U-shaped association between serum calcium and in-hospital mortality in patients with congestive heart failure

Abstract

Aims: Serum calcium level is widely used for evaluating disease severity, but its impact on clinical outcomes in patients with congestive heart failure (CHF) remains poorly understood. The aim of this study is to investigate the relationship between serum calcium levels and in-hospital mortality in CHF patients.

Methods and results: We conducted a retrospective analysis utilizing clinical data from the Medical Information Mart for Intensive Care database, encompassing a cohort of 15 983 CHF patients. This cohort was stratified based on their serum calcium levels, with the primary objective being the determination of in-hospital mortality. To assess the impact of admission serum calcium levels on in-hospital mortality, we employed various statistical methodologies, including multivariable logistic regression models, a generalized additive model, a two-piecewise linear regression model, and subgroup analysis. Comparative analysis of the reference group (Q3) revealed increased in-hospital mortality in the first quintile (Q1, the group with the lowest blood calcium level) and the fifth quintile (Q5, the group with the highest blood calcium level), with fully adjusted odds ratios of 1.38 [95% confidence interval (CI): 1.13-1.68, P = 0.002] and 1.23 (95% CI: 1.01-1.5, P = 0.038), respectively. A U-shaped relationship was observed between serum calcium levels and in-hospital mortality, with the lowest risk occurring at a threshold of 8.35 mg/dL. The effect sizes and corresponding CIs below and above this threshold were 0.782 (95% CI: 0.667-0.915, P = 0.0023) and 1.147 (95% CI: 1.034-1.273, P = 0.0094), respectively. Stratified analyses confirmed the robustness of this correlation.

Conclusions: Our study identifies a U-shaped association between serum calcium levels and in-hospital mortality in CHF patients, with a notable inflection point at 8.35 mg/dL. Further investigation through prospective, randomized, and controlled studies is warranted to validate the findings presented in this study.

Keywords: Association; Blood calcium; Congestive heart failure; Generalized additive model; In‐hospital mortality; Subgroup analysis.

Figure 1

Flow chart of patient selection.

Figure 2

Dose–response relationships between blood calcium and in‐hospital mortality rate odds ratio. The horizontal axis represents the concentration of blood calcium. The unit of calcium is mg/dL. The vertical axis represents the patient's status and whether they have been discharged or died. Solid and dashed lines represent the predicted value and 95% confidence intervals. Adjusted for demographic variables (sex, age, and race), concomitant diseases (chronic obstructive pulmonary disease, acute myocardial infarction, mean corpuscular, diabetes, and hepatic failure), medical procedures (vent and intubated), medication situation (norepinephrine, dopamine, epinephrine, phenylephrine, and vasopressin), basic vital signs (temperature, respiratory rate, heart rate, and systolic blood pressure), blood biochemical indicators (anion gap, blood urea nitrogen, chloride, creatinine, haemoglobin, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, mean corpuscular volume, platelet, potassium, sodium, red blood cell count, red blood cell distribution width, and white blood cell count), Acute Physiology III, and Sequential Organ Failure Assessment. Only 99% of the data are shown.