Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure:
An open-label, blinded end point, randomized prospective trial (VitD-CHF trial)
Nicolas F. Schroten, MD; Willem P.T. Ruifrok, MD, PhD; Lennaert Kleijn, MD; Martin M. Dokter, BASc
Herman H. Silljé, PhD; Hiddo J. Lambers Heerspink, PhD; Stephan J.L. Bakker, MD, PhD
Ido P. Kema, PhD; Wiek H. van Gilst, PhD; Dirk J. van Veldhuisen, MD, PhD
Hans L. Hillege, MD, PhD; Rudolf A. de Boer, MD, PhD r.a.de.boer at umcg.nl
Received 30 December 2012; accepted 2 May 2013. published online 27 June 2013.
Background: Many chronic heart failure (CHF) patients have low vitamin D (VitD) and high plasma renin activity (PRA), which are both associated with poor prognosis.
Vitamin D may inhibit renin transcription and lower PRA.
We investigated whether vitamin D3 (VitD3) supplementation lowers PRA in CHF patients.
Methods and Results: We conducted a single-center, open-label, blinded end point trial in 101 stable CHF patients with reduced left ventricular ejection fraction. Patients were randomized to 6 weeks of 2,000 IU oral VitD3 daily or control. At baseline, mean age was 64 ± 10 years, 93% male, left ventricular ejection fraction 35% ± 8%, and 56% had VitD deficiency. The geometric mean (95% CI) of 25-hydroxyvitamin D3 increased from 48 nmol/L (43-54) at baseline to 80 nmol/L (75-87) after 6 weeks in the VitD3 treatment group and decreased from 47 nmol/L (42-53) to 44 nmol/L (39-49) in the control group (P < .001).
The primary outcome PRA decreased
- from 6.5 ng/mL per hour (3.8-11.2)
- to 5.2 ng/mL per hour (2.9-9.5)
in the VitD3 treatment group and increased from 4.9 ng/mL per hour (2.9-8.5) to 7.3 ng/mL per hour (4.5-11.8) in the control group (P = .002). This was paralleled by a larger decrease in plasma renin concentration in the VitD3 treatment group compared to control (P = .020).
No significant changes were observed in secondary outcome parameters, including N-terminal pro–B-type natriuretic peptide natriuretic peptide and fibrosis markers.
Conclusions: Most CHF patients had VitD deficiency and high PRA levels. Six weeks of supplementation with 2,000 IU VitD3 increased 25-hydroxyvitamin D3 levels and decreased PRA and plasma renin concentration.
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