Effect of vitamin D supplementation on blood pressure:a systematic review and meta-analysis incorporating individual patient data

D-PRESSURE Collaboration: et al.[Importance]: 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.Peer reviewe

On Modular Invariance and 3D Gravitational Instantons

We study the modular transformation properties of Euclidean solutions of 3D gravity whose asymptotic geometry has the topology of a torus. These solutions represent saddle points of the grand canonical partition function with an important example being the BTZ black hole, and their properties under modular transformations are inherited from the boundary conformal field theory encoding the asymptotic dynamics. Within the Chern Simons formulation, classical solutions are characterised by specific holonomies describing the wrapping of the gauge field around cycles of the torus. We find that provided these holonomies transform in an appropriate manner, there exists an associated modular invariant grand canonical partition function and that the spectrum of saddle points naturally includes a thermal bath in $AdS_3$ as discussed by Maldacena and Strominger. Indeed, certain modular transformations can naturally be described within classical bulk dynamics as mapping between different foliations with a "time" coordinate along different cycles of the asymptotic torus.Comment: 14 pages, RevTeX, typos corrected, to appear in Phys. Rev.

A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk

Non-invasive estimation of pulmonary hemodynamics from 2D-PC MRI with an arterial mechanics method

Pulmonary Hypertension (PH) is a challenging cardiopulmonary disease diagnosed when the mean pulmonary artery pressure (mPAP) is greater than 20&nbsp;mmHg. Unfortunately, mPAP can only be measured through invasive right heart catheterization (RHC) motivating the development of novel non-invasive estimates. Pulmonary hypertension patients (n&nbsp;=&nbsp;7) and control subjects (n&nbsp;=&nbsp;8) had 2D phase contrast (PC) MRI of the main pulmonary artery during rest and moderate exercise. A novel method utilizing arterial mechanics was used to estimate mPAP and other pulmonary hemodynamics measures from the 2D PC images. mPAP estimated from MRI was greater in the PH group than the control group at both rest (24&nbsp;±&nbsp;10 vs 12&nbsp;±&nbsp;5&nbsp;mmHg) and exercise (40&nbsp;±&nbsp;8 vs 17&nbsp;±&nbsp;9&nbsp;mmHg). Area under the curve (AUC) calculated from receiver operator curve (ROC) analysis showed MRI estimated mPAP had excellent diagnostic ability to diagnose PH patients vs control subjects at rest and exercise (rest AUC&nbsp;=&nbsp;0.91 [0.76 - 1.0], exercise AUC&nbsp;=&nbsp;0.96 [0.88 - 1.0]). These are promising proof-of-concept results that pulmonary hemodynamics could be non-invasively estimated from an MRI and arterial mechanics approach. Future studies to determine the clinical utility of this method are needed

Carotid Artery Longitudinal Displacement, Cardiovascular Disease and Risk Factors: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND:Associations between carotid artery longitudinal displacement, cardiovascular disease risk factors, and events were evaluated in a large, multi-ethnic cohort. MATERIALS AND METHODS:A novel, reproducible protocol was developed for measuring right common carotid artery longitudinal displacement using ultrasound speckle-tracking. Total longitudinal displacement was measured in 389 randomly selected participants from the Multi-Ethnic Study of Atherosclerosis that were free of cardiovascular disease at baseline. Univariate analyses and Pearson Correlations were used to define relationships between longitudinal displacement with traditional cardiovascular risk factors and traditional measures of arterial stiffness. Hazard ratios of longitudinal displacement for cardiovascular disease and coronary heart disease events were compared using Cox proportional hazards models. RESULTS:Participants were a mean (standard deviation) 59.0 (8.7) years old, 48% female, 39% White, 26% Black, 22% Hispanic, and 14% Chinese. They had 19 (4.9%) cardiovascular disease and 14 (3.6%) coronary heart disease events over a mean 9.5 years of follow-up. Less longitudinal displacement was associated with Chinese (β = -0.11, p = 0.02) compared to White race/ethnicity and greater longitudinal displacement was associated with higher carotid intima-media thickness (β = 0.26, p = 0.004). Longitudinal displacement was not associated with other cardiovascular disease risk factors or markers of arterial stiffness. After adjustment for age and sex, and heart rate, Chinese race/ethnicity (β = -0.10, p = 0.04) and carotid intima-media thickness (β = 0.30 p = 0.003) were associated independently with longitudinal displacement. Longitudinal displacement predicted coronary heart disease (Hazard ratio [HR] 3.3, 95% Confidence intervals [CI] 0.96-11.14, p = 0.06) and cardiovascular disease (HR 2.1, 95% CI 0.6-7.3, p = 0.23) events. CONCLUSIONS:Less longitudinal displacement is associated with Chinese ethnicity and greater carotid artery longitudinal displacement is associated with thicker intima-media thickness. Longitudinal displacement may predict adverse coronary heart disease and cardiovascular disease events