Joshua D Bundy1,2, Xuan Cai2, Rupal C Mehta2,3, Julia J Scialla4, Ian H de Boer5, Chi-Yuan Hsu6, Alan S Go7, Mirela A Dobre8, Jing Chen9, Panduranga S Rao10, Mary B Leonard11, James P Lash12, Geoffrey A Block13, Raymond R Townsend14, Harold I Feldman14,15,16, Edward R Smith17, Andreas Pasch18, Tamara Isakova19,3. 1. Department of Preventive Medicine, jbundy1@tulane.edu tamara.isakova@northwestern.edu. 2. Center for Translational Metabolism and Health, Institute for Public Health and Medicine, and. 3. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 4. Department of Medicine, Duke Clinical Research Institute, Duke University, Durham, North Carolina. 5. Department of Medicine, University of Washington, Seattle, Washington. 6. Department of Medicine, University of California San Francisco School of Medicine, San Francisco, California. 7. Comprehensive Clinical Research Unit, Kaiser Permanente Northern California Division of Research, Oakland, California. 8. Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio. 9. Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana. 10. Department of Medicine, University of Michigan Health System, Ann Arbor, Michigan. 11. Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California. 12. Department of Medicine, University of Illinois College of Medicine at Chicago, Chicago, Illinois. 13. Department of Product Development, Reata Pharmaceuticals, Inc., Irving, Texas. 14. Department of Medicine. 15. Department of Biostatistics, Epidemiology, and Informatics, and. 16. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. 17. Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia; and. 18. Calciscon AG, Biel-Nidau, Switzerland. 19. Center for Translational Metabolism and Health, Institute for Public Health and Medicine, and jbundy1@tulane.edu tamara.isakova@northwestern.edu.
Abstract
BACKGROUND AND OBJECTIVES: Patients with CKD are at high risk for cardiovascular disease, ESKD, and mortality. Vascular calcification is one pathway through which cardiovascular disease risks are increased. We hypothesized that a novel measure of serum calcification propensity is associated with cardiovascular disease events, ESKD, and all-cause mortality among patients with CKD stages 2-4. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 3404 participants from the prospective, longitudinal Chronic Renal Insufficiency Cohort Study, we quantified calcification propensity as the transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. We used multivariable-adjusted Cox proportional hazards regression models to assess the associations of T50 with risks of adjudicated atherosclerotic cardiovascular disease events (myocardial infarction, stroke, and peripheral artery disease), adjudicated heart failure, ESKD, and mortality. RESULTS: The mean T50 was 313 (SD 79) minutes. Over an average 7.1 (SD 3.1) years of follow-up, we observed 571 atherosclerotic cardiovascular disease events, 633 heart failure events, 887 ESKD events, and 924 deaths. With adjustment for traditional cardiovascular disease risk factors, lower T50 was significantly associated with higher risk of atherosclerotic cardiovascular disease (hazard ratio [HR] per SD lower T50, 1.14; 95% confidence interval [95% CI], 1.05 to 1.25), ESKD within 3 years from baseline (HR per SD lower T50, 1.68; 95% CI, 1.52 to 1.86), and all-cause mortality (HR per SD lower T50, 1.16; 95% CI, 1.09 to 1.24), but not heart failure (HR per SD lower T50, 1.06; 95% CI, 0.97 to 1.15). After adjustment for eGFR and 24-hour urinary protein, T50 was not associated with risks of atherosclerotic cardiovascular disease, ESKD, and mortality. CONCLUSIONS: Among patients with CKD stages 2-4, higher serum calcification propensity is associated with atherosclerotic cardiovascular disease events, ESKD, and all-cause mortality, but this association was not independent of kidney function. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_10_28_CJN04710419.mp3.
BACKGROUND AND OBJECTIVES:Patients with CKD are at high risk for cardiovascular disease, ESKD, and mortality. Vascular calcification is one pathway through which cardiovascular disease risks are increased. We hypothesized that a novel measure of serum calcification propensity is associated with cardiovascular disease events, ESKD, and all-cause mortality among patients with CKD stages 2-4. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 3404 participants from the prospective, longitudinal Chronic Renal Insufficiency Cohort Study, we quantified calcification propensity as the transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. We used multivariable-adjusted Cox proportional hazards regression models to assess the associations of T50 with risks of adjudicated atherosclerotic cardiovascular disease events (myocardial infarction, stroke, and peripheral artery disease), adjudicated heart failure, ESKD, and mortality. RESULTS: The mean T50 was 313 (SD 79) minutes. Over an average 7.1 (SD 3.1) years of follow-up, we observed 571 atherosclerotic cardiovascular disease events, 633 heart failure events, 887 ESKD events, and 924 deaths. With adjustment for traditional cardiovascular disease risk factors, lower T50 was significantly associated with higher risk of atherosclerotic cardiovascular disease (hazard ratio [HR] per SD lower T50, 1.14; 95% confidence interval [95% CI], 1.05 to 1.25), ESKD within 3 years from baseline (HR per SD lower T50, 1.68; 95% CI, 1.52 to 1.86), and all-cause mortality (HR per SD lower T50, 1.16; 95% CI, 1.09 to 1.24), but not heart failure (HR per SD lower T50, 1.06; 95% CI, 0.97 to 1.15). After adjustment for eGFR and 24-hour urinary protein, T50 was not associated with risks of atherosclerotic cardiovascular disease, ESKD, and mortality. CONCLUSIONS: Among patients with CKD stages 2-4, higher serum calcification propensity is associated with atherosclerotic cardiovascular disease events, ESKD, and all-cause mortality, but this association was not independent of kidney function. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_10_28_CJN04710419.mp3.
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