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A Meta-analysis of Randomized Controlled Trials

Heiner C. Bucher, MD; Richard J. Cook, PhD; Gordon H. Guyatt, MD, MSc; Jefferey D. Lang, MD, FRCPC; Deborah J. Cook, MD, FRCPC; Rose Hatala, MD, FRCPC; Dereck L. Hunt, MD

JAMA. 1996;275(13):1016-1022.

Abstract
Objective.
—To review the effect of supplemental calcium on blood pressure.

Data Source.
—We searched MEDLINE and EMBASE for 1966 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials.

Study Selection.
—We included any study in which investigators randomized people to calcium supplementation or placebo and measured blood pressure for at least 2 weeks. Fifty-six articles met the inclusion criteria, and 33 were eligible for analysis, involving a total of 2412 patients.

Data Extraction.
—Two pairs of independent reviewers abstracted data and assessed validity according to six quality criteria.

Data Synthesis.
—We calculated the differences in blood pressure change between the calcium supplementation group and the control group and pooled the estimates, with each trial weighted with the inverse of the variance using a random-effects model. Predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodological quality of the studies. The pooled analysis showed a reduction in systolic blood pressure of -1.27 mm Hg (95% confidence interval [CI], -2.25 to -0.29 mm Hg; P=.01) and in diastolic blood pressure of -0.24 mm Hg (95% CI, -0.92 to 0.44 mm Hg; P=.49). None of the possible mediators of blood pressure reduction explained differences in treatment effects.

Conclusions.
—Calcium supplementation may lead to a small reduction in systolic but not diastolic blood pressure. The results do not exclude a larger, important effect of calcium on blood pressure in subpopulations. In particular, further studies should address the hypothesis that inadequate calcium intake is associated with increased blood pressure that can be corrected with calcium supplementation.

(JAMA. 1996;275:1016-1022)

Author Affiliations
From the Departments of Clinical Epidemiology and Biostatistics (Drs Bucher, Guyatt, and D. Cook) and Medicine (Drs Guyatt, Lang, D. Cook, Hatala, and Hunt), McMaster University, Hamilton, Ontario; and Department of Health Studies and Gerontology, Faculty of Applied Health Sciences, University of Waterloo, Kitchener, Ontario (Dr R. Cook).

Footnotes
Reprints: Gordon H. Guyatt, MD, MSc, Department of Clinical Epidemiology and Biostatistics, Room 2C10, McMaster University Medical Center, 1200 Main St W, Hamilton, Ontario, Canada L8N 3Z5.

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