NIV Congres

Introduction: Patients with peripheral artery disease (PAD) suffer from widespread atherosclerosis and an increased risk of cardiovascular events. Advanced Glycation End products (AGEs) play an important role in the development of atherosclerosis and cardiovascular disease. Earlier, we reported the independent predictive value of AGEs for mortality in patients with diabetes mellitus and patients with renal failure. Recently, we reported that AGEs are increased in PAD patients, independent from cardiovascular risk factors. In the present study we hypothesized that AGEs deposition predicts mortality in patients with PAD.

Methods: PAD patients were recruited from the outpatient clinic of vascular surgery of our hospital. PAD was established by a resting ankle-brachial index ≤ 0.90 and confirmed by computed tomographic angiography, magnetic resonance angiography, catheter angiogra­phy, or duplex ultrasonography. Patients with renal failure (eGFR < 15 ml/min per 1.73 m²) were excluded. Cardiovascular risk factors were assessed. Primary end-point was all-cause mortality. The follow-up was performed by evaluating hospital records and contact with the general practitioner. AGEs level was assessed by skin autofluorescence (SAF) using the AGE-reader, a previously validated non-invasive method. SAF results were split into quartiles. Kaplan-Meier analysis with log-rank test and Cox regression analysis were performed. Data are shown as mean ± SD, number (%) or median (Q1-Q3).

Results: Between 2007 and 2008, 258 PAD patients (188 men and 70 women) were included with a mean age of 66 ± 10 year. Patients had a mean body mass index of 27 ± 4 kg/m². Systolic and diastolic blood pressure were 140 (129-160) and 80 (70-85) mmHg, respectively. A total of 199 (77%) patients were on lipid lowering drugs and 213 (83%) used blood pressure lowering drugs. 61 (24%) had diabetes mellitus and 131 (51%) were smokers. Mean SAF was 2.77 ± 0.66 arbitrary units (AU). Median follow-up time was 4.0 (2.3-4.7) years. A total of 47 (18%) patients died. Kaplan-Meier analysis showed that SAF predicted mortality (log-rank test p = 0.015). Cox regression showed that patients with a higher SAF value (4th quartile, mean SAF of 3.66 ± 0.35 AU) had a 5.0-fold (95% CI1.7-14.7), p= 0.004 increased risk for mortality (crude model) as compared to the patients with lower SAF values (1st quartile, mean SAF of 1.97 ± 0.27 AU), and 3.5-fold (95% CI 1.2-10.6), p = 0.025 after correction for cardiovascular risk factors.

Conclusion: AGEs deposition, measured by SAF, predicts mortality in PAD patients, independent from cardiovascular risk factors. Possibly, SAF can identify patients at highest cardiovascular risk that may benefit from more aggressive treatment of all modifiable risk factors.