Submitted to: Circulation
Publication Type: Abstract Only
Publication Acceptance Date: 12/8/2006
Publication Date: 2/27/2007
Citation: Matthan, N.R., Jalbert, S.M., Dolnikowski, G., Schaefer, E., Lichtenstein, A.H. 2007. Gender and age specific differences in the kinetic behavior of TRL, IDL and LDL apolipoprotein B-100 and HDL apolipoprotein A-I. Circulation. 115(8): e262, P188. Interpretive Summary:
Technical Abstract: Gender specific differences in lipid and lipoprotein profile, predominantly higher LDL-C, VLDL-C and TG, and lower HDL-C levels have been observed in males compared to females. These differences are influenced by menopausal status and age. To investigate mechanism(s) involved, apolipoprotein (apo) B-100 and apo A-I kinetic behavior was studied in 20 younger men (n=12) and women (n=8, premenopausal) aged <50 years, and 24 older men (n=12) and women (n=12, postmenopausal) aged >50 yrs. Subjects were provided with a Western diet for 4-6 weeks, after 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 LDL apoB-100, and HDL apoA-I. Data were fit to a multicompartmental model using SAAM II to calculate fractional catabolic rate (FCR) and production rate (PR). Plasma LDL-C, TRL-C and TG levels were lower (-38%, -44% and -45%, respectively, p<0.05) in the premenopausal women compared to the younger men. Plasma TRL and LDL apoB-100 pool sizes were correspondingly lower by 47% and 25% (p<0.05), respectively, in the younger women than men. These differences were accounted for by lower TRL and LDL apoB-100 FCR (p<0.05), with no significant change in PR. No significant differences were observed in the plasma lipoprotein profile and kinetic parameters between the postmenopausal women and older men. Despite higher plasma HDL-C (50%) and HDL apoA-I (13%) levels in women compared to men, apoA-I pool size was similar, as were the kinetic parameters. In both men and women, plasma TRL-C and LDL-C levels were negatively correlated with TRL apoB-100 FCR (r=-0.34, p=0.02) and LDL apoB-100 FCR (r=-0.63, p<0.0001), respectively, but not PR. In conclusion, these data suggest that the mechanism for the lower TRL-C and LDL-C levels and apoB-100 pool sizes observed in premenopausal women was determined predominantly by higher TRL and LDL catabolism or clearance rather than lower production. The similar apoB-100 kinetic profiles between postmenopausal women and older men could explain, in part, the higher CVD risk in men and postmenopausal women relative to younger women.