Binge drinking causes endothelial dysfunction, which is not prevented by wine polyphenols: a small trial in healthy volunteers.

BACKGROUND: Binge drinking (the consumption of large quantities (>5 units) of alcohol in a short period) is associated with increased cardiovascular mortality. Wine polyphenols are considered to be protective against cardiovascular diseases. We conducted an experimental study to evaluate the acute effects of alcohol consumption on flow-mediated vasodilation and general cardiovascular parameters, using beverages with high polyphenolic content (HPC) and low polyphenolic content (LPC). METHODS: Two groups of ten volunteers were asked to drink two different kinds of beverages. in 45 minutes, three units of red wine or an alcoholic beverage with a low polyphenolic count were consumed. Then 45 minutes were allowed for complete uptake of the alcohol or polyphenolic compounds. Next, all volunteers underwent blood pressure readings, ECG and flow-mediated vasodilation. Blood samples were taken at the same time for routine chemistry, inflammation parameters and lipids. Then the entire cycle was repeated once (in total six units of alcohol in 180 minutes). RESULTS: No differences were found between the two drinks. Alcohol itself dose-dependently increased forearm blood flow by vasodilation of both arterioles and distribution arteries. However, flow-mediated vasodilation (FMD) for the LPC group (n=10) decreased from 7.31 +/- 4.78 (% +/- sd) to 2.82 +/- 2.9 after three drinks and 1.21 +/- 3.25 after six drinks. The FMD values for the HPC group (n=10) decreased from 8.61 +/- 1.78 to 1.78 +/- 3.71 and 1.19 +/- 2.6. There were no significant changes between the LPC and the LPC group at the three time points. CONCLUSION: Although ethanol produces vasodilation at the level of the distribution artery as well as at an arteriolar level, it causes a decrease in flow-mediated vasodilation. This endothelial dysfunction is not corrected by the polyphenols present in wine.

PR and OTc interval prolongation on the electrocardiogram after binge drinking in healthy individuals.

BACKGROUND: Acute, excessive alcohol intake has been associated with an increased cardiovascular mortality in otherwise healthy individuals. It predisposes to accelerated atherosclerosis resulting in acute coronary events but also arrhythmias have been described, such as atrial fibrillation and life-threatening re-entrant ventricular arrhythmias. QTc prolongation is associated with an increased risk of ventricular tachyarrhythmias and an independent risk factor for sudden cardiac death. The aim of the study is to investigate the effect of binge drinking on the conduction intervals in healthy individuals. METHODS: Ten of the volunteers drank red wine while the other ten volunteers drank a sweet designer drink. A follow-up of blood pressure, heart rate, ECG and laboratory findings was performed at an ethanol level of 0, 0.4 and 0.8%, respectively. RESULTS: Fifteen volunteers showed a prolongation of the PR interval, 13 of the QRS complex, 9 of the QT interval and 13 of the QTc interval. PR interval increased from 149 +/- 16 ms to 163 +/- 11 ms (p < 0.05). The heart rate-adjusted QT interval increased from 400 +/- 24 ms to 426 +/- 52 ms (p < 0.05). Heart rate and systolic blood pressure did not significantly change due to the ingestion. CONCLUSION: Acute ingestion of alcohol in a healthy population can induce prolongation of PR and QTc interval.

Variability of flow mediated dilation: consequences for clinical application.

BACKGROUND: Flow mediated vasodilatation (FMD), a non-invasive tool to assess endothelial function, has been shown to have prognostic value for the development of cardiovascular disease. Conventional B-mode ultrasonography has been criticised for its 'limited' resolution in vivo, which complicates reliable detection of the minute diameter changes during reactive hyperaemia. In the present study we evaluated the physical resolution, reproducibility and the capability to detect FMD impairment of a wall tracking system (WTS). METHODS: The resolution of WTS was compared with that of intravascular ultrasound (IVUS) in pig femoral arteries in vivo. Subsequently, intra- and interobserver variability of FMD testing with WTS was evaluated in 75 healthy volunteers. Finally, the effect of smoking as single risk factor for atherosclerosis on FMD in vivo was assessed. RESULTS: WTS and IVUS readings were not different (difference in arterial cross sectional area 1.97 mm(2), r=0.87). Intrasession coefficient of variation in baseline diameter was 1.1% (extremes 0.06--2.0%). Inter-session baseline diameter variation was 3.6 and 3.8% for each observer and 4.1% between observers. Intra-individual variability in FMD between sessions was considerable with coefficients of variation of 13.9% for FMD and 9.3% for NTG. Smokers had impaired FMD responses compared with matched non-smokers (4.7+/-2.4 vs. 9.6+/-4.4%, P<0.001), whereas NTG induced vasodilatation did not differ (13.4+/-6.2 vs. 15.4+/-5.1%; p=ns). CONCLUSION: WTS is a suitable technique for reproducibly assessing the brachial artery diameter in vivo with a accuracy comparable to that of IVUS. Using this sensitive technique the reproducibility of FMD in vivo proves to be poor mainly due to physiological factors. Whereas this seriously limits the use of FMD as follow-up parameter for individual subjects, FMD is demonstrated to be a useful research tool at group level.

Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on postprandial endothelial function.

OBJECTIVES: The purpose of this study was to determine whether endothelial dysfunction as a consequence of direct postprandial lipid response might be favorably influenced by angiotensin-converting enzyme inhibitors or angiotensin AT1 receptor antagonists. BACKGROUND: Postprandial triglyceride-rich lipoproteins cause endothelial dysfunction. Angiotensin-converting enzyme inhibitors have been shown to improve vascular reactivity. For angiotensin II type 1 receptor antagonists this effect is as yet uncertain. METHODS: A randomized, double-blind, placebo-controlled crossover study in 30 healthy volunteers, aged 18 to 33 years, evaluated the effect of quinapril (40 mg daily for two weeks) and losartan (50 mg daily for two weeks) on basal as well as postprandial endothelial function measured noninvasively as percentage diameter change in the brachial artery after reactive hyperemia. Endothelium-independent dilation was measured after nitroglycerine spray sublingual. RESULTS: An acute oral fat load impaired endothelial function. Flow-mediated vasodilation (FMD) decreased from a median of 6.2% to 4.2% (p < 0.05). There was no significant difference in preprandial endothelial function after two weeks of treatment with either quinapril or losartan compared with placebo in these healthy volunteers. Both quinapril (FMD 6.4% to 6.3%) and losartan (7.1% to 5.4%) prevented endothelial dysfunction induced by an oral fat load, although the protective effect of quinapril appeared to be more profound. The response to the endothelium-independent vasodilator nitroglycerine was unaltered throughout the study. CONCLUSIONS: Both losartan and quinapril prevent endothelial dysfunction induced by triglyceride-rich lipoproteins in healthy volunteers. However, the protective effect of quinapril is more pronounced.

Nitric oxide production is reduced in patients with chronic renal failure.

In patients with chronic renal failure (CRF), atherosclerosis is a major cause of cardiovascular morbidity and mortality. Generally, atherosclerosis has been associated with a reduced bioavailability of nitric oxide (NO). Experimental studies have indicated the presence of enhanced NO degradation by reactive oxygen species as well as decreased NO production as possible causes for this reduced NO bioavailability. So far, the question whether or not NO production is impaired in patients with CRF has never been investigated. Therefore, we measured whole body NO production in 7 patients with CRF, and in 7 matched healthy subjects. To assess the relative importance of a dysfunction of NO synthase (NOS), we compared the NO production of these patients to that of 2 other groups known to have endothelial dysfunction, ie, 7 patients with familial hypercholesterolemia (FH) who did not yet have signs of clinical cardiovascular disease (all nonsmokers), and 5 cigarette smokers. These groups were also compared with 7 nonsmoking, age-matched healthy subjects. Whole body NO production, determined as in vivo arginine-to-citrulline conversion, was assessed by giving an intravenous infusion of [15N2]-arginine as a substrate for NOS and measuring isotopic plasma enrichment of [15N]-citrulline by LC-MS. NO production in the CRF patients (0.13+/-0.02 micromol. kg-1. h-1) was significantly lower (P<0.05) than in the corresponding control group (0.23+/-0.09 micromol. kg-1. h-1). NO production also tended to be lower in the FH patients (0.16+/-0.04 micromol. kg-1. h-1), but the difference with the corresponding control group did not reach significance (0.22+/-0.06 micromol. kg-1. h-1). In the group of smokers, NO production was similar to that in nonsmokers (0. 22+/-0.09 micromol. kg-1. h-1). In conclusion, it is demonstrated for the first time that basal whole body NO production is reduced in patients with CRF. This finding implies that therapeutic interventions to endothelial dysfunction in these patients should be primarily directed toward improvement of NO production. The finding of only a tendency toward reduction of NO production in patients with FH and the absence of a reduction in cigarette smokers suggests that other mechanisms such as enhanced NO degradation may be involved in the decrease of NO bioavailability in these groups.

Origin of superoxide production by endothelial nitric oxide synthase.

Using fluorescence optical and electron spin resonance spectroscopy, we have investigated the production of superoxide by bovine endothelial nitric oxide synthase (NOS). In contrast to neuronal NOS, the heme moiety is identified as the exclusive source of superoxide production by endothelial NOS. Thus, calmodulin-mediated enzyme regulation affects production of nitric oxide and superoxide simultaneously and inseparably. The balance between the nitric oxide/superoxide reaction pathways may be shifted by addition of exogenous heme-specific agents, such as tetrahydrobiopterin. Our results have direct relevance for the pathophysiology of atherosclerosis.

The prevalence of age-related maculopathy in the Rotterdam Study.

PURPOSE: To determine the prevalence of age-related maculopathy in an elderly population in The Netherlands. METHODS: Fundus photographs of 6251 participants of the Rotterdam Study, a single-center prospective follow-up study in persons 55 to 98 years of age, were reviewed for the presence of drusen, pigmentary abnormalities, and atrophic or neovascular age-related macular degeneration. RESULTS: The prevalence of at least one drusen of 63 microns or larger increased from 40.8% in persons 55 to 64 years of age to 52.6% in those 85 years of age or older. Similarly, the prevalence of the following abnormalities increased significantly in these age categories: drusen of 125 microns or larger from 4.8% to 17.5%, retinal pigment epithelial hypopigmentations from 3.5% to 9.0%, and increased retinal pigment from 3.7% to 15.3%. Atrophic or neovascular age-related macular degeneration was present in 1.7% of the total population. Atrophic age-related macular degeneration increased from 0.1% in persons 55 to 64 years of age to 3.7% in those 85 years of age or older. Neovascular age-related macular degeneration increased from 0.1% to 7.4% in these age groups. No sex differences were observed for these lesions. CONCLUSIONS: The prevalence of atrophic or neovascular age-related macular degeneration is 1.7%. In those 55 years of age or older, the prevalence increases strongly with age and it is similar in men and women. Neovascular age-related macular degeneration was twice as common as atrophic age-related macular degeneration. These findings suggest that age-related maculopathy may be less common in this European population than in similar populations in the United States.