470 research outputs found
The role of urate and xanthine oxidase in vascular oxidative stress:Future directions
No full textVascular oxidative stress has been shown to be a potent factor in the pathophysiology of endothelial dysfunction. Despite current optimal evidence-based therapy, mortality from various cardiovascular disorders remains high. The search for newer, novel ways of attenuating endothelial dysfunction has yielded several new and exciting possibilities, one of which is the manipulation of urate levels using xanthine oxidase inhibitors. Agents such as allopurinol have shown marked improvements in vascular endothelial function in various cohorts at risk of cardiovascular events. Most of the evidence so far comes from smaller mechanistic studies. The few large randomized controlled trials have failed to show any significant mortality benefit using these agents. This article highlights the potential avenues of further research such as dose-response, and the potential for these agents to regress left ventricular hypertrophy. The role of newer agents such as febuxostat and oxypurinol are discussed as well as potential reasons why some of the current newer agents have failed to live up to the promising early-phase data. It is crucial that these remaining questions surrounding urate, xanthine oxidase and the role of various agents that affect this important oxidative stress-generating system are answered, and therefore these promising agents should not be discarded prematurely
Effects of valsartan on exercise time in symptomatic diastolic heart failure: Diovan Diastolic Dysfunction (DDD) study results
No full textEffects of valsartan on exercise time in symptomatic diastolic heart failure: Diovan Diastolic Dysfunction (DDD) study results
No full textEffect of vitamin D supplementation on blood pressure:a systematic review and meta-analysis incorporating individual patient data
No full textImportance Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.Objective To systematically review whether supplementation with vitamin D or its analogues reduce BP.Data Sources We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.Study Selection We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.Data Extraction and Synthesis We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.Main Outcomes and Measures Difference in SBP and DBP measured in an office setting.Results We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, −0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, −0.1 [95% CI, −0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, −0.5 [95% CI, −1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, −0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.Conclusions and Relevance Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.<br/
A randomized, double-blind, placebo-controlled study to determine the effects of valsartan on exercise time in patients with symptomatic heart failure with preserved ejection fraction
No full textAims To determine whether valsartan improves treadmill exercise time, in patients with symptomatic heart failure with a preserved ejection fraction (HFPEF), compared with placebo.Methods and results In this multicentred, double-blind, 14-week study, patients were randomized to receive valsartan (V) 80 mg or placebo (P) once daily on top of background medications. The dose of valsartan was force-titrated up to 320 mg. A total of 152 patients were randomized (V = 70, P = 82). Most patients had well-controlled hypertension (V = 91.2%, P = 89.0%) (mean baseline systolic BP similar to 130 mmHg) and >50% were receiving an angiotensin-converting enzyme inhibitor and/or beta-blocker (V = 57.4%, P = 54.9%). The mean ejection fraction at baseline was 70.48% in the placebo group (n = 64) and 71.52% in the valsartan group (n = 79). Valsartan had no significant effect on exercise time (primary variable), gas exchange variables, 6 min walk test distance, exertion-related symptoms, brain natriuretic peptide levels, echocardiographic parameters, or quatity-of-life scores. Valsartan significantly lowered peak exercise systolic BP (-13.1 mmHg vs. placebo; P < 0.001) and improved ratings of perceived exertion (Borg score) (-0.69 vs. placebo; P = 0.008).Conclusion In this population, which predominantly included patients with well-controlled hypertension and symptomatic HFPEF, addition of valsartan did not increase exercise time within 14 weeks. However, valsartan 320 mg reduced blood pressure and improved symptoms of perceived exertion (Borg score) during exercise and was generally well-tolerated.</p
Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress
No full textOxidative stress plays an important role in the progression of vascular endothelial dysfunction. The two major systems generating vascular oxidative stress are the NADPH oxidase and the xanthine oxidase pathways. Allopurinol, a xanthine oxidase inhibitor, has been in clinical use for over 40 years in the treatment of chronic gout. Allopurinol has also been shown to improve endothelial dysfunction, reduce oxidative stress burden and improve myocardial efficiency by reducing oxygen consumption in smaller mechanistic studies involving various cohorts at risk of cardiovascular events. This article aims to explain the role of xanthine oxidase in vascular oxidative stress and to explore the mechanisms by which allopurinol is thought to improve vascular and myocardial indices
Effect of vitamin D on blood pressure: a systematic review and meta-analysis
No full textObjectives Vitamin D insufficiency has been linked to hypertension and cardiovascular events in observational studies. It is unclear whether vitamin D supplementation can reduce blood pressure, and, if so, by how much.Methods We performed a systematic review and meta-analysis to examine whether vitamin D reduces blood pressure. Databases including MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane library were searched, supplemented by searches of grey literature, unpublished trials and references from included studies. Studies were assessed by two reviewers independently according to a prespecified protocol. Interventions included activated vitamin D, unactivated vitamin D2 and D3 and ultraviolet B radiation.Results Eleven randomized, controlled trials fulfilled the inclusion criteria. Studies were small and of variable methodological quality. Mean baseline blood pressure was more than 140/90 mmHg in eight studies. Meta-analysis of these eight studies showed a nonsignificant reduction in systolic blood pressure in the vitamin D group compared with placebo [-3.6mmHg, 95% confidence interval (CI) -8.0 to 0.7]. A small, statistically significant reduction was seen in diastolic blood pressure (-3.1mmHg, 95% CI -5.5 to -0.6). Subgroup analysis suggested that unactivated vitamin D produced a greater fall in systolic blood pressure than activated vitamin D (-6.2mmHg, 95% CI -12.32 to -0.04, vs. +0.7 mmHg, 95% CI -4.8 to 6.2). No reduction in blood pressure was seen in studies examining patients who were normotensive at baseline.Conclusion We found weak evidence to support a small effect of vitamin D on blood pressure in studies of hypertensive patients. J Hypertens 27: 1948-1954 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.</p
Letter by Struthers et al regarding article, "cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function"
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Careful screening to target interventions to prevent sudden cardiac death
No full text1. Cardiac death is due not only to coronary artery disease, but also to left ventricular (LV) abnormalities (fibrosis, dysfunction) and arrhythmogenic triggers, such as autonomic imbalance. 2. Nitric oxide deficiency could be a key mediator leading not only to coronary atherosclerosis, but also to LV abnormalities and autonomic imbalance. 3. It may be possible to screen for the above abnormalities (e.g. echocardiography and brain natriuretic peptide levels for LV abnormalities, 24 h tapes for autonomic imbalance and QT interval analysis). 4. Once individuals are identified as being at high risk, a range of interventions is possible (e.g. intensive statin therapy or angiotensin-converting enzyme inhibitors if LV abnormalities or autonomic imbalance are found)
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