Comparison of the associations of apolipoprotein B and low-density lipoprotein cholesterol with other cardiovascular risk factors in the Insulin Resistance Atherosclerosis Study (IRAS)

Background-Risk factors for vascular disease include obesity, dyslipidemia, hypertension, dysglycemia, insulin resistance, inflammation, thrombosis, and subclinical atherosclerosis. This study compares the associations of apolipoprotein B (apoB) and LDL cholesterol (LDLC) with a wide array of measures of these risk factors. Methods and Results-In 1522 individuals in the Insulin Resistance Atherosclerosis Study, anthropometric measures and measures of lipids, apoB, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), fasting and postglucose load glucose and insulin concentrations, and carotid artery intima-media thickness (IMT) were taken and insulin sensitivity was determined by frequently sampled intravenous glucose tolerance test. There were significant differences in measures of abdominal obesity, dyslipidemia, hyperinsulinemia, and thrombosis between subjects with elevated apoB but normal LDLC versus those with elevated LDLC but normal apoB. In each statistically significant comparison, the elevated-apoB group had higher associated risk than the elevated-LDLC group. Moreover, apoB is highly significantly (P<0.0001) correlated with each measure in the direction of higher risk, whereas LDLC was significantly correlated (P<0.05) only with blood pressure, triglyceride, fibrinogen, and C-reactive protein. After further adjustment for LDLC, apoB correlations remained significant, whereas several LDLC correlations adjusted for apoB became significant in the direction of lower risk. Conclusions-Elevated apoB is more strongly associated than LDLC with other risk factors, including measures in the National Cholesterol Education Program guidelines for lipid treatment and other more recently established risk factors. This may provide new insight into why apoB is a better predictor of vascular risk than LDLC.