**9. Endothelial dysfunction**

Vitamin D deficiency has been associated with endothelial dysfunction. A study involving 23 asymptomatic subjects demonstrated impaired brachial artery flow-mediated dilatation (FMD) in subjects with significant vitamin D deficiency. Improvement was seen with vitamin D repletion [58].

In contrast, there was no improvement in endothelial-dependent vasodilation with active treatment (ergocalciferol 50,000 IU/week) versus placebo in an 8 week trial in non-hypertensive, overweight, vitamin D deficient individuals [59].

**219**

*Vitamin D and Cardiovascular Disease: The Final Chapter?*

Similarly, a prospective placebo-controlled pilot study evaluated the effects of vitamin D repletion on endothelial function and inflammation in subjects with both vitamin D deficiency and coronary artery disease. The study was conducted over a 12-week period in 90 subjects. No significant differences between the groups were found in reactive hyperemia index (using RH-PAT), blood pressure, and levels of hs-CRP, IL-6, IL-12, interferon gamma (INF-gamma), and CXCL-10 [60].

Additionally, in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) (N = 852), vitamin D levels were positively related to endothelial-independent vasodilation in women only. There were no significant relationships between vitamin D levels and indices of endothelium-dependent vasodilatation in both men

Lastly, a recent systematic review including 31 trials and individual-level metaanalysis (2,571 patients) assessed the relationship between vitamin D and various markers of vascular function. The analysis found that most vascular markers studied were not significantly effected by vitamin D supplementation [62].

The impact of vitamin D supplementation on patients with heart failure has not

The RECORD trial (Randomized Evaluation of Calcium Or vitamin D) was a trial designed for the secondary prevention of fractures in 5292 participants aged ≥70 years (conducted between 1999 and 2002). Subjects received oral vitamin D3 (800 IU/d) plus calcium (1,000 mg calcium carbonate/d), vitamin D3 alone, calcium alone, or a placebo. An analysis of unpublished data from the trial, suggested that vitamin D supplementation may decrease heart failure events in the elderly. The trial had pre-specified CV endpoints of time to first cardiac failure, time to first MI, time to first stroke, and time to first composite outcome of cardiac failure, MI, or stroke. The trial, though, was not designed as a CV outcomes trial, and outcomes were not subject to an adjudication committee nor verified against medical records. Furthermore, significance for heart failure event reduction was reached only when

Several small placebo-controlled studies have been conducted to analyze the effects of vitamin D supplementation on differing endpoints in patients with heart

adults with vitamin D deficiency (25-vitamin D < 20 ng/mL) and systolic heart failure, subjects were given 100,000 IU of oral vitamin D2 or placebo at baseline and 10 weeks. Functional outcomes, quality of life and biomarkers (B-type natriuretic peptide (BNP) and tumor necrosis factor (TNF alpha)) were measured at baseline, 10 and 20 weeks. BNP was significantly reduced in the active treatment group versus placebo, but TNF alpha was not. Despite reduced BNP levels, physical function, as measured by the 6-minute walk test and the timed get up and go test, did not improve. There was also no change in the Functional Limitations Profile measure in the active versus placebo group. A small, but significant worsening in quality of life with active treatment was noted, despite a non-significant increase in

In a small randomized, double-blind, placebo-controlled trial (N = 105) in older

Schleithoff et al. examined cytokine profiles with vitamin D3 supplementation in

younger patients with heart failure. A dose of 2,000 IU per day reduced the proinflammatory marker TNF-alpha levels and increased the anti-inflammatory cytokine interleukin-10 levels, but no significant effects on BNP levels were seen [20].

*DOI: http://dx.doi.org/10.5772/intechopen.90106*

been the focus of large randomized trials.

off-trial data were used [63].

failure. Results have been conflicting.

activity level, suggesting a chance finding [64].

and women [61].

**10. Heart failure**

*Vitamin D and Cardiovascular Disease: The Final Chapter? DOI: http://dx.doi.org/10.5772/intechopen.90106*

Similarly, a prospective placebo-controlled pilot study evaluated the effects of vitamin D repletion on endothelial function and inflammation in subjects with both vitamin D deficiency and coronary artery disease. The study was conducted over a 12-week period in 90 subjects. No significant differences between the groups were found in reactive hyperemia index (using RH-PAT), blood pressure, and levels of hs-CRP, IL-6, IL-12, interferon gamma (INF-gamma), and CXCL-10 [60].

Additionally, in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) (N = 852), vitamin D levels were positively related to endothelial-independent vasodilation in women only. There were no significant relationships between vitamin D levels and indices of endothelium-dependent vasodilatation in both men and women [61].

Lastly, a recent systematic review including 31 trials and individual-level metaanalysis (2,571 patients) assessed the relationship between vitamin D and various markers of vascular function. The analysis found that most vascular markers studied were not significantly effected by vitamin D supplementation [62].
