Serum Calcification Propensity and Coronary Artery Calcification Among Patients With CKD: The CRIC (Chronic Renal Insufficiency Cohort) Study

Abstract

Rationale & objective: Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and increases risks for cardiovascular disease events and mortality. We hypothesized that a novel serum measure of calcification propensity is associated with CAC among patients with CKD stages 2 to 4.

Study design: Prospective cohort study.

Setting & participants: Participants from the Chronic Renal Insufficiency Cohort (CRIC) Study with baseline (n=1,274) and follow-up (n=780) CAC measurements.

Predictors: Calcification propensity, quantified as transformation time (T₅₀) from primary to secondary calciprotein particles, with lower T₅₀ corresponding to higher calcification propensity. Covariates included age, sex, race/ethnicity, clinical site, estimated glomerular filtration rate, proteinuria, diabetes, systolic blood pressure, number of antihypertensive medications, current smoking, history of cardiovascular disease, total cholesterol level, and use of statin medications.

Outcomes: CAC prevalence, severity, incidence, and progression.

Analytical approach: Multivariable-adjusted generalized linear models.

Results: At baseline, 824 (65%) participants had prevalent CAC. After multivariable adjustment, T₅₀ was not associated with CAC prevalence but was significantly associated with greater CAC severity among participants with prevalent CAC: 1-SD lower T₅₀ was associated with 21% (95% CI, 6%-38%) greater CAC severity. Among 780 participants followed up an average of 3 years later, 65 (20%) without baseline CAC developed incident CAC, while 89 (19%) with baseline CAC had progression, defined as annual increase≥100 Agatston units. After multivariable adjustment, T₅₀ was not associated with incident CAC but was significantly associated with CAC progression: 1-SD lower T₅₀ was associated with 28% (95% CI, 7%-53%) higher risk for CAC progression.

Limitations: Potential selection bias in follow-up analyses; inability to distinguish intimal from medial calcification.

Conclusions: Among patients with CKD stages 2 to 4, higher serum calcification propensity is associated with more severe CAC and CAC progression.

Keywords: Coronary artery disease; calcification propensity; calciprotein particles; cardiovascular disease (CVD); chronic kidney disease (CKD); coronary artery calcium (CAC); epidemiology; risk factors; transformation time (T(50)).