Abstract 09: HDL That Contains Apolipoprotein C-III is Not Inversely Associated with Risk of Coronary Events: The Multi-Ethnic Study of Atherosclerosis
Background: Apolipoprotein A-I (apoA-I), the major protein component of high density lipoprotein (HDL), is inversely associated with risk of coronary heart disease (CHD). However, the cardioprotective benefits of HDL levels remain controversial. HDL is comprised of a heterogeneous group of lipoproteins, and subtypes of HDL could have different cardioprotective potential. Apolipoprotein C-III (apoC-III) is a small pro-inflammatory protein that resides on the surface of some lipoproteins. In case-control studies of mostly white participants, the presence or absence of apoC-III defines lipoprotein subtypes that show differential associations with CHD risk.
Methods and Results: We used a novel in-house combo ELISA to measure the concentration of total apoC-III, apoA-I with and without apoC-III in 5668 white, black, Hispanic and Chinese members of the Multi-Ethnic Study of Atherosclerosis without known cardiovascular disease from the baseline visit in 2000-2002. A total of 386 incident CHD events occurred by 2012. In Cox regression models adjusted for lifestyle and clinical risk factors, apoA-I without apoC-III was inversely associated with risk of CHD (HR per 1 SD increase on the ln-scale = 0.85; 95% CI, 0.75-0.97) whereas apoA-I with apoC-III was not associated with CHD (HR=1.07; 95% CI, 0.94-1.22) (p for heterogeneity= 0.05)(Figure). ApoC-III was found on approximately 7% of apoA-I across all ethnicities. Total plasma apoC-III was positively associated with CHD, but this was not robust to multivariable adjustment. There was no evidence of effect-modification by race/ethnicity.
Conclusions: While total apoC-III levels are not independently associated with CHD, the presence of apoC-III on HDL appears to modify the inverse association with CHD. HDL with apoC-III may mark a dysfunctional subtype of HDL. Such novel measures could be relevant as therapeutic targets and for evaluation of future CHD risk.
Author Disclosures: M.K. Jensen: C. Other Research Support; Modest; Roche Pharmaceutical. S.A. Aroner: None. J.D. Furtado: C. Other Research Support; Modest; Roche Pharmaceutical. K.J. Mukamal: None. W.S. Post: None. J.F. Polak: None. F.M. Sacks: C. Other Research Support; Significant; Roche Pharmaceutical. R. McClelland: None.
- © 2015 by American Heart Association, Inc.