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

By M. Bolland, A. Grey, A. Avenell, G. Gamble, I. Reid. British medical journal, 2011

784 citations recorded by the source corpus.

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.

Subfields: Orthopedics and Sports Medicine, Pathology and Forensic Medicine, Rheumatology

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Citations in the corpus

Mendelian randomization for cardiovascular diseases: principles and applications (2023, positive): “42 On top of this evidence, MR investigations have found that genetically predicted lifelong higher serum calcium levels are associated with an increased risk of coronary artery disease, 21 myocardial infarction, 21 and overall CVD. 42 Hence, triangulating the evidence across study designs supports ”
Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014, background): “The scientific literature is highly controversial in this area [31–34].”
Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity – A Comprehensive Review (2016, positive): “However, calcium supplements with or without vitamin D may significantly increase risk of MI in long-term randomized trials.(328,329) In observational analyses, dietary and blood magnesium levels are inversely associated with CVD, especially fatal CHD(330); long-term trials have not been performed.”
European guidance for the diagnosis and management of osteoporosis in postmenopausal women (2018, background): “Adding to the controversies over calcium, a meta-analysis has concluded that calcium supplements without co-administered vitamin D were associated with an increase in the risk of myocardial infarction by around 30% [157].”
European guidance for the diagnosis and management of osteoporosis in postmenopausal women (2008, result): “In contrast, a recent meta-analysis concluded that calcium supplements without co-administered vitamin D were associated with an increase in the risk of myocardial infarction by around 30 % [149].”