Prevalence of lipoprotein (a) [Lp(a)] excess in coronary artery disease

Abstract

Lipoprotein (a) [Lp(a)] is composed of 1 low-density lipoprotein (LDL) particle, to which 1 molecule of apolipoprotein (a) is covalently linked. Elevated levels of Lp(a) have been associated with coronary artery disease (CAD) and Lp(a) has been shown to be highly heritable. Our purpose was to determine the prevalence of familial Lp(a) excess in patients with CAD. We determined plasma levels of Lp(a) in 180 patients (150 men and 30 women) with angiographically documented CAD before age 60 years, and in 459 control subjects (276 men and 183 women) clinically free of cardiovascular disease. In addition, Lp(a) levels were determined in families of 102 of the CAD probands (87 men and 15 women). No gender differences in Lp(a) levels were observed between men and women (patients or control subjects). Patients with CAD had higher Lp(a) levels than did control subjects (19 ± 21 vs 13 ± 15 mg/dl, p < 0.001). The prevalence of Lp(a) excess (defined as >90th percentile of controls) was 17% in patients with CAD (p < 0.05). Lp(a) levels were not correlated with cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol or apolipoproteins A-I or B. There was a weak correlation between Lp(a) and triglycerides (r = 0.166, p < 0.05) in patients and control subjects. Stepwise discriminant analysis revealed that Lp(a) was a risk factor for the presence of CAD in men, independent of smoking, hypertension, diabetes, LDL and HDL cholesterol, or apolipoprotein A-I and B levels. Family studies revealed that Lp(a) levels are strongly genetically determined. Spearman rank correlations for Lp(a) levels between proband-spouse (r = −0.004, p = 0.948) and midparent-midoffspring (r = 0.580, p < 0.001) indicate that Lp(a) levels are largely genetically determined. The prevalence of familial Lp(a) excess was 16% (14 of 87) in men and 20% (6 of 30) in women. Our data indicate that Lp(a) is a common genetic disorder in patients with premature CAD and that it is highly heritable. In addition, Lp(a) levels are independent of other lipoprotein parameters.