Risk of Lipids on Coronary Heart Disease

Prognostic models are widely used in medicine to estimate particular patients' risk of developing disease. For cardiovascular disease risk numerous prognostic models have been developed for predicting cardiovascular disease including those by Wilson et al. using the Framingham Study[17], by Assmann et al. using the Procam study[22] and by Conroy et al.[33] using a pool of European cohorts. The prognostic models developed by these researchers differed in their approach to estimating risk but all included one or more of the lipid determinations: Total cholesterol (TC). Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL), or ratios TC/HDL and LDL/HDL. None of these researchers included both LDL and TC in the same model due to the high correlation between these measurements. In this thesis we will examine some questions about the inclusion of lipid determinations in prognostic models: Can the effect of LDL and TC on the risk of dying from CHD be differentiated? If one measure is demonstrably stronger than the other, then a single model using that variable would be considered advantageous. Is it possible to derive a single measure from TC and LDL that is a stronger predictor than either measure? If so, then a new summarization of the lipid measurements should be used in prognostic modeling. Does the addition of HDL to a prognostic model improve the predictive accuracy of the model? If it does, then this determination that is almost universally determined should be used when developing prognostic models. We use data from nine independent studies to examine these issues. The studies were chosen because they include longitudinal follow-up of participants and included lipid determinations in the baseline examination of participants. There are many methodologies available for developing prognostic models, including logistic regression and the proportional hazards model. We used the proportional hazards model since we have follow-up times and times to death from CHD on all of the participants in the included studies. We summarized our results using a meta-analytic approach. Using the meta-analytic approach, we addressed the additional question of whether the results vary significantly among the different studies and also whether adding additional characteristics to the prognostic models changes the estimated effect of the lipid determinations. All of our results are presented stratified by gender and, when appropriate, by race. Finally, because our studies were not selected randomly, we also examined whether there is evidence of bias in our meta-analyses. For this examination we used funnel plots with related methodology for testing whether there is evidence of bias in the results.