The role of serum phosphate and calcium levels in coronary artery calcification progression: A multicenter, longitudinal cohort study

Background: Higher serum phosphate levels are associated with cardiovascular diseases, including coronary artery calcification (CAC). However, there exists limited evidence supporting a causal relationship between phosphate levels and CAC progression. Methods: Using the KOrea Initiatives on Coronary Artery Calcification (KOICA) registry, we assessed CAC using the CAC score assessed by cardiac computed tomography (CT) in participants with normal serum phosphate (2.5–4.5 ​mg/dL) and calcium levels and without renal dysfunction (estimated glomerular filtration rate ≥60 ​mL/min/1.73 ​m²). The effect of serum phosphate and calcium levels on the prevalence and severity of CAC at baseline and the longitudinal progression of CAC were analyzed using multivariable regression models. Results: A total of 12,251 individuals and 31,251 CT scans were selected for analysis, with a median follow-up duration of 3.5 (interquartile range 2.1–5.1) years. In the baseline cross-sectional analysis, serum phosphate levels were associated with higher CAC prevalence (OR per 1 ​mg/dL increase, 1.09, 95 ​% CI 1.06–1.11, p ​< ​0.001) and CAC severity (β-coefficient per 1 ​mg/dL increase, 0.35, 95 ​% CI 0.25, 0.45, p ​< ​0.001). In longitudinal analysis, serum phosphate levels also showed a significant association with higher probability of CAC progression (HR per 1 ​mg/dL increase, 1.19, 95 ​% CI, 1.06, 1.32; p ​< ​0.001) and faster CAC score progression (β coefficient per 1 ​mg/dL, 2.54 ​× ​10⁻²; 95 ​% CI, 1.43 ​× ​10⁻²–3.67 ​× ​10⁻²; p ​< ​0.001). Conclusion: Higher serum phosphate levels, even within the normal range, are associated with faster CAC progression. Further studies are needed to demonstrate the possibility of slowing CAC development through the regulation of calcium-phosphate metabolism.