Effect of Cholecalciferol Supplementation During Winter Months in Patients With Hypertension: A Randomized, Placebo-Controlled Trial.

Am J Hypertens. 2012 Aug 2. doi: 10.1038/ajh.2012.111.
Larsen T, Mose FH, Bech JN, Hansen AB, Pedersen EB.
Department of Medical Research, Holstebro Hospital, Holstebro, Denmark.

Background: Low 25-hydroxy-vitamin D (25(OH)D) levels are inversely related to blood pressure (BP) and have been associated with incident hypertension. In people living at northern latitudes diminished cholecalciferol synthesis in the winter increases the risk of vitamin D deficiency. We wanted to test the hypothesis that daily cholecalciferol supplementation in the winter lowers BP in patients with hypertension.

Methods: We investigated the effect of 75 µg (3,000 IU) cholecalciferol per day in a randomized, placebo-controlled, double-blind study in 130 hypertensive patients residing in Denmark (56º N). Ambulatory BP (24-h BP) and arterial stiffness were measured before and after 20 weeks of treatment, that took place between October and March.

Results: A total of 112 patients (mean age 61 ± 10) with a baseline p-25(OH)D of 23 ± 10 ng/ml completed the study. Compared with placebo, a nonsignificant 3/1 mm Hg (P = 0.26/0.18) reduction was found in 24-h BP. In patients with vitamin D insufficiency (<32 ng/ml) at baseline (n = 92), 24-h BP decreased by 4/3 mm Hg (P = 0.05/0.01). Central BP (CBP) estimated by applanation tonometry and calibrated with a standardized office BP was reduced by 7/2 mm Hg (P = 0.007/0.15) vs. placebo. No differences in carotid-femoral pulse wave velocity (PWV) or central augmentation index (AIx) were found between treatment arms.

Conclusions: Cholecalciferol supplementation, by a dose that effectively increased vitamin D levels, did not reduce 24-h BP, although central systolic BP decreased significantly.

In a post-hoc subgroup analysis of 92 subjects with baseline p-25(OH)D levels <32 ng/ml, significant decreases in 24-h systolic and diastolic BP occurred during cholecalciferol supplementation.

American Journal of Hypertension 2012; doi:10.1038/ajh.2012.111. PMID: 22854639

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Letter to the Editor about the above paper: works with vitamin D deficient patients

Vitamin D and Arterial Hypertension: Treat the Deficiency!

Am J Hypertens (2012); doi: 10.1093/ajh/hps058; First published online: December 27, 2012
Katharina Kienreich1, Andreas Tomaschitz2, Nicolas Verheyen2, Thomas R. Pieber1 and Stefan Pilz1,3
1 Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Austria;
2 Department of Internal Medicine, Division of Cardiology, Medical University of Graz, Austria;
3 Department of Epidemiology and Biostatistics and EMGO Institute of Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Correspondence: Katharina Kienreich ([email protected]).
Received September 28, 2012.; Accepted October 18, 2012.

To the Editor: We read with interest the work by Larsen et al. titled “Effect of Cholecalciferol Supplementation During Winter Months in Patients With Hypertension: A Randomized, Placebo-Controlled Trial.” Larsen et al. have shown in a randomized controlled trial among 130 hypertensive patients that vitamin D supplementation did not significantly reduce 24-hour systolic blood pressure (BP). Interestingly, in a subgroup analysis of patients with 25-hydroxy-vitamin D (25(OH)D) levels below 32ng/ml (n = 92), they observed a significant decrease of both systolic and diastolic blood pressure as well as central BP (CBP) in the treatment compared to the placebo group.1

Observational data and meta-analyses have already shown that low 25(OH)D serum levels are associated with higher cardiovascular risk as well as higher BP.2,3 The reduction of systolic BP as well as systolic CBP in a subgroup of the work by Larsen et al. supports the notion that a potential beneficial effect of vitamin D supplementation on the cardiovascular system is restricted to vitamin D–deficient individuals whereas vitamin D therapy seems to exert no cardiovascular-protective actions in individuals with vitamin D sufficiency. This has to be considered in future interventional studies and it is therefore of concern that the large interventional vitamin D studies, i.e., the VITAL trial by Manson et al., include participants regardless of their vitamin D status at baseline.4 Such study designs may be biased by null findings in vitamin D–sufficient individuals.

Therefore, and in line with the conclusion by Larsen et al., we want to underline that future randomized controlled trials in vitamin D–deficient hypertensive patients are urgently warranted.

© American Journal of Hypertension, Ltd 2012. All rights reserved. For Permissions, please email: journals.permissions at oup.com
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REFERENCES

1.↵ Larsen T, Mose FH, Bech JN, Hansen AB, Pedersen EB. Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial. Am J Hypertens 2012; 25: 1215–1222. Abstract/FREE Full Text
2.↵ Pilz S, Tomaschitz A, März W, Drechsler C, Ritz E, Zittermann A, Cavalier E, Pieber TR, Lappe JM, Grant WB, Holick MF, Dekker JM. Vitamin D, cardiovascular disease and mortality. Clin Endocrinol (Oxf) 2011; 75: 575–584. CrossRefMedline
3.↵ Burgaz A, Orsini N, Larsson SC, Wolk A. Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis. J Hypertens 2011; 29:636–645.
CrossRefMedlineWeb of Science
4.↵ Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, Zaharris E, Macfadyen JG, Danielson E, Lin J, Zhang SM, Buring JE. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials 2012; 33: 159–171. CrossRefMedline

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