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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1691.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

TRL, IDL, and LDL Apolipoprotein B-100 and HDL Apolipoprotein A-I Kinetics as a Function of Age and Menopausal Status

Nirupa R. Matthan; Susan M. Jalbert; Stefania Lamon-Fava; Gregory G. Dolnikowski; Francine K. Welty; Hugh R. Barrett; Ernst J. Schaefer; Alice H. Lichtenstein

From the Cardiovascular Nutrition (N.R.M., S.M.J., A.H.L.), Lipid Metabolism (S.L.-F., E.J.S.), and Mass Spectrometry Laboratories (G.G.D.), Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Mass; Division of Cardiology (F.K.W.), Beth Israel Deaconess Medical Center, Boston, Mass; and University of Western Australia/Western Australia Institute for Medical Research (H.R.B.), Perth, Australia.

Reprint requests to Dr Nirupa Matthan, Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington St, Boston, MA 02111. E-mail nirupa.matthan{at}tufts.edu

Objective— To determine mechanisms contributing to the altered lipoprotein profile associated with aging and menopause, apolipoprotein B-100 (apoB-100) and apoA-I kinetic behavior was assessed.

Methods and Results— Eight premenopausal (25±3 years) and 16 postmenopausal (65±6 years) women consumed for 6 weeks a standardized Western diet, at the end of which a primed-constant infusion of deuterated leucine was administered in the fed state to determine the kinetic behavior of triglyceride-rich lipoprotein (TRL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) apoB-100, and high-density lipoprotein (HDL) apoA-I. Data were fit to a multicompartmental model using SAAM II to calculate fractional catabolic rate (FCR) and production rate (PR). Total cholesterol, LDL cholesterol (LDL-C), TRL-C, and triglyceride levels were higher (50%, 55%, 130%, and 232%, respectively) in the postmenopausal compared with the premenopausal women, whereas HDL-C levels were similar. Plasma TRL, IDL, and LDL-apoB-100 levels and pool sizes (PS) were significantly higher in the postmenopausal than premenopausal women. These differences were accounted for by lower TRL, IDL, and LDL apoB-100 FCR (P<0.05), with no difference in PR. There was no significant difference between groups in HDL-C levels or apoA-I kinetic parameters. Plasma TRL-C concentrations were negatively correlated with TRL apoB-100 FCR (r=–0.46; P<0.05) and positively correlated with PR (r=0.62; P<0.01). Plasma LDL-C concentrations were negatively correlated with LDL apoB-100 FCR (r=–0.70; P<0.001) but not PR.

Conclusions— The mechanism for the increase in TRL and LDL apoB-100 PS observed in the postmenopausal women was determined predominantly by decreased TRL and LDL catabolism rather than increased production. No differences were observed in HDL apoA-I kinetics between groups.

Postmenopausal women have higher VLDL-C and LDL-C levels compared with premenopausal women. To determine mechanism, apolipoprotein kinetic studies were conducted in 24 women. Postmenopausal women had higher TRL and LDL pool sizes, which were accounted for by lower TRL and LDL apoB-100 catabolic rates. No significant difference in plasma HDL-C levels or apoA-I kinetics parameters were observed between groups.

Key Words: apolipoprotein • lipids • lipoproteins • stable isotopes • menopausal status • aging

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