Mariana Lazo1, Marc K Halushka2, Lu Shen3, Nisa Maruthur4, Casey M Rebholz3, Andreea M Rawlings3, Ron C Hoogeveen5, Tina E Brinkley6, Christie M Ballantyne5, Brad C Astor7, Elizabeth Selvin4. 1. Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Electronic address: mlazo@jhu.edu. 2. Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD. 3. Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 4. Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 5. Department of Medicine, Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, TX. 6. Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC. 7. Departments of Medicine and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Abstract
BACKGROUND: Experimental studies in animals suggest that circulating soluble receptor for advanced glycation end products (sRAGE) decrease oxidative stress, inflammation, and fibrosis. The association between sRAGE and incident heart failure has not been systematically examined in a prospective study. METHODS: We conducted a prospective analysis of a subsample of 1,086 participants from the Atherosclerosis Risk in Communities Study who attended visit 2 (1990-1992) without a history of coronary heart disease, stroke, or heart failure and with measured plasma sRAGE levels. Incident heart failure was defined as death from heart failure or hospitalization due to heart failure during a median of 20 years of follow-up. RESULTS: In this sample of a community-based population (mean age 63 years, 60% women, 78% white), there were 126 incident cases of heart failure. Lower levels of sRAGE were significantly associated with an increased risk of heart failure; the adjusted hazard ratios (95% CIs) of heart failure were 1.0 (reference), 1.81 (0.94-3.49), 1.57 (0.80-3.08), and 3.37 (1.75-6.50), for fourth, third, second, and first quartiles, respectively (P for trend = .001). We did not observe significant interactions by diabetes status or by race or obesity status. CONCLUSIONS: Lower circulating levels of sRAGE are independently associated with the development of heart failure in a community-based population. Our results add to the growing evidence that sRAGE is a valuable predictor of cardiovascular disease.
BACKGROUND: Experimental studies in animals suggest that circulating soluble receptor for advanced glycation end products (sRAGE) decrease oxidative stress, inflammation, and fibrosis. The association between sRAGE and incident heart failure has not been systematically examined in a prospective study. METHODS: We conducted a prospective analysis of a subsample of 1,086 participants from the Atherosclerosis Risk in Communities Study who attended visit 2 (1990-1992) without a history of coronary heart disease, stroke, or heart failure and with measured plasma sRAGE levels. Incident heart failure was defined as death from heart failure or hospitalization due to heart failure during a median of 20 years of follow-up. RESULTS: In this sample of a community-based population (mean age 63 years, 60% women, 78% white), there were 126 incident cases of heart failure. Lower levels of sRAGE were significantly associated with an increased risk of heart failure; the adjusted hazard ratios (95% CIs) of heart failure were 1.0 (reference), 1.81 (0.94-3.49), 1.57 (0.80-3.08), and 3.37 (1.75-6.50), for fourth, third, second, and first quartiles, respectively (P for trend = .001). We did not observe significant interactions by diabetes status or by race or obesity status. CONCLUSIONS: Lower circulating levels of sRAGE are independently associated with the development of heart failure in a community-based population. Our results add to the growing evidence that sRAGE is a valuable predictor of cardiovascular disease.
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