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.
Study Goal
The researchers aimed to investigate the effects of calcium supplements on cardiovascular risk in postmenopausal women and update the meta-analysis on calcium supplements and cardiovascular risk.
Results Summary
The study found that calcium supplements, with or without vitamin D, modestly increased the risk of cardiovascular events, particularly myocardial infarction. This effect was obscured in the WHI CaD Study due to widespread personal calcium supplement use.
Population
36,282 community-dwelling postmenopausal women.
Effective Dosage
1g calcium and 400 IU vitamin D daily.
Duration
Seven years.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
calcium and vitamin D (1g calcium and 400 IU vitamin D daily) | increase | myocardial infarction | women not taking personal calcium supplements at randomisation | hazard ratios ranged from 1.13 to 1.22 | increased the risk | #1 |
calcium and vitamin D (1g calcium and 400 IU vitamin D daily) | increase | stroke | women not taking personal calcium supplements at randomisation | hazard ratios ranged from 1.13 to 1.22 | increased the risk | #2 |
calcium and vitamin D | increase | myocardial infarction | participants in meta-analyses of three placebo controlled trials | relative risk 1.21 (95% confidence interval 1.01 to 1.44) | increased the risk | #3 |
calcium and vitamin D | increase | stroke | participants in meta-analyses of three placebo controlled trials | relative risk 1.20 (1.00 to 1.43) | increased the risk | #4 |
calcium and vitamin D | increase | composite of myocardial infarction or stroke | participants in meta-analyses of three placebo controlled trials | relative risk 1.16 (1.02 to 1.32) | increased the risk | #5 |
calcium or calcium and vitamin D | increase | myocardial infarction | 28,072 participants from eight trials of calcium supplements and the WHI CaD participants not taking personal calcium supplements | relative risk 1.24 (1.07 to 1.45) | increased the risk | #6 |
calcium or calcium and vitamin D | increase | composite of myocardial infarction or stroke | 28,072 participants from eight trials of calcium supplements and the WHI CaD participants not taking personal calcium supplements | relative risk 1.15 (1.03 to 1.27) | increased the risk | #7 |
calcium and vitamin D (1g calcium and 400 IU vitamin D daily) | no change | cardiovascular risk | women taking personal calcium supplements | - | did not alter | #8 |
calcium supplements with or without vitamin D | increase | cardiovascular events | - | - | modestly increase the risk | #9 |
calcium supplements with or without vitamin D | increase | myocardial infarction | - | - | modestly increase the risk | #10 |
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.