High density lipoprotein subfractions and the risk of coronary heart disease: 9-years follow-up in the Caerphilly Study.

Whether the protective effect of high density lipoprotein (HDL) on incident coronary heart disease (CHD) can be attributed to one or both HDL subfractions remains controversial. The associations of HDL(2) and HDL(3) cholesterol with the incidence of CHD in the 9-year follow-up of the Caerphilly study are described. A total of 2398 middle-aged British men were recruited from the general population between 1984 and 1988 and were followed, on average, for 9 years. Total and HDL(3) cholesterol were measured by a two-step precipitation technique on fresh, fasting samples from 2225 men. HDL(2) cholesterol was calculated by subtracting HDL(3) from total HDL cholesterol. Relative odds and 95% confidence intervals (CI) for incident CHD were obtained by use of a logistic regression model. During follow-up, 282 (12%) men developed a major new CHD event. Total HDL and HDL(3) cholesterol were significantly and inversely associated with the risk of incident CHD. When divided into fifths of the distributions of total HDL and HDL(3) cholesterol, multivariate-adjusted relative odds were 1.00, 0.95, 0.72, 0.85, 0.38 and 1.00, 1.05, 0.92, 0.67, 0.39, respectively graded from the least to the most quintile, with the lowest quintile group as referent. Tests for trend were significant (P for trend 0.003 and 0.001, respectively). In a multivariate model, the contribution of HDL(3) was significant (standardized relative odds, 0.76; 95% CI, 0.64-0.91), whereas HDL(2) was not significant. No linear combination of the two subfractions was a better predictor of CHD than total HDL cholesterol alone. HDL(3) cholesterol was an independent predictor of incident CHD and may be more closely related to the development of CHD than HDL(2) cholesterol. The prediction of the risk of CHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. In our view, the only way to improve our understanding of this situation is to measure both subfractions independently of each other and not to calculate one by subtraction.