The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.</p> <p>Methods</p> <p>We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B₆25 mg and vitamin B₁₂0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.</p> <p>Results</p> <p>After a mean treatment period of 3.9 ± 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 μmol/L, 95% CI 7.5 to 8.4 versus 11.8 μmol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 ± 0.17 mm vitamins versus 0.83 ± 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.</p> <p>Conclusion</p> <p>Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.</p> <p>Trial Registration</p> <p>Clinical Trial Registration URL: <url>http://www.actr.org.au/</url></p> <p>Trial Registration number: 12605000005651</p

The endothelial glycocalyx: composition, functions, and visualization

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging

Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease

Background Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris. In this study, we compared percutaneous coronary revascularization with lipid-lowerin Methods We studied 341 patients with stable coronary artery disease, relatively normal left ventricular function, asymptomatic or mild-to-moderate angina, and a serum level of low-density lipoprotein (LDL) cholesterol of at least 115 mg per deciliter (3.0 mmol per liter) who were referred for percutaneous revascularization. We randomly assigned the patients either to receive medical treatment with atorvastatin, at 80 mg per day (164 patients), or to undergo the recommended percutaneous revascularization procedure (angioplasty) followed by usual care, which could include lipid-lowering treatment (177 patients). The follow-up period was 18 months. Results Twenty-two (13 percent) of the patients who received aggressive lipid-lowering treatment with atorvastatin (resulting in a 46 percent reduction in the mean serum LDL cholesterol level, to 77 mg per deciliter [2.0 mmol per liter]) had ischemic events, as compared with 37 (21 percent) of the patients who underwent angioplasty (who had an 18 percent reduction in the mean serum LDL cholesterol level, to 119 mg per deciliter [3.0 mmol per liter]). The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period (P=0.048, which was not statistically significant after adjustment for interim analyses). This reduction in events was due to a smaller number of angioplasty procedures, coronary-artery bypass operations, and hospitalizations for worsening angina. As compared with the patients who were treated with angioplasty and usual care, the patients who received atorvastatin had a significantly longer time to the first ischemic event (P=0.03). Conclusions In low-risk patients with stable coronary artery disease, aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events. (N Engl J Med 1999;341:70-6.) (C) 1999, Massachusetts Medical Society

Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease

Background Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris. In this study, we compared percutaneous coronary revascularization with lipid-lowerin Methods We studied 341 patients with stable coronary artery disease, relatively normal left ventricular function, asymptomatic or mild-to-moderate angina, and a serum level of low-density lipoprotein (LDL) cholesterol of at least 115 mg per deciliter (3.0 mmol per liter) who were referred for percutaneous revascularization. We randomly assigned the patients either to receive medical treatment with atorvastatin, at 80 mg per day (164 patients), or to undergo the recommended percutaneous revascularization procedure (angioplasty) followed by usual care, which could include lipid-lowering treatment (177 patients). The follow-up period was 18 months. Results Twenty-two (13 percent) of the patients who received aggressive lipid-lowering treatment with atorvastatin (resulting in a 46 percent reduction in the mean serum LDL cholesterol level, to 77 mg per deciliter [2.0 mmol per liter]) had ischemic events, as compared with 37 (21 percent) of the patients who underwent angioplasty (who had an 18 percent reduction in the mean serum LDL cholesterol level, to 119 mg per deciliter [3.0 mmol per liter]). The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period (P=0.048, which was not statistically significant after adjustment for interim analyses). This reduction in events was due to a smaller number of angioplasty procedures, coronary-artery bypass operations, and hospitalizations for worsening angina. As compared with the patients who were treated with angioplasty and usual care, the patients who received atorvastatin had a significantly longer time to the first ischemic event (P=0.03). Conclusions In low-risk patients with stable coronary artery disease, aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events. (N Engl J Med 1999;341:70-6.) (C) 1999, Massachusetts Medical Society