Cardiovascular diseases and hard drinking waters: implications from a systematic review with meta-analysis of case-control studies.

This systematic review with meta-analysis, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, aims at evaluating the potential correlation between magnesium and calcium concentration in drinking waters and the risk of cardiovascular diseases (CVD), which impose a considerable burden in high-income countries. Included studies were of the case-control studies type. From an initial list of 643 potentially eligible articles, seven studies were finally retained in the quantitative analysis. Since each one of them assessed different ion concentrations, subjects exposed to the highest concentration versus those exposed to the lowest concentration were compared. By including an overall figure of 44,000 subjects, the result suggests a protective effect of the ions on CVD prevention, with an effect-size (ES) of 0.82 (95% confidence interval CI = [0.70-0.95], p-value = 0.008) for calcium, and ES = 0.75 (95% CI = [0.66-0.86], p-value = 0.000) for magnesium. Hard water consumption seems to be protective against CVD. However, the high heterogeneity (I2 = 75.24, p-value = 0.001 for calcium; I2 = 72.96, p-value = 0.0024 for magnesium) and the existence of publication bias limits the robustness and generalizability of these findings. Further high-quality studies are needed to reproduce and confirm these results.