**8. Hypertension**

<15 ng/ml were not associated with a risk of cardiovascular diseases, but did relate to all‐cause mortality. There was an association between 25(OH)D levels and incidence of type 2 diabetes, but there was no evidence that vitamin D supplementation improved outcomes in these subjects [51]. Follow‐up of 3135 patients from the Osteoporotic Fractures in Men (MrOS) study and included in the MrOS Sleep Study failed to establish a significant association between

Aside from actual CVD events and mortality, other endpoints using surrogate markers have been studied. In a prospective Austrian cohort of 3258 patients referred for coronary angiog‐ raphy and followed up for 7.7 years, low 25(OH)D levels correlated inversely with markers of inflammation (C‐reactive protein and interleukin‐6), oxidative burden (serum phospholipid and glutathione), and cell adhesion (vascular cell adhesion molecule‐1 and intercellular

A myriad of observational data relates low vitamin D status to an increased prevalence of hypertension. In the Third National Health and Nutrition Examination Survey (NHANES‐III), systolic blood pressure (BP) had a significant inverse correlation to 25(OH)D levels. Mean systolic and diastolic BP were 3.0 and 1.6 mm Hg (*P* < 0.05) lower for participants in the highest quintile compared with the lowest, after adjusting for potential confounders. Age‐adjusted

A prospective analysis among 1211 non‐hypertensive US men found an inverse relationship between vitamin D levels and development of hypertension over a 15‐year follow‐up period. VDR BsmI and FokI polymorphisms were also associated with increased risk of hypertension

Additionally, a more recent study involving 746 patients failed to demonstrate significant relationship between serum vitamin D levels and the severity and extent of coronary artery

Aside from the link between developing hypertension and low vitamin D levels, the Framing‐ ham Offspring Study suggested that low serum vitamin D levels may augment the risk associated with existing hypertension to dramatically raise the risk of future cardiovascular

Many randomized interventional studies have focused on improving surrogate endpoints rather than hard CV outcomes. Those focusing primarily on CV outcomes are sparse. Most of the available studies have varied methodologically in defining baseline vitamin D status, dose

These flaws are seen in studies that evaluate all‐cause mortality and those evaluating CVD

A meta‐analysis of randomized placebo control trials with varying levels of vitamin D using mortality as a secondary endpoint found a significant 8% reduction in mortality in individuals

systolic BP was significantly lower in individuals with vitamin D sufficiency [5].

circulating 25(OH) vitamin D and risk of CVD events [52].

adhesion molecule‐1) [6].

10 A Critical Evaluation of Vitamin D - Clinical Overview

[53].

disease [54].

events [55].

outcomes.

**7. Randomized controlled trials**

used, and definition and ascertainment of outcomes.

Contrary to observational evidence, randomized controlled trials have failed to demonstrate significant changes in blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency after supplementation [60–62].

In a trial involving 283 blacks (median age, 51 years) randomized into a four-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 UI/day of vitamin D, no effect was found on diastolic blood pressure, but there was a slight effect in lowering systolic blood pressure [63].

In VitDISH, a double-blind, placebo-controlled randomized trial, including 159 patients, vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension [64]. A study including patients with resistant hypertension who received vitamin D3 supplementation for 6 months also showed similar results. Effects on left ventricular hypertrophy were also negligible, although the shortterm follow-up may have been a limitation in assessing this outcome variable [65].
