Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis.

AIMS: Cholesterol efflux capacity (CEC) as a measure of high-density lipoprotein functionality is independently and inversely associated with increased risk of cardiovascular events and mortality, and advanced plaque morphology. Adipokines, adipose tissue-derived factors, can influence systemic lipoprotein metabolism, and participate in the regulation of vascular function and inflammation. We aimed to investigate the association between CEC and circulating adipokine levels (anti-inflammatory adiponectin, and pro-inflammatory chemerin and resistin) in subjects with severe carotid atherosclerotic disease and evaluate its impact on post-surgical outcomes. METHODS AND RESULTS: This is a cross-sectional study with a 5-year follow-up component. Consecutive patients with severe carotid atherosclerosis scheduled for a carotid endarterectomy were recruited from hospital-based centres in Montreal, Canada (n = 285). Fasting blood samples were collected pre-operatively and used to measure plasma total and high-molecular weight (HMW) adiponectin, chemerin, and resistin, and to perform cholesterol efflux assays in J774 macrophage-like cells. Five-year post-surgery outcomes were obtained through medical chart review. Subjects had a mean age of 70.1 ± 9.4, were 67.0 % male, had various comorbidities (hypercholesterolemia [85.3 %], hypertension [83.5 %], type 2 diabetes [34.5 %], coronary artery disease [38.6 %]), and previously experienced cerebrovascular symptomatology (77.9 %). CEC was independently and positively associated with total and HMW adiponectin levels (ß [95 % confidence interval]; 0.216 [0.134-0.298] and 0.107 [0.037-0.176], respectively) but not with chemerin or resistin. Total adiponectin had the greatest association accounting for 8.3 % of the variance in CEC. Interaction regression models demonstrated a significant interaction between adiponectin and chemerin in increasing CEC. Notably, with each unit increase in CEC there was a 93.9 % decrease in the odds of having an ischemic cerebrovascular event 5 years post-surgery (0.061 [0.007-0.561]). CONCLUSIONS: Our findings demonstrated circulating adiponectin to have a strong association with increased CEC in subjects with severe carotid atherosclerosis and high CEC to be associated with more favourable post-surgical outcomes. These findings reflect the importance of adipose tissue health in influencing CEC levels and atherosclerotic cardiovascular disease risk.