Gender-Specific Differences in the Kinetics of Nonfasting TRL, IDL, and LDL Apolipoprotein B-100 in Men and Premenopausal Women

Abstract

Objective-To investigate mechanisms underlying gender differences in serum lipoprotein concentrations, the kinetic behavior of apoB-100 was assessed. Methods and Results-Twenty subjects (Ͻ50 years; 12 men and 8 premenopausal women) were provided a Western diet for 4 to 6 weeks, after which the kinetics of apoB-100 in triglyceride-rich, intermediate-density, and low-density lipoprotein (TRL, IDL, and LDL) were determined in the fed state. Nonfasting plasma TC, LDL-C, and triglyceride concentrations were 23%, 34%, and 57% lower, respectively, in the women compared with men. Plasma TRL and LDL apoB 100 pool sizes were lower by 40% and 30%, respectively. These differences were accounted for by higher TRL and LDL apoB 100 fractional catabolic rates (FCR), rather than differences in production rates (PR). Plasma TRL-C and LDL-C were positively correlated with TRL and LDL apoB 100 concentrations and pool size, and negatively correlated with TRL and LDL apoB 100 FCR (women: rϭϪ0.59, PϽ0.01 and rϭϪ0.54, PϽ0.04, and men: rϭϪ0.43, PϽ0.05 and rϭϪ0.44, PϽ0.05). No significant associations were observed between plasma TRL-C and LDL-C and PR. Conclusions-These data suggest the mechanism for lower TRL-C and LDL-C concentrations in women was determined predominantly by higher TRL and LDL FCR rather than lower PR. This could explain, in part, the lower CVD risk in premenopausal women relative to men. Key Words: apolipoproteins Ⅲ gender Ⅲ metabolism Ⅲ stable isotopes Ⅲ CVD C ardiovascular disease (CVD) incidence differs between men and women. Among men aged 20 to 44 years the prevalence of CVD is one-third higher than women of the same age (34% versus 24%, respectively). Between the ages of 45 to 54 years, the prevalence is similar, but above the age of 55 years, it is higher in women. 1 Among women, CVD death rates after menopause are 2 to 3 times higher than women of the same age before menopause. [2][3][4] Lipid abnormalities, hypertension, smoking, diabetes, atherogenic diet, and sedentary lifestyle are well established risk factors for CVD. 1,5 Among the lipid risk factors, elevated LDL-C and triglycerides, and decreased HDL-C concentrations have been independently linked to the progression of CVD. Gender, age and menopausal differences in plasma concentrations of both LDL-C and HDL-C have been documented. 6 -11 Men tend to have higher plasma LDL-C and lower HDL-C concentrations than comparably aged premenopausal women, and some studies have also reported higher VLDL-C, triglycerides, and apoB concentrations. 9,10,[12][13][14][15][16][17] Data from cross sectional 9,10,17-24 and longitudinal studies 23,25-27 have shown that post-compared to premenopausal women have higher plasma total, LDL-C, VLDL-C, and triglyceride concentrations. It has been hypothesized that these differences might partly explain the lower CVD risk in premenopausal women and the higher but comparable CVD risk between postmenopausal women and men. However, limited information is available on the mechanism(s) underlying the gender related differences on ci...

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