The Role of Serum Calcium Levels in the Progression of Arterial Stiffness: Cross-Sectional and Longitudinal Analyses in a Multicenter Cohort

Abstract

Increased arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) is a well-known risk factor for hypertension and future cardiovascular events. The relationship between serum calcium levels and increased arterial stiffness is not well understood. Individuals undergoing baPWV measurements as part of a generalized health examination, with normal serum calcium (8.5-10.5 mg/dL) and phosphate levels and no significant renal dysfunction, were selected from the Korea Initiatives on Coronary Artery (KOICA) registry. The cross-sectional relationship between serum calcium levels and baPWV, and the longitudinal effect of baseline serum calcium levels on baPWV progression in those with repeated baPWV measurements, were analyzed using multivariable regression models. A total of 9150 individuals with baseline baPWV and 2329 individuals (5451 PWV measurements) with follow-up baPWV were selected for cross-sectional and longitudinal analyses, respectively. After adjustment for confounders, higher serum calcium levels were associated with increased baseline baPWV (β-coefficient per 1 mg/dL increase, 19.61; 95% CI 7.77-31.45; p = 0.001). Higher serum calcium was also independently associated with a greater annualized baPWV progression rate longitudinally (β-coefficient per 1 mg/dL increase, 5.17; 95% CI, 1.82-8.67; p = 0.004). Subgroup analysis showed that the effect of serum calcium on baPWV progression had a significant interaction with baseline baPWV, systolic blood pressure, and the presence of diabetes (interaction p < 0.001). In conclusion, higher serum calcium levels within the normal range were associated with faster arterial stiffness progression measured by baPWV. Further studies are required to explore the potential for modulating calcium metabolism to slow arterial stiffness progression.