Cholesterol efflux capacity, carotid atherosclerosis, and cerebrovascular symptomatology.

OBJECTIVE To investigate the association of cholesterol efflux capacity with carotid atherosclerosis and cerebrovascular disease. APPROACH AND RESULTS Patients with high-grade carotid stenosis (n=154) were recruited from Vascular Surgery clinics and 9 healthy controls from the McGill University Health Network, Montreal, Canada. Cerebrovascular symptomatology history was obtained. Stenosis was assessed by carotid ultrasound. Fasting blood samples were collected and depleted of apolipoprotein B particles by polyethylene glycol precipitation from serum. Cholesterol efflux was determined by incubating apolipoprotein B-depleted serum in cAMP-stimulated J774 cells for 6 hours. Carotid specimens were classified by 2 vascular pathologists using the American Heart Association atheromatous plaque classification. Differences in efflux were assessed according to (1) stenosis, (2) American Heart Association classification, and (3) cerebrovascular symptomatology. Normalized efflux was significantly lower in patients with carotid atherosclerosis compared with controls (0.97±0.16 versus 1.5±0.46; P<0.0001). Efflux was inversely associated with stenosis; the odds ratio for 80% to 99% versus 50% to 79% stenosis of tertile 1 (lowest) versus tertile 3 (highest) of efflux was 3.78 (95% confidence interval, 1.18-12.06) after adjusting for age, sex, low-density lipoprotein, and high-density lipoprotein. There were significant differences in cholesterol efflux between American Heart Association fibroatheroma (Va, 0.91±0.13), mainly calcific (Vb, 0.97±0.15), and mainly fibrotic (Vc, 1.03±0.21; P=0.05). There were no significant differences in efflux according to symptomatology. CONCLUSIONS Cholesterol efflux capacity is inversely associated with increasing carotid stenosis and is associated with more advanced carotid plaque morphology, suggesting that cholesterol efflux capacity may be a biomarker for severity of carotid atherosclerotic burden. Whether therapies targeting high-density lipoprotein quality could be useful for stabilizing carotid atherosclerosis needs to be assessed.