Atherosclerosis
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Randomized Controlled Trial
L-arginine and tetrahydrobiopterin protects against ischemia/reperfusion-induced endothelial dysfunction in patients with type 2 diabetes mellitus and coronary artery disease.
Diminished levels of L-arginine and endothelial nitric oxide synthase (eNOS) uncoupling through deficiency of tetrahydrobiopterin (BH(4)) may contribute to endothelial dysfunction. We investigated the effect of L-arginine and BH(4) administration on ischemia-reperfusion (I/R)-induced endothelial dysfunction in patients with type 2 diabetes and coronary artery disease (CAD). Forearm blood flow was measured by venous occlusion plethysmography in 12 patients with type 2 diabetes or impaired glucose tolerance and CAD. ⋯ Endothelium-independent vasodilatation (EIDV) induced by nitroprusside was unaffected by I/R. Venous total biopterin levels in the infused arm increased from 37+/-7 at baseline to 6644+/-1240 nmol/l during infusion of L-arginine and BH(4) (P<0.0001), whereas there was no difference in biopterin levels during saline infusion. In conclusion L-arginine and BH(4) supplementation reduces I/R-induced endothelial dysfunction, a finding which may represent a novel treatment strategy to limit I/R injury in patients with type 2 diabetes and CAD.
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Retinal vein occlusion (RVO) is one of the most common retinal vascular disorders. During the last years, high levels of homocysteine (Hcy) have been demonstrated to be an independent risk factor for RVO. Aim of this study was to investigate the association among circulating B-group vitamins, Hcy and RVO. ⋯ At the univariate analysis, the lowest tertile of vitamin B6 [odds ratio (OR) 4.03; 95% confidence interval (CI) 2.58-6.31; P<0.0001)] and folate (OR 6.13; 95% CI 3.85-9.76, P<0.0001), and the highest tertile of Hcy (OR 8.08; 95% CI 5.05-12.92, P<0.0001) were found to be significantly associated with RVO. Moreover, at multivariate analysis, after adjustment for traditional cardiovascular risk factors, Hcy, and circulating levels of vitamins, respectively, the lowest tertile of vitamin B6 (OR 3.29; 95% CI 1.89-5.70, P<0.0001) and folate (OR 5.41; 95% CI 3.08-9.51, P<0.0001) and the highest tertile of Hcy (OR 2.58; 95% CI 1.12-5.94, P<0.0001) maintained their significant association with RVO. In conclusion, the present study documents, on a large sample of patients, that low vitamin B6 levels, low folic acid levels and elevated Hcy levels are each independently associated with RVO.
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Randomized Controlled Trial
Dose-dependent effect of rosuvastatin on apolipoprotein B-100 kinetics in the metabolic syndrome.
In a randomized, double-blind, crossover trial of 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week placebo wash-outs between treatments, the dose-dependent effect of rosuvastatin on apolipoprotein (apo) B-100 kinetics in metabolic syndrome subjects were studied. Compared with placebo, there was a significant dose-dependent decrease with rosuvastatin in plasma cholesterol, triglycerides, LDL cholesterol, apoB and apoC-III concentrations and in the apoB/apoA-I ratio, lathosterol:cholesterol ratio, HDL cholesterol concentration and campesterol:cholesterol ratio also increased significantly. Rosuvastatin significantly increased the fractional catabolic rates (FCR) of very-low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and LDL-apoB and decreased the corresponding pool sizes, with evidence of a dose-related effect. ⋯ In the metabolic syndrome, rosuvastatin decreases the plasma concentration of apoB-containing lipoproteins by a dose-dependent mechanism that increases their rates of catabolism. Higher dose rosuvastatin may also decrease LDL apoB production. The findings provide a dose-related mechanism for the benefits of rosuvastatin on cardiovascular disease in the metabolic syndrome.
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A hallmark feature of atherosclerosis is inflammation mediated by prostaglandins (PGs) catalyzed by the enzyme cyclooxygenase (COX). The present study explored whether the COX-2 G-765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atherosclerosis Risk in Communities (ARIC) Study. ⋯ We have found the COX-2 G-765C polymorphism to be a risk factor for incident stroke in African-Americans. This study provides additional evidence for utilizing inflammation-related genetic polymorphisms for identifying individuals at increased risk for stroke.
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Randomized controlled trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have consistently demonstrated significant reductions in cardiovascular morbidity and mortality. Statins are currently the most widely used drugs in many countries. ⋯ However, with increased use and dose of statins and their over-the-counter availability in some countries more cases of other rare side effects may be seen in clinical practice. In the present article we review the literature concerning the statin-related adverse effects other than muscle and liver injury and we provide insight into their clinical relevance and possible underlying mechanisms.