RELATIONS BETWEEN PLASMA-LIPIDS AND POSTHEPARIN PLASMA LIPASES AND VLDL AND LDL SUBFRACTION PATTERNS IN NORMOLIPEMIC MEN AND WOMEN

VLDL(1), VLDL(2), IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL(1) and VLDL(2) rose as plasma triglycerides (TGs) increased across the normal range, but the association of plasma TGs with VLDL(1) showed a steeper slope than that of VLDL(2) (P < .001). Plasma TG level was the most important determinant of LDL subfraction distribution. The least dense species, LDL-I, decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG level in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range the LDL-III concentration was low (approximate to 30 mg/dL) and changed little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentration in men (r = - .45, P < .001) but not in women (r = -.1, NS). Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL-III concentrations in men than in women (P < .001); 42% of the men had an LDL-III in the range associated with high risk of heart disease (> 100 mg lipoprotein/dL plasma) compared with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with LDL-III (r = .39, P = .001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III. Subjects develop elevated levels of large TO-rich VLDL(1) for a number of reasons, including failure of insulin action. The increase in the concentration of VLDL(1) expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species. A hepatic lipase activity in the male range (due possibly to androgen/estrogen imbalance in women) is then required to lipolyze TO-enriched LDL-II and to generate a concentration of small, dense LDL-III that exceeds the risk limit of 100 mg/dL.