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Associations of Serum Calciprotein Particle Size and Transformation Time with Arterial Calcification, Arterial Stiffness, and Mortality in Incident Hemodialysis Patients.

RATIONALE & OBJECTIVE
Characteristics of the transformation of primary to secondary calciprotein particles (CPP) in serum, including the size of secondary CPP (CPP2) aggregates and the time of transformation (T50), may be markers for arterial calcification in patients undergoing hemodialysis (HD). We examined the associations of CPP2 aggregate size and T50 with arterial calcification in incident HD patients.


STUDY DESIGN
Prospective cohort study SETTING & PARTICIPANTS: Incident HD patients (n=402 with available CPP2 measures and n=388 with available T50 measures) from the Predictors of Arrhythmic and Cardiovascular Risk in ESRD (PACE) study PREDICTORS: Serum CPP2 size and T50 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, repeated 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 T50 were correlated with baseline fetuin-A (r=-0.59 for CPP2 and 0.44 for T50, p<0.001 for both), but neither was associated with baseline measures of arterial calcification or arterial stiffness. Baseline CPP2 size and T50 were not associated with repeated measures of PWV. During a median follow-up of 3.5 years (IQR 1.7-6.2), larger CPP2 was associated with higher risk of mortality [HR: 1.17 (95% CI 1.05, 1.31) per 100 nm larger CPP2 size] after adjusting for demographics and comorbidities, but there was no association between baseline T50 and risk of mortality.


LIMITATIONS
Possible imprecision in assays, small sample size, limited generalizability to incident hemodialysis populations with different racial composition, and residual confounding.


CONCLUSIONS
In incident HD patients, neither CPP2 size nor T50 was associated with prevalent arterial calcification and stiffness. Larger CPP2 was associated with risk of mortality, but this finding needs to be confirmed in future studies.