Abstract
RATIONALE & OBJECTIVE: Characteristics of the transformation of primary to secondary calciprotein particles (CPPs) in serum, including the size of secondary CPP (CPP2) aggregates and the time of transformation (T(50)), may be markers for arterial calcification in patients undergoing hemodialysis (HD). We examined the associations of CPP2 aggregate size and T(50) with arterial calcification in incident HD patients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Incident HD patients (n=402with available CPP2 measures and n=388with available T(50) measures) from the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) Study PREDICTORS: Serum CPP2 size and T(50) at baseline. OUTCOMES: Primary outcomes were baseline coronary artery and thoracic aorta calcifications. Exploratory outcomes included baseline arterial stiffness, measured by pulse wave velocity (PWV) and ankle brachial index, and longitudinally, repeat measures of PWV and all-cause mortality. ANALYTICAL APPROACH: Tobit regression, multiple linear regression, Poisson regression, linear mixed-effects regression, and Cox proportional hazards regression. RESULTS: Mean age was 55±13 years, 41% were women, 71% were Black, and 57% had diabetes mellitus. Baseline CPP2 size and T(50) were correlated with baseline fetuin A level (r=-0.59 for CPP2 and 0.44 for T(50); P<0.001 for both), but neither was associated with baseline measures of arterial calcification or arterial stiffness. Baseline CPP2 size and T(50) were not associated with repeat measures of PWV. During a median follow-up of 3.5 (IQR, 1.7-6.2) years, larger CPP2 was associated with higher risk for mortality (HR, 1.17 [95% CI, 1.05-1.31] per 100nm larger CPP2 size) after adjusting for demographics and comorbid conditions, but there was no association between baseline T(50) and risk for mortality. LIMITATIONS: Possible imprecision in assays, small sample size, limited generalizability to incident HD populations with different racial composition, and residual confounding. CONCLUSIONS: In incident HD patients, neither CPP2 size nor T(50) was associated with prevalent arterial calcification and stiffness. Larger CPP2 was associated with risk for mortality, but this finding needs to be confirmed in future studies.