANTS--The Lipid Research Clinics Coronary Primary Prevention Trial participants (n = 3806) were men, aged 35 to 59 years, with plasma cholesterol levels of 6.85 mmol/L (265 mg/dL) or greater, low-density lipoprotein cholesterol levels of 4.91 mmol/L (190 mg/dL) or greater, and triglyceride levels less than 3.39 mmol/L. Subjects were randomly assigned to either cholestyramine or placebo treatment. The Lp(a) levels were measured in plasma samples obtained prior to randomization in 233 cases (participants who developed CHD in the course of the study) and 390 matched CHD-free controls. A total of 96.95% of the subjects were white, 2.25% were black, and 0.80% were of other race. MAIN OUTCOME MEASURE--Coronary heart disease (either fatal or nonfatal) events during a follow-up of 7 to 10 years. RESULTS--The Lp(a) levels were significantly higher (21%) in cases than in controls (23.7 mg/dL [0.59 mmol/L] and 19.5 mg/dL [0.49 mmol/L], respectively; P < .02). This difference was still statistically significant (P < .01) after controlling for age, body mass index, cigarette smoking, blood pressure, low-density lipoprotein cholesterol level, and high-density lipoprotein cholesterol level. When subjects were divided by treatment, both cholestyramine-treated and placebo-treated CHD subjects had Lp(a) levels 20% to 22% greater than their matched controls. However, possibly because of smaller sample sizes, these differences were no longer statistically significant. CONCLUSIONS--Our data are consistent with the concept that an elevated Lp(a) level is an independent risk factor for CHD in hypercholesterolemic white men.