Dietary Sodium Restriction Reverses Vascular Endothelial Dysfunction in Middle-Aged/Older Adults With Moderately Elevated Systolic Blood Pressure

ObjectivesThis study sought to determine the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP) (130–159 mm Hg) and the associated physiological mechanisms.BackgroundVascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown.MethodsSeventeen subjects (11 men and 6 women; mean age, 62 ± 7 years) completed a, randomized crossover study of 4 weeks of both low (DSR) and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition.ResultsUrinary sodium excretion was reduced by ∼50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following DSR (p < 0.005). Low sodium markedly enhanced NO-mediated EDD (greater ΔFBFACh with endothelial NO synthase inhibition) without changing endothelial NO synthase expression/activation (Ser 1177 phosphorylation), restored BH4 bioactivity (less ΔFMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less ΔFMDBA and ΔFBFACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (all p < 0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged.ConclusionsDSR largely reversed both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP-lowering effects

Montmorency cherry supplementation attenuates vascular dysfunction induced by prolonged forearm occlusion in overweight, middle-aged men

Flavonoid supplementation improves brachial artery flow-mediated dilation (FMD), but it is not known whether flavonoids protect against vascular dysfunction induced by ischemia-reperfusion (IR) injury and associated respiratory burst. In a randomized, double-blind, placebo-controlled, crossover study, we investigated whether 4 wk supplementation with freeze-dried Montmorency cherry (MC) attenuated suppression of FMD after IR induced by prolonged forearm occlusion. Twelve physically inactive overweight, middle-aged men (52.8 ± 5.8 yr, BMI: 28.1 ± 5.3 kg/m2) consumed MC (235 mg/day anthocyanins) or placebo capsules for 4 wk, with supplementation blocks separated by 4 wk washout. Before and after each supplementation block, FMD responses and plasma nitrate and nitrite ([ N O − 2 ]) concentrations were measured at baseline and 15, 30, and 45 min after prolonged (20 min) forearm occlusion. FMD response was significantly depressed by the prolonged occlusion ( P < 0.001). After a 45-min reperfusion, FMD was restored to baseline levels after MC (ΔFMD presupplementation: -30.5 ± 8.4%, postsupplementation: -0.6 ± 9.5%) but not placebo supplementation (ΔFMD presupplementation: -11.6 ± 10.6, postsupplementation: -25.4 ± 4.0%; condition × supplement interaction: P = 0.038). Plasma [ N O − 2 ] decreased after prolonged occlusion but recovered faster after MC compared with placebo (Δ45 min to baseline; MC: presupplementation: -15.3 ± 9.6, postsupplementation: -6.2 ± 8.1; Placebo: presupplementation: -16.3 ± 5.9, postsupplementation: -27.7 ± 11.1 nmol/l; condition × supplement × time interaction: P = 0.033). Plasma peroxiredoxin concentration ([Prx2]) was significantly higher after MC (presupplementation: 22.8 ± 1.4, postsupplementation: 28.0 ± 2.4 ng/ml, P = 0.029) but not after placebo supplementation (presupplementation: 22.1 ± 2.2, postsupplementation: 23.7 ± 1.5 ng/ml). In conclusion, 4 wk MC supplementation enhanced recovery of endothelium-dependent vasodilatation after IR, in parallel with faster recovery of plasma [ N O − 2 ], suggesting NO dependency. These protective effects seem to be related to increased plasma [Prx2], presumably conferring protection against the respiratory burst during reperfusion. NEW & NOTEWORTHY This is the first study to demonstrate that 4 wk of Montmorency cherry powder supplementation exerted protective effects on endothelium-dependent vasodilation after transient ischemia-reperfusion injury in overweight, physically inactive, nonmedicated, hypertensive middle-aged men. These effects seem to be due to increased nitric oxide availability, as evidenced by higher plasma nitrite concentration and peak arterial diameter during the flow-mediated dilation measurement. This may be a consequence of increased concentration of peroxiredoxin and other antioxidant systems and, hence, reduced reactive oxygen species exposure.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was partially funded by a grant from the Cherry Research Committee, Aboo-Bakkar was supported by a Ph.D. studentship from the Universiti Kuala Lumpur, and Fulford’s salary was provided by National Institute for Health Research.accepted version (12 month embargo

Weight change and sulfonylurea therapy are related to 3 year change in microvascular function in people with type 2 diabetes

Aims/hypothesis: Although cardiovascular disease is the biggest cause of death in people with diabetes, microvascular complications have a significant impact on quality of life and financial burden of the disease. Little is known about the progression of microvascular dysfunction in the early stages of type 2 diabetes before the occurrence of clinically apparent complications. We aimed to explore the determinants of endothelial-dependent and -independent microvascular function progression over a 3 year period, in people with and without both diabetes and few clinical microvascular complications. Methods: Demographics were collected in 154 participants with type 2 diabetes and in a further 99 participants without type 2 diabetes. Skin microvascular endothelium-dependent response to iontophoresis of acetylcholine and endothelium-independent responses to sodium nitroprusside were measured using laser Doppler fluximetry. All assessments were repeated 3 years later. Results: People with type 2 diabetes had impaired endothelial-dependent microvascular response compared with those without (AUC 93.9 [95% CI 88.1, 99.4] vs 111.9 [102.3, 121.4] arbitrary units [AU] × min, p < 0.001, for those with vs without diabetes, respectively). Similarly, endothelial-independent responses were attenuated in those with diabetes (63.2 [59.2, 67.2] vs 75.1 [67.8, 82.4] AU × min, respectively, p = 0.002). Mean microvascular function declined over 3 years in both groups to a similar degree (pinteraction 0.74 for response to acetylcholine and 0.69 for response to sodium nitroprusside). In those with diabetes, use of sulfonylurea was associated with greater decline (p = 0.022 after adjustment for co-prescriptions, change in HbA1c and weight), whereas improving glycaemic control was associated with less decline of endothelial-dependent microvascular function (p = 0.03). Otherwise, the determinants of microvascular decline were similar in those with and without diabetes. The principal determinant of change in microvascular function in the whole population was weight change over 3 years, such that those that lost ≥5% weight had very little decline in either endothelial-dependent or -independent function compared with those that were weight stable, whereas those who gained weight had a greater decline in function (change in endothelial-dependent function was 1.2 [95% CI -13.2, 15.7] AU × min in those who lost weight; -15.8 [-10.5, -21.0] AU × min in those with stable weight; and -37.8 [-19.4, -56.2] AU × min in those with weight gain; ptrend < 0.001). This association of weight change with change in endothelial function was driven by people with diabetes; in people without diabetes, the relationship was nonsignificant. Conclusions/interpretation: Over 3 years, physiological change in weight was the greatest predictor of change in microvascular function.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by the Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006).published version, accepted version (12 month embargo

Reservoir-Excess Pressure Parameters Independently Predict Cardiovascular Events in Individuals With Type 2 Diabetes

The parameters derived from reservoir-excess pressure analysis (RPA) have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM, and whether they would predict cardiovascular events in individuals with T2DM.We studied 306people with T2DM and cardiovascular disease (CVD)(DMCVD:70.4±7.8yrs), 348people with T2DM but without CVD (DM:67.7±8.4yrs) and 178peoplewithout T2DM or CVD (CTRL:67.2±8.9yrs). RPA-derived parameters including reservoir pressure integral (INTPR), peak reservoir pressure (MAXPR), excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant (DRC) were obtained by radial artery tonometry. INTPR was lower in DMCVD and DM than CTRL. MAXPR was lower, and INTXSP was greater in DMCVD than DM and CTRL. SRC was lower in a stepwise manner among groups(DMCVD&lt;DM&lt;CTRL).DRC was greater in DMCVD than CTRL. In the sub group of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9non-cardiovascular causes) and 108cardiovascular events occurred during a 3-yr follow-up period. Logistic regression analysis revealed that INTPR [odds ratio 0.59(95%CI:0.45-0.79)] and DRC [odds ratio 1.60(95%CI:1.25-2.06)] were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors(both p&lt;0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered RPA-derived parameters are associated with T2DM. Furthermore, baseline values of INTPR and DRC independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM

Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes:The SUMMIT VIP Study

Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD

SDSS-III: Massive Spectroscopic Surveys of the Distant Universe, the Milky Way Galaxy, and Extra-Solar Planetary Systems

Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z<0.7 and at z~2.5. SEGUE-2, which is now completed, measured medium-resolution (R=1800) optical spectra of 118,000 stars in a variety of target categories, probing chemical evolution, stellar kinematics and substructure, and the mass profile of the dark matter halo from the solar neighborhood to distances of 100 kpc. APOGEE will obtain high-resolution (R~30,000), high signal-to-noise (S/N>100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)Comment: Revised to version published in The Astronomical Journa

Concentric left ventricular morphology in aerobically trained kayak canoeists

Etude de la structure et de la fonction cardiaque par échocardiographie ultrasonographique chez des canoéistes et kayakistes très entraînés, comparés à des sujets modéremment actifs et sédentaires