Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis

Abstract

BackgroundThe contribution of high‐density lipoprotein to cardiovascular benefit is closely linked to its role in the cellular cholesterol efflux process; however, various clinical and biochemical variables are known to modulate the overall cholesterol efflux process. The aim of this study was to evaluate the extent to which clinical and biological anomalies associated with the establishment of the metabolic syndrome modulate cholesterol efflux capacity and contribute to development of atherosclerosis.Methods and ResultsThis study involved patients (n=1202) displaying atherogenic dyslipidemia in primary prevention who were referred to our prevention center. Among these patients, 25% presented at least 3 criteria of the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III. We measured the capacity of 40‐fold diluted serum to mediate cholesterol efflux from cholesterol‐loaded human THP‐1 macrophages. Cholesterol efflux capacity was reduced progressively by 4% to 11% (P<0.0001) as a function of the increasing number of coexisting criteria for the metabolic syndrome from 1 to 5. This observation was primarily related to reductions in scavenger receptor class B member 1 and ATP binding cassette subfamily G member 1–dependent efflux. Multivariate analyses indicate that serum efflux capacity was significantly associated with established metabolic syndrome (odds ratio 0.45; 95% CI 0.28–0.72; P=0.009) independent of age, low‐density lipoprotein cholesterol, status with regard to lipid‐lowering therapy, smoking status, and alcohol consumption.ConclusionsOur study revealed that individual criteria of metabolic syndrome are closely related synergistically to cholesterol efflux capacity. In addition, established metabolic syndrome and cholesterol efflux capacity were independently associated with clinical features of atherosclerosis.

Nutritionally Derived Metabolic Cues Typical of the Obese Microenvironment Increase Cholesterol Efflux Capacity of Adipose Tissue Macrophages

“…Therefore high‐glucose can have divergent effects on ABCA1‐expression dependent on the predominant transcription factor present within the cell. The ability of HDL to support cholesterol efflux is also modulated in individuals with the metabolic syndrome, particularly via SR‐BI and ABCG1 pathways, indicative that a multitude of steps in reverse cholesterol transport are reduced in the setting of cardiometabolic disease . Our study has shown that the microenvironment of obese adipose tissue results in increased ABCA1 activity, in contrast to peripheral cells from diabetic patients, again indicative that the primary source of tissue macrophages is a critical determinant of cellular ABCA1.…”

Proteomic Profiles of Adipose and Liver Tissues from an Animal Model of Metabolic Syndrome Fed Purple Vegetables

“…Cholesterol efflux capacity was progressively reduced in patients with MetS with increasing number of MetS risk factors [ 43 ]. It also was negatively correlated with fasting blood glucose and systolic blood pressure [ 43 ]. Efflux capacity is inversely associated with the risk of coronary heart disease (CHD) [ 44 ].…”

Relationship Among Fatty Liver, Specific and Multiple‐Site Atherosclerosis, and 10‐Year Framingham Score

“…This is a retrospective, secondary analysis of a prospective cohort of consecutive patients between the ages of 18 and 75 years, seen in the Primary Cardiovascular Prevention Center at the Pitié‐Salpêtrière Hospital from January 2010 to June 2016. This cohort was initially designed to focus on cardiovascular risk evaluation and prevention and on atherosclerosis imaging . Therefore, included patients had to have at least one CVRF (e.g., age > 60 years in women and > 50 years in men; type 2 diabetes; dyslipidemia; high blood pressure; tobacco consumption) but no previous history of clinical cardiovascular events (e.g., myocardial infarction, coronary by‐pass surgery or coronary angioplasty, stroke).…”

“…This cohort was initially designed to focus on cardiovascular risk evaluation and prevention and on atherosclerosis imaging. (6,(13)(14)(15)(16) Therefore, included patients had to have at least one CVRF (e.g., age > 60 years in women and > 50 years in men; type 2 diabetes; dyslipidemia; high blood pressure; tobacco consumption) but no previous history of clinical cardiovascular events (e.g., myocardial infarction, coronary by-pass surgery or coronary angioplasty, stroke). For the purpose of this study we also excluded patients with excessive alcohol consumption (> 50 g/day in both men and women), any other identified cause of chronic liver disease including hepatitis B or C, and positive test for human immunodeficiency virus.…”