Serum carboxymethyl-lysine, an advanced glycation end product, is associated with arterial stiffness in older adults

Semba, Richard D.; Sun, Kai; Schwartz, Ann V.; Varadhan, Ravi; Harris, Tamara B.; Satterfield, Suzanne; Garcia, Melissa; Ferrucci, Luigi; Newman, Anne B.

doi:10.1097/hjh.0000000000000460

Cited by 64 publications

(40 citation statements)

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“…Our results are in agreement with previous studies, which demonstrated that skin AGEs are associated with arterial stiffening in type 1 diabetes mellitus, 16 heart disease, and 10 end-stage renal disease 11 and in the elderly. 12,19 We found relatively small standardized regression coefficients in these associations. In comparison, sβs and 95% CIs of the associations between mean arterial pressure and age on the one hand and cfPWV on the other were 0.37 (0.31-0.43) and 0.31 (0.24-0.38), respectively, in our study.…”

Section: Discussionmentioning

confidence: 66%

“…This is in contrast with other studies that demonstrated an association between the plasma AGEs, CML, and CEL, and arterial stiffening in other populations. 13,14,[17][18][19] In the case of CML, it has recently been described that the trapping of CML by the RAGE in adipose tissue causes a decrease in AGE plasma levels in individuals with T2DM. 34 Therefore, plasma CML may not be a good reflection of CML accumulation in tissues in individuals with T2DM.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14][15][16][17][18][19][20] Only one case-control study investigated this association in individuals with T2DM. This study found no association between serum pentosidine and heart-brachial pulse-wave velocity or brachialankle pulse-wave velocity after adjustment for renal function.…”

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confidence: 99%

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Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening

et al. 2016

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Abstract-Arterial stiffening, as characterized by an increase in carotid-femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (sβ 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (sβ 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulsewave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction<0.10). These results support the hypothesis that accumulation of advanced glycation end products is involved in arterial stiffening and may explain part of the increased risk of cardiovascular disease in individuals with type 2 diabetes mellitus. carotid to femoral pulse-wave velocity (cfPWV) or pulse pressure, both measures of aortic stiffening, in a population-based setting, including individuals with normal glucose metabolism (NGM), impaired glucose metabolism (IGM), and T2DM. In view of these considerations, the aims of our study were, first, to evaluate the independent association between SAF and plasma AGEs on the one hand and measures of arterial stiffening, ie, cfPWV, central pulse pressure, and 24-hour ambulatory pulse pressure, on the other. Second, to examine whether these associations differed between individuals with NGM, IGM, or T2DM. Methods Study Population and DesignIn this study, we used data from The Maastricht Study, an observational prospective population-based cohort study. The rationale and methodology have been described previously. 22 In brief, the study focuses on the cause, pathophysiology, complications, and comorbidities of type 2 diabetes mellitus (T2DM) and is characterized by an extensive phenotyping approach. Eligible for participation were all individuals aged between 40 and 75 years and living in the southern part of the Netherlands. Participants were recruited through mass media campaigns and from the municipal registries and the regional Diabetes Patient Registry via mailings. Recruitment was stratified according to known T2DM status for reasons of efficiency. The present report includes cross-sectional data from the ...

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening

et al. 2016

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“…Alterations in blood flow dynamics result in the expression of mechanosensitive genes, which induce vascular remodeling, oxidative stress, and pro-atherogenic changes in the vascular wall (Ungvari et al, 2010). Upregulation of the renin-angiotensin system (Spinetti et al, 2004; Wang et al, 2007; Wang et al, 2005) and elevation in advanced glycation end products (Semba et al, 2009; Semba et al, 2015) also contribute to arterial wall stiffness.…”

Section: Cerebrovascular Biology and Agingmentioning

confidence: 99%

The impact of cerebrovascular aging on vascular cognitive impairment and dementia

Yang

Sun

et al. 2017

Ageing Research Reviews

158

128

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As human life expectancy rises, the aged population will increase. Aging is accompanied by changes in tissue structure, often resulting in functional decline. For example, aging within blood vessels contributes to a decrease in blood flow to important organs, potentially leading to organ atrophy and loss of function. In the central nervous system, cerebral vascular aging can lead to loss of the integrity of the blood-brain barrier, eventually resulting in cognitive and sensorimotor decline. One of the major of types of cognitive dysfunction due to chronic cerebral hypoperfusion is vascular cognitive impairment and dementia (VCID). In spite of recent progress in clinical and experimental VCID research, our understanding of vascular contributions to the pathogenesis of VCID is still very limited. In this review, we summarize recent findings on VCID, with a focus on vascular age-related pathologies and their contribution to the development of this condition.

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“…AGE-CML has been shown to be positively associated with incident and prevalent diabetes and also cardiovascular disease risk factors (9–11). The direction of association for sRAGE with diabetes and cardiovascular risk factors, however, has varied substantially by population type.…”

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confidence: 99%

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort

et al. 2017

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BACKGROUND Advanced glycation end products (AGEs) and their receptors are regarded as central to the development of diabetic complications, but associations with diabetes and cardiometabolic outcomes in previous studies are mixed. METHODS Using ELISA assays, we measured N(6)-carboxymethyllysine (AGE-CML), soluble receptor for AGEs (sRAGE), and endogenous secreted receptor for AGEs (esRAGE) in 1874 participants from the Atherosclerosis Risk in Communities study. We conducted a cross-sectional analysis to evaluate associations of these biomarkers with demographics, diabetes, hyperglycemia, cardiometabolic measures, and genetic variants in the gene encoding RAGE, AGER (advanced glycosylation end-product specific receptor). RESULTS After adjustment for demographics and body mass index (BMI), there were no significant differences in AGE-CML, sRAGE, or esRAGE by diabetes or hemoglobin A1c. Black race and AGER genetic variants were strongly associated with lower sRAGE and esRAGE even after adjustment [percent difference (95% CI) in black vs whites in sRAGE: −29.17 (−34.86 to −23.48), esRAGE: −26.97 (−33.11 to −20.84); with rs2070600 in sRAGE: −30.13 (−40.98 to −19.29), and esRAGE: −30.32 (−42.42 to −18.21); with rs2071288 in sRAGE: −20.03 (−34.87 to −5.18), and esRAGE: −37.70 (−55.75 to −19.65)]. Estimated glomerular filtration rate and albuminuria significantly correlated with sRAGE and esRAGE. BMI and C-reactive protein significantly negatively correlated with AGE-CML, sRAGE, and esRAGE. AGE-CML was modestly correlated with fructosamine and glycated albumin. CONCLUSIONS AGE-CML, sRAGE, and esRAGE were more related to genetic, kidney, and inflammatory measures than to diabetes in this community-based population. Our results suggest that, when measured by ELISA, these biomarkers lack specificity and are of limited value in evaluating the role of these compounds in diabetes.

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Serum carboxymethyl-lysine, an advanced glycation end product, is associated with arterial stiffness in older adults

Cited by 64 publications

References 50 publications

Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening

Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening

The impact of cerebrovascular aging on vascular cognitive impairment and dementia

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort

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