© 1995 American Heart Association, Inc.
Articles |
Relations Between Plasma Lipids and Postheparin Plasma Lipases and VLDL and LDL Subfraction Patterns in Normolipemic Men and Women
From the Department of Pathological Biochemistry, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
Correspondence to Dr C.E. Tan, Department of Pathological Biochemistry, University of Glasgow, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK.
Abstract VLDL1,
VLDL2, 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 VLDL1 and VLDL2 rose
as plasma triglycerides (TGs) increased across the normal
range, but the association of plasma TGs with VLDL1 showed
a steeper slope than that of VLDL2
(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 (
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 TG-rich VLDL1 for a number of reasons, including
failure of insulin action. The increase in the concentration of
VLDL1 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 TG-enriched LDL-II and to generate a
concentration of small, dense LDL-III that exceeds the risk limit of
100 mg/dL.
Key Words: VLDL subfraction • IDL • LDL subfractions • atherogenic lipoprotein phenotype • hepatic lipase
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