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6 Vitamin D: Cardiovascular Function and Disease 131

increased IL-10, with no effect on CRP, in German patients with congestive heart
failure [144]. Calcitriol supplementation decreased blood levels of IL-1 and IL-6 in
hemodialysis patients [171]. Serum levels of 25OHD were inversely associated
with CRP and IL-6 in German coronary angiography patients [138]. In contrast, a
study which gave lower doses of vitamin D (£800 IU/day) did not find any effect
from it on IL-6 or [186].

6.4.4.2 Cardiovascular Function

Evidence has continued to emerge from animal models that vitamin D deficiency
results in cardiac hypertrophy and fibrosis [187], possibly involving activation of the
renin–angiotensin system [188]. MMPs may be involved in this cardiac hypertrophy
since vitamin D supplementation lowers blood MMP-9 and MMP-2 [189]; and raised
plasma levels of MMP-9 have been reported in men who had increased left-ventricu-
lar end-diastolic dimensions and wall thickness from the Framingham study [190].
Evidence has continued to emerge indicating that vitamin D deficiency may influ-
ence arterial function. As mentioned above, vitamin D suppresses MMPs which may
prevent MMP-induced intimal thickening of blood vessels [168], and thereby reduce
arterial stiffness. This possibility is supported by an earlier study of hypertension
patients, which found that serum 25OHD levels, after 3 min of arterial occlusion of
the calf, were associated positively with blood flow (r = 0.72) and negatively with
vascular resistance (r = −0.78) [191]. Serum 25OHD also was correlated positively
with brachial artery distensibility and flow-mediated dilatation, after adjustment for
age and blood pressure, in patients with end-stage renal disease [192]. Carotid artery
intimal medial thickening is associated inversely with serum 25OHD in type 2 dia-
3
betes patients [193]; while vitamin D supplementation increases flow-mediated bra-
chial artery dilatation in type 2 diabetes patients who have 25OHD levels below
50 nmol/L [194]. The above studies provide an explanation for an inverse association
between serum 25OHD and microvascular complications observed in Japanese
patients with type 2 diabetes [195]. The inverse associations between serum 25OHD
and flow-mediated dilatation suggest vitamin D may improve impaired endothelial
function arising from reduced nitric oxide synthesis by the endothelium [196] and
thereby reduce risk of coronary heart disease [197, 198].
These changes in endothelial function may also reduce blood pressure since serum
25OHD levels are inversely associated both with pulse pressure, a marker of vascular
resistance, and with systolic blood pressure [53]. Alternatively, vitamin D may lower
blood pressure by downregulating the renin–angiotensin system [88, 199].

6.4.5 Summary

The past decade has seen a dramatic increase in the number of publications on
vitamin D and CV disease. The critical development has been the publication in