Associations of HDL 2 and HDL 3 Subfractions With Ischemic Heart Disease in Men

Abstract

Individuals with elevated plasma concentrations of HDL cholesterol are at lower risk for ischemic heart disease (IHD). Whether the cardioprotective effects of HDL can be attributed to one or both HDL subfractions (HDL ₂ and HDL ₃ ) remains, however, controversial. The relationship of HDL subfractions to the incidence of IHD was investigated in a sample of 1169 French-Canadian men younger than 60 years and living in the Quebec City suburbs. Between 1980 to 1981 and 1990, 83 of the 944 men with complete follow-up in 1990 (80.8%) had a first IHD. Men who developed IHD had lower HDL, HDL ₂ , and HDL ₃ cholesterol concentrations at baseline than men who remained free from IHD. Adjusted relative risk (RR) of IHD was calculated among quartiles of HDL cholesterol and HDL subfractions with the use of Cox survival models. Men in the fourth quartile of HDL ₂ (RR=0.21; 95% confidence interval [CI], 0.08 to 0.56) and HDL ₃ cholesterol distributions (RR=0.37; 95% CI, 0.15 to 0.94) were at lower risk for IHD than men in the first quartile. Despite the fact that the respective contributions of HDL ₂ and HDL ₃ to IHD risk were of the same magnitude in a multivariate model that included both subfractions, the contribution of the HDL ₂ subfraction was statistically significant (standardized RR=0.84; 95% CI, 0.74 to 0.95), whereas it did not reach significance for HDL ₃ (standardized RR=0.87; 95% CI, 0.69 to 1.11). Neither the linear combination of HDL ₂ and HDL ₃ nor their ratio provided further information on the risk of IHD compared with HDL cholesterol alone or with the ratio of total to HDL cholesterol. >From a statistical standpoint, the present data suggest that the HDL ₂ subfraction may be more closely related to the development of IHD than the HDL ₃ subfraction. However, the qualitative difference in the relative predictive value of each subfraction was trivial, since it only corresponded to a modest quantitative difference. Thus, the possibility that a significant proportion of the cardioprotective effect of elevated HDL cholesterol levels may be mediated by the HDL ₃ subfraction still cannot be excluded. Finally, from a clinical point of view and within the limits of resolution provided by these data, the measurement of HDL subfractions does not appear to provide any additional information on the risk of IHD than HDL cholesterol alone or the ratio of total to HDL cholesterol.