Use of lipoprotein particle measures for assessing coronary heart disease risk post-American Heart Association/American College of Cardiology guidelines: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE The American College of Cardiology and American Heart Association have issued guidelines indicating that the contribution of apolipoprotein B-100 (ApoB) to cardiovascular risk assessment remains uncertain. The present analysis evaluates whether lipoprotein particle measures convey risk of coronary heart disease (CHD) in 4679 Multi-Ethnic Study of Atherosclerosis (MESA) participants. APPROACH AND RESULTS Cox regression analysis was performed to determine associations between lipids or lipoproteins and primary CHD events. After adjustment for nonlipid variables, lipoprotein particle levels in fourth quartiles were found to convey significantly greater risk of incident CHD when compared to first quartile levels (hazard ratio [HR]; 95% confidence interval [CI]): ApoB (HR, 1.84; 95% CI, 1.25-2.69), ApoB/ApoA-I (HR, 1.91; 95% CI, 1.32-2.76), total low-density lipoprotein-particles (LDL-P; HR, 1.77; 95% CI, 1.21-2.58), and the LDL-P/HDL-P (high-density lipoprotein-P) ratio (HR, 2.28; 95% CI, 1.54-3.37). Associations between lipoprotein particle measures and CHD were attenuated after adjustment for standard lipid panel variables. Using the American Heart Association/American College of Cardiology risk calculator as a baseline model for CHD risk assessment, significant net reclassification improvement scores were found for ApoB/ApoA-I (0.18; P=0.007) and LDL-P/high-density lipoprotein-P (0.15; P<0.001). C-statistics revealed no significant increase in CHD event discrimination for any lipoprotein measure. CONCLUSIONS Lipoprotein particle measures ApoB/ApoA-I and LDL-P/high-density lipoprotein-P marginally improved net reclassification improvement scores, but null findings for corresponding c-statistic are not supportive of lipoprotein testing. The attenuated associations of lipoprotein particle measures with CHD after the adjustment for lipids indicate that their measurement does not detect risk that is unaccounted for by the standard lipid panel. However, the possibility that lipoprotein measures may identify CHD risk in a subpopulation of individuals with normal cholesterol, but elevated lipoprotein particle numbers cannot be ruled out.