Endocrinol Metab.  2017 Sep;32(3):339-349. 10.3803/EnM.2017.32.3.339.

Calcium and Cardiovascular Disease

• Reid IR
• Birstow SM
• Bolland MJ

• KMID: 2389814
• DOI: http://doi.org/10.3803/EnM.2017.32.3.339

Abstract

Circulating calcium is a risk factor for vascular disease, a conclusion arising from prospective studies involving hundreds of thousands of participants and extending over periods of up to 30 years. These associations may be partially mediated by other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index, but there appears to be a residual independent effect of serum calcium. Polymorphisms of the calcium-sensing receptor associated with small elevations of serum calcium are also associated with cardiovascular disease, suggesting that calcium plays a causative role. Trials of calcium supplements in patients on dialysis and those with less severe renal failure demonstrate increased mortality and/or acceleration of vascular disease, and meta-analyses of trials in those without overt renal disease suggest a similar adverse effect. Interpretation of the latter trials is complicated by a significant interaction between baseline use of calcium supplements and the effect of randomisation to calcium in the largest trial. Restriction of analysis to those who are calcium-naive demonstrates a consistent adverse effect. Observational studies of dietary calcium do not demonstrate a consistent adverse effect on cardiovascular health, though very high or very low intakes may be deleterious. Thus, obtaining calcium from the diet rather than supplements is to be encouraged.

Keyword

Calcium; Calcium, dietary; Cardiovascular diseases; Myocardial infarction; Risk factors; Osteoporosis

MeSH Terms

Acceleration
Blood Pressure
Body Mass Index
Calcium*
Calcium, Dietary
Cardiovascular Diseases*
Dialysis
Diet
Humans
Mortality
Myocardial Infarction
Osteoporosis
Prospective Studies
Receptors, Calcium-Sensing
Renal Insufficiency
Risk Factors
Vascular Diseases
Calcium
Calcium, Dietary
Receptors, Calcium-Sensing

Figure

• 

  Fig. 1 Forest plots showing the relationships between serum calcium at baseline and subsequent cardiovascular events over a weighted mean follow-up period of 12.4 years. Only studies reporting a linear relationship are included. Data are shown separately for odds and hazard ratios, which are expressed per standard deviation of serum calcium. 95% confidence intervals (CIs) are shown. The result of each meta-analysis is shown as a diamond. Adapted from Reid et al., with permission from John Wiley and Sons [1]. MI, myocardial infarction; CHD, coronary heart disease.

• 

  Fig. 2 Effects of calcium supplements on serum total calcium concentration in normal postmenopausal women. (A) The calcaemic effects of calcium (500 mg) as citrate administered fasting (closed circles) are contrasted with those of a dairy product meal with the same calcium content. (B) The calcaemic effects of calcium (500 mg) as citrate are contrasted when administered fasting (closed circles) or with a meal (open circles). (C) The calcaemic effects of 1 g calcium as citrate is shown at baseline in calcium-naive women (closed circles) or after 3 months of daily use of a 1 g calcium supplement (open circles). Adapted from Bristow et al., with permission from Cambridge University Press [3436]. aSignificantly different from citrate-fasting (P<0.05).

• 

  Fig. 3 Kaplan-Meier survival curves for time to incident myocardial infarction or stroke by treatment allocation in a meta-analysis of patient-level data from five trials of calcium supplements used as monotherapy (n=8,151) (A, B), and calcium-naive women in the Women's Health Initiative (WHI) calcium and vitamin D trial (n=16,718) (C, D). The magnitude and time-course of the effects of calcium supplements on the two groups of vascular events were very similar in these independent databases. Adapted from Radford et al. [44]. HR, hazard ratio; CI, confidence interval.

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