Low density lipoprotein (LDL) plasma concentration is increased in the elderly. In this group, the incidence of coronary artery disease (CAD) is greater and LDL remains an important risk factor for CAD development. In this study, the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptors was studied in 10-subject groups of the elderly (70 +/- 4 yr), middle-aged (42 +/- 5 yr) and young (23 +/- 2 yr). All were normolipidemic, nonobese, nondiabetic subjects who did not have CAD. The emulsion was labeled with 14C-cholesteryl oleate and injected intravenously into the subjects. Blood samples were drawn at regular intervals over 24 h to determine the plasma decay curve of the emulsion radioactive label and to estimate its plasma fractional clearance rate (FCR, in h(-1)). FCR of the emulsion label was smaller in elderly compared to young subjects (0.032 +/- 0.035 and 0.071 +/- 0.049 h(-1), respectively; mean +/- SD, P< 0.05). FCR of the middle-aged subjects (0.050 +/- 0.071 h(-1)) was intermediate between the values of the elderly and young subjects, although not statistically different from them. A negative correlation was found betweeen the emulsion FCR and subjects' age (r = -0.47, P = 0.008). We conclude that aging is accompanied by progressively diminished clearance of the emulsion cholesterol esters and, by analogy, of the native LDL.
Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 ± 0.03 vs 0.558 ± 0.11) and against LDL with a low degree of oxidative modification (0.100 ± 0.01 vs 0.217 ± 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation.
Objective - placebo (7.9±8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2±31.9min; diltiazem: 19.3±29.6min; placebo: 46.1±55.3min; p<0.05).
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