Skin Autofluorescence–Indicated Advanced Glycation End Products as Predictors of Cardiovascular and All‐Cause Mortality in High‐Risk Subjects: A Systematic Review and Meta‐analysis

Cavero‐Redondo, Iván; Soriano-Cano, Alba; Álvarez‐Bueno, Celia; Cunha, Pedro; Martínez‐Hortelano, José Alberto; Garrido‐Miguel, Miriam; Berlanga-Macías, Carlos; Martínez‐Vizcaíno, Vicente

doi:10.1161/jaha.118.009833

Cited by 51 publications

(44 citation statements)

References 54 publications

(82 reference statements)

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“…Improvements in both the quantitative and qualitative definitions of MetS agree with previous research, indicating that HbA1c is a good predictor of mortality and cardiovascular events [11]. Additionally, these findings are in line with previous evidence of a strong association between HbA1c and skin autofluorescence-indicated advanced glycation end-products (AGEs) [40], a tissue biomarker considered an indicator closely related with PWv, IMT and ACR [41], and associated with mortality and cardiovascular events [42].…”

Section: Discussionsupporting

confidence: 88%

Metabolic Syndrome Including Glycated Hemoglobin A1c in Adults: Is It Time to Change?

Cavero‐Redondo

Martínez‐Vizcaíno

Álvarez‐Bueno

et al. 2019

JCM

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1) Background: To assess the suitability of replacing conventional markers used for insulin resistance and dysglycemia by HbA1c in both the quantitative and qualitative metabolic syndrome (MetS) definition criteria; (2) Methods: Confirmatory factorial analysis was used to compare three quantitative definitions of MetS that consisted of many single-factor models, one of which included HbA1c as the dysglycemia indicator. After that, the model with the better goodness-of-fit was selected. Furthermore, a new MetS qualitative definition was proposed by replacing fasting plasma glucose with HbA1c > 5.7% in the International Diabetes Federation (IDF) definition. The clinical performance of these two MetS criteria (IDF and IDF-modified including HbA1c as the dysglycemia indicator) to predict vascular damage (pulse wave velocity [PWv], intima media thickness [IMT] and albumin-to-creatinine ratio [ACR]) was estimated; (3) Results: The single-factor model including HbA1c showed the better goodness-of-fit (χ 2 = 2.45, df = 2, p = 0.293, CFI = 0.999, SRMR = 0.010). Additionally, the IDF-modified criteria gained in clinical performance to predict vascular damage (diagnostic Odds Ratio: 6.94, 1.34 and 1.90) for pulse wave velocity (PWv), intima media thickness (IMT) and albumin-to-creatinine ratio (ACR), respectively; and (4) Conclusions: These data suggest that HbA1c could be considered as a useful component to be included in the MetS definition.

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Section: Discussionsupporting

confidence: 88%

Metabolic Syndrome Including Glycated Hemoglobin A1c in Adults: Is It Time to Change?

Cavero‐Redondo

Martínez‐Vizcaíno

Álvarez‐Bueno

et al. 2019

JCM

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“…The deterioration of EC with AGE accumulation may, therefore, be the result of AGEs causing the functional decline of several organ systems that regulate EC, regardless of DM status. A recent meta-analysis demonstrated that SAF levels were a predictor of mortality in high-risk patients [15]. This could potentially be explained by the association between high SAF levels and reduced EC observed in the present study.…”

Section: Discussionsupporting

confidence: 56%

“…Skin autofluorescence (SAF) has recently been developed as an accurate and noninvasive method to measure AGE accumulation in the skin. SAF has received attention as its results can provide a useful predictor of allcause mortality and cardiovascular mortality in patients who are high-risk [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients

Kunimoto

Shimada

Yokoyama

et al. 2020

BMC Cardiovasc Disord

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Background: Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. Methods: We enrolled 319 consecutive CVD patients aged ≥40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). Results: The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P < 0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P < 0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13-4.05; P = 0.02). Conclusion: High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM.

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“…Indeed, MI rat model established in this study was characterized by increased amount of VAs. MACE was reported to be closely associated with AGEs content in high-risk patients with atherosclerotic cardiovascular diseases [24]. In the present study, our cohort analysis suggested that post-MI PVCs were more frequent in STEMI patients complicated with diabetes.…”

Section: Discussionsupporting

confidence: 56%

Hyper-Activation of Endoplasmic Reticulum Stress PERK/Calcineurin/RyR2 Signaling Pathway is Involved in AGEs-Exacerbated Post- Myocardial Infarction Ventricular Arrhythmias

Liu¹,

Zhang²,

Pan³

et al. 2020

Preprint

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Background: The current study was aimed to investigate the mechanisms of advanced glycation end products (AGEs) in exacerbating post- myocardial infarction (MI) ventricular arrhythmias (VAs). Methods: Correlation between premature ventricular contractions (PVCs) and serum AGEs concentrations was analyzed in a cohort consisted of 101 STEMI patients with culprit vessel of left anterior descending artery (LAD). Established MI rat model were treated with AGEs and/or anti- receptor for AGE (RAGE) antibody. Electrocardiography was used to record VAs. Myocytes were isolated from adjacent area around infracted region. Immunofluorescent stains were used to evaluate association between FKBP12.6 (FK506-bindingprotein 12.6) and ryanodine receptor 2 (RyR2). Calcium sparks were evaluated by confocal microscope. Protein expression and phosphorylation were assessed by Western blotting. A colorimetric method was used to determine the enzymatic activity of calcineurin (CaN). [3H]-ryanodine binding assay was carried out to detect the RyR2 channel activity. Results: In the cohort study, significantly increased amount of (PVCs) were found in STEMI patients with diabetes (P<0.05). Serum AGEs concentration was significantly positively correlated with PVCs amount in STEMI patients (r=0.416, P<0.001). Multivariate analysis showed serum AGEs concentration was independently and positively related to frequent PVCs (adjusted hazard ratio, 1.86; 95% CI, 1.09-3.18, P=0.022). In the animal study, increased glucose regulated protein 78 (GRP78) expression, protein kinase RNA-like ER kinase (PERK) phosphorylation, CaN enzymatic activity, FKBP12.6-RyR2 disassociation, RyR2 channel opening and endoplasmic reticulum (ER) calcium releasing were found in MI animals exposed to AGEs, which were attenuated by anti-RAGE antibody treatment. This RAGE blocking also significantly lowered the VAs amount in MI animals exposed to AGEs. Conclusions: Hyper-activation of ER stress- mediated PERK/CaN/RyR2 signaling participated in AGEs- exacerbated post-MI VAs.

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Skin Autofluorescence–Indicated Advanced Glycation End Products as Predictors of Cardiovascular and All‐Cause Mortality in High‐Risk Subjects: A Systematic Review and Meta‐analysis

Cited by 51 publications

References 54 publications

Metabolic Syndrome Including Glycated Hemoglobin A1c in Adults: Is It Time to Change?

Metabolic Syndrome Including Glycated Hemoglobin A1c in Adults: Is It Time to Change?

Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients

Hyper-Activation of Endoplasmic Reticulum Stress PERK/Calcineurin/RyR2 Signaling Pathway is Involved in AGEs-Exacerbated Post- Myocardial Infarction Ventricular Arrhythmias

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