A growing body of data suggests that low vitamin D levels may adversely affect cardiovascular
health. For many cardiovascular events, seasonal variability with peak incidence in the
winter months is proven. This may be attributable at least in part to declining body stores
of vitamin D beginning with September. Recently, there have been several case reports about
severe cardiomyopathy caused by vitamin D deficiency, especially in dark-skinned children who
had low vitamin D levels. The heart is an important target organ for vitamin D, both on a
genomic and nongenomic level. Myocytes express the vitamin D receptor and several models of
hypertension in animal studies have shown that vitamin D treatment is able to prevent cardiac
hypertrophy [9-10]. Vitamin D seems to inhibit activation of the cardiac renin-angiotensin
system as well as the expression of genes involved in the development of myocardial
hypertrophy. There is accumulating evidence that vitamin D deficiency may be an important
factor in the development of congestive heart failure and sudden cardiac death.
In chronic hemodialysis patients, vitamin D supplementation has been associated with
reduction of cardiac hypertrophy and a reduction of QT dispersion, the latter being
considered a major risk factor for sudden cardiac death. A small study from 1984 showed an
improvement in left ventricular function after treatment with cholecalciferol in hemodialysis
patients. A recent study from our group has reported a negative correlation of 25(OH)D levels
with NT-pro-BNP levels, New York Heart Association functional classes and impaired left
ventricular function. Furthermore, hazard ratios for death attributable to heart failure and
sudden cardiac death were 2.84 and 5.05, respectively, when patients with 25(OH)D <25ng/ml
were compared with those having serum levels of 25(OH)D >75 ng/ml [11]. The anti-inflammatory
properties of vitamin D also appear to play a role in congestive heart failure, as studied in
a recent interventional trial. In animal models, vitamin D deficiency was proven to be
associated with developing myocardial hypertrophy and fibrosis with aberrant cardiac
contractility and relaxation. Moreover, vitamin D deficiency can raise parathyroid hormone
secretion, which in turn may increase insulin resistance and be associated with the
development of diabetes, hypertension and inflammation. In summary, vitamin D seems to exert
a multitude of different effects all working in concert to protect the vascular and cardiac
system by influencing various hierarchical levels of biologic response.
Recently, a randomized controlled trial in a subgroup of patients with heart failure(n=105, ≥
70 years) was able to demonstrate a significant decrease in BNP levels at 10 and 20 weeks,
while the primary endpoint "functional capacity" and quality of life did not differ between
intervention and placebo group.
Because in this latter trial, even the intervention group did not reach normal vitamin D
levels, we will use a higher dose of vitamin D given in shorter intervals.