Effect of integration of supplemental nutrition with public health programmes in pregnancy and early childhood on cardiovascular risk in rural Indian adolescents: long term follow-up of Hyderabad nutrition trial.

OBJECTIVE: To determine whether integration of nutritional supplementation with other public health programmes in early life reduces the risk of cardiovascular disease in undernourished populations. DESIGN: Approximately 15 years' follow-up of participants born within an earlier controlled, community trial of nutritional supplementation integrated with other public health programmes. SETTING: 29 villages (15 intervention, 14 control) near Hyderabad city, south India. PARTICIPANTS: 1165 adolescents aged 13-18 years. INTERVENTION: Balanced protein-calorie supplementation (2.51 MJ, 20 g protein) offered daily to pregnant women and preschool children aged under 6 years, coupled with integrated delivery of vertical public health programmes. MAIN OUTCOME MEASURES: Height, adiposity, blood pressures, lipids, insulin resistance (homoeostasis model assessment (HOMA) score), and arterial stiffness (augmentation index). RESULTS: The participants from the intervention villages were 14 mm (95% confidence interval 4 to 23; P=0.007) taller than controls but had similar body composition. The participants from the intervention villages had more favourable measures of insulin resistance and arterial stiffness: 20% (3% to 39%; P=0.02) lower HOMA score and 3.3% (1% to 5.7%; P=0.008) lower augmentation index. No strong evidence existed for differences in blood pressures and serum lipids. CONCLUSIONS: In this undernourished population, integrated delivery of supplemental nutrition with other public health programmes in pregnancy and early childhood was associated with a more favourable profile of cardiovascular disease risk factors in adolescence. This pragmatic study provides the most robust evidence to date on this important hypothesis for which classic trials are unlikely. Improved maternal and child nutrition may have a role in reducing the burden of cardiovascular disease in low income and middle income countries.

In vivo aspirin supplementation inhibits nitric oxide consumption by human platelets.

Antiplatelet therapies improve endothelial function in atherosclerosis, suggesting that platelets regulate vascular nitric oxide (NO) bioactivity in vivo. Herein, washed platelets consumed NO on activation in an aspirin-sensitive manner, and aspirin enhanced platelet NO responses in vitro. To examine whether in vivo aspirin can inhibit platelet NO consumption, a double-blind placebo-controlled study was conducted. After a 2-week nonsteroidal anti-inflammatory drug (NSAID)-free period, healthy men were randomly assigned and administered aspirin (75 mg/d orally) or identical placebo for 14 days, then crossed over to the opposite arm. Following in vivo aspirin, NO consumption by platelets was inhibited 91%. Rate of onset and recovery following aspirin withdrawal was consistent with cyclooxygenase 1 (COX-1) inhibition. In a small substudy, NO consumption by platelets from postmenopausal women was faster in hypercholesterolemics and less sensitive to aspirin (ie, 39% versus 76% inhibition for hypercholesterolemics or normocholesterolemics, respectively). However, 150 mg aspirin/day increased inhibition of NO consumption by platelets of hypercholesterolemics to 80%. Comparisons of platelet COX-1 or -2 expression and urinary 11-dehydro-thromboxane B2 excretion suggested that aspirin was less able to block platelet activation in vivo in hypercholesterolemia. In conclusion, aspirin inhibits NO consumption by platelets from healthy subjects, but its beneficial effects on NO bioactivity may be compromised in some hypercholesterolemic patients.

Alpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress in healthy men.

AIMS: Alpha-lipoic acid (ALA) is a thiol compound with antioxidant properties used in the treatment of diabetic polyneuropathy. ALA may also improve arterial function, but there have been scant human trials examining this notion. This project aimed to investigate the effects of oral and intra-arterial ALA on changes in systemic and regional haemodynamics, respectively. METHODS: In study 1, 16 healthy older men aged 58 +/- 7 years (mean +/- SD) received 600 mg of ALA or placebo, on two occasions 1 week apart, in a randomized cross-over design. Repeated measures of peripheral and central haemodynamics were then obtained for 90 min. Central blood pressure and indices of arterial stiffness [augmentation index (AIx) and estimated aortic pulse wave velocity] were recorded non-invasively using pulse wave analysis. Blood samples obtained pre- and post-treatments were analysed for erythrocyte antioxidant enzyme activity, plasma nitrite and malondialdehyde. In study 2 the effects of incremental cumulative doses (0.5, 1.0, 1.5 and 2.0 mg ml(-1) min(-1)) of intra-arterial ALA on forearm blood flow (FBF) were assessed in eight healthy subjects (aged 31 +/- 5 years) by conventional venous occlusion plethysmography. RESULTS: There were no significant changes on any of the central or peripheral haemodynamic measures after either oral or direct arterial administration of ALA. Plasma ALA was detected after oral supplementation (95% confidence intervals 463, 761 ng ml(-1)), but did not alter cellular or plasma measures of oxidative stress. CONCLUSIONS: Neither oral nor intra-arterial ALA had any effect on regional and systemic haemodynamics or measures of oxidative stress in healthy men.

Nebivolol increases arterial distensibility in vivo.

Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. beta-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that beta-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of beta-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating beta-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6+/-3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of -1+/-3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of -5+/-3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of N(G)-monomethyl-L-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a beta2 adrenoceptor-dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.