Ce. Tan et al., RELATIONS BETWEEN PLASMA-LIPIDS AND POSTHEPARIN PLASMA LIPASES AND VLDL AND LDL SUBFRACTION PATTERNS IN NORMOLIPEMIC MEN AND WOMEN, Arteriosclerosis, thrombosis, and vascular biology, 15(11), 1995, pp. 1839-1848
VLDL(1), VLDL(2), IDL, and LDL and its subfractions (LDL-I, LDL-II, an
d 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 tr
iglycerides (TGs) increased across the normal range, but the associati
on 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, decrease
d 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 lev
el 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 l
ow (approximate to 30 mg/dL) and changed little. As plasma TGs rose fr
om 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentrat
ion in men (r = - .45, P < .001) but not in women (r = -.1, NS). Conve
rsely, above the TG threshold of 1.3 mmol/L there was a steeper rise i
n LDL-III concentrations in men than in women (P < .001); 42% of the m
en had an LDL-III in the range associated with high risk of heart dise
ase (> 100 mg lipoprotein/dL plasma) compared with only 17% of the wom
en. Other influences on the LDL subfraction profile were the activitie
s of lipases and parameters indicative of the presence of insulin resi
stance. Men on average had twice the hepatic lipase activity of women.
This enzyme was not strongly associated with variation in the LDL sub
fraction profile in men, but in women it was correlated with LDL-III (
r = .39, P = .001) and remained a significant predictor in multivariat
e analysis. Increased waist/hip ratio, fasting insulin, and glucose we
re correlated negatively with LDL-I and positively with LDL-III, prima
rily, at least in the case of LDL-III, through raising plasma TGs. On
the basis of these cross-sectional observations we postulate the follo
wing model for the generation of LDL-III. Subjects develop elevated le
vels of large TO-rich VLDL(1) for a number of reasons, including failu
re of insulin action. The increase in the concentration of VLDL(1) exp
ands the plasma TG pool, and this, via the action of cholesteryl ester
transfer protein (which facilitates neutral lipid exchange between li
poprotein particles), promotes the net transfer of TGs into LDL-II, th
e 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.