Biomedical subjects

Michael E Widlansky

Publications and source records attributed to Michael E Widlansky.

5 recordsLinked to original sources

PubMed2005

Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease.

We previously demonstrated that black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. To investigate potential mechanisms of this effect, we examined plasma catechins and systemic markers of oxidation, inflammation, and antioxidant protection from 66 subjects enrolled in that study. We collected samples at baseline, 2 h after 450 ml of black tea (acute), after 4 weeks of 900 ml of black tea per day (chronic), and after acute and chronic consumption of water. Total catechins increased 33% after acute tea (P < 0.05) and 29% after chronic tea (P < 0.05). Of individual catechins, plasma epicatechin gallate (ECG) concentration significantly increased with acute tea consumption, and plasma epicatechin (EC) increased with chronic tea consumption. Tea consumption did not improve plasma antioxidant capacity and did not reduce urinary 8-hydroxy-2'-deoxyguanosine, or urinary 8-isoprostane levels. Changes in catechin levels did not correlate with changes in endothelial function, plasma markers of oxidative stress, or C-reactive protein. In contrast, endothelial function at baseline correlated with dietary flavonoid intake (beta = 0.32, P = 0.02) and with baseline plasma EC concentration after adjusting for confounding variables (beta = 0.39, P = 0.03). These findings suggest that the benefits of black tea consumption on endothelial function may not be attributable to tea catechins or a systemic antioxidant or anti-inflammatory effect. Chronic dietary flavonoid status appears to relate to endothelial function, possibly suggesting that other flavonoids or polyphenolic components of tea favorably influence vascular health and risk for cardiovascular disease.

Catechin↗

PubMed2004

Body mass index and total and cardiovascular mortality in men with a history of cardiovascular disease.

BACKGROUND: Previous studies designed to identify an association between body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) and cardiovascular or total mortality in populations with known atherosclerotic disease have shown conflicting results. In this study, we used the Physicians' Health Study enrollment cohort to examine the risk of total and cardiovascular mortality among men reporting a history of myocardial infarction or stroke, excluding those who reported a history of cancer. METHODS: Cause-specific death was ascertained for 5010 men during a mean follow-up of 5.0 years. End points were classified as total deaths and deaths due to cardiovascular causes. Four BMI categories (<22.0, 22.0-24.9 [referent], 25.0-27.9, and > or =28.0) were created a priori. We used proportional hazards models to calculate age and multivariate-adjusted relative risks (RRs) for each BMI category for each end point. RESULTS: Compared with men with a BMI of 22.0 to 24.9, men with a BMI of 28.0 or greater had an age-adjusted RR of 1.11 (95% confidence interval [CI], 0.91-1.36), a multivariate RR of 1.04 (95% CI, 0.84-1.28) in a model that did not include biological mediators of obesity, and a multivariate RR of 1.06 (95% CI, 0.78-1.44) in a model that included these mediators. The RRs for cardiovascular mortality were similar, at 1.07 (95% CI, 0.85-1.35), 1.01 (95% CI, 0.79-1.29), and 1.01 (95% CI, 0.71-1.43), respectively. A BMI of less than 22.0 was associated with a small increased risk of total mortality and cardiovascular mortality. CONCLUSION: These findings indicate that elevated BMI may not be strongly associated with total or cardiovascular mortality among men with previously manifested coronary artery disease.

Aged↗

PubMed2004

Coronary endothelial dysfunction is not rapidly reversible with ascorbic acid.

In humans with cardiovascular risk factors, increased vascular production of superoxide anion may contribute to endothelial dysfunction by its reacting with nitric oxide and reducing its biological activity. High concentrations of ascorbic acid scavenge superoxide anion and restore normal endothelium-dependent vasodilation in humans with cardiovascular risk factors. To investigate the contribution of increased superoxide anion to endothelial dysfunction in atherosclerotic coronary arteries, we examined the effect of sequential infusions of ascorbic acid (final concentration 0.1, 1.0, and 10 mmol/L) or placebo on coronary endothelial function in 26 subjects referred for cardiac catheterization to evaluate coronary artery disease. Coronary vasomotor function was evaluated using intracoronary agonist infusion, quantitative angiography, and intracoronary Doppler measurements. At baseline, endothelium-dependent vasodilation of epicardial arteries and coronary microvessels was impaired to an equivalent extent in the ascorbic acid and placebo groups. Sequential ascorbic acid infusions had no effect on the acetylcholine-induced change in coronary artery diameter (-11+/-8, -12+/-10, and -9+/-9%) compared with the effect of placebo (-14+/-13, -16+/-10, and -13+/-9%) infusions (p=0.98). Similarly, the changes in coronary blood flow during acetylcholine infusions were equivalent during ascorbic acid (51+/-44, 67+/-66, and 62+/-52%) and placebo (61+/-104, 55+/-93, and 50+/-69%) infusions (p=0.63). Ascorbic acid also had no effect on the dilator response to intracoronary nitroglycerin (p=0.19). These data argue against an important role for superoxide-mediated "inactivation" of nitric oxide or another rapidly reversible form of oxidative stress as a mechanism of coronary endothelial dysfunction in patients with coronary atherosclerosis.

Acetylcholine↗

PubMed2003

The clinical implications of endothelial dysfunction.

Defining new approaches for the prevention and treatment of atherosclerosis is an important priority. Recently, measurement of endothelial function in patients has emerged as a useful tool for atherosclerosis research. Risk factors are associated with impaired endothelial function, and clinical syndromes relate, in part, to a loss of endothelial control of vascular homeostasis. Recent studies have shown that the severity of endothelial dysfunction relates to cardiovascular risk. A growing number of interventions known to reduce cardiovascular risk have been shown to improve endothelial function. This work suggests that studies of endothelial function could be used in the care of patients and as a surrogate marker for the evaluation of new therapeutic strategies. This article will review this growing literature in an effort to evaluate the current clinical utility of endothelial dysfunction.

Arteriosclerosis↗

PubMed2003

Short- and long-term COX-2 inhibition reverses endothelial dysfunction in patients with hypertension.

Hypertension is associated with endothelial dysfunction that is attributable to oxidative stress and a proinflammatory state. Under these conditions, enhanced expression of cyclooxygenase-2 might lead to increased production of vasoconstrictor prostanoids and reactive oxygen species that reduce the bioavailability of endothelium-derived nitric oxide. To investigate the contribution of cyclooxygenase-2 activity to endothelial dysfunction in human hypertension, we evaluated brachial artery vasodilator function by ultrasound in 29 hypertensive patients before and after treatment with the selective cyclooxygenase-2 inhibitor celecoxib or placebo in a randomized, double-blind study. Brachial artery flow-mediated dilation improved from a baseline of 7.9+/-4.5% to 9.9+/-5.1% (P=0.005) 3 hours after the first dose and to 10.1+/-6.1% (P=0.006) after 1 week of treatment with celecoxib. In contrast, placebo treatment had no significant effect on flow-mediated dilation (8.1+/-4.4%, 8.3+/-3.5%, and 8.0+/-3.2%, respectively). Neither treatment altered nitroglycerin-mediated dilation, extent of reactive hyperemia, or baseline arterial diameter. Celecoxib treatment had no significant effect on the urinary concentrations of F2 isoprostane or thromboxane metabolites. However, urinary concentrations of the prostacyclin metabolite 2,3-dinor-6-ketoprostglandin F1alpha were significantly lower after 1 week of celecoxib treatment. Thus, cyclooxygenase-2 products contribute to endothelial dysfunction in hypertension, and treatment with a cyclooxygenase-2 inhibitor could have a beneficial effect in this setting. However, cyclooxygenase-2 inhibition also has an adverse effect on prostacyclin production that could promote thrombosis, and the net clinical consequences of improved endothelial function versus loss of prostacyclin merits further investigation.

Adult↗