Clinical InvestigationSoluble receptor for advanced glycation end products and the risk for incident heart failure: The Atherosclerosis Risk in Communities Study
Section snippets
Study population
The Atherosclerosis Risk in Communities (ARIC) Study is an ongoing cohort study of 15,792 initially middle-aged adults recruited from 4 US communities: Forsyth Country, North Carolina; Jackson, Mississippi; suburban Minneapolis, Minnesota; and Washington County, Maryland.10 The first examination of participants took place from 1987 to 1989, with 3 follow-up visits, occurring approximately 3 years apart, and a fifth visit in 2011 to 2013. The study population for the present study is composed of
Sources of funding
The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This research was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK076770 and a grant from the American Heart Association to Dr Selvin.
The authors
Results
Baseline characteristics of the study population by overall and race-specific quartiles of sRAGE are shown in Table I. Blacks had substantially lower levels of sRAGE and a higher prevalence of diabetes and hypertension. Regardless of the race/ethnicity, the following were factors associated with low levels of sRAGE: male sex, diabetes, and hypertension; higher BMI; higher CRP; and higher GGT levels.
During a median follow-up of 20 years, there were 126 cases of heart failure among the 1,086
Discussion
In this community-based population of middle-aged individuals without clinically evident cardiovascular disease and normal kidney function, we found that low levels of sRAGE were independently associated with increased risk of heart failure over a median of 20 years of follow-up. Furthermore, addition of sRAGE to the ARIC heart failure prediction model resulted in a small but significant improvement in prediction. As it has been postulated, low sRAGE levels were significantly correlated with
Author contributions
M.L. conceived the study question, analyzed and interpreted the data, and drafted the manuscript and is the guarantor of this work; L.S. analyzed the data; M.K.H., N.M., C.R., A.R., T.B., R.H., C.B., and B.A. interpreted the data and critically revised the manuscript for intellectual content; E.S. conceived the study question, interpreted the data, critically revised the manuscript for intellectual content, obtained funding, and supervised the study.
The following are the supplementary data
Acknowledgements
The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This research was supported by The National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK076770 and a grant from the American Heart Association to Dr Selvin.
The authors
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2021, European Journal of Integrative MedicineCitation Excerpt :AGEs can promote cross-linking between collagens. Cross-linked collagen is difficult to degrade, leading to myocardial fibrosis and stiffness [33,34]. In addition, accumulated AGEs can activate the NF-κB signaling pathway through RAGE [35].
Association between the soluble receptor for advanced glycation end products (sRAGE) and NAFLD in participants in the Atherosclerosis Risk in Communities Study
2021, Digestive and Liver DiseaseCitation Excerpt :Analyses of RAGE activity in cardiovascular disease, diabetes and obesity have suggested that sRAGE may function as a decoy receptor for AGEs thereby preventing RAGE-mediated inflammatory signaling and downstream effects including thrombosis, atherosclerosis and insulin resistance [8,23,31,32]. It has, therefore, been postulated that high levels of sRAGE may serve in a protective role in these disorders whereas low levels may indicate injury and a proinflammatory state [23,31]. Further studies in diabetes, however, have challenged this paradigm for chronic disease and have suggested that constitutive pathway activation may lead to high, rather than low, levels of sRAGE [13,31,33].
The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes
2021, Redox BiologyCitation Excerpt :For adults who in the main had no documented pre-existing chronic conditions at baseline, findings were mixed. In non-prescreened adults from the general population, positive [80] or no significant associations [40,81] were generally reported, whereas for individuals with no prior history of CVD, the associations with incident disease or adverse events were found to be negative [38,82,83]. In contrast, studies carried out in diabetics (type I or type 2) consistently reported that high levels of sRAGE were predictive of cardiovascular events and/or mortality [26,36,84–86].
The different roles for the advanced glycation end products axis in heart failure and acute coronary syndrome settings
2019, Nutrition, Metabolism and Cardiovascular DiseasesCitation Excerpt :These levels allow sRAGE to function as a decoy for AGEs, limiting their interaction with RAGE and conferring vascular protection [32]. Supporting this, in a cohort from the ARIC study without a history of coronary artery disease, stroke or HF, lower circulating levels of sRAGE were independently associated with the development of HF over a median of 20 years of follow-up [33]. However, under several pathological conditions, such as hypertension [29], hypercholesterolemia [34], inflammation [35] or coronary artery disease [28,31], levels of sRAGE become reduced, limiting its ability to work as a decoy.
Conflict of interest: None.