植物雌激素对血压的影响

目的研究大豆饮食中所含的植物雌激素对健康人血压、血脂谱的影响。方法213名健康受试者(男性108人,绝经后女性105人),年龄50-75岁,随机、双盲接受特定大豆蛋白饮食(试验组)或酪蛋白安慰剂(安慰剂组)干预,为期3个月。建立多变量模型以评价治疗效果。结果饮食干预后,仅在试验组受试者尿液中植物雌激素含量增高。试验组血压较安慰剂组下降明显[收缩压(-7.5±1.2)mm Hg比(-3.6±1.1)mm Hg,P<0.01;舒张压(-4.3±0.8)mm Hg比(-1.9±0.7)mm Hg,P<0.05;平均压(-5.5±1.0)mm Hg比(-0.9±1.0)mm Hg,P<0.008]。试验组血脂水平较安慰剂组有显著改变(P<0.001),其中试验组低密度脂蛋白胆固醇/高密度脂蛋白胆固醇比值显著下降[(-0.33±0.10) mmol/L比(0.04±0.10) mmol/L,P<0.05],甘油三酯水平也有显著下降[(-0.20±0.05)mmol/L比(-0.01±0.05)mmol/L,P<0.05],而脂蛋白(a)水平升高(±95%可信区间)[42(17-67)mg/L比4(-22-31)mg/L,P<0.05]。两组中总胆固醇和低密度脂蛋白胆固醇水平均下降,高密度脂蛋白胆固醇水平升高。副作用的发生率两组相似,并且都没有观察到男性激素水平发生改变。结论在正常血压男性和绝经后女性人群中,大豆饮食对血压和血脂水平有改善作用。     

Dietary soy containing phytoestrogens does not activate the hemostatic system in postmenopausal women

The soybean is rich in isoflavone phytoestrogens, which are ligands for estrogen receptors, but it is unknown whether soy/phytoestrogens have similar procoagulant effects to estrogen. In this randomized double-blind trial, 40 healthy postmenopausal women of age 50-75 yr received soy protein isolate (40 g soy protein, 118 mg isoflavones) (n = 19) or casein placebo (n = 21). Plasma markers of coagulation, fibrinolysis, and endothelial dysfunction were measured at baseline and 3 months. The baseline characteristics of the two groups were similar. Compared with casein placebo, soy decreased triglycerides (P < 0.005) and low-density lipoprotein/high-density lipoprotein ratio (P < 0.001) and increased lipoprotein (a) (P < 0.05). Activity of coagulation factor VII (VIIc) decreased similarly in both groups (P < 0.005). Prothrombin fragments 1 + 2 (a marker of thrombin generation) decreased in the soy group (P < 0.005), but the change was not different from the casein group. There was no effect of soy on soluble fibrin (a marker of fibrin production), plasminogen activator inhibitor-1 (a marker of fibrinolytic inhibitory potential), D-dimer (a marker of fibrin turnover), or von Willebrand factor (a marker of endothelial damage). In conclusion, the results of the current study do not support biologically significant estrogenic effects of soy/phytoestrogens on coagulation, fibrinolysis, or endothelial function.     

The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women

OBJECTIVE: To assess the effect of a dietary soy protein supplement containing isoflavones on lipids and indices of bone resorption in postmenopausal women. DESIGN: Placebo-controlled, double-blind, randomized study. PATIENTS: One hundred and six postmenopausal women were randomized to dietary soy supplementation (n = 51) or placebo (n = 55) for 3 months, of which 78 were included in the final analysis. MEASUREMENTS: Lipid profiles including total, low-density lipoprotein (LDL) and HDL cholesterol as well as triacylglycerol were measured. Pyridinoline and deoxypyridinoline were used as markers of bone resorption. Urinary isoflavone excretion was measured to assess compliance. RESULTS: There was a significantly greater increase in urinary isoflavone excretion detected in the soy group compared to placebo. Lipid profiles improved with significant decreases in LDL cholesterol (-0.60 +/- 0.10 vs.-0.29 +/- 0.09 mmol/l, P < 0.05), triacylglycerol (-0.22 +/- 0.07 vs. +0.01 +/- 0.05 mmol/l, P < 0.005) and the LDL : HDL ratio (-0.32 +/- 0.10 vs. +0.20 +/- 0.10, P < 0.005) in the soy group compared to placebo. There were no significant differences between the soy and placebo groups for urinary excretion of pyridinoline (-3.8 +/- 3.1 vs.-0.8 +/- 3.1 nmol/mmolCr, P = 0.4) or deoxypyridinoline (-0.8 +/- 0.9 vs.-0.3 +/- 0.7 nmol/mmolCr, P = 0.4). CONCLUSIONS: In postmenopausal women, dietary supplementation with soy protein containing isoflavones does not appear to have oestrogenic effects on markers of bone resorption. Soy protein favourably affected lipids; however, these effects (fall in triacylglycerol and no change in HDL) differ from those observed with oral oestrogen. These findings suggest that soy may not have biologically significant oestrogenic effects on bone resorption and we hypothesize that the lipid effects may be mediated, at least in part, through nonoestrogenic mechanisms.     

Effects of fenofibrate on lipoproteins, vasomotor function, and serological markers of inflammation, plaque stabilization, and hemostasis

We investigated the effects of fenofibrate, peroxisome proliferator-activated receptors (PPARs) agonist, on endothelial function in patients with hypertriglyceridemia. We administered placebo or fenofibrate 200 mg daily to 25 patients with hypertriglyceridemia for 8 weeks. This study was randomized, double-blind, placebo-controlled, crossover in design. Compared with placebo, fenofibrate significantly changed lipoprotein levels including non-HDL cholesterol and significantly improved the percent flow-mediated dilator response to hyperemia by 13 +/- 6% (P < 0.001) and lowered plasma levels of tumor necrosis factor-alpha by 13 +/- 3% (P < 0.001). Fenofibrate reduced fibrinogen and plasminogen activator inhibitor type 1 antigen levels by 17 +/- 3 and 10 +/- 3%, respectively (P < 0.001 and P = 0.014, respectively). However, fenofibrate did not significantly change plasma levels of nitrate, malondialdehyde, tissue factor activity, and serological markers of plaque stabilization. Fenofibrate significantly changed lipoprotein levels and improved the percent flow-mediated dilator response to hyperemia as well as lowered levels of tumor necrosis factor-alpha (TNF-alpha), fibrinogen, and plasminogen activator inhibitor type 1 antigen.     

Role of erythropoietin in cortisol-induced hypertension

The mechanism of cortisol-induced hypertension remains unknown. We investigated a possible role of erythropoietin (EPO) as a mediator of hypertension in healthy male subjects treated with cortisol. In Study 1, blood pressure (BP) and serum EPO concentrations were measured on alternate days in nine subjects treated with 80 mg of cortisol per day for 5 days. In Study 2 the same parameters were measured in eight subjects randomised to cortisol (80 mg/day) or placebo and 10 subjects randomised to cortisol (200 mg/day) or placebo for 5 days. In Study 1, cortisol caused a significant increase in systolic BP (SBP) (115 +/- 2 vs 126 +/- 2 mm Hg, control vs day 5, P < 0.001) and serum EPO concentrations (14.5 +/- 2.7 vs 24.3 +/- 2.7 mU/mL, P < 0.001). In Study 2 both doses of cortisol increased SBP (118 +/- 2 vs 113 +/- 2 mm Hg, 80 mg cortisol vs placebo, P < 0.05 and 129 +/- 3 vs 113 +/- 2 mm Hg, 200 mg cortisol vs placebo, P < 0.001). Serum EPO concentrations were significantly increased at 200 mg cortisol (25.2 +/- 11.9 vs 15.9 +/- 3.5 mU/mL, P < 0.01) but not 80 mg cortisol (21.3 +/- 2.9 vs 14.9 +/- 3.1 mU/mL). In the 200 mg group there was a positive correlation between the change in SBP and the change in serum EPO concentration (r2 = 0.43, P < 0.05). These results point to a possible role for EPO as the mediator of cortisol-induced hypertension. Journal of Human Hypertension (2000) 14, 195-198.     

Effects of pioglitazone in familial combined hyperlipidaemia

OBJECTIVES: Familial combined hyperlipidaemia (FCH) is associated with insulin resistance. We hypothesized that pioglitazone treatment of FCH patients might increase insulin sensitivity, but may also improve serum lipid levels, body fat distribution, intramyocellular lipids (IMCL) and endothelial function. DESIGN: Double blind, randomized, cross-over study. SUBJECTS: Seventeen FCH patients. INTERVENTIONS: Sixteen weeks of pioglitazone treatment (30 mg) compared with 16 weeks of placebo. MAIN OUTCOME MEASUREMENTS: Insulin sensitivity was measured using the hyperinsulinaemic euglycaemic clamp procedure, body fat distribution and IMCL using magnetic resonance techniques and endothelial function using flow-mediated vasodilatation. RESULTS: Pioglitazone improved insulin sensitivity (M value 37.7 +/- 3.6 micromol min(-1) kg(-1) vs. 33.0 +/- 3.3 micromol min(-1) kg(-1) during placebo, P < 0.05) and LDL composition by increasing the K value (-0.11 +/- 0.06 vs. -0.20 +/- 0.06 during placebo, P < 0.05). However, pioglitazone did not affect other serum lipid levels. Endothelial function, body fat distribution and IMCL were also not affected. In addition, pioglitazone was associated with a decrease in liver enzymes (alkaline phosphatase). CONCLUSION: Pioglitazone treatment of FCH patients without type 2 diabetes mellitus increases insulin sensitivity, decreases liver enzymes and improves LDL composition but has a neutral effect on total serum lipid levels. The change in insulin sensitivity might be too small to induce changes in endothelial function, body fat distribution and IMCL.     

Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia

Experimental hyperhomocysteinemia after an oral methionine or homocysteine load is associated with impaired nitric oxide-dependent vasodilatation in healthy human beings. However, it remains unproven that this effect is mediated by elevations in plasma homocysteine. There is evidence that an increase in plasma homocysteine may increase the formation of asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase. The methyl groups within ADMA are derived from the conversion of S -adenosylmethionine to S -adenosylhomocysteine intermediates in the methionine/homocysteine pathway. No previous study has assessed the role of methylation status, its impact on ADMA formation, and their association with endothelial function in healthy human beings. In a randomized, placebo-controlled, crossover study, 10 healthy subjects (mean age, 29.1 +/- 3.9 years) were administered an oral dose of methionine (0.1 g/kg), l -homocysteine (0.01 g/kg), N-acetylcysteine (NAC) (0.1 g/kg), or placebo. Endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery was impaired after both the methionine and homocysteine load compared with placebo at 4 hours (36 +/- 15, 67 +/- 23 vs 219 +/- 26 microm, respectively, P < .001). N-Acetylcysteine had no effect on flow-mediated dilatation. Plasma total homocysteine was significantly elevated at 4 hours after methionine (23.1 +/- 6.2) and homocysteine (41.5 +/- 8.9) loading, but significantly reduced after NAC 2.4 +/- 0.6 vs 7.1 +/- 2.1 micromol/L in the placebo (P < .001). Plasma S-adenosylmethionine/S-adenosylhomocysteine ratio was significantly (P < .001) increased at 4 hours after methionine (10.9 +/- 0.7) compared with homocysteine (5.4 +/- 0.4), NAC (5.0 +/- 0.3), and placebo (6.0 +/- 0.5). Plasma ADMA concentrations were not altered by any intervention. Our results suggest that endothelial dysfunction due to methionine or homocysteine loading is not associated with an increase in plasma ADMA or a disruption in methylation status.     

Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial

OBJECTIVE: Cigarette smoking is associated with increased plasma homocysteine concentrations, endothelial dysfunction and arterial stiffening. Homocysteine per se induces endothelial dysfunction and arterial stiffening and might account, at least partly, for the vascular abnormalities observed in smokers. We sought to determine whether folic acid supplementation, by reducing plasma homocysteine concentrations, enhanced endothelial function and reduced arterial stiffness in smokers. DESIGN: Double-blind, randomized controlled, parallel-group, trial. SETTING: Academic medical centre. SUBJECTS: A consecutive sample of 24 healthy cigarette smokers (age 37.8 +/- 2.5 years, mean +/- SEM). INTERVENTION: Subjects were randomly assigned to 4-week folic acid 5 mg day-1 or placebo. MAIN OUTCOME MEASURES: The following were measured before and after treatment: (i) peripheral vasoreactivity (forearm arterial blood flow, FABF) during intra-arterial administration of endothelium-dependent (acetylcholine 1.5, 4.5 and 15 microg min-1) and endothelium-independent (sodium nitroprusside 1, 2 and 4 microg min-1) vasodilators; (ii) carotid-femoral pulse-wave velocity (PWV); (iii) blood pressure (BP). RESULTS: Folic acid reduced homocysteine concentrations (10.8 +/- 0.6 vs. 8.2 +/- 0.5 micromol L-1, P < 0.001) and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (ratio between the FABF in the infused and control arm during increasing infusion rates at baseline 1.09 +/- 0.03 vs. 1.41 +/- 0.09 after treatment, P < 0.01; 1.39 +/- 0.07 vs. 1.83 +/- 0.12, P < 0.01; 1.65 +/- 0.16 vs. 2.72 +/- 0.36, P < 0.05) whilst endothelium-independent vasodilatation was unaffected. A significant fall in BP was also observed (mean BP 88 +/- 2 vs. 83 +/- 1 mmHg, P < 0.01). By contrast, PWV did not significantly change (8.4 +/- 0.3 vs. 7.8 +/- 0.4 m s-1). No significant changes in plasma homocysteine concentrations, FABF, BP, and PWV were observed in the placebo group. A multiple regression analysis showed that changes in folic acid plasma concentrations independently predicted both FABF changes during maximal acetylcholine-mediated vasodilatation (P < 0.01) and BP changes (P = 0.01). CONCLUSIONS: Short-term folic acid supplementation significantly enhanced endothelial function and reduced BP in young chronic smokers. These effects were largely independent from the homocysteine lowering effects. Thus, a simple, nontoxic, and relatively inexpensive vitamin intervention might be useful in primary cardiovascular prevention in this high-risk group.     

Patients with type 2 diabetes have exaggerated brachial and central exercise blood pressure: relation to left ventricular relative wall thickness

BACKGROUND: A hypertensive response to exercise has prognostic significance. Patients with type 2 diabetes have vascular abnormalities which may predispose to exaggerated brachial and central blood pressure (BP) during exercise. This study aimed to test this hypothesis and to determine the clinical significance of high exercise BP by examining its relation to left ventricular (LV) mass. METHODS: Brachial and central BP were recorded at rest and in response to maximal exercise in 73 diabetic patients (aged 54 +/- 10 years) and 73 controls (aged 53 +/- 12 years). Brachial BP was recorded using mercury sphygmomanometry and LV mass using 2D-echocardiography. Central BP was estimated by radial tonometry using an exercise-validated generalized transfer function. RESULTS: At rest there were no significant (P > 0.05) differences between groups in brachial or central BP. The diabetic patients had significantly increased exercise brachial systolic BP (SBP: 199 +/- 25 mm Hg vs. 185 +/- 21 mm Hg; P = 0.002) and central SBP (158 +/- 17 mm Hg vs. 149 +/- 15 mm Hg; P = 0.002). There was a significantly higher prevalence of an exaggerated exercise BP response (> or =210/105 mm Hg; men and > or =190/105 mm Hg; women) in the diabetic patients (51% vs. 22%; P < 0.01). Compared with those with normal exercise BP, LV relative wall thickness (RWT) was significantly higher (0.41 +/- 0.09 vs. 0.36 +/- 0.08; P < 0.05) and LV hypertrophy was more prevalent (35% vs. 16%; P < 0.05) in those with a hypertensive response. After accounting for other confounding variables, exercise central SBP remained independently associated with LV RWT (beta = 0.22; P = 0.006). CONCLUSION: Diabetic patients are more likely to exhibit exaggerated exercise BP. Regardless of disease status, high exercise central SBP may contribute to cardiovascular risk via adverse cardiac remodeling.     

Effect of short-term weight loss on the metabolic syndrome and conduit vascular endothelial function in overweight adults

Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.     

High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort

OBJECTIVES: This study sought to determine the effect of lipoprotein(a), or Lp(a), levels and apolipoprotein(a), or apo(a), sizes on endothelial function and to explore ethnic differences in their effects. BACKGROUND: Although high levels of Lp(a) have been shown to confer increased cardiovascular risk in Caucasians, its significance in non-Caucasian populations is uncertain. The pathogenic role of the apo(a) component of Lp(a) is also unclear. METHODS: The relationship of Lp(a) levels and apo(a) sizes to endothelial function was examined in a multiethnic cohort of 89 healthy subjects (age 42 +/- 9 years; 50 men, 39 women) free of other cardiac risk factors. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent, nitrate-induced dilation (NTG) were assessed by ultrasound imaging of the brachial artery. RESULTS: Plasma Lp(a) levels were lowest in Caucasians (18.3 +/- 21.1 mg/dl, n = 40); intermediate in Hispanics (30.2 +/- 30.5 mg/dl, n = 21); and highest in African Americans (68.8 +/- 46.0 mg/dl, n = 28). Lipoprotein(a) levels were found to correlate inversely to FMD (r = -0.33, p < 0.005) but not to NTG (r = 0.06, p = 0.60). This association remained significant after adjusting for gender (p = 0.002). In addition, subjects with small apo(a) size of 相似文献   

Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise.

OBJECTIVES: The aim of the study was to test the hypothesis that angiotensin II (Ang II) blockade would improve exercise tolerance in patients with diastolic dysfunction and a marked increase in systolic blood pressure (SBP) during exercise. BACKGROUND: Diastolic dysfunction may be exacerbated during exercise, especially if there is a marked increase in SBP. Angiotensin II may contribute to the hypertensive response to exercise and impair diastolic performance. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover study of two weeks of losartan (50 mg q.d.) on exercise tolerance and quality of life. The subjects were 20 patients, mean age 64 +/- 10 years with normal left ventricular systolic function (EF >50%), no ischemia on stress echocardiogram, mitral flow velocity E/A <1, normal resting SBP (<150 mm Hg), and a hypertensive response to exercise (SBP >200 mm Hg). Exercise echocardiograms (Modified Bruce Protocol) and the Minnesota Living With Heart Failure questionnaire were administered at baseline, and after each two-week treatment period, separated by a two-week washout period. RESULTS: Resting blood pressure (BP) was unaltered by placebo or losartan. During control, patients were able to exercise for 11.3 +/- 2.5 (mean +/- SD) min, with a peak exercise SBP of 226 +/- 24 mm Hg. After two weeks of losartan, baseline BP was unaltered, but peak SBP during exercise decreased to 193 +/- 27 mm Hg (p < 0.05 vs. baseline and placebo), and exercise time increased to 12.3 +/- 2.6 min (p < 0.05 vs. baseline and placebo). With placebo, there was no improvement in exercise duration (11.0 +/- 2.0 min) or peak exercise SBP (217 +/- 26 mm Hg). Quality of life improved with losartan (18 +/- 22, p < 0.05) compared to placebo (22 +/- 26). CONCLUSIONS: In patients with Doppler evidence of diastolic dysfunction at rest and a hypertensive response to exercise, Ang II receptor blockade blunts the hypertensive response to exercise, increases exercise tolerance and improves quality of life.     

Effect of losartan in aging-related endothelial impairment

Aging is associated with progressive deterioration in endothelial function. We hypothesized that losartan may represent a useful therapeutic strategy to ameliorate endothelial function in aged subjects. Eighteen healthy older subjects (mean age 75 +/- 3 years) were prospectively randomized in a double-blind, crossover fashion to receive either losartan 50 mg/day or placebo for 6 weeks. Subjects were switched to the opposite arm after a 2- week washout period. Flow-mediated dilation (FMD) in the brachial artery and plasma levels of vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM), moncocyte chemoattractant 1 protein, and E-selectin were measured in both arms at the beginning and end of the 6-week period. Losartan resulted in a 6-mm Hg decrease in systolic blood pressure (from 130 +/- 12 to 124 +/- 13 mm Hg), which was no different from placebo (132 +/- 12 to 127 +/- 13 mm Hg). FMD increased from 3.1 +/- 0.6% to 3.9 +/- 0.6% after losartan, and decreased from 3.3 +/- 0.3% to 2.4 +/- 0.6% after placebo (p = NS for both). In contrast, losartan reduced circulating concentrations of vascular cell adhesion molecule 1 (750 +/- 73 to 572 +/- 39), ICAM (405 +/- 26 to 196 +/- 10), and moncocyte chemoattractant 1 protein (560 +/- 56 to 423 +/- 35) (p <0.01 for all by analysis of variance), but not E-selectin. On univariate analyses, the strongest predictor of baseline endothelial function and change in FMD with losartan was low-density lipoprotein. There was a negative correlation between baseline endothelial function and change in FMD in response to losartan (r(2) = -0.75, p = 0.0003). Baseline ICAM levels alone significantly correlated with low-density lipoprotein cholesterol (r(2) = 0.54, p = 0.02) and weakly correlated with total cholesterol (r(2) = 0.47, p = 0.05). Thus, administration of losartan for a duration of 6 weeks has favorable effects on inflammatory markers in healthy older subjects, but does not alter peripheral conduit endothelial function.     

Cardiovascular risk markers in hypothalamic amenorrhoea

OBJECTIVE: To determine whether women with oestrogen deficiency due to hypothalamic amenorrhoea (HA) would demonstrate a lipid and lipoprotein pattern similar to that seen in menopause with higher total cholesterol (TC), LDL, triglyceride and Lp(a) and lower HDL levels than women with regular menstrual cycles. DESIGN: Cross-sectional. PATIENTS: Fifty subjects: 21 women with HA and 30 eumenorrhoeic controls (NL) matched for age, BMI and fat-free mass. MEASUREMENTS: Lipid and lipoprotein levels. RESULTS: There was a significant difference in Lp(a) levels in the HA group between women with >19% fat intake and those <19% fat intake (352+/-231 vs. 116+/-62 mg/l, P = 0.006). Percent fat intake was the most significant determinant of Lp(a) levels in HA, accounting for 51% of the variation in Lp(a) levels. Mean HDL levels were higher in the women with HA compared with the controls (1.3+/- 0.3 vs. 1.1+/-0.2 mmol/l, P = 0.002). There was no significant difference between the groups in TC [4.4+/-0.9 (HA) vs. 4.1+/-0.8 mmol/l (NL), P>0.05], LDL [2.8+/-0.6 (HA) vs. 2.7+/-0.7 mmol/l (NL), P>0.05], triglycerides [1.8+/-0.5 (HA) vs. 1.7+/-0.5 mmol/l (NL), P>0.05] or Lp(a) [234+/-199 (HA) vs. 247+/-222 (NL) mg/l, P>0.05] levels. CONCLUSION: Reduced Lp(a) levels were associated with low dietary fat in women with HA. Moreover, in contrast to menopausal oestrogen deficiency, young women with HA and oestrogen deficiency have increased levels of HDL and no increases in TC, LDL and triglycerides. These data suggest that the negative effects of oestrogen deficiency on cardiovascular risk factors may be modified in women with hypothalamic amenorrhoea.     

Oral L-arginine improves endothelial dysfunction in patients with essential hypertension

BACKGROUND: L-Arginine is a nitric oxide precursor, which augments endothelium-dependent vasodilatation in hypercholesterolemic humans and animals. Endothelium-dependent vasodilation is attenuated in patients with hypertension; however the effects of oral L-arginine on endothelial function of the conduit arteries in patients with essential hypertension have not previously been investigated. METHODS: In a prospective randomized double blind trial, 35 patients with essential hypertension received either 6 g L-arginine (18 subjects) or placebo (17 subjects). Patients were examined for flow-mediated endothelium-dependent dilatation of the brachial artery before and 1.5 h after administration of L-arginine or placebo. At the end of the protocol the nitrate-induced, endothelium-independent vasodilatation was evaluated. RESULTS: Two groups of L-arginine and placebo were similar regarding age, sex, blood lipids, smoking, diabetes, coronary artery disease, body mass index, intima-media thickness of the common carotid artery, clinics blood pressure and baseline brachial artery parameters. Administration of L-arginine or placebo did not change significantly heart rate, blood pressure, baseline diameter, blood flow or reactive hyperemia. L-Arginine resulted in a significant improvement of flow-mediated dilatation (1.7+/-3.4 vs. 5.9+/-5.4%, P=0.008) while placebo did not significantly change this parameter (3.0+/-2.7 vs. 3.1+/-2.2%, P=ns). The effect of L-arginine on flow-mediated dilatation was significantly different from the effect of placebo (P=0.05). L-Arginine did not significantly influence nitrate-induced dilatation (16+/-6.9 vs. 17.7+/-6.7%, P=ns). CONCLUSIONS: Oral administration of L-arginine acutely improves endothelium-dependent, flow-mediated dilatation of the brachial artery in patients with essential hypertension. The long-term effects of L-arginine in these patients require further investigation.     

Modulation of very low-density lipoprotein secretion by dietary protein is age-dependent in rats

The Triton WR-1339 technique was used in order to study age-dependent changes of the rate of very low-density lipoprotein (VLDL) lipid secretion in rats consuming either casein or soy protein isolate. There was a significantly higher influx of lipoprotein cholesterol and triglycerides into the plasma compartment (of fasted animals) after a casein than after a soy diet, both in 10-week-old animals (cholesterol: 0.78 +/- 0.06 vs. 0.52 +/- 0.03 mmol X 1(-1) X h-1) and 25-week-old animals (cholesterol: 0.50 +/- 0.07 vs. 0.32 +/- 0.05 mmol X 1(-1) X h-1), but secretion rates diminished with age. The higher secretion rates following casein were paralleled by higher serum cholesterol levels in the fasted younger animals and also, though to a lesser degree, in the fed animals. These data contribute further evidence to our earlier proposal that dietary protein may induce different serum lipid levels by the modulating rate of lipid influx into the plasma compartment.     

Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study

OBJECTIVES: Hypopituitary adults with growth hormone deficiency (GHD) have an increased cardiovascular mortality, although the mechanisms remain unclear. Endothelial dysfunction, characterized by reduced nitric oxide (NO) bioavailability, is a key early event in atherogenesis and is associated with increased vascular smooth muscle tone and arterial stiffening. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study, we investigated the effects of GH replacement on endothelial function and large-artery stiffness in 32 GHD adults (19 males, 13 females) (age range 19-64 years) over a 6-month period. Thirty-two age- and sex-matched healthy controls were also studied. MEASUREMENTS: Endothelial function was assessed using ultrasonic wall tracking to measure flow-mediated dilatation (FMD) of the brachial artery. Large artery stiffness was assessed by pulse wave analysis of the radial artery pressure waveform, allowing determination of the corresponding central arterial pressure waveform and derivation of the augmentation index. Fasting lipid profiles, glucose and insulin were also measured. RESULTS: At baseline, FMD (mean +/- SD) was impaired in GH-deficient subjects vs. controls (3.4 +/- 2.3 vs. 5.7 +/- 2.0%, P < 0.0001), although endothelium-independent dilatation was similar. The augmentation index was higher in GH-deficient subjects vs. controls (23 +/- 12 vs. 14 +/- 14%, P < 0.01). GH-deficient subjects had higher LDL cholesterol (4.1 +/- 0.8 vs. 3.5 +/- 0.8 mmol/l, P < 0.01) and lower HDL cholesterol (1.1 +/- 0.3 vs. 1.4 +/- 0.4 mmol/l, P < 0.01). In GH-deficient subjects, there were inverse correlations between LDL cholesterol and FMD (r = -0.40, P < 0.05) and between FMD and the augmentation index (r = - 0.58, P < 0.01). Regression analysis identified FMD as an independent predictor of the augmentation index (P < 0.0001). In comparison with baseline, GH replacement resulted in an increase in FMD (5.0 +/- 2.6 vs. 2.8 +/- 1.9%, P < 0.01). There were decreases in central aortic systolic pressure (117 +/- 15 vs. 123 +/- 17 mmHg, P < 0.01), diastolic pressure (82 +/- 10 vs. 86 +/- 8 mmHg, P < 0.01) and the augmentation index (22 +/- 8% vs. 26 +/- 10%, P < 0.05) despite unchanged brachial pressure indices. LDL cholesterol also decreased (3.5 +/- 0.8 vs. 4.2 +/- 0.8 mmol/l, P < 0.01). There were no significant changes in the placebo group. CONCLUSIONS: Adult GHD is associated with endothelial dysfunction and increased large-artery stiffness. An improvement in endothelial function and a reduction in arterial stiffness following GH replacement suggests an important therapeutic role for GH in reducing cardiovascular risk associated with adult GHD.     

Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women

Plant estrogen or phytoestrogens (PE) are increasingly consumed for the purposes of menopause symptom relief and prevention of cardiovascular and other diseases. The objective of this study was to evaluate the effects of PE on plasma lipids and lipoproteins and on endothelial function. Twenty healthy, postmenopausal women, 50 to 70 years old, and with evidence of endothelial dysfunction, were treated with a soybean PE tablet of 80 mg/day of isoflavones. Endothelial function was assessed noninvasively using brachial ultrasound. A double-blind, placebo-controlled, randomized crossover design was employed. After 3 weeks stabilization on a standard fat-reduced diet, subjects received PE or placebo for 8 weeks in random order, separated by a washout period of 8 weeks. Compared with placebo, there were no significant effects of PE on blood pressure and plasma lipid or lipoprotein concentrations. Flow-mediated endothelium-dependent dilation (FMD) in response to reactive hyperemia was not significantly changed by PE ingestion (3. 3 +/- 0.7% on placebo vs 4.1 +/- 0.7% on PE, p >0.4). Variation in FMD was not correlated with change in plasma isoflavone concentration (r = -0.09, p >0.7). Glyceryl trinitrate endothelium-independent dilation was not significantly changed with PE (15.9 +/- 1.3% vs 13.7 +/- 1.2%, p >0.1). These results fail to show a significant impact of medium-term supplementation with 80 mg/day of isoflavones on lipid and lipoprotein levels or on endothelial function in healthy, postmenopausal women.     

Baroreflex sensitivity changes with calcium antagonist therapy in elderly subjects with isolated systolic hypertension

In order to study the effects of calcium-blocking therapy on cardiovascular homeostasis in elderly subjects with isolated systolic hypertension, we performed a randomised double-blind placebo-controlled crossover study of 6 weeks therapy with modified-release nifedipine or placebo. Changes with calcium-blocker treatment in clinic and 24-h blood pressure (BP), heart rate, BP variability, baroreflex sensitivity (BRS) by three methods (Valsalva manoeuvre, phenylephrine and sodium nitroprusside injection), and in baroreflex- and non-baroreflex-mediated reflexes (tilt and cold face stimulus) were studied in 14 elderly subjects (mean age [+/- SEM] 70 +/- 1 years) with sustained isolated systolic hypertension (clinic BP 179 +/- 3/85 +/- 1 mm Hg). Clinic systolic BP, but not diastolic BP, was reduced with treatment (by 14 +/- 6 mm Hg, P = 0.03, diastolic BP 4 +/- 3 mm Hg, P = 0.16). Twenty-four hour BP was also reduced by nifedipine treatment (by 18 +/- 3/9 +/- 2 mm Hg, both P < 0.001). Clinic and 24-h heart rate, and daytime BP variability, were unchanged with treatment. BRS was significantly increased during nifedipine therapy by all three measurement methods (all P < 0.05). With 60 degrees tilt during active treatment, subjects exhibited a greater heart rate increase (P < 0.01), and a reduced fall in systolic (P < 0.05) and diastolic BP (P < 0.05). Thus despite the arteriosclerosis and reductions in large artery compliance described in elderly patients with isolated systolic hypertension, clinically important improvements in clinic and ambulatory BP and some aspects of cardiovascular homeostasis can be achieved with calcium-channel blocking therapy.     

Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).

Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.