Benjamin Lidgard1, Leila Zelnickv1, Amanda H Anderson2, Harold Feldman3, Alan Go4, Jiang He2, Mayank Kansal5, Madhumita Jena Mohanty6, Rupal Mehta7, Michael G Shlipak8, Elsayed Soliman9, Matt R Weir10, Nisha Bansal1. 1. Division of Nephrology, University of Washington, Seattle, Washington. 2. Department of Epidemiology, Tulane University, New Orleans, Louisiana. 3. CRIC Scientific and Data Coordinating Center, University of PennsylvaniaPhiladelphia, Pennsylvania. 4. Kaiser Permanente Division of Research, Northern California, Oakland, California. 5. Department of Medicine, University of Illinois at Chicago, Chicago, Illinois. 6. Division of Nephrology, Wayne State University, Detroit, Michigan. 7. Division of Nephrology, Northwestern University, Chicago, Illinois. 8. Division of Nephrology, University of California, San Francisco, San Francisco, California. 9. Department of Medicine, Wake Health, Winston-Salem, North Carolina. 10. Division of Nephrology, University of Maryland, College Park, Maryland.
Abstract
Background: Several cardiac biomarkers of cardiac stress, inflammation, and fibrosis (N-terminal pro brain-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hsTnT], growth differentiation factor 15 [GDF-15], and soluble ST2 [sST2]) have been associated with atherosclerotic disease in the general population. We hypothesized that these cardiac biomarkers may also be associated with the atherosclerotic cardiovascular disease in patients with CKD. Methods: We analyzed levels of NT-proBNP, hsTnT, GDF-15, and sST2 in a cohort of 2732 participants with mild to moderate CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. Outcomes included incident atherosclerotic disease, defined as the first instance of myocardial infarction, stroke, or peripheral vascular disease. We used Cox proportional hazard models to the test the association of each cardiac biomarker with risk of incident atherosclerotic disease, adjusting for multiple possible confounders. Results: When modeled continuously (per SD increase in the log-transformed biomarker), NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic disease after adjustment for multiple potential confounders: (NT-proBNP HR, 1.51; 95% CI, 1.27 to 1.81; hsTnT HR, 1.61; 95% CI, 1.38 to 1.89; GDF-15 HR, 1.44; 95% CI, 1.19 to 1.73; and sST2 HR, 1.19; 95% CI, 1.04 to 1.36). Conclusions: NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic cardiovascular disease in patients with CKD. These associations may highlight important mechanisms for the development of atherosclerotic disease in CKD.
Background: Several cardiac biomarkers of cardiac stress, inflammation, and fibrosis (N-terminal pro brain-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hsTnT], growth differentiation factor 15 [GDF-15], and soluble ST2 [sST2]) have been associated with atherosclerotic disease in the general population. We hypothesized that these cardiac biomarkers may also be associated with the atherosclerotic cardiovascular disease in patients with CKD. Methods: We analyzed levels of NT-proBNP, hsTnT, GDF-15, and sST2 in a cohort of 2732 participants with mild to moderate CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. Outcomes included incident atherosclerotic disease, defined as the first instance of myocardial infarction, stroke, or peripheral vascular disease. We used Cox proportional hazard models to the test the association of each cardiac biomarker with risk of incident atherosclerotic disease, adjusting for multiple possible confounders. Results: When modeled continuously (per SD increase in the log-transformed biomarker), NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic disease after adjustment for multiple potential confounders: (NT-proBNP HR, 1.51; 95% CI, 1.27 to 1.81; hsTnT HR, 1.61; 95% CI, 1.38 to 1.89; GDF-15 HR, 1.44; 95% CI, 1.19 to 1.73; and sST2 HR, 1.19; 95% CI, 1.04 to 1.36). Conclusions: NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic cardiovascular disease in patients with CKD. These associations may highlight important mechanisms for the development of atherosclerotic disease in CKD.
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