Abstract Background and aims Disruption of serum calcium homeostasis has been implicated in ischemic stroke outcomes, yet evidence remains inconsistent. This systematic review and meta-analysis evaluated associations between calcium levels and prognosis in ischemic stroke. Methods PubMed, Web of Science, and Scopus were systematically searched for clinical studies assessing the association of serum calcium with stroke severity, early neurological deterioration (END), functional outcomes, and mortality. Two reviewers independently screened studies, extracted data, and performed a risk-of-bias assessment. Pooled correlation coefficients (r) and odds ratios (OR) were calculated, and heterogeneity was assessed using the I2 statistic. Results Twenty-three studies, including 34,900 ischemic stroke patients, were analyzed. Ionized calcium demonstrated the most consistent prognostic associations: lower levels were associated with higher NIHSS scores, increased risk of END, and higher mortality, with U-shaped associations observed in large cohorts. Functional outcomes were inconsistent: higher albumin-corrected calcium was occasionally linked to the poor functional outcome (higher mRS scores, OR 1.30, 95% CI 1.06–1.58), whereas total calcium showed no consistent effect. Overall, elevated calcium was associated with increased odds of poor outcome (OR 1.28, 95% CI 1.06–1.55), though study heterogeneity highlights variability in these associations. Conclusions Ionized calcium is the most common form of calcium and the only active form contributing to physiological processes. Lower ionized calcium is associated with greater stroke severity, higher risk of END, and increased mortality, while elevated albumin-corrected calcium may predict poorer functional outcomes. Heterogeneity across studies, particularly for total calcium and functional outcomes, underscores the need for further research to clarify these associations. Conflict of interest Afshin Moradi: nothing to disclose. Asal Ebrahimian: nothing to disclose. Alibay Jafarli: nothing to disclose. Mehdi Farhoudi: nothing to disclose.
Ebrahimian et al. (Fri,) studied this question.