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Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis.
J Am Heart Assoc 2018; 7(11)JA

Abstract

BACKGROUND

Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear.

METHODS AND RESULTS

We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level meta-analysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, -0.23 to 0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, -0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues.

CONCLUSIONS

Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.

Authors+Show Affiliations

Department of Medicine for the Elderly, NHS Tayside, Dundee, United Kingdom.School of Medicine, University of Dundee, United Kingdom.School of Medicine, University of Dundee, United Kingdom.Clinical Trial Service Unit and MRC Population Health Research Unit, University of Oxford, United Kingdom.Department of Experimental Medicine, Sapienza University of Rome, Italy.Department of Nephrology, Herlev and Gentofte Hospital, Copenhagen, Denmark.Department of Experimental Medicine, Sapienza University of Rome, Italy.Clinical Trial Service Unit and MRC Population Health Research Unit, University of Oxford, United Kingdom.Tan Tock Seng Hospital, Lee Kong Chian School of Medicine Nanyang Technological University, Singapore.Department of Nephrology, Barts Health NHS Trust, London, United Kingdom.University of Wisconsin School of Medicine and Public Health and William S. Middleton Veterans Affairs Hospital, Madison, WI.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.Department of Population Health Science, Georgia Prevention Institute Augusta University, Augusta, Georgia, USA.Blizard Institute, Queen Mary University of London, United Kingdom.University Clinic in Nephrology and Hypertension, Department of Medical Research, Regional Hospital West Jutland and Aarhus University, Aarhus, Denmark.Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.Department of Internal Medicine, Zealand University Hospital, Roskilde, Denmark.University Clinic in Nephrology and Hypertension, Department of Medical Research, Regional Hospital West Jutland and Aarhus University, Aarhus, Denmark.Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Austria.Department of Nephrology, Odense University Hospital and Institute of Clinical Research University of Southern Denmark, Odense, Denmark.Department of Endocrinology, Wolfson Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Division of Cardiology, Jacobi Medical Center, NY.Department of Angiology, Ospedale La Carita, Locarno, Switzerland.CNR-IFC Clinical Epidemiology and Pathphysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy.School of Medicine, University of Dundee, United Kingdom m.witham@dundee.ac.uk.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

29848497

Citation

Beveridge, Louise A., et al. "Effect of Vitamin D Supplementation On Markers of Vascular Function: a Systematic Review and Individual Participant Meta-Analysis." Journal of the American Heart Association, vol. 7, no. 11, 2018.
Beveridge LA, Khan F, Struthers AD, et al. Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis. J Am Heart Assoc. 2018;7(11).
Beveridge, L. A., Khan, F., Struthers, A. D., Armitage, J., Barchetta, I., Bressendorff, I., ... Witham, M. D. (2018). Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis. Journal of the American Heart Association, 7(11), doi:10.1161/JAHA.117.008273.
Beveridge LA, et al. Effect of Vitamin D Supplementation On Markers of Vascular Function: a Systematic Review and Individual Participant Meta-Analysis. J Am Heart Assoc. 2018 05 30;7(11) PubMed PMID: 29848497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis. AU - Beveridge,Louise A, AU - Khan,Faisel, AU - Struthers,Allan D, AU - Armitage,Jane, AU - Barchetta,Ilaria, AU - Bressendorff,Iain, AU - Cavallo,Maria Gisella, AU - Clarke,Robert, AU - Dalan,Rinkoo, AU - Dreyer,Gavin, AU - Gepner,Adam D, AU - Forouhi,Nita G, AU - Harris,Ryan A, AU - Hitman,Graham A, AU - Larsen,Thomas, AU - Khadgawat,Rajesh, AU - Marckmann,Peter, AU - Mose,Frank H, AU - Pilz,Stefan, AU - Scholze,Alexandra, AU - Shargorodsky,Marina, AU - Sokol,Seth I, AU - Stricker,Hans, AU - Zoccali,Carmine, AU - Witham,Miles D, Y1 - 2018/05/30/ PY - 2018/6/1/entrez PY - 2018/6/1/pubmed PY - 2019/11/8/medline KW - endothelial function KW - paricalcitol KW - systematic review KW - vascular function KW - vitamin D JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 7 IS - 11 N2 - BACKGROUND: Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. METHODS AND RESULTS: We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level meta-analysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, -0.23 to 0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, -0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. CONCLUSIONS: Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/29848497/Effect_of_Vitamin_D_Supplementation_on_Markers_of_Vascular_Function:_A_Systematic_Review_and_Individual_Participant_Meta_Analysis_ L2 - http://www.ahajournals.org/doi/full/10.1161/JAHA.117.008273?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -