Serum Calcium Concentrations and Risk of All-Cause and Cause-Specific Mortality: Results From 2 Prospective Cohorts

Context Calcium plays a critical role in various physiological activities. However, the association between circulating calcium concentrations and mortality in a general healthy population remains undetermined. Objective To examine the association of serum calcium concentrations with all-cause and cause-specific mortality. Methods Leveraging data from the UK Biobank (n = 361 662) and the US National Health and Nutrition Examination Survey (NHANES, n = 36 985), we prospectively examined the association of serum calcium concentrations with all-cause and cause-specific mortality using Cox proportional hazard and restricted cubic spline models. Results During a median follow-up of 12.0 years, UK Biobank documented 18 327 deaths, including 3119 (17.0%) from cardiovascular disease (CVD) and 9599 (52.4%) from cancer. We found a U-shaped relationship of albumin-adjusted calcium concentrations with all-cause and CVD mortality. Compared with participants with moderate calcium levels (the third quintile, Q3), those with low and high levels had an increased risk of all-cause (hazard ratio [HR] 1.02 for Q1 vs Q3; 1.10 for Q5 vs Q3) and CVD mortality (HR 1.11 for Q1 vs Q3; 1.25 for Q5 vs Q3). In contrast, there was a linear positive relationship with cancer mortality (HR 1.09 for Q5 vs Q1). Similar results for all-cause, CVD, and cancer mortality were observed in US NHANES. Conclusion Our findings provide novel insights into the association between serum calcium concentrations and mortality in the general healthy population.