Improving the Prediction of Cardiovascular Risk: Interaction between LDL and HDL Cholesterol

Background. The ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (or the ratio of low-density lipoprotein [LDL] to HDL) is currently advocated to estimate the coronary risk associated with LDL and HDL cholesterol levels. Methods. We analyzed the relation between LDL and HDL cholesterol levels to predict the risk of future coronary events. Using data from the Lipid Research Clinics Follow-up Cohort, we developed multivariate equations to predict coronary deaths among 4684 men and women followed for approximately 12 years. We used these equations to compare the predictive power of the LDL/HDL ratio with the independent effects of LDL and HDL and an LDL-HDL interaction term. We then used each model to forecast the 10-year risk of coronary death based on various lipid levels after adjustment for conventional risk factors (eg, blood pressure, gender, cigarette smoking). Results. Levels of LDL and HDL and the interaction between them are all independent risk factors for coronary death. The benefits of increasing HDL are strongest among persons with high LDL. Conversely, the benefits of decreasing LDL are greatest among those with low HDL. We confirmed these observations in a published dataset showing the effects of treatment of hyperlipidemia. Predictions of benefits of treatment that were based on interaction of LDL and HDL were more accurate than predictions without interaction. Conclusions. The LDL/HDL ratio alone may not fully capture the complex interaction between LDL and HDL and the relation of each to coronary risk.