HDL Efflux and GlycA

By Anand Rohatgi, M.D., M.S.C.S., FACC, FAHA Associate Professor of Internal Medicine
and Kayla A. Riggs, M.D., Internal Medicine Resident

Cholesterol efflux is one of the primary functions of high-density lipo­protein (HDL) and has been shown to be independently and inversely associated with incident cardiovascular events. Inflammation impairs HDL function. A relatively new biomarker of inflammation, GlycA, has been shown in several large cohorts to be independently associated with incident cardiovascular events. GlycA is measured through NMR spectroscopy and is an integrated glycosylation marker of five acute-phase reactants: alpha1-anti­trypsin, haptoglobin, alpha1-antichymotrypsin, alpha1-acid glycoprotein, and transferrin. We assessed the hypothesis that GlycA is associated with impaired HDL function measures and that the association between GlycA and incident cardiovascular events is partially explained by dysfunctional HDL. 

Our study utilized data from the Dallas Heart Study (DHS), a multiethnic, probability-based population cohort. The primary end point was first nonfa­tal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 11.4 years resulting in 171 events.

GlycA is higher in women and in African-Americans, correlated with hs-CRP (correlation coefficient 0.58 p<0.0001), and is relatively normally distributed with a tail to extreme high values. In linear regression model­ing, HDL parameters, HDL-C, HDL-P, and cholesterol efflux were inversely associated with GlycA when adjusting for traditional risk factors, hs-CRP, and all HDL measures. Modeling for incident cardiovascular events and ad­justing for traditional risk factors, we confirmed in the DHS that GlycA was independently and directly associated with incident cardiovascular events. Further adjustment for cholesterol efflux did not attenuate this associa­tion, and cholesterol efflux remained inversely associated with the primary outcome. Therefore, dysfunctional cholesterol efflux does not mediate the association between GlycA and incident cardiovascular events. 

Further studies are warranted to investigate the impact of inflammation on HDL function and cardiovascular disease. GlycA can be measured in the clinical setting but is currently not widely used, likely due to its novelty and cost because it is slightly more expensive than current, commonly used mea­sures of inflammation. As further studies understand GlycA, it may become more commonly used to assess inflammation in the clinical setting.