Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease

CONTEXT: Epidemiological studies have established a relationship between cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of ischemic heart disease (IHD), but up to half of patients with IHD may have cholesterol levels in the normal range. OBJECTIVE: To assess the ability to predict the risk of IHD using a cluster of nontraditional metabolic risk factors that includes elevated fasting insulin and apolipoprotein B levels as well as small, dense LDL particles. DESIGN: Nested case-control study. SETTING: Cases and controls were identified from the population-based cohort of the Quebec Cardiovascular Study, a prospective study conducted in men free of IHD in 1985 and followed up for 5 years. PARTICIPANTS: Incident IHD cases were matched with controls selected from among the sample of men who remained IHD free during follow-up. Matching variables were age, smoking habits, body mass index, and alcohol consumption. The sample included 85 complete pairs of nondiabetic IHD cases and controls. MAIN OUTCOME MEASURES: Ability of fasting insulin level, apolipoprotein B level, and LDL particle diameter to predict IHD events, defined as angina, coronary insufficiency, nonfatal myocardial infarction, and coronary death. RESULTS: The risk of IHD was significantly increased in men who had elevated fasting plasma insulin and apolipoprotein B levels and small, dense LDL particles, compared with men who had normal levels for 2 of these 3 risk factors (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3-15.4). Multivariate adjustment for LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) did not attenuate the relationship between the cluster of nontraditional risk factors and IHD (OR, 5.2; 95% CI, 1.7-15.7). On the other hand, the risk of IHD in men having a combination of elevated LDL-C and triglyceride levels and reduced HDL-C levels was no longer significant (OR, 1.4; 95% CI, 0.5-3.5) after multivariate adjustment for fasting plasma insulin level, apolipoprotein B level, and LDL particle size. CONCLUSION: Results from this prospective study suggest that the measurement of fasting plasma insulin level, apolipoprotein B level, and LDL particle size may provide further information on the risk of IHD compared with the information provided by conventional lipid variables.