Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels.

Hypertriglyceridemia is a complex pathological entity strongly connected to low HDL-C levels but controversially related to the risk of coronary artery disease. In this study, we evaluated the main steps of the antiatherogenic pathway called reverse cholesterol transport in a group of patients with primary hypertriglyceridemia and low HDL-C levels in comparison to normotriglyceridemic subjects with or without hypoalphalipoproteinemia. In patients with primary hypertriglyceridemia, low HDL-C levels were accompanied by decreased apo A-I and apo A-II concentrations. These reductions were manifested by a selective reduction in LpA-I:A-II particles. In addition, apo C-III Lp non B was found to be elevated and HDL lipid percentage composition showed a triglyceride enrichment and cholesterol depletion. The capacity of serum samples from hypertriglyceridemic patients to promote cellular cholesterol efflux was reduced, as evidenced by using two different cellular models, Fu5AH and J774 cells. This impaired cholesterol efflux promotion was also corroborated by incubations of isolated HDL fractions with Fu5AH cells. Lecithin:cholesterol acyltransferase (LCAT) activity, the driving force of reverse cholesterol transport, showed a tendency towards lower values in hypertriglyceridemic patients, but this difference was not statistically significant. Additionally, cholesteryl ester transfer protein (CETP) activity was increased in this group of patients. Therefore, hypertriglyceridemia was found to induce quantitative and qualitative alterations in HDL and its subclasses and, consequently, in some steps of reverse cholesterol transport. The abnormalities found in this antiatherogenic pathway and its promoters could constitute a possible connection between hypertriglyceridemia and atherosclerosis.

Higher values of hepatic lipase activity in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins.

OBJECTIVE: To investigate the enzymatic activity of hepatic lipase (HL) in postmenopausal women (PMW) and reproductive age women (RAW); and to evaluate the relationship between this enzyme and the atherogenic intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), and antiatherogenic high density lipoproteins (HDL) and its subfractions (HDL2 and HDL3). DESIGN: We studied 55 PMW receiving no hormonal treatment in a cross-sectional study in comparison with a control group of 55 RAW, matched by body mass index. Follicle-stimulating hormone was > 40 mUI/ml in PMW and 3-12 mUI/ml in RAW. PMW presented at least 1 year of natural menopause and no more than 10 years of amenorrhea with E2 serum concentration < 15 pg/ml. RESULTS: HL activity was significantly higher in PMW versus RAW (14.0 +/- 1.4 vs. 10.9 +/- 0.4 micromol of fatty acids/ml of postheparin plasma, respectively, mean +/- SEM, p < 0.001). In PMW, IDL cholesterol showed a positive correlation with LDL cholesterol (r = 0.28, p < 0.05), and HDL2 cholesterol was inversely correlated with HL activity (r = 0.31, p < 0.05). HL was positively correlated with plasma concentration of LDL cholesterol in both groups (r = 0.27, p < 0.05). The higher values of HL activity and IDL cholesterol were independent of age. CONCLUSIONS: Higher HL activity is associated with a more atherogenic profile in PMW.

VLDL compositional changes and plasma levels of triglycerides and high density lipoprotein.

VLDL chemical composition is related to plasma levels of triglycerides and HDL-cholesterol. We evaluated patients with primary hypertriglyceridemia with or without hypoalphalipoproteinemia and subjects with normotriglyceridemia with hypoalphalipoproteinemia. The pattern observed in all the groups was an enrichment in the triglyceride content of VLDL and in apo B-VLDL. Compared to controls, LpC-III:B levels were higher in hypertriglyceridemic patients with low or normal HDL-cholesterol levels (7.3 +/- 0.6 vs. 14.9 +/- 1.8 and 12.3 +/- 2.8 mg/dl; P < 0.005 and P < 0.01, respectively) and LpE:B concentration was only increased in patients with hypertriglyceridemia and normal HDL-cholesterol levels (3.1 +/- 0.5 vs. 6.3 +/- 1.0 mg/dl; P < 0.01). The activity of the cholesteryl ester transfer protein was higher in hypertriglyceridemic patients with low HDL-cholesterol levels than in controls (380 +/- 25 vs. 262 +/- 14% cholesteryl esters/ml.h; P < 0.001). The most atypical VLDL particle was found in patients who combined an accumulation of VLDL particles and a reduction in HDL-cholesterol concentration. These two parameters represent both ends of the cholesteryl ester-triglyceride transfer, a crucial factor for VLDL chemical composition and HDL levels.

A comparative study of two hormone replacement therapy regimens on safety and efficacy variables.

OBJECTIVE: To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women. METHODS: In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Student's t-test for paired samples, whereas between-group statistics were performed using the Student's t-test for independent groups. RESULTS: Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups. CONCLUSIONS: Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms.

Soccer players under regular training show oxidative stress but an improved plasma antioxidant status.

Physical activity is known to induce oxidative stress in individuals subjected to intense exercise. In this study, we investigated the lipoprotein profile and the plasma antioxidant status in a group of soccer players engaged in a regular training programme. As was expected for aerobic exercise, high-density lipoprotein-cholesterol (HDL-C) and HDL3-C levels were significantly increased in the sportsmen (P<0.05). Total plasma antioxidant capacity was 25% higher in sportsmen than in controls (P<0.005). Accordingly, plasma hydrosoluble antioxidant levels (ascorbic acid and uric acid) were found to be significantly elevated in the soccer players (P<0.005). In addition, these subjects showed high concentrations of alpha-tocopherol in plasma compared with controls (P<0.005). Furthermore, an increase in plasma superoxide dismutase activity was also observed in relation to exercise (P<0.01). The elevation in plasma activities of antioxidant enzymes and the higher levels of free radical scavengers of low molecular mass may compensate the oxidative stress caused by physical activity. High levels of high-density lipoprotein in plasma may offer additional protection by inhibiting low-density lipoprotein oxidation and thus liposoluble antioxidant consumption. Therefore, soccer players under regular training show an improved plasma antioxidant status in comparison to sedentary controls.

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL