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Cardiovascular Systematic Review of Vitamin D- Mar 2010

Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events

Wang L, Manson JE, Song Y, Sesso HD from http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=12010001316

CRD summary

This review concluded that limited data suggested moderate-to-high doses of vitamin D supplements may reduce cardiovascular disease risk, but calcium supplements may not. Given the potential for missed studies, clinical differences between studies and paucity of good quality data, the reliability of the pooled results is uncertain. However, the authors' conclusions seemed suitably cautious.

Authors' objectives

To assess whether vitamin D and calcium supplements reduced the risk for cardiovascular events in adults.


MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published in English from 1966 to July 2009; search terms were reported. Reference lists of retrieved articles were searched.

Study selection

Two reviewers independently selected prospective studies of adults (?19 years) that compared vitamin D supplements, calcium supplements or a combination against no supplements. Studies had to report cardiovascular disease outcomes (cardiovascular disease death, nonfatal coronary heart disease, myocardial infarction and nonfatal stroke). Many of the included studies were only in women, or only in patients who received haemodialysis; some studies were only in men and others in a mixed population. Where reported, mean age ranged from 54 to 74 years. Supplement doses varied. All trials had placebo groups.

Validity assessment

Studies were graded for quality in the following categories: good (no obvious bias); fair (bias was insufficient to invalidate the results); and poor (substantial bias).

The authors did not state how many reviewers performed the study quality assessment.

Data extraction

Data were extracted on order to calculate relative risks (RR) and 95% confidence intervals (CI). One reviewer extracted data and two other reviewers checked independently. Disagreements were resolved by consensus.

Methods of synthesis

Meta-analyses were used to pool relative risks and 95% CIs from randomised controlled trials (RCTs) using a random effects model. Heterogeneity was calculated using the Cochran Q statistic. Publication bias was assessed using the Begg adjusted rank correlation test.

Results of the review

Seventeen studies were included: eight prospective cohort studies (n=271,214); eight RCTs (n=43,646, range 192 to 36,282 participants); and one nested case-control study (n=1,000). Follow-up periods ranged from 90 days to eight years. Four cohort studies were rated good, three fair and two poor. Four RCTs were rated fair and four poor.

Five studies of patients who received dialysis showed consistent reductions in cardiovascular mortality in those who received vitamin D supplements; one study of a general population showed no statistically significant reductions. Four studies of initially healthy persons found no differences in incidence of cardiovascular events between calcium supplement recipients and non recipients.

RCTs showed no statistically significant reductions in cardiovascular events with vitamin D supplementation (RR 0.90, 95% CI 0.77 to 1.05; two studies), calcium supplementation (RR 1.14, 95% CI 0.92 to 1.41; three studies) and a combination of vitamin D and calcium supplementation (RR 1.04 95% CI 0.92 to 1.18; two studies) compared with placebo. There was no evidence for publication bias or significant heterogeneity.

Authors' conclusions

Limited data suggested that vitamin D supplements at moderate-to-high doses may reduce cardiovascular disease risk; calcium supplements seemed to have minimal cardiovascular effects.

CRD commentary

The review addressed a clear question and was supported by appropriate inclusion criteria. Attempts to identify relevant studies were undertaken by searching electronic databases and checking references, but the restriction to studies published in English means that relevant studies may have been missed and the review may have been prone to language and publication biases. Suitable methods were employed to reduce risks of reviewer error and bias for the processes of data extraction and study selection; the authors did not report on whether such methods were used when assessing study quality. There was a paucity of good-quality evidence and the authors' assessment of study quality was used when interpreting the results of the review. However, the very limited reporting of criteria used to assess bias made it difficult to assess the relative merits of individual studies. Sufficient study details were provided and an appropriate meta-analysis of the data was undertaken. The authors noted that none of the RCTs were designed to answer the review question. Although the reliability of the pooled results is uncertain, the authors' conclusions seemed suitably cautious.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that future studies of vitamin D and calcium supplement use among initially healthy persons were needed urgently, particularly large-scale randomised trials with adequate doses and with cardiovascular disease ascertained as the primary end point.


American Heart Association (grant 0735390N) and the National Heart, Lung, and Blood Institute (grant HL075445).

Bibliographic detail
Wang L, Manson JE, Song Y, Sesso HD. Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Annals of Internal Medicine 2010; 152(5): 315-323
Link to Pubmed record 20194268
URL for original research http://www.annals.org/content/152/5/315.abstract
URL for additional data http://www.annals.org/content/152/5/315.short
Subject index terms status Subject indexing assigned by CRD
Subject index terms Calcium; Calcium Carbonate; Cardiovascular Diseases /prevention & control; Dietary Supplements; Heart Failure /prevention & control; Humans; Vitamin D /metabolism
Accession number 12010001316
Database entry date 10 March 2010
Record status

This record is a structured abstract produced by CRD. The original has met a set of quality criteria. Since September 1996 abstracts have been sent to authors for comment. Additional factual information is incorporated into the record. Noted as  A:.....

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