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.

E-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD. This study sought to determine the early vascular impact of switching from TC to EC in chronic smokers. The authors conducted a prospective, randomized control trial with a parallel nonrandomized preference cohort and blinded endpoint of smokers ≥18 years of age who had smoked ≥15 cigarettes/day for ≥2 years and were free from established cardiovascular disease. Participants were randomized to EC with nicotine or EC without nicotine for 1 month. Those unwilling to quit continued with TC in a parallel preference arm. A propensity score analysis was done to adjust for differences between the randomized and preference arms. Vascular function was assessed by FMD and pulse wave velocity. Compliance with EC was measured by carbon monoxide levels. Within 1 month of switching from TC to EC, there was a significant improvement in endothelial function (linear trend β = 0.73%; 95% confidence interval [CI]: 0.41 to 1.05; p < 0.0001; TC vs. EC combined: 1.49%; 95% CI: 0.93 to 2.04; p < 0.0001) and vascular stiffness (-0.529 m/s; 95% CI: -0.946 to -0.112; p = 0.014). Females benefited from switching more than males did in every between-group comparison. Those who complied best with EC switch demonstrated the largest improvement. There was no difference in vascular effects between EC with and without nicotine within the study timeframe. TC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use [VESUVIUS]; NCT02878421; ISRCTN59133298).

OBJECTIVE: Vascular disease in type 1 diabetes is a complex and multifactorial process, which probably begins in childhood in association with the onset of diabetes. To determine the possible factors involved, we measured microvascular responses to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators in 56 patients with type 1 diabetes (aged 9-22 years) and 22 control subjects. RESEARCH DESIGN AND METHODS: Skin perfusion was measured at the dorsum of the foot using laser Doppler flowmetry during low-current iontophoresis of acetylcholine and sodium nitroprusside. Maximum vasodilator function was measured during local 44 degrees C skin heating. RESULTS: Vascular responses were significantly reduced in patients with type 1 diabetes compared with responses in control subjects: acetylcholine (P<0.01, analysis of variance [ANOVA]), sodium nitroprusside (P<0.01, ANOVA), and local heating (P<0.02. Mann-Whitney U test). Endothelium-dependent responses were related to duration of diabetes (r = -0.38, P<0.01) and to glycemic control (r = 0.37, P<0.01). Significant correlations were found in the patient group between responses to acetylcholine and sodium nitroprusside (r = 0.28, P<0.05) but not to heating, suggesting that a common factor (e.g., nitric oxide activity) may be responsible for the abnormal vascular responses to these chemicals. CONCLUSIONS: Early changes in microvascular function are present in young patients with type 1 diabetes, long before the initial clinical presentation. These abnormalities may be related to complex interactions between structural abnormalities and functional changes in the endothelium, smooth muscle, and nitric oxide activity.

OBJECTIVE: To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI. RESEARCH DESIGN AND METHODS: We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI. Key secondary end points included other measures of LV remodeling and clinical and biochemical parameters. RESULTS: In our cohort, dapagliflozin had no effect on LVESV or any other parameter of LV remodeling. However, it reduced diastolic blood pressure and loop diuretic requirements while increasing hemoglobin, hematocrit, and ketone bodies. There was a trend toward lower weight. CONCLUSIONS: We were unable to determine with certainty whether dapagliflozin in patients with T2DM and HF had any effect on LV remodeling. Whether the benefits of dapagliflozin in HF are due to remodeling or other mechanisms remains unknown.

Aim: We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes. Methods and results: We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study. Conclusion: Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.