REDUCED HDL2 CHOLESTEROL SUBSPECIES AND ELEVATED POSTHEPARIN HEPATIC LIPASE ACTIVITY IN OLDER MEN WITH ABDOMINAL OBESITY AND ASYMPTOMATIC MYOCARDIAL-ISCHEMIA

Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60+/-years, mean+/-SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio [WHR]), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162+/-71 versus 102+/-39 mg/dl,p<0.001) and lower HDL-C (33+/-6 versus 37+/-7 mg/dl,p<0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p<0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34+/-8 versus 27+/-10-mu-mol/ml.hr-1, p<0.03) and was correlated with log insulin area (r=0.36, p<0.05) and WHR (r=0.32, p<0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r=-0.46, p<0.01, n=41) as well as WHR (r=-0.49, p<0.001, n=47) and log insulin area (r=-0.37, p<0.05, n=47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL, subspecies levels may predispose these older men to atherosclerosis.