Louise A Beveridge1, Allan D Struthers1, Faisel Khan1, Rolf Jorde2, Robert Scragg3, Helen M Macdonald4, Jessica A Alvarez5, Rebecca S Boxer6, Andrea Dalbeni7, Adam D Gepner8, Nicole M Isbel9, Thomas Larsen10, Jitender Nagpal11, William G Petchey12, Hans Stricker13, Franziska Strobel14, Vin Tangpricha5, Laura Toxqui15, M Pilar Vaquero15, Louise Wamberg16, Armin Zittermann17, Miles D Witham1. 1. Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland. 2. Tromsø Endocrine Research Group, Institute of Clinical Medicine, UiT (Universitetet i Tromsø), The Arctic University of Norway, Tromsø, Norway. 3. School of Population Health, University of Auckland, Auckland, New Zealand. 4. School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland. 5. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. 6. Division of Geriatric Medicine, University of Colorado School of Medicine, Aurora. 7. Department of Medicine, University of Verona, Verona, Italy. 8. Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison. 9. Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia. 10. Department of Medical Research, Holstebro Hospital, Holstebro, Denmark. 11. Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi, India. 12. Department of Nephrology, Cambridge University Hospitals NHS (National Health Service) Foundation Trust, Cambridge, England. 13. Angiology Unit, Ospedale La Carità, Locarno, Switzerland. 14. Department of Internal Medicine, Asklepios-Paulinenklinik, Wiesbaden, Germany. 15. Department of Metabolism and Nutrition, Institute of Food Science, Technology, and Nutrition, Spanish National Research Council, Madrid, Spain. 16. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 17. Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bochum, Germany.
Abstract
IMPORTANCE: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE: To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES: Difference in SBP and DBP measured in an office setting. RESULTS: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.
IMPORTANCE: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE: To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES: Difference in SBP and DBP measured in an office setting. RESULTS: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.
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