Postprandial lipoprotein responses in hypertriglyceridemic subjects with and without cardiovascular disease

Abstract

Three groups of age- and weight-matched men (aged 40 to 70 years) without diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180 mg/dL and no cardiovascular disease (CVD); HTG — CVD (n = 11), hypertriglyceridemic (HTG) (TG > 240 mg/dL) without CVD; and HTG + CVD (n = 10), HTG (TG > 240 mg/dL) with documented CVD. HTG + CVD subjects had higher fasting and post-oral glucose tolerance test insulin levels than the other two groups, respectively. Very—low-density lipoprotein (VLDL) + chylomicrons (CMs), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL) subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups, except for higher VLDL lipid to apolipoprotein (apo) B ratios ( P < .04) in the HTG + CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial responses of the core lipids (TG and cholesterol esters ICE]) in all of the iipoprotein subfractions were similar in the two HTG groups at each time point. However, both controls and HTG — CVD subjects had increases in HDL-M phospholipid (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG + CVD group, on the other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D PL. These changes resulted in significant increases in HDL-M and HDL-D PI. to apo A-I ratios in both controls and HTG — CVD subjects between 6 and 12 hours, whereas there was no increase seen in the HTG + CVD group. The HTG — CVD group also had a significantly greater increase in the VLDL + CM PL to apo B ratio ( P = .038) at 3 hours than the HTG + CVD group. This diminished amount of surface lipid per VLDL particle may account for the late decrease in the HDL-D PI. to apo A-I ratio seen in HTG + CVD patients. There were no other postprandial lipid or apolipoprotein differences between the two HTG groups. We conclude therefore that the major postprandial lipoprotein abnormality in these HTG + CVD patients was a failure to increase the PL content per particle in VLDL + CM, HDL-M, and HDL-D. This abnormality could prevent the usual increase in reverse cholesterol transport seen in postprandial plasma and therefore contribute to their increased incidence of CVD. The greater insulin resistance seen in these patients also appears to contribute significantly to their CVD.