Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis

John A Ford; Graeme S MacLennan; Alison Avenell; Mark Bolland; Andrew Grey; Miles Witham; RECORD Trial Group

doi:10.3945/ajcn.113.082602

Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis

John A Ford, Graeme S MacLennan, Alison Avenell, Mark Bolland, Andrew Grey, Miles Witham, RECORD Trial Group

The University of Auckland

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Abstract

BACKGROUND: Low 25-hydroxyvitamin D status has been associated with increased cardiovascular events in epidemiologic studies.

OBJECTIVE: We assessed whether vitamin D supplementation reduces cardiac failure, myocardial infarction (MI), and stroke through an analysis of the Randomised Evaluation of Calcium Or vitamin D (RECORD) randomized controlled trial (RCT), a systematic review, and a meta-analysis.

DESIGN: Two analyses were undertaken. The first analysis was a trial analysis. The RECORD was a factorial RCT that compared vitamin D3 (800 IU/d), calcium (1000 mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events were collected throughout the trial and 3-y posttrial follow-up. Data were analyzed by using Cox regression. The second analysis was a systematic review. MEDLINE, EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched for RCTs that evaluated vitamin D from 1980 to 2013. RCTs with ≥1 y of follow-up and participants mean or median age ≥60 y were included. Meta-analyses were based on a Bayesian fixed-effects model by using a complementary log-log link function to account for varying lengths of follow-up.

RESULTS: In the trial analysis, we showed that, for the 5292 participants in the RECORD trial, HRs (95% CIs) for vitamin D compared with no vitamin D for cardiac failure, MI, and stroke were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8, 1.32), respectively. Twenty-one studies met the inclusion criteria for the systematic review (n = 13,033). Estimated HRs (credible intervals) for vitamin D compared with the placebo or control for on-study events for cardiac failure, MI, and stroke were 0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29), respectively.

CONCLUSION: Vitamin D supplementation might protect against cardiac failure in older people but does not appear to protect against MI or stroke.

Original language	English
Pages (from-to)	746-755
Number of pages	10
Journal	The American Journal of Clinical Nutrition
Volume	100
Issue number	3
Early online date	23 Jul 2014
DOIs	https://doi.org/10.3945/ajcn.113.082602
Publication status	Published - Sept 2014

Bibliographical note

© 2014 American Society for Nutrition.

We thank the patients who took part in the RECORD study without whose help this study would not have been possible. We also thank the following study authors for supplying additional data and clarifications: Cyrus Cooper, Itsuo Goari, Hazel Inskip, Wim Janssens, Glenn Liu, Per Magnusson, JoAnn Manson, Toshio Matsumoto, Susan Ott, Kerrie Sanders, Klaus Witte, Weino Xia, and Kun Zhu. We thank Daryll Archibald for checking data extraction in trials that involved AA. The RECORD Trial Group included the RECORD Trial Management Group [the Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom (AM Grant, A Avenell, MK Campbell, AM McDonald, GS MacLennan, an dGC McPherson); the University of Southampton, Southampton, United Kingdom (FH Anderson); the Medical Research Council Epidemiology Resource Centre, University of Southampton, Southampton, United Kingdom (C Cooper); the Newcastle University, Newcastle, United Kingdom (RM Francis); the Glasgow Caledonian University, Glasgow, United Kingdom (C Donaldson); The Hull York Medical School, Hull, United Kingdom (WJ Gillespie); the Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (CM Robinson); the Department of
Health Sciences, York, United Kingdom (DJ Torgerson); and the Queens Medical Centre, Nottingham, United Kingdom (WA Wallace). Additional members of the RECORD Trial Group are listed in the RECORD trial. The authors’ responsibilities were as follows—AA, GSM, and MW: conceived the idea; JAF, AA, and GSM: undertook the hands-on research including the data collection and statistical analysis; JAF: wrote the first draft of the manuscript; AA: had primary responsibility for the final content of the manuscript; and all authors: made major, significant contributions to redrafting of the manuscript and contributed to the research design. AA and GSM took part in two of the trials in the systematic review. MW took part in one of the trials in the systematic review. JAF, MB, and AG had no other conflicts of interest. Details of conflicts of interest for other members of the RECORD Trial Group are provided in reference 13. Shire Pharmaceuticals and Nycomed were given the opportunity to comment on the penultimate version of the RECORD main trial report in The Lancet.

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10.3945/ajcn.113.082602Licence: Unspecified

Ford 2014
This is a pre-copyedited, author-produced version of an article accepted for publication in American Journal of Clinical Nutrition following peer review. The version of record [insert complete citation information here] is available online at: https://academic.oup.com/ajcn/article/100/3/746/4576427
Accepted author manuscript, 655 KBLicence: Unspecified

Alison Avenell
- School of Medicine, Medical Sciences & Nutrition, Health Services Research Unit (HSRU) - Clinical Chair in Health Services Research
- Institute of Applied Health Sciences
Person: Clinical Academic
Graeme MacLennan
Person: Academic, Academic Related - Research

Cite this

@article{6e69fb2a76c747a889970226d1407c8d,

title = "Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis",

abstract = "BACKGROUND: Low 25-hydroxyvitamin D status has been associated with increased cardiovascular events in epidemiologic studies.OBJECTIVE: We assessed whether vitamin D supplementation reduces cardiac failure, myocardial infarction (MI), and stroke through an analysis of the Randomised Evaluation of Calcium Or vitamin D (RECORD) randomized controlled trial (RCT), a systematic review, and a meta-analysis.DESIGN: Two analyses were undertaken. The first analysis was a trial analysis. The RECORD was a factorial RCT that compared vitamin D3 (800 IU/d), calcium (1000 mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events were collected throughout the trial and 3-y posttrial follow-up. Data were analyzed by using Cox regression. The second analysis was a systematic review. MEDLINE, EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched for RCTs that evaluated vitamin D from 1980 to 2013. RCTs with ≥1 y of follow-up and participants mean or median age ≥60 y were included. Meta-analyses were based on a Bayesian fixed-effects model by using a complementary log-log link function to account for varying lengths of follow-up.RESULTS: In the trial analysis, we showed that, for the 5292 participants in the RECORD trial, HRs (95% CIs) for vitamin D compared with no vitamin D for cardiac failure, MI, and stroke were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8, 1.32), respectively. Twenty-one studies met the inclusion criteria for the systematic review (n = 13,033). Estimated HRs (credible intervals) for vitamin D compared with the placebo or control for on-study events for cardiac failure, MI, and stroke were 0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29), respectively.CONCLUSION: Vitamin D supplementation might protect against cardiac failure in older people but does not appear to protect against MI or stroke.",

author = "Ford, {John A} and MacLennan, {Graeme S} and Alison Avenell and Mark Bolland and Andrew Grey and Miles Witham and {RECORD Trial Group}",

note = "{\textcopyright} 2014 American Society for Nutrition. We thank the patients who took part in the RECORD study without whose help this study would not have been possible. We also thank the following study authors for supplying additional data and clarifications: Cyrus Cooper, Itsuo Goari, Hazel Inskip, Wim Janssens, Glenn Liu, Per Magnusson, JoAnn Manson, Toshio Matsumoto, Susan Ott, Kerrie Sanders, Klaus Witte, Weino Xia, and Kun Zhu. We thank Daryll Archibald for checking data extraction in trials that involved AA. The RECORD Trial Group included the RECORD Trial Management Group [the Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom (AM Grant, A Avenell, MK Campbell, AM McDonald, GS MacLennan, an dGC McPherson); the University of Southampton, Southampton, United Kingdom (FH Anderson); the Medical Research Council Epidemiology Resource Centre, University of Southampton, Southampton, United Kingdom (C Cooper); the Newcastle University, Newcastle, United Kingdom (RM Francis); the Glasgow Caledonian University, Glasgow, United Kingdom (C Donaldson); The Hull York Medical School, Hull, United Kingdom (WJ Gillespie); the Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (CM Robinson); the Department of Health Sciences, York, United Kingdom (DJ Torgerson); and the Queens Medical Centre, Nottingham, United Kingdom (WA Wallace). Additional members of the RECORD Trial Group are listed in the RECORD trial. The authors{\textquoteright} responsibilities were as follows—AA, GSM, and MW: conceived the idea; JAF, AA, and GSM: undertook the hands-on research including the data collection and statistical analysis; JAF: wrote the first draft of the manuscript; AA: had primary responsibility for the final content of the manuscript; and all authors: made major, significant contributions to redrafting of the manuscript and contributed to the research design. AA and GSM took part in two of the trials in the systematic review. MW took part in one of the trials in the systematic review. JAF, MB, and AG had no other conflicts of interest. Details of conflicts of interest for other members of the RECORD Trial Group are provided in reference 13. Shire Pharmaceuticals and Nycomed were given the opportunity to comment on the penultimate version of the RECORD main trial report in The Lancet.",

year = "2014",

month = sep,

doi = "10.3945/ajcn.113.082602",

language = "English",

volume = "100",

pages = "746--755",

journal = "The American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "American Society for Nutrition",

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TY - JOUR

T1 - Cardiovascular disease and vitamin D supplementation

T2 - trial analysis, systematic review, and meta-analysis

AU - Ford, John A

AU - MacLennan, Graeme S

AU - Avenell, Alison

AU - Bolland, Mark

AU - Grey, Andrew

AU - Witham, Miles

AU - RECORD Trial Group

N1 - © 2014 American Society for Nutrition. We thank the patients who took part in the RECORD study without whose help this study would not have been possible. We also thank the following study authors for supplying additional data and clarifications: Cyrus Cooper, Itsuo Goari, Hazel Inskip, Wim Janssens, Glenn Liu, Per Magnusson, JoAnn Manson, Toshio Matsumoto, Susan Ott, Kerrie Sanders, Klaus Witte, Weino Xia, and Kun Zhu. We thank Daryll Archibald for checking data extraction in trials that involved AA. The RECORD Trial Group included the RECORD Trial Management Group [the Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom (AM Grant, A Avenell, MK Campbell, AM McDonald, GS MacLennan, an dGC McPherson); the University of Southampton, Southampton, United Kingdom (FH Anderson); the Medical Research Council Epidemiology Resource Centre, University of Southampton, Southampton, United Kingdom (C Cooper); the Newcastle University, Newcastle, United Kingdom (RM Francis); the Glasgow Caledonian University, Glasgow, United Kingdom (C Donaldson); The Hull York Medical School, Hull, United Kingdom (WJ Gillespie); the Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (CM Robinson); the Department of Health Sciences, York, United Kingdom (DJ Torgerson); and the Queens Medical Centre, Nottingham, United Kingdom (WA Wallace). Additional members of the RECORD Trial Group are listed in the RECORD trial. The authors’ responsibilities were as follows—AA, GSM, and MW: conceived the idea; JAF, AA, and GSM: undertook the hands-on research including the data collection and statistical analysis; JAF: wrote the first draft of the manuscript; AA: had primary responsibility for the final content of the manuscript; and all authors: made major, significant contributions to redrafting of the manuscript and contributed to the research design. AA and GSM took part in two of the trials in the systematic review. MW took part in one of the trials in the systematic review. JAF, MB, and AG had no other conflicts of interest. Details of conflicts of interest for other members of the RECORD Trial Group are provided in reference 13. Shire Pharmaceuticals and Nycomed were given the opportunity to comment on the penultimate version of the RECORD main trial report in The Lancet.

PY - 2014/9

Y1 - 2014/9

N2 - BACKGROUND: Low 25-hydroxyvitamin D status has been associated with increased cardiovascular events in epidemiologic studies.OBJECTIVE: We assessed whether vitamin D supplementation reduces cardiac failure, myocardial infarction (MI), and stroke through an analysis of the Randomised Evaluation of Calcium Or vitamin D (RECORD) randomized controlled trial (RCT), a systematic review, and a meta-analysis.DESIGN: Two analyses were undertaken. The first analysis was a trial analysis. The RECORD was a factorial RCT that compared vitamin D3 (800 IU/d), calcium (1000 mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events were collected throughout the trial and 3-y posttrial follow-up. Data were analyzed by using Cox regression. The second analysis was a systematic review. MEDLINE, EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched for RCTs that evaluated vitamin D from 1980 to 2013. RCTs with ≥1 y of follow-up and participants mean or median age ≥60 y were included. Meta-analyses were based on a Bayesian fixed-effects model by using a complementary log-log link function to account for varying lengths of follow-up.RESULTS: In the trial analysis, we showed that, for the 5292 participants in the RECORD trial, HRs (95% CIs) for vitamin D compared with no vitamin D for cardiac failure, MI, and stroke were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8, 1.32), respectively. Twenty-one studies met the inclusion criteria for the systematic review (n = 13,033). Estimated HRs (credible intervals) for vitamin D compared with the placebo or control for on-study events for cardiac failure, MI, and stroke were 0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29), respectively.CONCLUSION: Vitamin D supplementation might protect against cardiac failure in older people but does not appear to protect against MI or stroke.

AB - BACKGROUND: Low 25-hydroxyvitamin D status has been associated with increased cardiovascular events in epidemiologic studies.OBJECTIVE: We assessed whether vitamin D supplementation reduces cardiac failure, myocardial infarction (MI), and stroke through an analysis of the Randomised Evaluation of Calcium Or vitamin D (RECORD) randomized controlled trial (RCT), a systematic review, and a meta-analysis.DESIGN: Two analyses were undertaken. The first analysis was a trial analysis. The RECORD was a factorial RCT that compared vitamin D3 (800 IU/d), calcium (1000 mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events were collected throughout the trial and 3-y posttrial follow-up. Data were analyzed by using Cox regression. The second analysis was a systematic review. MEDLINE, EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched for RCTs that evaluated vitamin D from 1980 to 2013. RCTs with ≥1 y of follow-up and participants mean or median age ≥60 y were included. Meta-analyses were based on a Bayesian fixed-effects model by using a complementary log-log link function to account for varying lengths of follow-up.RESULTS: In the trial analysis, we showed that, for the 5292 participants in the RECORD trial, HRs (95% CIs) for vitamin D compared with no vitamin D for cardiac failure, MI, and stroke were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8, 1.32), respectively. Twenty-one studies met the inclusion criteria for the systematic review (n = 13,033). Estimated HRs (credible intervals) for vitamin D compared with the placebo or control for on-study events for cardiac failure, MI, and stroke were 0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29), respectively.CONCLUSION: Vitamin D supplementation might protect against cardiac failure in older people but does not appear to protect against MI or stroke.

U2 - 10.3945/ajcn.113.082602

DO - 10.3945/ajcn.113.082602

M3 - Article

C2 - 25057156

SN - 0002-9165

VL - 100

SP - 746

EP - 755

JO - The American Journal of Clinical Nutrition

JF - The American Journal of Clinical Nutrition

IS - 3

ER -

Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis

Abstract

Bibliographical note

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Alison Avenell

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