Abstract
Background and aimsThe soluble receptor for advanced glycation end products (sRAGE) has been implicated in diabetic vascular complications. We have examined the association between sRAGE and cardiac markers [NT-proBNP and cardiac troponin T (cTnT)] and subclinical vascular markers in older men with and without diabetes. MethodsWe performed a cross-sectional study of 1159 men aged 71–92 years with no history of cardiovascular disease (myocardial infarction, stroke, heart failure, coronary artery bypass graft operation or angioplasty). Prevalent diabetes included men with a doctor diagnosis of diabetes, men with fasting glucose ≥7 mmol/l or HbA1c ≥ 6.5% (N = 180). Subclinical vascular measurements included carotid intima media thickness (cIMT), arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure and arterial wave reflections [central augmentation pressure (AP) and augmentation index (AIx)]. ResultssRAGE was strongly and positively associated with renal dysfunction in men with and without diabetes. sRAGE was significantly and positively associated with NT-proBNP (but not cTnT) and AP and AIx in both groups of men after adjustment for CVD risk and metabolic risk markers, renal function and inflammation. However, no association was seen between sRAGE and central aortic blood pressure, cIMT or arterial stiffness as determined by PWV in either group. ConclusionsHigher plasma sRAGE was associated with increased NT-proBNP and markers of arterial wave reflections in men both with and without diabetes. Increased sRAGE may contribute to or be a marker of worsening cardiac dysfunction or HF. Further studies with cardiac imaging data are required to confirm this.
Highlights
Advanced glycation end products (AGEs) are bioactive molecules found in high amounts in the western diet, which have been implicated in the pathogenesis of atherosclerosis and heart failure (HF), in patients with diabetes [1e4]
To address the controversy regarding the possible role of soluble receptor for advanced glycation end products (sRAGE) in CVD, we have investigated the association between circulating sRAGE and early markers of vascular disease including arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure, arterial wave reflections [central augmentation pressure (AP), augmentation index (AIx)] and intima-media thickness (IMT), as well as biomarkers of subclinical myocardial injury and stress [cardiac troponin T and N-terminal pro B-type natriuretic peptide (NT-proBNP)], separately in those with and without diabetes
SRAGE related positively to age and eGFR but weak positive associations were seen with IL-6, and a significant positive association was seen with use of antihypertensive treatment
Summary
Advanced glycation end products (AGEs) are bioactive molecules found in high amounts in the western diet, which have been implicated in the pathogenesis of atherosclerosis and heart failure (HF), in patients with diabetes [1e4]. Numerous studies highlight the interaction between AGEs with their receptor (RAGE), which is expressed in the vasculature, kidney and inflammatory cells, as a potential contributor to increased oxidative stress and inflammation, vascular endothelial dysfunction and arterial stiffening [1,2]. To address the controversy regarding the possible role of sRAGE in CVD, we have investigated the association between circulating sRAGE and early markers of vascular disease including arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure, arterial wave reflections [central augmentation pressure (AP), augmentation index (AIx)] and intima-media thickness (IMT), as well as biomarkers of subclinical myocardial injury and stress [cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP)], separately in those with and without diabetes. Subclinical vascular measurements included carotid intima media thickness (cIMT), arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure and arterial wave reflections [central augmentation pressure (AP) and augmentation index (AIx)]. Further studies with cardiac imaging data are required to confirm this
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