The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: The stanford coronary risk intervention project baseline survey

Abstract

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL 3c (7.2 to 7.8 nm), HDL 3b (7.8 to 8.2 nm), HDL 3a (8.2 to 8.8 nm), HDL 2a (8.8 to 9.7 nm), and HDL 2b (9.7 to 12 nm). HDL peak diameter was determined from the predominant peak of the HDL particle distribution when plotted against particle diameter. Four men who were non-insulin-dependent diabetics as defined by a fasting glucose exceeding 140 mg/dL had significantly higher plasma HDL 3b levels and significantly smaller HDL peak diameters than nondiabetic men, and were therefore excluded from further analyses. In the remaining 93 nondiabetic men, plasma HDL 3b levels correlated positively with indices of truncal obesity (waist to hip ratio and subscapular skinfold), whereas plasma HDL 2b levels correlated negatively with indices of total adiposity (body mass index [BMI]) and truncal obesity (subscapular and abdominal skinfold). Fasting plasma insulin levels correlated negatively with HDL 3a , HDL 2a , and HDL 2b . Obesity significantly affected the relationships of resting heart rate with insulin and HDL subclasses. In heavier men (BMI > 25.8 kg/m 2 ) but not in the less-obese men (BMI < 25.8 kg/m 2 ), resting heart rate was negatively correlated with HDL 3a , HDL 2a , and HDL 2b levels and HDL peak diameter and positively correlated with fasting plasma insulin concentrations. Although the reported physical activity in heavier men also correlated with HDL 3a , HDL 2a , and resting heart rate, the associations of resting heart rate with HDL 3a , HDL 2a , and HDL 2b could not be attributed to activity level. These analyses suggest that the influences of plasma insulin, regional adiposity, physical activity, and resting heart rate on HDL involve specific HDL subclasses. In the presence of increased adiposity, sympathetic drive and physical inactivity may reduce levels of larger HDL and the peak diameter of the major HDL subspecies.

Obesity favors apolipoprotein E- and C-III-containing high density lipoprotein subfractions associated with risk of heart disease

“…Consistent with previous studies, we found that the distribution of HDL sizes was significantly shifted from large to small in obesity (43)(44)(45)(46)(47)(48). This shift involved a lower prevalence of large-size HDL with apoE and a higher prevalence of small-size HDL with apoE in the obese group.…”

The Atherogenic Lipoprotein Profile Associated With Obesity and Insulin Resistance Is Largely Attributable to Intra-Abdominal Fat

“…In this model, the cholesterol concentration in the fractions corresponding to VLDL (fractions 31-38), IDL (fractions 29 and 30), buoyant LDL (fractions [12][13][14], dense LDL (fractions 7-9), and HDL (fractions 1-5) was associated with IAF, whereas S I made no additional contribution to any of the fractions. In a third model, we included BMI as an independent variable together with IAF, S I , and SCF, and found that the cholesterol concentration in the fractions corresponding to VLDL (fractions [31][32][33][34][35][36][37][38], IDL (fraction 30), and dense LDL (fractions 8 -10) was associated with IAF, whereas S I again made no additional contribution. Thus IAF, but not S I , had independent effects to determine the cholesterol concentration beyond those of SCF and BMI.…”

“…Thus an increase in the waist-to-hip ratio (WHR) has been found to be associated with small dense LDL particles (26), as has been an increase in IAF mass (27,28) or insulin sensitivity (29,30). This pattern of central fat distribution has also been associated with an increase in VLDL and intermediate-density lipoprotein (IDL) (26,31) and a decrease in HDL 2 cholesterol (26,32,33). Although these analyses strongly suggest that central fat distribution and/or insulin resistance is an important determinant of adverse changes in lipoprotein profile, we believed that a critical examination of this issue in a large number of apparently healthy subjects was required to determine the impact of differences in body fat distribution and insulin sensitivity on plasma lipids.…”

Clustered Cardiovascular Risk Factors Are Associated with Inflammatory Markers in Adolescents

“…%BF was estimated by tetrapolar bioelectrical impedance (BIA-T, Quantum II, RJL System, MI, USA) according to Williams et al [16]. …”