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Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis.
BMJ 2011; 342:d2040BMJ

Abstract

OBJECTIVES

To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women's Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk.

DESIGN

Reanalysis of WHI CaD Study limited access dataset and incorporation in meta-analysis with eight other studies. Data source WHI CaD Study, a seven year, randomised, placebo controlled trial of calcium and vitamin D (1g calcium and 400 IU vitamin D daily) in 36,282 community dwelling postmenopausal women. Main outcome measures Incidence of four cardiovascular events and their combinations (myocardial infarction, coronary revascularisation, death from coronary heart disease, and stroke) assessed with patient-level data and trial-level data.

RESULTS

In the WHI CaD Study there was an interaction between personal use of calcium supplements and allocated calcium and vitamin D for cardiovascular events. In the 16,718 women (46%) who were not taking personal calcium supplements at randomisation the hazard ratios for cardiovascular events with calcium and vitamin D ranged from 1.13 to 1.22 (P = 0.05 for clinical myocardial infarction or stroke, P = 0.04 for clinical myocardial infarction or revascularisation), whereas in the women taking personal calcium supplements cardiovascular risk did not alter with allocation to calcium and vitamin D. In meta-analyses of three placebo controlled trials, calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.21 (95% confidence interval 1.01 to 1.44), P = 0.04), stroke (1.20 (1.00 to 1.43), P = 0.05), and the composite of myocardial infarction or stroke (1.16 (1.02 to 1.32), P = 0.02). In meta-analyses of placebo controlled trials of calcium or calcium and vitamin D, complete trial-level data were available for 28,072 participants from eight trials of calcium supplements and the WHI CaD participants not taking personal calcium supplements. In total 1384 individuals had an incident myocardial infarction or stroke. Calcium or calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.24 (1.07 to 1.45), P = 0.004) and the composite of myocardial infarction or stroke (1.15 (1.03 to 1.27), P = 0.009).

CONCLUSIONS

Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.

Authors+Show Affiliations

Department of Medicine, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21505219

Citation

Bolland, Mark J., et al. "Calcium Supplements With or Without Vitamin D and Risk of Cardiovascular Events: Reanalysis of the Women's Health Initiative Limited Access Dataset and Meta-analysis." BMJ (Clinical Research Ed.), vol. 342, 2011, pp. d2040.
Bolland MJ, Grey A, Avenell A, et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. BMJ. 2011;342:d2040.
Bolland, M. J., Grey, A., Avenell, A., Gamble, G. D., & Reid, I. R. (2011). Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. BMJ (Clinical Research Ed.), 342, pp. d2040. doi:10.1136/bmj.d2040.
Bolland MJ, et al. Calcium Supplements With or Without Vitamin D and Risk of Cardiovascular Events: Reanalysis of the Women's Health Initiative Limited Access Dataset and Meta-analysis. BMJ. 2011 Apr 19;342:d2040. PubMed PMID: 21505219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. AU - Bolland,Mark J, AU - Grey,Andrew, AU - Avenell,Alison, AU - Gamble,Greg D, AU - Reid,Ian R, Y1 - 2011/04/19/ PY - 2011/4/21/entrez PY - 2011/4/21/pubmed PY - 2011/6/29/medline SP - d2040 EP - d2040 JF - BMJ (Clinical research ed.) JO - BMJ VL - 342 N2 - OBJECTIVES: To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women's Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk. DESIGN: Reanalysis of WHI CaD Study limited access dataset and incorporation in meta-analysis with eight other studies. Data source WHI CaD Study, a seven year, randomised, placebo controlled trial of calcium and vitamin D (1g calcium and 400 IU vitamin D daily) in 36,282 community dwelling postmenopausal women. Main outcome measures Incidence of four cardiovascular events and their combinations (myocardial infarction, coronary revascularisation, death from coronary heart disease, and stroke) assessed with patient-level data and trial-level data. RESULTS: In the WHI CaD Study there was an interaction between personal use of calcium supplements and allocated calcium and vitamin D for cardiovascular events. In the 16,718 women (46%) who were not taking personal calcium supplements at randomisation the hazard ratios for cardiovascular events with calcium and vitamin D ranged from 1.13 to 1.22 (P = 0.05 for clinical myocardial infarction or stroke, P = 0.04 for clinical myocardial infarction or revascularisation), whereas in the women taking personal calcium supplements cardiovascular risk did not alter with allocation to calcium and vitamin D. In meta-analyses of three placebo controlled trials, calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.21 (95% confidence interval 1.01 to 1.44), P = 0.04), stroke (1.20 (1.00 to 1.43), P = 0.05), and the composite of myocardial infarction or stroke (1.16 (1.02 to 1.32), P = 0.02). In meta-analyses of placebo controlled trials of calcium or calcium and vitamin D, complete trial-level data were available for 28,072 participants from eight trials of calcium supplements and the WHI CaD participants not taking personal calcium supplements. In total 1384 individuals had an incident myocardial infarction or stroke. Calcium or calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.24 (1.07 to 1.45), P = 0.004) and the composite of myocardial infarction or stroke (1.15 (1.03 to 1.27), P = 0.009). CONCLUSIONS: Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/21505219/Calcium_supplements_with_or_without_vitamin_D_and_risk_of_cardiovascular_events:_reanalysis_of_the_Women's_Health_Initiative_limited_access_dataset_and_meta_analysis_ L2 - http://www.bmj.com/cgi/pmidlookup?view=long&pmid=21505219 DB - PRIME DP - Unbound Medicine ER -