Effects of white and red wine on endothelial function in subjects with coronary artery disease

BACKGROUND: Levels of anti-oxidant polyphenols are higher in red than in white wine and are thought to contribute to the reduced cardiovascular risk associated with moderate consumption of wine observed in epidemiological studies. AIM: To compare the acute effects of acute ingestion of white and red wine on endothelial function in subjects with coronary artery disease (CAD). METHODS: Fourteen subjects with proven CAD were randomised to consume white and red wine with a light meal in a single blind cross-over study. Flow-mediated dilatation (FMD) of the brachial artery was measured using high-resolution ultrasonography. Endothelial function, lipid profile, plasma alcohol and polyphenols were measured at baseline, 60 and 360 min after wine consumption. RESULTS: At baseline, FMD was similar (white wine 1.6 +/- 1.9%, red wine 1.8 +/- 1.7%). At 360 min after ingestion of wine there was no difference in FMD, which improved nearly threefold after both wines (white wine 4.7 +/- 2.2%, red wine 3.4 +/- 2.9%; P = 0.002). There was no detectable change in plasma polyphenol levels after either wine. CONCLUSIONS: These data suggest that wine acutely improves endothelial function in patients with CAD. This improved endothelial function might contribute to a reduced risk of cardiovascular events.     

Impairment of endothelial function after a high-fat meal in patients with coronary artery disease.

OBJECTIVE: To determine the effect of postprandial lipid changes on endothelial function in patients with coronary artery disease (CAD) after a high-fat meal. METHODS: We studied 50 CAD patients and 25 control participants, who were all normocholesterolemic. Flow-mediated vasodilatation of the brachial artery was evaluated by the high-resolution ultrasound technique before and after a single high-fat meal (800 calories; 50 g fat). RESULTS: Postprandial serum triglyceride level increased significantly at 2-7 h and mean flow-mediated vasodilatation was impaired significantly (from 4.22 +/- 0.44 to 2.75 +/- 0.33%, P < 0.01) for 75 subjects. The increment in 2 h serum triglyceride level correlated positively with the decrement in postprandial flow-mediated vasodilatation (r = 0.459, P < 0.01). Postprandial triglyceride level was significantly higher in CAD patients than in control participants. Flow-mediated vasodilatation was significantly impaired in CAD patients (from 3.04 +/- 0.39 to 1.69 +/- 0.23%, P < 0.01) and control participants (from 6.58 +/- 0.52 to 4.87 +/- 0.19%, P < 0.05) after a high-fat meal. The impairment of flow-mediated dilatation was more severe in CAD patients (44.41%) than in control participants (25.99%, P < 0.01). CONCLUSION: Postprandial endothelium-dependent vasodilatation after a single high-fat meal was severely impaired in normocholesterolemic CAD patients and control participants. The disordered postprandial metabolism of triglyceride-rich lipoproteins may play an atherogenic role by inducing endothelial dysfunction.     

Lopinavir-ritonavir: effects on endothelial cell function in healthy subjects

To differentiate between the effects that antiretroviral drugs have on the endothelium and the secondary effects that they have on immune function, viral load, and dyslipidemia, 6 non-human immunodeficiency virus-infected human subjects were treated with lopinavir-ritonavir for 1 month and, on the basis of forearm blood flow, the treatment's effects on endothelial cell function were measured. Surprisingly, after exposure to lopinavir-ritonavir, absolute forearm blood-flow responses to the endothelium-dependent vasodilator, acetylcholine, increased significantly (P=.03), and forearm blood flow decreased to a greater extent during specific inhibition of NO synthase by N(G)-monomethyl-L-arginine. Thus, in this small cohort of subjects, short-term treatment with lopinavir-ritonavir does not appear to directly promote endothelial cell dysfunction.     

Acute effects of triiodothyronine on endothelial function in human subjects

CONTEXT: Thyroid hormone regulates several cardiovascular functions, and low T(3) levels are frequently associated with cardiovascular diseases. Whether T(3) exerts any acute and direct effect on endothelial function in humans is unknown. OBJECTIVE: Our objective was to clarify whether acute changes in serum T3 concentration affect endothelial function. DESIGN, SETTING, AND SUBJECTS: Ten healthy subjects (age, 24 +/- 1 yr) participated in a double-blind, placebo-controlled trial at a university hospital. INTERVENTIONS: T3 (or placebo) was infused for 7 h into the brachial artery to raise local T3 to levels observed in moderate hyperthyroidism. Vascular reactivity was tested by intraarterial infusion of vasoactive agents. MAIN OUTCOME MEASURES: We assessed changes in forearm blood flow (FBF) measured by plethysmography. RESULTS: FBF response to the endothelium-dependent vasodilator acetylcholine was enhanced by T3 (P = 0.002 for the interaction between T3 and acetylcholine). The slopes of the dose-response curves were 0.41 +/- 0.06 and 0.23 +/- 0.04 ml/dl x min/microg in the T3 and placebo study, respectively (P = 0.03). T3 infusion had no effect on the FBF response to sodium nitroprusside. T3 potentiated the vasoconstrictor response to norepinephrine (P = 0.006 for the interaction). Also, the slopes of the dose-response curves were affected by T3 (1.95 +/- 0.77 and 3.83 +/- 0.35 ml/dl x min/mg in the placebo and T3 study, respectively; P < 0.05). The increase in basal FBF induced by T3 was inhibited by NG-monomethyl-L-arginine. CONCLUSIONS: T3 exerts direct and acute effects on the resistance vessels by enhancing endothelial function and norepinephrine-induced vasoconstriction. The data may help clarify the vascular impact of the low T3 syndrome and point to potential therapeutic strategies.     

Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.

OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.     

高血压病患者脂餐后血管内皮功能受损

目的探讨高血压病患者高脂餐后血管内皮功能变化.方法 20例高血压病患者和20名正常对照者在禁食12 h后接受高脂餐负荷试验.分别测定餐前及餐后2、4、5、7 h血清血脂浓度.采用高分辨血管外超声法检测餐前及餐后4 h肱动脉血流介导的内皮依赖性血管舒张功能.结果两组受试者的空腹血脂水平无显著差异;餐后2、4、5 h血清甘油三酯(TG)浓度较空腹状态有显著升高.但高血压病组具有较高的餐后4、5、7 h血清TG浓度及其净增加值.两组受试者餐后内皮依赖性血管舒张功能均较空腹时显著受损.高血压病组,(5.38±1.95)% vs(2.21±1.06)%;对照组,(9.38±2.42)% vs(6.25±2.23)%;P<0.001.高血压病组的空腹以及餐后内皮依赖性血管舒张功能较对照组均显著受损(P<0.001),且餐后内皮依赖性血管舒张功能的受损程度显著高于对照组[(58±14)% vs (33±17)%,P<0.001].相关分析显示餐后4 h 血清TG浓度净增加值与餐后内皮依赖性血管舒张功能的变化率显著正相关(r=0.373,P<0.05).结论高血压病患者餐后显著而持久的高甘油三酯血症可导致餐后内皮依赖性血管舒张功能严重损害.     

高脂餐后内皮依赖性血管舒张功能变化及其影响因素

目的：探讨高脂餐后血清甘油三酯（ＴＧ）代谢与内皮依赖性血管舒功能变化的关系。方法７５例血清总胆固醇（ＴＧ）正常的受试在禁食１２ｈ后,接受高脂餐负荷试验。分别采集餐前及餐后２、４、５、７ｈ静脉血标本,用以测定血清ＴＧ浓度以及血清ＴＣ、低密度脂蛋白－胆固醇（ＬＤＬ－Ｃ）、高密度脂蛋白－胆固醇（ＨＤＬ－Ｃ）浓度。采用高分辨血管外超声法检测餐前及餐后４ｈ肱动脉血流介导的内皮依赖性血管舒张功能。结果餐后２     

Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes

Asymmetric dimethylarginine (ADMA), a compound detectable in human plasma, is an endogenous inhibitor of NO synthase. Endothelial dysfunction is an early event in atherogenesis, and large-vessel atherosclerosis is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. Fifty patients with type 2 diabetes mellitus were studied at baseline and 5 hours after ingestion of a high-fat meal. Plasma ADMA measured by using high-performance liquid chromatography increased from 1.04+/-0.99 to 2.51+/-2.27 micromol/L (P:<0.0005). Brachial arterial vasodilation after reactive hyperemia, a NO-dependent function, measured by high-resolution ultrasound, decreased from 6.9+/-3.9% at baseline to 1.3+/-4.5% (P:<0.0001). These changes occurred in association with increased plasma levels of triglycerides and very low density lipoprotein triglycerides, with reduced low density lipoprotein cholesterol and high density lipoprotein cholesterol, and with no changes in total cholesterol. The increase in plasma ADMA in response to a high-fat meal was significantly and inversely related to the decrease in percent vasodilation. In 10 of the subjects studied with a similar protocol on another day, no significant changes in the brachial artery flow responses or in plasma ADMA were observed 5 hours after ingestion of a nonfat isocaloric meal. The data suggest that ADMA may contribute to abnormal blood flow responses and to atherogenesis in type 2 diabetics.     

Vitamin C preserves endothelial function in patients with coronary heart disease after a high-fat meal

BACKGROUND: It has been suggested that an oxidative mechanism is involved with the impaired endothelium-dependent vasodilatation that occurs after a high-fat meal. Hypothesis: The study was undertaken to evaluate the effect of a single oral dose of vitamin C (2 g) on postprandially impaired endothelium-dependent vasodilatation in patients with coronary heart disease (CHD). METHODS: This study included 74 patients with CHD and 50 subjects without CHD with risk factors. The two groups were divided into two subgroups that did or did not receive 2 g of vitamin C (CHD/VitC and CHD/control, n = 37; non-CHD/VitC and non-CHD/control, n = 25) after a high-fat meal (800 calories, 50 g fat). Serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the fasting state and at 2, 4, 5, and 7 h after the high-fat meal were measured. Endothelial function was assessed in the brachial artery by high-resolution ultrasound at baseline and at 4 h postprandially. RESULTS: The postprandial serum triglyceride concentration increased significantly at 2-5 h after the high-fat meal in all groups. The fasting flow-mediated dilatation (FMD) (p < 0.02) and nitroglycerin-induced dilatation (NID) (p < 0.05) of patients with CHD were impaired compared with those of non-CHD subjects. Postprandial FMD was significantly aggravated in the non-CHD/control group (p < 0.01) and the CHD/control group (p < 0.001), but the postprandial FMD in patients and subjects taking vitamin C showed no significant change, although the CHD/VitC group had a mild tendency toward improvement (p = 0.064) and non-CHD/VitC group had a mild tendency toward aggravation (p = 0.852). The change of NID after a high-fat meal did not reach statistical significance in the four groups. The decrement of postprandial FMD correlated positively with the increment of 2-h serum triglyceride concentration in the patients without vitamin C (n = 62, r = 0.545, p < 0.001). CONCLUSIONS: The postprandial state after a high-fat meal is critical in atherogenesis, as it induces endothelial dysfunction through an oxidative stress mechanism. Vitamin C treatment has a promising benefit for patients with CHD.     

Effect of alcohol on endothelial function in healthy subjects

While studies have shown that red wine improves endothelial function, the effect of pure alcohol, the common denominator of all alcoholic beverages, on endothelial function has not been defined. The effect of oral intake of alcohol (one ounce--a dose corresponding to two drink equivalents) on flow-mediated dilatation of the brachial artery was studied in 12 healthy subjects using high-resolution ultrasonography according to a randomized, sham procedure-controlled, single-blind protocol. Alcohol produced a significant vasodilatation of the brachial artery at resting conditions. Furthermore, it led to a significant increase of the brachial artery diameter at reactive hyperemia; however, the percentage flow-mediated dilatation did not change. This study shows, for the first time, that acute moderate intake of alcohol has a potent dilating effect on large arteries both at resting and at reactive hyperemic conditions, without affecting flow-mediated dilatation as a percentage. This may be useful for explaining the divergent effect of different alcoholic beverages on endothelial function and provides valuable insight into the mechanisms involved in the vascular effects of alcohol.     

Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects

Dapagliflozin is a potent and selective inhibitor of sodium-glucose co-transporter type 2 that is being developed for the treatment of type 2 diabetes mellitus. This open-label, randomized, two-period, two-treatment (single doses of 10-mg dapagliflozin fasted or fed), crossover study was conducted to evaluate the effect of a high-fat meal on the pharmacokinetics of dapagliflozin in 14 healthy subjects. Compared to the fasted state, a high-fat meal decreased mean dapagliflozin maximum plasma concentrations (C(max) ) by 31%, increased the time to C(max) (T(max) ) by 1 h, but did not affect overall dapagliflozin systemic exposure [area under the plasma concentration-time curve (AUC)]. As the cumulative (daily) amount of glucose excreted in the urine induced by dapagliflozin is dependent upon dapagliflozin AUC, the effect of food on dapagliflozin C(max) is unlikely to have a clinically meaningful effect on dapagliflozin's efficacy. On the basis of these findings, dapagliflozin can be administered without regard to meals.     

Acute effects of positive end-expiratory pressure on left ventricle diastolic function in healthy subjects

We evaluated the acute effect of the application of positive end-expiratory pressure (PEEP) on LV diastolic function in 10 healthy subjects. We assessed load dependent diastolic function by Doppler examination of transmitral flow and load independent diastolic function by color M-mode propagation velocity of early flow into the LV cavity (Vp). During the application of PEEP in comparison to the baseline, we found a significant reduction of the E wave peak velocity [79 (64–83) vs. 65 (57–72) cm/s; p = 0.028] and a significant reduction in Vp [84 (73–97) vs. 53 (48–66); p = 0.012]. Moreover, we found a significant reduction in left atrial area [15 (13–18) vs. 12 (10–14) cm²; p = 0.018] and right atrial area [12 (11–15) vs. 11 (9–12) cm²; p = 0.015]. No difference was found in global LV systolic function. The application of PEEP acutely modifies the diastolic flow pattern across the mitral valve, and reduces atrial dimensions. The work was presented in part as an oral communication at the 2004 SMART.     

The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects

OBJECTIVE: Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years. METHODS: In a double-blind, randomised, placebo controlled study, 173 healthy volunteers took one of six oil supplements for 8 months. Supplements were placebo, oleic acid rich sunflower oil, evening primrose oil, soya bean oil, tuna fish oil, and tuna/evening primrose oil mix. Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside, respectively. RESULTS: Acetylcholine, but not sodium nitroprusside responses were significantly improved after tuna oil supplementation (P=0.02). Additionally, there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation. No significant changes in vascular response were seen after supplementation with any of the other oils. CONCLUSIONS: Fish oil supplementation has a beneficial effect on endothelial function, even in normal healthy subjects. Modification of the diet by an increase of 6% in eicosapentaenoic acid and 27% in docosahexaenoic acid (equivalent to eating oily fish 2-3 times/week) might have significant beneficial effects on cardiovascular function and health.     

Cardioprotective effect of a biofermented nutraceutical on endothelial function in healthy middle-aged subjects

We tested a biofermented nutraceutical (FPP) that has been previously shown to positively modulate nitric oxide (NO). Forty-two healthy middle-aged subjects were given 3 grams of FPP three times a day for 6 weeks, and tests were repeated at 3 and 6 weeks; the control group was given a placebo. Flow-mediated dilation (FMD) was measured together with NO compounds (nitrogen oxides [NOx]: NO(2)(-)+NO(3)(-)) plasma levels and asymmetrical dimethylarginine (ADMA). In the interventional group, overall FMD significantly increased from 4.2% to 7.3% (p<0.05 vs. placebo). A significant increase in plasma NO and a decrease in ADMA were detected after consumption of FPP (p<0.01). Although larger studies are awaited, it appears that, at least in healthy individuals, such nutraceutical intervention by positively acting on significant cardiovascular parameters can be considered in the armamentarium of a proactive age-management strategy.     

Effect of a single high-fat meal on endothelial function in patients with the metabolic syndrome: role of tumor necrosis factor-alpha

Background and aimsA single high-fat meal may induce endothelial activation and dysfunction in both normal subjects and in patients with type 2 diabetes. The aim of this study was to assess the effect of a high-fat meal on endothelial function in patients with the metabolic syndrome.Methods and resultsTwenty-five patients with the metabolic syndrome (ATP III criteria) were matched for sex, age and body mass index with 25 subjects without the metabolic syndrome. All subjects ate under supervision a high fat meal (760 calories) with 59% energy from fat, 12% energy from protein and 29% energy from carbohydrates. Compared with the control group, subjects with the metabolic syndrome had reduced endothelial function, as assessed with the l-arginine test, and higher circulating levels of TNF-α. Following the high-fat meal, both triglyceride and TNF-α levels increased more in subjects with the metabolic syndrome than in subjects without, while endothelial function decreased more in subjects with the metabolic syndrome. There was a significant relation between increases in TNF-α levels and decreases in endothelial function score in subjects with the metabolic syndrome (r = −0.39, P = 0.03).ConclusionTNF-α levels are increased in subjects with the metabolic syndrome; moreover, a high-fat meal produces further increase in its levels associated with endothelial dysfunction.