Serum Levels of Calcium, Phosphate, and Vitamin D and Incident Arrhythmias: A Prospective Cohort Study of 348,094 UK Biobank Participants

Background/Objectives: Evidence of associations between serum calcium, phosphate, and vitamin D concentrations and development of arrhythmias is limited and inconsistent. This study aimed to investigate the quantification and characterization of the dose–response relationship between serum mineral levels and arrhythmia subtypes in a general population cohort. Methods: We included 348,094 UK Biobank participants without prevalent cardiovascular disease or arrhythmias in whom serum calcium, phosphate, and vitamin D concentrations were available. Serum calcium and phosphate levels were multiplied to derive calcium–phosphate product. Incident outcomes were all arrhythmias and subtypes: AF, other (non-AF) arrhythmias, bradyarrhythmia, and ventricular arrhythmias. Cox proportional hazards regression models were conducted. Results: Compared with the lowest quartile, participants in the highest quartile of serum calcium had a significantly lower risk of all arrhythmias (hazard ratio [HR] 0.92, 95% confidence interval [CI], 0.88–0.95), particularly AF (0.89, 0.85–0.93). Negative associations were found between serum vitamin D and arrhythmias, especially ventricular arrhythmias (HR 0.68, 95% CI 0.57–0.81). Higher serum phosphate and calcium–phosphate product were associated with higher risk of all outcomes. Restricted cubic splines revealed nonlinear associations for calcium and vitamin D but linear associations for phosphate and calcium–phosphate product. The associations were not modified by kidney function. Conclusions: Lower calcium and vitamin D concentrations and higher serum phosphate and calcium–phosphate product were associated with increased risk of arrhythmias and presented a dose–response manner. These findings may indicate that maintaining optimal serum calcium, phosphate, and vitamin D may be important for reducing arrhythmic risk, emphasizing the need for targeted monitoring and management, particularly in high-risk populations.