Association Of Skin Autofluorescence Research Articles

The AGE-RAGE axis associates with chronic pulmonary diseases and smoking in the Rotterdam study

BackgroundChronic obstructive pulmonary disease (COPD) and asthma associate with high morbidity and mortality. High levels of advanced glycation end products (AGEs) were found in tissue and plasma of COPD patients but their role in COPD and asthma is unclear.MethodsIn the Rotterdam Study (n = 2577), AGEs (by skin autofluorescence (SAF)), FEV1 and lung diffusing capacity (DLCOc and DLCOc /alveolar volume [VA]) were measured. Associations of SAF with asthma, COPD, GOLD stage, and lung function were analyzed using logistic and linear regression adjusted for covariates, followed by interaction and stratification analyses. sRAGE and EN-RAGE associations with COPD prevalence were analyzed by logistic regression.ResultsSAF associated with COPD prevalence (OR = 1.299 [1.060, 1.591]) but not when adjusted for smoking (OR = 1.106 [0.89, 1.363]). SAF associated with FEV1% predicted (β=-3.384 [-4.877, -1.892]), DLCOc (β=-0.212 [-0.327, -0.097]) and GOLD stage (OR = 4.073, p = 0.001, stage 3&4 versus 1). Stratified, the association between SAF and FEV1%predicted was stronger in COPD (β=-6.362 [-9.055, -3.670]) than non-COPD (β=-1.712 [-3.306, -0.118]). Association of SAF with DLCOc and DLCOc/VA were confined to COPD (β=-0.550 [-0.909, -0.191]; β=-0.065 [-0.117, -0.014] respectively). SAF interacted with former smoking and COPD prevalence for associations with lung function. Lower sRAGE and higher EN-RAGE associated with COPD prevalence (OR = 0.575[0.354, 0.931]; OR = 1.778[1.142, 2.768], respectively).ConclusionsAssociations between SAF, lung function and COPD prevalence were strongly influenced by smoking. SAF associated with COPD severity and its association with lung function was more prominent within COPD. These results fuel further research into interrelations and causality between SAF, smoking and COPD.Take-home messageSkin AGEs associated with prevalence and severity of COPD and lung function in the general population with a stronger effect in COPD, calling for further research into interrelations and causality between SAF, smoking and COPD.

Advanced glycation end products measured by skin autofluorescence and subclinical cardiovascular disease: the Rotterdam Study

BackgroundAdvanced glycation end products (AGEs) have been linked to cardiovascular disease (CVD), especially coronary heart disease (CHD), but their role in CVD pathogenesis remains unclear. Therefore, we investigated cross-sectional associations of skin AGEs with subclinical atherosclerosis, arterial stiffness, and hypertension after confirming their relation with CHD.MethodsIn the population-based Rotterdam Study, skin AGEs were measured as skin autofluorescence (SAF). Prevalent MI was obtained from digital medical records. Carotid plaques, carotid intima-media thickness (IMT), coronary artery calcification (CAC), pulse wave velocity (PWV), and hypertension were assessed. Associations of SAF with endophenotypes were investigated in logistic and linear regression models adjusting for common cardiovascular risk factors. Effect modification by sex, diabetes mellitus, and chronic kidney disease (CKD) was tested.Results3001 participants were included (mean age 73 (SD 9) years, 57% women). One unit higher SAF was associated with the presence of carotid plaques (OR 1.2 (0.92, 1.57)), a higher max IMT (0.08 SD (0.01, 0.15)), higher CAC (OR 2.2 (1.39, 3.48)), and PWV (0.09 SD (0.01, 0.16)), but not with hypertension (OR 0.99 (0.81, 1.21)). The associations with endophenotypes were more pronounced in men and participants with diabetes or CKD with significant interactions.ConclusionsPreviously documented associations between SAF and CVD, also found in our study, may be explained by the endophenotypes atherosclerosis and arterial stiffness, especially in men and individuals with diabetes or CKD, but not by hypertension. Longitudinal studies are needed to replicate these findings and to test if SAF is an independent risk factor or biomarker of CVD.Trial registration: The Rotterdam Study has been entered into the Netherlands National Trial Register (NTR; www.trialregister.nl) and the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under shared catalogue number NTR6831.

Association of skin autofluorescence with depressive symptoms and the severity of depressive symptoms: The prospective REACTION study

AimMillions of people are afflicted by depression, a highly prevalent mental illness with increased morbidity and mortality. Advanced glycation end-products (AGEs) are potential risk factors for depression. We aimed to investigate the correlation of AGEs with depressive symptoms and the severity of depressive symptoms. MethodsThis study was nested in the prospective REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study and included 4420 eligible participants. skin autofluorescence (SAF) was used to measure skin AGEs. Depressive symptoms were evaluated by the Self-Rating Depression Scale (SDS). Multiple logistic regression analysis was used to assess the association of AGEs with depressive symptoms and the severity of depressive symptoms. ResultsLogistic analysis showed a significantly positive relationship between quartiles of SAF-AGEs and the risk of depressive symptoms with the OR [95% confidence interval (CI), p value] of 1.24 (95% CI: 1.03–1.50, p = 0.022), 1.39 (95% CI: 1.15–1.68, p = 0.001) and 1.57 (95% CI: 1.28–1.91, p < 0.001) for multivariable-adjusted model respectively. And SAF-AGEs were associated with the severity of depressive symptoms with the multivariable-adjusted OR (95% CI, p value) of 1.06 (95% CI:0.79–1.43, p = 0.681), 1.47 (95% CI: 1.08–1.99, p = 0.014), and 1.54 (95% CI: 1.12–2.11, p = 0.008) respectively. Stratified analyses showed that SAF-AGEs were significantly associated with the severity of depressive symptoms only in females, overweight people, individuals with hypertension, and those without diabetes and insomnia. ConclusionsThe present study showed that a higher SAF-AGEs level was associated with depressive symptoms and the severity of depressive symptoms.

Advanced glycation end-products, cardiac function and heart failure in the general population: The Rotterdam Study

Aims/hypothesisThe aim of this work was to assess the association of advanced glycation end-products (AGEs), measured by skin autofluorescence (SAF), with prevalent heart failure, and with systolic and diastolic cardiac function, in a large population-based cohort study.MethodsWe assessed the cross-sectional association between SAF and prevalent heart failure among 2426 participants from the population-based Rotterdam Study, using logistic regression. Next, among individuals free of heart failure (N=2362), we examined the link between SAF (on a continuous scale) and echocardiographic parameters of left ventricular (LV) systolic and diastolic function using linear regressions. Analyses were adjusted for traditional cardiovascular risk factors.ResultsHigher levels of SAF were associated with higher odds of prevalent heart failure (multivariable adjusted OR 2.90 [95% CI 1.80, 4.62] for one unit higher SAF value). Among individuals without heart failure, one unit increase in SAF was associated with 0.98% lower LV ejection fraction (mean difference [β] −0.98% [95% CI −1.45%, −0.50%]). The association was stronger among participants with diabetes (β −1.84% [95% CI −3.10%, −0.58%] and β −0.78% [95% CI −1.29%, −0.27%] among participants with and without diabetes, respectively). Associations of SAF with diastolic function parameters were not apparent, except in men with diabetes.Conclusions/interpretationAGE accumulation was independently associated with prevalent heart failure. Among individuals free of heart failure, AGEs were associated with cardiac function, in particular systolic function. This association was present in participants with and without diabetes and was more prominent in those with diabetes.Graphical abstract

Advanced glycation end products, their receptor and the risk of dementia in the general population: A prospective cohort study

AbstractBackgroundAdvanced glycation end products (AGEs) and their receptor (RAGE) are implicated in the pathophysiology of dementia and potentially underlie the relation between diabetes and neurodegeneration. We determined the link between two proteins involved in the AGE‐RAGE system, namely Extracellular Newly identified RAGE binding protein (EN‐RAGE) and the soluble form of RAGE (sRAGE), and dementia prevalence and incidence. Additionally, we assessed the association between skin auto fluorescence (SAF), a proxy for AGEs tissue accumulation, and cognition.MethodWithin the prospective Rotterdam Study, plasma EN‐RAGE and sRAGE were measured in 1208 participants (mean age 74.1 (standard deviation (SD) 7.7); 57.5% women). Participants were categorized into tertiles, to compare participants with high, intermediate and low concentrations, with the lowest tertile as the reference. Associations of SAF, measured in 3009 participants (mean age 72.3 (SD 9.4); 56.4% women), and cognition were assessed using linear models. We adjusted for age, sex, diabetes, APOE ε4 carrier status and other potential confounders, including cardiovascular risk factors, and additionally stratified by sex and APOE ε4 status.ResultParticipants with higher EN‐RAGE and lower sRAGE levels were more likely to have dementia (adjusted odds ratio (OR); 3.64 [95% confidence interval 1.56‐8.50] and OR 0.39 [0.17‐0.83], for high level compared to low level). During follow‐up (median 12.4 years), 161 participants developed dementia, of whom 130 Alzheimer’s disease (AD). Higher EN‐RAGE was non‐significantly associated with higher risk of dementia during the first years of follow‐up (adjusted hazard ratio (HR); 1.48 [0.52‐4.25] after 4 years of follow‐up), while a lower risk was found over the entire follow‐up duration (HR 0.65 [0.42‐1.01]) (Figure 1). Higher SAF was associated with lower global cognitive function (adjusted difference in z score per SAF standard deviation (SD); 0.07 [0.04‐0.11]). This effect was stronger for carriers of the APOE ε4 allele (0.15 [0.07‐0.22]).ConclusionOur results indicate involvement of the AGE‐RAGE system in the pathophysiology of dementia, independent of the history of diabetes, showing involvement of EN‐RAGE and sRAGE, and of SAF in cognitive functioning. These associations were stronger for APOE ε4 carriers, suggesting a combined role of AGEs and APOE in neurodegeneration.

Skin autofluorescence in people with type 1 diabetes and people without diabetes: An eight-decade cross-sectional study with evidence of accelerated aging and associations with complications.

To measure skin autofluorescence in youth (<18 y.o.) and adults (≥18 y.o.) and to assess its relationship with type 1 diabetes, chronic complications and smoking. In a cross-sectional study (n=383) skin autofluorescence was measured in 269 people with type 1 diabetes (67 with vascular complications) and 114 people without diabetes, covering eight decades of age. Associations of skin autofluorescence with demographics and traditional risk factors were assessed. Skin autofluorescence increased with age in people with diabetes: for those with complications it increased by a mean ± se of 0.029±0.003 arbitrary units per year (r=0.76) and, for those without complications, it increased by 0.028±0.002 arbitrary units (r=0.77). These increases were higher than for people without diabetes, whose skin autofluorescence increased by 0.022±0.002 arbitrary units (r=0.78) per year (p=0.004). Mean ±se age-adjusted skin autofluorescence was higher in people with diabetes complications vs people without diabetes complications (1.85±0.04 vs 1.66±0.02 arbitrary units) and people without diabetes (1.48±0.03 arbitrary units; all P<0.0001). Age-adjusted skin autofluorescence was higher in current smokers and recent ex-smokers vs non-smokers and longer-term ex-smokers (1.86±0.06 vs 1.63±0.02 arbitrary units; P=0.0005). Skin autofluorescence area under the receiver-operating characteristic curve was 0.89 (95% CI 0.85-0.94) for retinopathy and 0.56 (95% CI 0.47-0.65) for nephropathy. Skin autofluorescence increases with age, but faster in people with diabetes, particularly in those with complications and in smokers, consistent with accelerated aging. Skin autofluorescence may facilitate complication screening and prediction. Longitudinal studies are merited.

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study.

Tissue advanced glycation end product (AGE) accumulation has been proposed as a marker of cumulative metabolic stress that can be assessed noninvasively by measurement of skin autofluorescence (SAF). In persons on haemodialysis, SAF is an independent risk factor for cardiovascular events (CVEs) and all-cause mortality (ACM), but data at earlier stages of chronic kidney disease (CKD) are inconclusive. We investigated SAF as a risk factor for CVEs and ACM in a prospective study of persons with CKD stage 3. Participants with estimated glomerular filtration rate (eGFR) 59 to 30 mL/min/1.73 m2 on two consecutive previous blood tests were recruited from 32 primary care practices across Derbyshire, United Kingdom between 2008 and 2010. SAF was measured in participants with CKD stage 3 at baseline, 1, and 5 years using an AGE reader (DiagnOptics). Data on hospital admissions with CVEs (based on international classification of diseases [ICD]-10 coding) and deaths were obtained from NHS Digital. Cox proportional hazards models were used to investigate baseline variables associated with CVEs and ACM. A total of 1,707 of 1,741 participants with SAF readings at baseline were included in this analysis: The mean (± SD) age was 72.9 ± 9.0 years; 1,036 (60.7%) were female, 1,681 (98.5%) were of white ethnicity, and mean (±SD) eGFR was 53.5 ± 11.9 mL/min/1.73 m2. We observed 319 deaths and 590 CVEs during a mean of 6.0 ± 1.5 and 5.1 ± 2.2 years of observation, respectively. Higher baseline SAF was an independent risk factor for CVEs (hazard ratio [HR] 1.12 per SD, 95% CI 1.03-1.22, p = 0.01) and ACM (HR 1.16, 95% CI 1.03-1.30, p = 0.01). Additionally, increase in SAF over 1 year was independently associated with subsequent CVEs (HR 1.11 per SD, 95% CI 1.00-1.22; p = 0.04) and ACM (HR 1.24, 95% CI 1.09-1.41, p = 0.001). We relied on ICD-10 codes to identify hospital admissions with CVEs, and there may therefore have been some misclassification. We have identified SAF as an independent risk factor for CVE and ACM in persons with early CKD. These findings suggest that interventions to reduce AGE accumulation, such as dietary AGE restriction, may reduce cardiovascular risk in CKD, but this requires testing in prospective randomised trials. Our findings may not be applicable to more ethnically diverse or younger populations.

Association of advanced glycation end-product accumulation with overactive bladder in community-dwelling elderly: A cross-sectional Sukagawa study

ObjectiveThis study aimed to evaluate the influence of advanced glycation end-product (AGE) accumulation on the prevalence and severity of overactive bladder (OAB) in community-dwelling elderly adults. MethodsWe conducted a cross-sectional study involving 269 Japanese community dwellers aged ≥75 years in 2015. AGE accumulation was non-invasively measured via skin autofluorescence (SAF) values using AGE Reader. The primary and secondary outcomes were the presence and severity of OAB evaluated using the Overactive Bladder Symptom Score (OABSS). Individuals with an urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The associations of SAF with the prevalence and severity of OAB were assessed using logistic and linear regression models, respectively, adjusted for clinically important confounders. ResultsThe median age of participants was 78 years. Of 269 participants, 110 (40.9%) were men and 75 (27.9%) had OAB. The median SAF was 2.2 arbitrary units (AUs). Increasing median SAF was observed with increasing age. Multivariable analysis revealed that SAF was not associated with either the likelihood of having OAB (odds ratio per AU=0.77, 95% confidence interval: 0.37–1.62) or the natural log-transformed OABSS (β per AU=−0.07, 95% confidence interval: −0.26–0.12). ConclusionsIn this study, AGE accumulation, as assessed by SAF, was not associated with the prevalence and severity of OAB in Japanese community-dwelling elderly people aged ≥75 years.

Association of skin autofluorescence with plaque vulnerability evaluated by optical coherence tomography in patients with cardiovascular disease

Background and aimsAccumulation of advanced glycation end products (AGEs) can be measured non-invasively by skin autofluorescence (SAF) whose values are elevated in patients with cardiovascular disease (CVD). Optical coherence tomography (OCT) is an intravascular imaging modality that could allow visualization of plaque composition. We aim to examine the relationship between SAF and plaque composition evaluated by frequency-domain OCT in patients with CVD. MethodsWe prospectively enrolled 108 patients with CVD, who underwent OCT images during percutaneous coronary intervention (PCI). We divided the population into two groups: high SAF group (greater than or equal to 2.6) and low SAF one (less than 2.6). OCT findings were then compared between high and low SAF groups. ResultsThe high SAF group showed much more thin cap fibroatheroma (TCFA), and calcified or ruptured plaques compared to the low SAF group. In multivariable analysis, low-density lipoprotein-cholesterol (LDL) (odds ratio: 1.15; 95% confidence interval: 1.00 to 1.32; p = 0.043), TG (OR for 10 mg/dl increase: 1.04; 95% confidence interval: 1.01 to 1.13; p = 0.016), and SAF (4.28; 1.86 to 9.84; p < 0.001) were independent correlates of TCFA, whereas SAF (2.61; 1.02 to 6.70; p = 0.047), estimated glomerular filtration rate (0.68; 0.49 to 0.93; p = 0.017) and LDL (1.19; 1.01 to 1.41; p = 0.037) were independent predictors of ruptured plaques. SAF and diabetes were independently associated with calcified plaques. ConclusionsHigh SAF were associated with plaque vulnerability in patients with CVD, thus suggesting the clinical utility of SAF measurement in identifying high-risk patients for future cardiovascular events.

Skin autofluorescence, arterial stiffness and Framingham risk score as predictors of clinical outcome in chronic kidney disease patients: a cohort study.

The risk of cardiovascular disease (CVD) is predicted by Framingham's CVD risk scores (FRS) but the high CVD-related mortality in patients with chronic kidney disease (CKD) is only partially explained by traditional CVD risk markers. Therefore, there is a need to explore whether other CVD risk markers may improve risk prediction. Although arterial stiffness measured by augmentation index (AIx) and tissue content of advanced glycation end-products (AGEs) measured by skin autofluorescence (SAF) are two biomarkers that associate with CVD and mortality in CKD, it is not known how they compare with FRS. We evaluated associations between SAF, AIx and FRS, and their associations with CVD and mortality in CKD patients. SAF (AGE Reader) and AIx (SphygmoCor; adjusted for 75 heart beats per minute) were measured in 261 clinically stable and extensively phenotyped patients with CKD Stage 5 (median age 56 years, 66% male, 20% diabetes; 130 non-dialysed, 93 patients on peritoneal dialysis and 38 patients on haemodialysis). Multivariate receiver operator characteristics (ROC) curve analysis and multivariate Cox models followed by C-statistics were used to evaluate CVD-related and all-cause mortality risk associated with SAF, AIx and FRS during follow-up for median 25 months with 46 deaths. In multivariate regression analysis, SAF associated with FRS, haemoglobin, fat body mass index and CVD, and inversely with per cent handgrip strength (HGS). AIx associated with FRS, and inversely with per cent HGS. Associations of SAF and AIx with high-sensitivity C-reactive protein (hsCRP), serum albumin, statin therapy and renal replacement therapy were not statistically significant. In ROC analysis, area under the curve (AUC) for CVD mortality ranged from AUC = 0.72 (AIx and FRS, respectively) to AUC = 0.78 (FRS + AIx), and for all-cause mortality from AUC = 0.70 (AIx) to AUC = 0.79 (FRS + AIx). In multivariate Cox analysis, after adjusting for 1-standard deviation (1-SD) of FRS, 1-SD increase of SAF associated with all-cause mortality and 1-SD increase of AIx associated with CVD mortality and all-cause mortality. After further adjustments for hsCRP, albumin and presence of CVD, AIx (but not SAF) remained independently associated with CVD mortality, hazard ratio (HR) 2.14 [95% confidence interval (95% CI) 1.18-3.89] and all-cause mortality, HR 1.74 (95% CI 1.16-2.60). In patients with CKD Stage 5, SAF and aortic stiffness associated with mortality, independently of FRS. After adjusting for additional confounders including inflammation, aortic stiffness remained as an independent predictor of outcome. Since the contribution of SAF and aortic stiffness compared with FRS in ROC curve analysis was relatively modest, this underlines the importance of traditional CVD risk factors in CKD.

Association of advanced glycation end products, evaluated by skin autofluorescence, with lifestyle habits in a general Japanese population.

ObjectiveAccumulation of advanced glycation end products (AGEs) occurs during normal aging but markedly accelerates in people with diabetes. AGEs may play a role in various age-related disorders. Several studies have demonstrated that skin autofluorescence (SAF) reflects accumulated tissue levels of AGEs. However, very few studies have investigated SAF in the general population. The purpose of the present study was to more thoroughly evaluate the potential association among SAF, chronological age, and lifestyle habits in the general population.MethodsA large cross-sectional survey of 10,946 Japanese volunteers aged 20 to 79 years was conducted. Volunteers completed a self-administered questionnaire and underwent SAF measurement on their dominant forearms. The associations of SAF with age and lifestyle habits were analyzed using a multiple stepwise regression analysis.ResultsAge was independently correlated with SAF. Lifestyle habits such as physical activity, nonsmoking, adequate sleep, low mental stress level, eating breakfast, and abstaining from sugary food were each independently associated with lower SAF.ConclusionsSAF was associated with age and healthy lifestyle habits in this general Japanese population. The present study suggests that SAF measurement is a convenient tool for evaluating habitual lifestyle behaviors and may have potential for preventative health education.

Association of skin autofluorescence with periodontal inflammation in adults with type 1 diabetes.

Association of skin autofluorescence with periodontal inflammation in adults with type 1 diabetes.

Association of Skin Autofluorescence Levels With Kidney Function Decline in Patients With Peripheral Artery Disease.

Skin autofluorescence (SAF), a measure of advanced glycation end product accumulation, is associated with kidney function. We investigated the association of SAF with rate of kidney function decline in a cohort of patients with peripheral artery disease. We performed a post hoc analysis of an observational longitudinal cohort study. We included 471 patients with peripheral artery disease, and SAF was measured at baseline. Primary end point was rate of estimated glomerular filtration rate (eGFR) decline. Secondary end points were incidence of eGFR <60 and <45 mL/min/1.73 m(2) and rapid eGFR decline, defined as a decrease in eGFR of >5 mL/min/1.73 m(2)/y. During a median follow-up of 3 years, the mean change in eGFR per year was -1.8±4.4 mL/min/1.73 m(2)/y. No significant difference in rate of eGFR decline was observed per 1 arbitrary unit increase in SAF (-0.1 mL/min/1.73 m(2)/y; 95% confidence interval, -0.7 to 0.5; P=0.8). Analyses of the secondary end points showed that there was an association of SAF with incidence of eGFR <60 and <45 mL/min/1.73 m(2) (hazard ratio, 1.54; 95% confidence interval, 1.13-2.10; P=0.006 and hazard ratio, 1.76; 95% confidence interval, 1.20-2.59; P=0.004, respectively), but after adjustment for age and sex, significance was lost. There was no association of SAF with rapid eGFR decline. In conclusion, in this cohort of patients with peripheral artery disease, elevated SAF was associated with lower baseline eGFR. Although SAF has previously been established as a predictor for cardiovascular disease and mortality, it did not predict the rate of kidney function decline during follow-up in this study.

Skin Autofluorescence, a Non-Invasive Marker for AGE Accumulation, Is Associated with the Degree of Atherosclerosis

IntroductionAdvanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with the degree of atherosclerosis independent of diabetes and renal function.MethodsA cross-sectional study of 223 patients referred for primary (n = 163) or secondary (n = 60) prevention between 2006 and 2012 was performed. Skin AF was measured using the AGE-Reader. Ultrasonography was used to assess plaques in carotid and femoral arteries and computed tomography for the calculation of the coronary artery calcium score (CACS; in primary prevention only). Primary prevention patients were divided into a group with subclinical atherosclerosis defined as >1 plaque or CACS>100 (n = 67; age 53 year [interquartile range 48–56]; 49% male) and without (controls; 96; 43 [38–51]; 55%). Secondary prevention were patients with peripheral arterial disease (60; 64 [58–70]; 73%).ResultsSkin AF was higher in subclinical and clinical atherosclerosis compared with controls (skin AF 2.11 [interquartile range 1.83–2.46] and 2.71 [2.15–3.27] vs. 1.87 [1.68–2.12] respectively; P = 0.005 and <0.001). In a multivariate analysis, the association of skin AF with the atherosclerosis categories was independent of age, sex, diabetes, presence of the metabolic syndrome, Framingham Risk Score, and renal function. Skin AF correlated with most cardiovascular risk factors, Framingham risk score, and IMT and CACS.ConclusionsSkin AF is increased in documented subclinical and clinical atherosclerosis, independent of known risk factors such as diabetes and renal disease. These data suggest that AGEs may be associated with the burden of atherosclerosis and warrant a prospective study to investigate its clinical usability as a risk assessment tool for primary prevention.

PS1 - 4. Association of skin autofluorescence with cardiovascular disease

Skin autofluorescence (SAF) has been associated with cardiovascular disease (CVD), especially in patients with diabetes mellitus.

Skin autofluorescence, a marker for advanced glycation end product accumulation, is associated with arterial stiffness in patients with end-stage renal disease

Elevated cardiovascular mortality has been shown to be associated with increased arterial stiffness. However, the contribution of tissue accumulation of advanced glycation end products (AGEs) to increased arterial stiffness is unclear. We examined whether skin autofluorescence, a recently developed marker of tissue accumulation of AGEs, is associated with arterial stiffness in 120 Japanese patients with end-stage renal disease (ESRD) and 110 age- and sex-matched control subjects. The ESRD patients had significantly higher pulse wave velocity (PWV), a noninvasive measure of arterial stiffness, and skin autofluorescence than the control subjects. Skin autofluorescence was significantly associated with age in the group of all subjects ( R s = 0.255, Spearman rank correlation test) and that of control subjects ( R s = 0.493), but not in the group of ESRD subjects ( R s = 0.046). The PWV was significantly and positively associated with skin autofluorescence in the group of all subjects ( R s = 0.335), controls ( R s = 0.246), and ESRD subjects ( R s = 0.205). Multiple regression analyses showed that, in the group of all subjects, association of skin autofluorescence with PWV was significant even after adjustment for other covariates including the presence of ESRD and age. Moreover, for ESRD subjects, a significant association between skin autofluorescence and PWV was found, independent of age. Our findings demonstrate the potential usefulness of skin autofluorescence in people of color and demonstrate clinically for the first time the potential involvement of tissue accumulation of AGEs in the pathophysiology of arterial stiffness.