Joshua D Bundy1, Xuan Cai2, Julia J Scialla3, Mirela A Dobre4, Jing Chen5, Chi-Yuan Hsu6, Mary B Leonard7, Alan S Go8, Panduranga S Rao9, James P Lash10, Raymond R Townsend11, Harold I Feldman12, Ian H de Boer13, Geoffrey A Block14, Myles Wolf3, Edward R Smith15, Andreas Pasch16, Tamara Isakova17. 1. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: jdbundy@northwestern.edu. 2. Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. 3. Department of Medicine, Duke Clinical Research Institute, Duke University, Durham, NC. 4. Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH. 5. Department of Medicine, Tulane University School of Medicine, New Orleans, LA. 6. Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA. 7. Department of Pediatrics, Stanford University School of Medicine, Palo Alto. 8. Comprehensive Clinical Research Unit, Kaiser Permanente Northern California Division of Research, Oakland, CA. 9. Department of Medicine, University of Michigan Health System, Ann Arbor, MI. 10. Department of Medicine, University of Illinois College of Medicine at Chicago, Chicago, IL. 11. Departments of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. 12. Departments of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. 13. Department of Medicine, University of Washington, Seattle, WA. 14. Colorado Kidney Care, Denver, CO. 15. Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia. 16. Calciscon AG, Biel-Nidau, Switzerland. 17. Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: tamara.isakova@northwestern.edu.
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.
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.
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