Advanced glycation end products:An emerging biomarker for adverse outcome in patients with peripheral artery disease

AbstractPatients with peripheral artery disease (PAD) suffer from widespread atherosclerosis. Partly due to the growing awareness of cardiovascular disease, the incidence of PAD has increased considerably during the past decade. It is anticipated that algorithms to identify high risk patients for cardiovascular events require being updated, making use of novel biomarkers. Advanced glycation end products (AGEs) are moieties formed non-enzymatically on long-lived proteins under influence of glycemic and oxidative stress reactions. We elaborate about the formation and effects of AGEs, and the methods to measure AGEs. Several studies have been performed with AGEs in PAD. In this review, we evaluate the emerging evidence of AGEs as a clinical biomarker for patients with PAD

Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

<p>Abstract</p> <p>Background</p> <p>Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees.</p> <p>Methods</p> <p>Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed.</p> <p>Discussion</p> <p>Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process evaluation the guideline will be adjusted and, after authorisation, published. Together with several implementation aids, the published guideline will be disseminated broadly by the Netherlands Society of Occupational Medicine.</p> <p>Trial Registration</p> <p>ISRCTN73545254/NTR1190</p

New Glucose-Lowering Agents for Diabetic Kidney Disease

The prevalence of diabetes mellitus is increasing and is associated with a range of complications including nephropathy. New antidiabetic agents are sought which also have positive effects to diminish diabetic complications. Examples of promising new classes of such agents are glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. In addition to cardiovascular protective effects such as weight loss and decreased blood pressure of some of these agents, there is evidence for renoprotective effects with these agents. This review elaborates on the main results of renoprotective effects of these 3 treatment classes. In conclusion, currently available trials have demonstrated renoprotective effects for certain glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, and the sodium-glucose cotransporter 2 inhibitors, empagliflozin and canagliflozin. Dipeptidyl peptidase-4 inhibitors did not show a significant renoprotective effect. Nevertheless, larger studies with respect to renoprotective effects of these 3 drug classes are currently being performed, and thus, no conclusions for all of these agents can yet be made. Crown Copyright (C) 2018 Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. All rights reserved

Skin Autofluorescence as a Measure of Advanced Glycation End Products Deposition Predicts 5-Year Amputation in Patients With Peripheral Artery Disease

Objective-Patients with peripheral artery disease are at risk for critical limb ischemia and amputation. Accumulation of advanced glycation end products is increased and predictive for coronary and cerebrovascular events in several high cardiovascular risk groups. We hypothesized that accumulation of tissue advanced glycation end products, measured by skin autofluorescence (SAF), predicts amputation in patients with peripheral artery disease. Approach and Results-Between October 2007 and June 2008, 252 patients with peripheral artery disease were included at the outpatient clinic. During a 5-year follow-up, 22 (9%) had an amputation because of critical limb ischemia. Competing risks regression analysis showed a subproportional hazard ratio of 3.05 (95% confidence interval [CI], 1.87-4.96); P<0.0001 for amputation per unit incease of SAF. After correction for diabetes mellitus and Fontaine stage, subproportional hazard ratio was 2.72 (95% CI, 1.38-5.39); P= 0.004.In patients with Fontaine stage I and II only (n= 215), SAF was the only predictor for amputation, subproportional hazard ratio 4.05 (95% CI, 2.09-7.83); P<0.0001. Fontaine stage multiplied by SAF resulted in a significant increase of the area under the curve for prediction of amputation when compared with Fontaine stage only: area under the curve increased from 0.74 (95% CI, 0.63-0.86) to 0.83 (95% CI, 0.74-0.92); P= 0.003. Conclusions-Skin autofluorescence, as a measure of tissue advanced glycation end products deposition, predicts amputation in patients with peripheral artery disease during a 5-year follow-up, independent from the presence of diabetes mellitus and Fontaine stage. Even at lower Fontaine stage (I or II), SAF is a strong predictor of amputation. The multiplication of Fontaine stage by SAF results in a good prediction model of amputation

A systematic review of financial incentives given in the healthcare setting; do they effectively improve physical activity levels?

BACKGROUND: According to current physical activity guidelines, a substantial percentage of the population in high-income countries is inactive, and inactivity is an important risk factor for chronic conditions and mortality. Financial incentives may encourage people to become more active. The objective of this review was to provide insight in the effectiveness of financial incentives used for promoting physical activity in the healthcare setting. METHODS: A systematic literature search was performed in three databases: Medline, EMBASE and SciSearch. In total, 1395 papers published up until April 2015 were identified. Eleven of them were screened on in- and exclusion criteria based on the full-text publication. RESULTS: Three studies were included in the review. Two studies combined a financial incentive with nutrition classes or motivational interviewing. One of these provided a free membership to a sports facility and the other one provided vouchers for one episode of aerobic activities at a local leisure center or swimming pool. The third study provided a schedule for exercise sessions. None of the studies addressed the preferences of their target population with regard to financial incentives. Despite some short-term effects, neither of the studies showed significant long-term effects of the financial incentive. CONCLUSIONS: Based on the limited number of studies and the diversity in findings, no solid conclusion can be drawn regarding the effectiveness of financial incentives on physical activity in the healthcare setting. Therefore, there is a need for more research on the effectiveness of financial incentives in changing physical activity behavior in this setting. There is possibly something to be gained by studying the preferred type and size of the financial incentive

Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm

Objective: Advanced glycation end products (AGEs) are implicated in the pathogenesis of cardiovascular disease. Accumulation of AGEs is driven by oxidative or glycemic stress and can be assessed by skin autofluorescence (SAF). SAF is increased in patients with peripheral artery disease (PAD) and independently associated with mortality and major adverse cardiovascular events in these patients. PAD and abdominal aortic aneurysm (AAA) share several risk factors. Inflammation is an important process in AAA formation and increases levels of oxidative stress. We therefore hypothesized that SAF would be increased in AAA patients compared with controls. Methods: A case-control study was performed in 248 AAA patients and 124 controls without AAA or PAD matched for age and presence of diabetes mellitus. SAF was noninvasively assessed with the AGE Reader (Diagnoptics Technologies BV, Groningen, The Netherlands). Results: SAF was higher in AAA patients than in controls: 2.89 +/- 0.63 vs 2.68 +/- 0.63 arbitrary units (P = .003). PAD comorbidity was associated with increased SAF within the AAA patient group (P = .01). After correction for known factors influencing SAF (age, current smoking, hypertension, and estimated glomerular filtration rate), PAD comorbidity remained an independent determinant of SAF. Logistic regression analysis of the total cohort showed an unadjusted odds ratio (OR) of 1.74 (95% confidence interval [CI], 1.20-2.51) for the presence of AAA with each unit increase of SAF and an adjusted OR of 1.78 (95% CI, 1.22-2.60) after correction for cardiovascular comorbidity (cerebrovascular disease and coronary artery disease). After additional correction for sex, current smoking, hypertension, and use of lipid-lowering drugs, this significance was lost (adjusted OR, 1.53; 95% CI, 0.94-2.48). Conclusions: Skin accumulation of AGEs, measured by SAF, is increased in patients with AAA compared with controls without AAA or PAD, independent of the presence of coronary artery disease and cerebrovascular disease. In AAA patients, SAF is closely associated with the presence of PAD and cardiovascular risk factors

Skin autofluorescence is associated with 5-year mortality and cardiovascular events in patients with peripheral artery disease

Clinical epidemiolog

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

Objective 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. Approach and Results 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 5 mL/min/1.73 m(2)/y. During a median follow-up of 3 years, the mean change in eGFR per year was -1.84.4 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 Conclusions 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 as a Measure of Advanced Glycation End Products Deposition Is Elevated in Peripheral Artery Disease

<p>Objective-Evidence for an important role of advanced glycation end products (AGEs) in the development of atherosclerosis and cardiovascular disease beyond diabetes mellitus and renal disease is growing. Skin autofluorescence (SAF) is a validated noninvasive measure of tissue AGEs. We hypothesized that SAF is elevated in peripheral artery disease (PAD).</p><p>Methods and Results-A case-control study was performed in 492 patients with PAD and 164 controls, matched for age (mean 66 +/- 10 years) and presence of diabetes mellitus. Cardiovascular risk factors and comorbidity (coronary artery disease, cerebrovascular disease, abdominal aortic aneurysm) were assessed. SAF was measured with the AGE Reader. SAF was higher in patients compared with controls: geometric mean 2.77 (95% confidence interval [CI], 2.71-2.83) versus 2.44 (95% CI, 2.35-2.53) arbitrary units, P=0.4x10(-8). In logistic regression, the adjusted odds ratio for the presence of PAD was 2.47 (95% CI, 1.66-3.69) per 1 unit increase of SAF. PAD patients with cardiovascular comorbidity had a higher SAF compared with those without: geometric mean 2.93 (95% CI, 2.85-3.02) versus 2.63 (95% CI, 2.55-2.71) arbitrary units, P=0.4x10(-6), also after correction for confounders. Regression analysis showed that age, smoking, diabetes mellitus, chronic kidney disease, and a history of cerebrovascular disease or abdominal aortic aneurysm were independently associated with SAF in the patients with PAD.</p><p>Conclusion-Accumulation of tissue AGEs is increased in patients with PAD, independent of cardiovascular risk factors and comorbidity, although these conditions are associated with a further increase. These findings underscore the importance of AGEs in PAD, irrespective of the presence of diabetes mellitus and renal insufficiency. (Arterioscler Thromb Vasc Biol. 2013;33:131-138.)</p>

Classification variables for patient group definition.

<p>AU = arbitrary units; IMT = intima media thickness.</p