Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study

Abstract

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) increase atherosclerotic cardiovascular disease risk. Cholesterol efflux capacity (CEC) is a key metric of the anti-atherosclerotic functionality of high-density lipoproteins (HDL). The present study aimed to delineate if T2DM and MetS cross-sectionally associate with altered CEC in a large high cardiometabolic risk population. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma from 552 subjects of the CODAM cohort (288 controls, 126 impaired glucose metabolism [IGM], 138 T2DM). MetS was present in 297 participants. CEC was not different between different glucose tolerance categories but was lower in MetS (P < 0.001), at least partly attributable to lower HDL cholesterol (HDL-C) and apoA-I levels (P < 0.001 for each). Low grade inflammation was increased in IGM, T2DM and MetS as determined by a score comprising 8 different biomarkers (P < 0.05-< 0.001; n = 547). CEC inversely associated with low-grade inflammation taking account of HDL-C or apoA-I in MetS (P < 0.02), but not in subjects without MetS (interaction: P = 0.015). This study demonstrates that IGM and T2DM do not impact the HDL CEC function, while efflux is lower in MetS, partly dependent on plasma HDL-C levels. Enhanced low-grade inflammation in MetS may conceivably impair CEC even independent of HDL-C and apoA-I.

Longitudinal Changes in Cholesterol Efflux Capacities in Patients With Coronary Artery Disease Undergoing Lifestyle Modification Therapy

“…Several studies have shown that visceral AT is an important feature of an impaired cardiometabolic risk profile closely associated with HDL physicochemical properties such as smaller HDL‐Ps . For instance, investigators of the CODAM (Cohort on Diabetes and Atherosclerosis Maastrich) study recently reported that HDL‐CECs (measured using THP‐1 macrophages) were lower in patients with metabolic syndrome (who are frequently characterized by increased visceral AT and insulin resistance) . In our study, visceral AT was negatively associated with baseline HDL‐CECs measured with both cell types.…”

Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia

“…17, 22 After collecting venous blood, plasma For measurement of cIMT, B-mode ultrasound (Philips iU22, San Jose, CA, USA) was carried out using a linear array 5-12-MHz scan head. Far-wall cIMT measurements were performed with longitudinal 2-D images in the enddiastolic phase of the cardiac cycle using the QLAB instrument (Philips).…”

Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein

“…This approach avoids known limitations of prior HDL function assays (e.g. the cholesterol efflux assay) including significant heterogeneity with regards to types of cells used, type of readout reported, lack of standardization and confounding effects of triglycerides 7,15,32 . Determination of biochemical rather than biological properties (e.g.…”

“…These methods have major limitations including significant heterogeneity with regards to types of cells used, type of readout reported, lack of standardization and confounding effects of triglycerides 7,15 . These drawbacks pose difficulties for large clinical studies 16 .…”

“…HDL has a major role in lipid peroxide transport and high amount of lipid peroxides is related to abnormal HDL function. Thus HDL lipid peroxide content can be used to determine HDL function 9,17,20,31 and given the known limitations of prior assays of HDL function 7,15,27,32 , we developed an alternative fluorometric method that quantifies HDL lipid peroxide content (HDLox) 32 . This method is based on the enzyme horseradish peroxidase (HRP) and the fluorochrome Amplex Red that can quantify (without cholesterol oxidase) the lipid peroxide content per mg of HDL-C 32 .…”