Skin accumulation of advanced glycation endproducts is increased in AAA patients
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1 Skin accumulation of advanced glycation endproducts is increased in AAA patients Clark Zeebregts Professor of Vascular Surgery University Medical Center Groningen Department of Surgery Division of Vascular Surgery Groningen, The Netherlands Munich, Germany December 8, 2017
2 Disclosure Consultant for Vascutek Received research grants from W.L. Gore & Associates, LeMaitre Vascular, Atrium Maquet Getinge Group, and Cook Medical
3 Advanced glycation end products (AGEs) Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006; 114:
4 AGE Reader Courtesy by DiagnOptics, Groningen, The Netherlands.
5 AGEs and skin autofluorescence Formation and accumulation of AGEs in long-lived tissues occurs physiologically with ageing. Formation is enhanced in conditions associated with hyperglycemia or oxidative stress, such as DM, autoimmune disease, renal insufficiency and atherosclerosis. SAF is increased in patients with these conditions compared to controls. Increased SAF is associated with major adverse cardiovascular events in patients with DM, myocardial infarction and peripheral artery disease (PAD).
6 AGEs and AAA PAD and AAA disease share several risk factors and are frequently found in the same patient. Inflammation is an important pathway of AAA formation, mediating elastin and collagen degradation by proteases derived from inflammatory cells. Hypothesis: skin autofluorescence (SAF), as a measure of skin AGEs, is increased in patients with an AAA.
7 Aims of study To compare SAF levels in AAA patients and controls. To investigate whether SAF is associated with presence of AAA after correction for both cardiovascular risk factors (such as smoking) and cardiovascular comorbidity (expressed by a history of cerebrovascular disease (CVD) or coronary artery disease (CAD)).
8 Study population Boersema J, de Vos LC, Links TP, Mulder DJ, Smit AJ, Zeebregts CJ, Lefrandt JD. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm. J Vasc Surg 2017 Dec; 66(6):
9 Patient characteristics Boersema J, de Vos LC, Links TP, Mulder DJ, Smit AJ, Zeebregts CJ, Lefrandt JD. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm. J Vasc Surg 2017 Dec; 66(6):
10 Skin autofluorescence: AAA vs controls Boersema J, de Vos LC, Links TP, Mulder DJ, Smit AJ, Zeebregts CJ, Lefrandt JD. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm. J Vasc Surg 2017 Dec; 66(6):
11 Influence of peripheral artery disease Boersema J, de Vos LC, Links TP, Mulder DJ, Smit AJ, Zeebregts CJ, Lefrandt JD. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm. J Vasc Surg 2017 Dec; 66(6):
12 Multivariate analysis Boersema J, de Vos LC, Links TP, Mulder DJ, Smit AJ, Zeebregts CJ, Lefrandt JD. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm. J Vasc Surg 2017 Dec; 66(6):
13 Influence of treatment Boersema J, de Vos LC, Links TP, Mulder DJ, Smit AJ, Zeebregts CJ, Lefrandt JD. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm. J Vasc Surg 2017 Dec; 66(6):
14 Association between SAF and AAA Boersema J, de Vos LC, Links TP, Mulder DJ, Smit AJ, Zeebregts CJ, Lefrandt JD. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm. J Vasc Surg 2017 Dec; 66(6):
15 Discussion (1) In several cardiovascular risk groups and disease, such as renal insufficiency, DM, CAD and PAD, AGE levels are increased compared to controls. The present study adds AAA patients as a high cardiovascular risk group with increased accumulation of AGEs. de Vos LC, Noordzij MJ, Mulder DJ, Smit AJ, Lutgers HL, Dullaart RPF, Kamphuisen PW, Zeebregts CJ, Lefrandt JD. Skin autofluorescence as a measure of advanced glycation endproducts deposition is elevated in peripheral artery disease. Arterioscler Thromb Vasc Biol 2013; 33: de Vos LC, Mulder DJ, Smit AJ, Dullaart RPF, Kleefstra N, Lijfering WM, Kamphuisen PW, Zeebregts CJ, Lefrandt JD. Skin autofluorescence is associated with 5 year mortality and cardiovascular events in peripheral artery disease. Arterioscler Thromb Vasc Biol 2014; 34: Schutte E, de Vos LC, Lutgers HL, Lambers Heerspink HJ, Wolffenbuttel BHR, Vart P, Zeebregts CJ, Gansevoort RT, Lefrandt JD. The association of skin autofluorescence levels with kidney function decline in patients with peripheral artery disease. Arterioscler Thromb Vasc Biol 2016; 36:
16 Discussion (2) In a study of 8 AAA patients, AGEs and receptor for AGE in the aortic wall were increased as compared to 5 control samples from a tissue bank of autopsy materials. The same paper describes a reduction of incidence of AAA of 50% in AGE receptor knockout mice compared to control mice. Zhang F, Kent KC, Yamanouchi D, Zhang Y, Kato K, Tsai S, et al. Anti-receptor for advanced glycation end products therapies as novel treatment for abdominal aortic aneurysm. Ann Surg 2009; 250:
17 Conclusions SAF, as a noninvasive assessment of skin accumulation of AGEs, is increased in patients with AAA compared with controls, independent of cardiovascular comorbidity. Still, within the AAA patients, SAF is closely associated with the presence of PAD and cardiovascular risk factors. These findings suggest that accumulation of AGEs is increased in AAA patients, partly explained by presence of widespread atherosclerosis.
18 Future studies ARTERY (advanced glycation endproducts in patients with peripheral artery disease and abdominal aneurysm) study
19 Acknowledgements Ellen Boersema Lisanne de Vos Joop Lefrandt Udo Mulder Andries Smit Maarten van der Laan Ben Saleem Paul van Schaik Ignace Tielliu Bas Wallis de Vries Thank you for your attention!
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