Association of Serum Calcium with the Risk of Chronic Obstructive Pulmonary Disease: A Prospective Study from UK Biobank

Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.