Menopause Live - IMS Updates

Date of release: 19 December, 2011

Calcium and vitamin D in heart disease

Following the publication within the last year of two papers by Bolland and colleagues in the BMJ [1,2] regarding the relationship between calcium and vitamin D supplements and heart disease, there still seems to be confusion among practitioners despite vigorous discussion and uncertainty regarding the validity of the results. In April 2011, Bolland and colleagues published a meta-analysis that comprised a re-analysis of Women’s Health Initiative Calcium and Vitamin D Study (WHI CaD Study) limited access dataset with eight other studies [1]. There are three components to the paper, a re-analysis of the WHI CaD study, a new meta-analysis of the previous trials of calcium and vitamin D, and an update of the previous analysis published in 2010 [2]. A total of 36,282 women took part in the WHI CaD Study and were followed for 7 years; the main outcome measures were cardiovascular events (myocardial infarction, coronary revascularization, death from coronary heart disease and stroke). The meta-analysis discussed two recent systematic reviews which identified trials of co-administered calcium and vitamin D [3,4], which were brought up-to-date with as much relevant data as could be identified by the authors. 


The risk of having an myocardial infarction was slightly increased in women not already using calcium and vitamin D at the start of the study, who were randomized to it in the WHI study (hazard ratio (HR) 1.22; 95% confidence interval (CI) 1.00–1.50; p = 0.054). However, all-cause mortality was not increased in this group (HR 0.99; 95% CI 0.86–1.14; p = 0.89). Interestingly, women who were taking calcium supplements at baseline and who were assigned to calcium and vitamin D had a lower all-cause mortality when compared to those assigned to placebo (HR 0.84; 95% CI 0.73–0.97). The authors found a moderate increase in cardiovascular events with calcium and vitamin D usage and concluded that a reassessment of the role of calcium supplements in osteoporosis management is warranted – but is it?


Concerns over methodology and data interpretation are apparent even to the non-statistician. The trials included in the meta-analysis have variable endpoints and, due to their size, the WHI CaD data dominate the other components of the meta-analysis. Half the women in the WHI study are excluded for reasons that may not be apparent to the average clinician. The authors claim that the cardiovascular risk factors differed in users of calcium supplements, although, with the exception of weight, these differences were very small. They argued that inclusion would result in a comparison of high- and low-dose calcium rather than investigating the true effect of the calcium and vitamin D versus placebo. Use of calcium supplements at baseline was recalled in retrospect. Whilst there was a marginal increase in cardiovascular events, all-cause mortality did not increase. The WHI CaD study as a whole did not show an increase and there is always a risk when interpreting subgroup analyses from a statistical perspective. Also, viewing symptoms alone is inappropriate in this instance in that calcium supplementation frequently causes heart burn that may mimic cardiac pain in older women. Cardiovascular events were variably verified. In October 2011, a Drug Safety Update was published by the Medicine and Hormones Regulatory Authority, MHRA in the UK [5] (equivalent to the FDA in the US) that questioned the conclusions of this meta-analysis. Calcium and vitamin D are important in the prevention of osteoporosis in older women, although both the National Institute of Health and Clinical Excellence (NICE) and the National Osteoporosis Society advise that increasing dietary calcium is better for women than calcium supplementation. However, supplements should be offered unless the prescribers are confident that the woman in question has an adequate calcium and vitamin D intake. This advice may need to be modified in different populations around the world depending on their diet, but it should reassure prescribers who feel that a woman, particularly one who lives in a residential rather than a community setting and is therefore not very active, would benefit from this combination.


Mary Ann Lumsden
Consultant Gynecologist, Head of Reproductive & Maternal Medicine, University of Glasgow, UK


  1. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Womens Health Initiative limited access data-set and meta-analysis. BMJ 2011;342:d2040.

  2. Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691.

  3. Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007;115:846-54.

  4. Chung M, Balf EM, Brendel M, et al. Vitamin D and calcium: A Systematic Review of Health Outcomes. Evidence Report No 183. No 09-E015. Rockville, MD: Agency for Healthcare Research and Quality, 2009.

  5. Drug Safety Update Oct 2011 vol 5, issue 3:H1.