Hypocalcemia as a nontraditional risk factor for cardiovascular events and all-cause din patients with chronic kidney disease: insights from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Background: The clinical implication of hypocalcemia is elusive in patients with chronic kidney disease (CKD). The present study aimed to investigate whether low serum calcium levels increase the risk of major adverse cardiovascular events (MACEs) and cardiovascular mortality in patients with non-dialysis CKD. Methods: A total of 2,188 patients with CKD at stages 1 to 5 (pre-dialysis) were categorized by corrected calcium levels into low (<8.5 mg/dL), normal, and high (≥9.5 mg/dL) groups, and were prospectively observed for a median duration of 9.2 years. The study outcomes were MACE and all-cause death. Results: The analysis of the baseline characteristics revealed the correlation between low corrected calcium levels and clinically unfavorable features. The cumulative incidence of MACE and cardiovascular and all-cause death, but not nonfatal myocardial infarction and nonfatal stroke, significantly differed by corrected calcium levels. Cox regression analyses demonstrated that low corrected calcium levels were independently and significantly associated with the risk of MACE (adjusted hazard ratio [HR], 2.854; 95% confidence interval [CI], 1.439-5.659), cardiovascular death (adjusted HR, 5.256; 95% CI, 1.993-13.861), and all-cause death (adjusted HR, 1.902; 95% CI, 1.185-3.054), but not with the risk of nonfatal MI or nonfatal stroke. Conclusion: Hypocalcemia is significantly associated with the risk of adverse cardiovascular outcomes in patients with non-dialysis CKD. As a nontraditional risk factor for cardiovascular events and all-cause death in this population, the presence of hypocalcemia should urge more intense monitoring for the development of cardiovascular events.