Advanced Glycation End Products in Abdominal Aortic Aneurysms.

Vos, L.C. de (Lisanne) (2013) Advanced Glycation End Products in Abdominal Aortic Aneurysms. thesis, Medicine.

Text VosdeL.pdf Restricted to Registered users only Download (1MB)

Abstract

Introduction: Abdominal aortic aneurysm (AAA) is most often an asymptomatic but potentially deadly disease. Besides the risk of rupture, these patients have an increased risk to develop other cardiovascular (CV) diseases. Advanced glycation end products (AGEs) are sugar-modified proteins formed by oxidative and glycemic stress. Formation of cross-links between collagen and AGEs cause stiffening of arteries and myocardium. Binding to the receptor for AGEs (RAGE) causes intracellular stress responses which further enhance atherosclerosis and CV disease. Earlier, we showed the predictive value of AGEs for mortality and major adverse cardiac events (MACE) in diabetes mellitus and coronary artery disease. In the present study, we hypothesize that (1) AGEs are increased in AAA patients and (2) predict outcome (mortality, non-fatal MACE, and growth, rupture, and/or surgical repair of the AAA). Methods: We performed a case-control study and a prospective cohort study. AAA patients and controls were matched for age and the presence of diabetes mellitus. CV risk factors and comorbidity (coronary artery disease, cerebrovascular disease and peripheral arterial occlusive disease) were assessed. Tissue AGEs were noninvasively measured by skin autofluorescence (SAF) with the AGE ReaderTM. Independent student t test, χ2 test, linear and logistic regression analysis were performed. The predictive value of SAF for mortality, non-fatal MACE (myocardial infarction, transient ischemic attack, stroke, revascularisation procedures) and growth, rupture, and/or surgical repair of the AAA were assessed by Kaplan-Meier and Cox regression analysis. Data are shown as mean ± SD or number (%). Results: 246 patients and 123 controls with a mean age of 73 ± 7 years participated. SAF was higher in patients compared to controls: mean SAF of 2.89 ± 0.63 versus 2.57 ± 0.56 arbitrary units (AU), P=0.1x10-5. In a logistic regression of the combined groups of AAA patients and controls, the odds ratio for presence of AAA was 2.57 (95% confidence interval [CI]: 1.72-3.84) per 1 unit increase of SAF; 1.96 (95% CI: 1.10-3.50) after correction for CV risk factors, 2.24 (95% CI: 1.41-3.57) after correction for CV comorbidity and 1.84 (95% CI: 0.97-3.47) after correction for both. The prospective cohort study had a mean follow-up of 2.9 ± 1.5 years, 3 (1%) patients were lost to follow-up, 55 (22%) patients died, 27 (11%) from a CV cause. Non-fatal MACE occurred in 43 (18%) patients. Growth, rupture, and/or surgical repair of the AAA occurred in 75 (31%) patients. Kaplan-Meier curves showed no significant difference between patients above or below median SAF for any endpoint. Cox regression showed no predictive value of SAF for these endpoints, also after correction for CV risk factors and comorbidity. Discussion: Tissue AGEs accumulation, measured with SAF, is increased in patients with AAA as compared to controls, matched for age and the presence of diabetes mellitus. This increased SAF is largely explained by CV risk factors and comorbidity. This result is in contrast with other forms of CV disease in which SAF is increased independently from CV risk factors and comorbidity. Also, SAF does not predict mortality, non-fatal MACE or growth, rupture, and/or surgical repair of the AAA. SAF cannot be used for risk stratification in AAA patients. These findings suggest a different and possibly more limited role of AGEs in AAA patients in contrast to occlusive atherosclerotic disease.

Item Type:	Thesis (Thesis)
Supervisor name:	Lefrandt, Dr. J.D.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:44
Last Modified:	25 Jun 2020 10:44
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/563

Actions (login required)

View Item