Lipoprotein(a)-Cholesterol and Coronary Heart Disease in the Framingham Heart Study

Abstract

Abstract Background: Increased plasma lipoprotein(a) [Lp(a)] concentrations have been reported to be an independent risk factor for coronary heart disease (CHD) in some prospective studies, but not in others. These inconsistencies may relate to a lack of standardization and the failure of some immunoassays to measure all apolipoprotein(a) isoforms equally. Methods: We measured plasma Lp(a)-cholesterol [Lp(a)-C] in a Caucasian population of offspring and spouses of the Framingham Heart Study participants, using a lectin-based assay (LipoproTM). We compared the prevalence of increased Lp(a)-C to the presence of sinking pre-β-lipoprotein (SPB). We also related Lp(a)-C concentrations to the prevalence of CHD risk in the entire population. Results: The mean (± SD) Lp(a)-C concentration in the Framingham population (n = 3121) was 0.186 ± 0.160 mmol/L, with no significant gender or age differences. The mean Lp(a)-C concentrations in the absence or presence of SPB were 0.158 ± 0.132 mmol/L and 0.453 ± 0.220 mmol/L, respectively (P <0.0001). The mean Lp(a)-C concentration in men with CHD (n = 156) was 0.241 ± 0.204 mmol/L, which was significantly (P <0.001) higher, by 34%, than in controls. The odds ratio for CHD risk in men with Lp(a)-C ≥0.259 mmol/L (≥10 mg/dL), after adjusting for age, HDL-cholesterol, LDL-cholesterol, smoking, diabetes, blood pressure, and body mass index, was 2.293 (confidence interval, 1.55–3.94; P <0.0005). Lp(a)-C values correlated highly with a Lp(a)-mass immunoassay [ApotekTM Lp(a); r = 0.832; P <0.0001; n = 1000]. Conclusions: An increased Lp(a)-C value ≥0.259 mmol/L (≥10 mg/dL) is an independent CHD risk factor in men with a relative risk of more than 2, but was inconclusive in women. Lp(a)-C measurements offer an alternative to Lp(a)-mass immunoassays and can be performed on automated analyzers.