To determine if non-
high-density lipoprotein (
HDL) cholesterol is a more useful predictor of
coronary heart disease (CHD) risk than
low-density lipoprotein (
LDL) cholesterol and if
very-low-density lipoprotein (
VLDL) cholesterol is an independent predictor of CHD risk, data from the Framingham Heart Study (2,693 men, 3,101 women) were used for this analysis. All subjects were aged > or =30 years and free of CHD at baseline, and incident CHD was the end point (618 men, 372 women). Cox proportional-hazards models were used to assess the risk for CHD (relative risks and 95% confidence intervals) on the basis of the joint distribution of
LDL cholesterol and non-
HDL cholesterol (in milligrams per deciliter), as well as
LDL cholesterol, non-
HDL cholesterol, and
VLDL cholesterol as continuous variables. After multivariate adjustment, within non-
HDL cholesterol level, no association was found between
LDL cholesterol and the risk for CHD, whereas within
LDL cholesterol levels, a strong positive and graded association between non-
HDL cholesterol and risk for CHD was observed. When the analysis was repeated within
triglyceride levels (<200 vs > or =200 mg/dl), the risk pattern did not change significantly. Also,
VLDL cholesterol was found to be a significant predictor of CHD risk after adjusting for
LDL cholesterol at
triglyceride levels of > or =200 or <200 mg/dl. In conclusion, these results suggest that non-
HDL cholesterol level is a stronger predictor of CHD risk than
LDL cholesterol; that is,
VLDL cholesterol may play a critical role in the development of CHD.