Plasma triglyceride and high density lipoprotein cholesterol are poor surrogate markers of pro-atherogenic chylomicron remnant homeostasis in subjects with the metabolic syndrome

Deasy Irawati, John C. L. Mamo, Satvinder S. Dhaliwal, Mario J. Soares, Karin M. Slivkoff-Clark, Anthony P. James

Subjects with metabolic syndrome (MetS) exhibit impaired lipoprotein metabolism and have an increased risk of cardiovascular disease. Although the risk is attributed primarily to the risk associated with individual components, it is also likely affected by other associated metabolic defects. Remnants of postprandial lipoproteins show potent atherogenicity in cell and animal models of insulin resistance and in pre-diabetic subjects with postprandial dyslipidemia. However, few studies have considered regulation of chylomicron remnant homeostasis in MetS per se. This study measured the plasma concentration in Caucasian men and women of small dense chylomicrons following fasting and explored associations with metabolic and anthropometric measures. A total of 215 Australian Caucasian participants (median age 62 years) were investigated. Of them, 40 participants were classified as having MetS. Apolipoprotein (apo) B-48, an exclusive marker of chylomicrons, metabolic markers and anthropometric measures were determined following an overnight fast. The fasting apo B-48 concentration was 40 % higher in subjects with MetS than those without MetS. In all subjects, triglyceride (r = 0.445, P < 0.0005), non-HDL cholesterol (r = 0.28, P < 0.0005) and HDL cholesterol concentration (r = -0.272, P < 0.0005) were weakly associated with apo B-48 concentration. In subjects with MetS, the association of apo B-48 with triglyceride and non-HDL cholesterol was enhanced, but neither were robust markers of elevated apo B-48 in MetS (r = 0.618 and r = 0.595 respectively). There was no association between apo B-48 and HDL cholesterol in subjects with MetS. This study demonstrates a substantial accumulation of pro-atherogenic remnants in subjects with MetS. We have shown that in a Caucasian cohort, the fasting plasma concentration of triglyceride or HDL/non-HDL cholesterol serves as poor surrogate markers of atherogenic chylomicron remnants. These findings suggest that subjects with MetS exhibit a chronic defect in chylomicron metabolism that is likely to contribute to their increased CV risk.