Observational studies have suggested an inverse association between serum 25-hydroxyvitamin D levels and risk of cardiovascular disease (CVD) events.^1-3 Specifically, low vitamin D levels have been linked to an increased risk of myocardial infarction (MI), stroke, CVD mortality, and heart failure in case-control and other prospective epidemiologic studies.^4,5 Additionally, vitamin D receptors are expressed in vascular tissues, including the myocardium and vascular smooth muscle,⁶ directly influencing calcium influx, muscle relaxation, and diastolic function.⁷ Vitamin D also has effects on the renin-angiotensin-aldosterone system and parathyroid hormone and may influence endothelial function and arterial thrombogenesis.^8-10

Context The effect of vitamin D supplementation on the risk of type 2 diabetes mellitus (T2DM) remains controversial because most randomized controlled trials (RCTs) have been small or have reported low doses of vitamin D. Objective To conduct a meta-analysis of RCTs testing vitamin D supplementation in the prevention of T2DM. Data Sources Database search of Pubmed/MEDLINE, EMBASE and the Cochrane Library was performed by two reviewers from inception through September 15, 2019. Study Selection We included RCTs that reported the effect of vitamin D supplementation for at least 1 year on T2DM prevention. Data Extraction Two independent reviewers extracted the data. The risk ratios (RRs) and 95% confidence intervals (CIs) were reported. Primary outcome of the meta-analysis was the incidence of T2DM. Data Synthesis Nine RCTs were included (43,559 participants). The mean age (SD) was 63.5 (6.7) years. The RR for vitamin D compared with placebo was 0.96 (95% CI, 0.90-1.03); P = 0.30. In trials testing moderate to high doses of supplementation (≥1000 IU/d), all conducted among participants with prediabetes, the RR for vitamin D compared with placebo was 0.88 (95% CI, 0.79-0.99). In contrast, the trials testing lower doses, which were conducted in general population samples, showed no risk reduction (RR, 1.02 [95% CI, 0.94-1.10]); P, interaction by dose = 0.04. Conclusion In patients with prediabetes, vitamin D supplementation at moderate to high doses (>1000 IU/d), but not at lower doses, significantly reduced the incidence risk of T2DM, compared with placebo.

To investigate the association between using febuxostat and cardiovascular events. Systematic search of randomized controlled trials was performed using PubMed/MEDLINE, Cochrane review, and EMBASE databases through April 17, 2019. Meta-analysis was performed using random effect model and estimates were reported as risk difference (RD) with 95% CIs. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The main outcomes of interest were cardiovascular mortality and all-cause mortality. A total of 15 randomized controlled trials (16,070 participants) were included. The mean ± SD age was 58.1±11.7 years. At the median follow-up of 6.4 months, use of febuxostat was not associated with statistically significant risk of cardiovascular mortality (RD, 0.12%; 95% CI, -0.25% to 0.49%; I2=48%; low certainty evidence), all-cause mortality (RD, 0.20%; 95% CI, -0.28% to 0.68%; I2 =60%; very low certainty evidence), major adverse cardiovascular events (RD, 0.40%; 95% CI, -0.34% to 1.13%; I2=26%; low certainty evidence), myocardial infarction (RD, -0.06%; 95% CI, -0.29% to 0.17%; I2 =0%; moderate certainty evidence), stroke (RD, 0.10%; 95% CI, -0.15% to 0.35%; I2=0%; moderate certainty evidence), or new-onset hypertension (RD, 1.58%; 95% CI, -0.63% to 3.78%; I2=58%; very low certainty evidence). These findings were consistent in patients with existing cardiovascular disease. This meta-analysis suggested that use of febuxostat was not associated with higher risk of mortality or adverse cardiovascular outcomes in patients with gout and hyperuricemia. The results were limited by low to moderate certainty of evidence.