Low Plasma Ionized Calcium Is Associated With Increased Mortality: A Population-based Study of 106 768 Individuals

Low circulating total calcium or albumin-adjusted calcium has been associated with higher mortality, especially in hospital settings; however, these measures tend to misclassify patients with derangements in calcium homeostasis.

As the association of the biologically active ionized calcium with mortality is poorly elucidated, we tested the hypothesis that low plasma ionized calcium is associated with higher risk of all-cause and cause-specific mortality in the general population.

We included 106 768 individuals from the Copenhagen General Population Study. Information on all-cause and cause-specific mortality was from registries and risks were calculated using Cox regression and competing-risks regression by the STATA command stcompet.

During a median follow-up period of 9.2 years, 11 269 individuals died. Each 0.1 mmol/L lower plasma ionized calcium below the median of 1.21 mmol/L was associated with a multivariable adjusted hazard ratio of 1.23 (95% CI, 1.10-1.38) for all-cause mortality. Corresponding hazard ratios for cancer and other mortality were 1.29 (1.06-1.57) and 1.24 (1.01-1.53), respectively. In contrast, for cardiovascular mortality, only high plasma ionized calcium was associated with mortality with a hazard ratio of 1.17 (1.02-1.35) per 0.1 mmol/L higher plasma ionized calcium above the median. We found no interactions between plasma ionized calcium and preexisting cardiovascular or renal disease on all-cause mortality.

In the general population, low plasma ionized calcium was associated with increased all-cause, cancer, and other mortality, while high levels were associated with increased cardiovascular mortality.