Blood Calcification Propensity, Cardiovascular Events, and Survival in Patients Receiving Hemodialysis in the EVOLVE Trial

Abstract

Background and objectives: Patients receiving hemodialysis are at risk of cardiovascular events. A novel blood test (T₅₀ test) determines the individual calcification propensity of blood.

Design, setting, participants, & measurements: T₅₀ was determined in 2785 baseline serum samples of patients receiving hemodialysis enrolled in the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial and the T₅₀ results were related to patient outcomes.

Results: Serum albumin, bicarbonate, HDL cholesterol, and creatinine were the main factors positively/directly and phosphate was the main factor negatively/inversely associated with T₅₀. The primary composite end point (all-cause mortality, myocardial infarction [MI], hospitalization for unstable angina, heart failure, or peripheral vascular event [PVE]) was reached in 1350 patients after a median follow-up time of 619 days. After adjustments for confounding, a lower T₅₀ was independently associated with a higher risk of the primary composite end point as a continuous measure (hazard ratio [HR] per 1 SD lower T₅₀, 1.15; 95% confidence interval [95% CI], 1.08 to 1.22; P<0.001). Furthermore, lower T₅₀ was associated with a higher risk in all-cause mortality (HR per 1 SD lower T₅₀, 1.10; 95% CI, 1.02 to 1.17; P=0.001), MI (HR per 1 SD lower T₅₀, 1.38; 95% CI, 1.19 to 1.60; P<0.001), and PVE (HR per 1 SD lower T₅₀, 1.22; 95% CI, 1.05 to 1.42; P=0.01). T₅₀ improved risk prediction (integrated discrimination improvement and net reclassification improvement, P<0.001 and P=0.001) of the primary composite end point.

Conclusions: Blood calcification propensity was independently associated with the primary composite end point, all-cause mortality, MI, and PVE in the EVOLVE study and improved risk prediction. Prospective trials should clarify whether T₅₀-guided therapies improve outcomes.

Keywords: CPP; EVOLVE; T50; angina, unstable; bicarbonates; calcification propensity; calciprotein particles; cholesterol, HDL; cinacalcet hydrochloride; creatinine; follow-up studies; heart failure; hematologic tests; hemodialysis; hospitalization; humans; myocardial infarction; phosphates; prospective studies; renal dialysis; serum albumin.