Plasma Desmosine and Abdominal Aortic Aneurysm Disease

Abstract

Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the breakdown of elastin within the aortic tunica media, leading to aortic dilatation and rupture. The aim of this study was to investigate the association of plasma desmosine (pDES), an elastin-specific degradation product, with disease severity and clinical outcome in patients with AAA. Methods and Results We measured pDES and serum biomarker concentrations in 507 patients with AAAs (94% men; mean age, 72.4±6.1 years; mean AAA diameter, 48±8 mm) and 162 control subjects (100% men; mean age, 71.5±4.4 years) from 2 observational cohort studies. In the longitudinal cohort study (n=239), we explored the incremental prognostic value of pDES on AAA events. pDES was higher in patients with AAA compared with control subjects (mean±SD: 0.46±0.22 versus 0.33±0.16 ng/mL; P<0.001) and had the strongest correlation with AAA diameter (r=0.39; P<0.0001) of any serum biomarker. After adjustment for baseline AAA diameter, pDES was associated with an AAA event (hazard ratio, 2.03 per SD increase [95% CI, 1.02-4.02]; P=0.044). In addition to AAA diameter, pDES provided incremental improvement in risk stratification (continuous net reclassification improvement, 34.4% [95% CI, -10.8% to 57.5%; P=0.09]; integrated discrimination improvement, 0.04 [95% CI, 0.00-0.15; P=0.050]). Conclusions pDES concentrations predict disease severity and clinical outcomes in patients with AAA. Clinical Trial Registration http://www.isrctn.com. Unique identifier: ISRCTN76413758.

Keywords: abdominal aortic aneurysm; aortic rupture; desmosine; elastin.

Figure 1

Box plot of plasma desmosine (pDES) at baseline in the MA³RS (Magnetic Resonance Imaging for Abdominal Aortic Aneurysms to Predict Rupture or Surgery) study and UKAGS (UK Aneurysm Growth Study) cohorts. Horizontal lines represent median plasma desmosine, whereas diamonds represent mean plasma desmosine. The mean plasma desmosine level for all patients with abdominal aortic aneurysm (AAA) was 0.46±0.22 ng/mL; controls, 0.33±0.16 ng/mL (P<0.001, Kruskal‐Wallis test).

Figure 2

Box plot of plasma desmosine (pDES) for all patients, stratified by baseline abdominal aortic aneurysm diameter from the MA³RS (Magnetic Resonance Imaging for Abdominal Aortic Aneurysms to Predict Rupture or Surgery) study and UKAGS (UK Aneurysm Growth Study) cohorts. Horizontal lines represent median plasma desmosine, whereas diamonds represent mean plasma desmosine. Mean plasma desmosine at ≥55 mm, 0.57±0.24 ng/mL; 35 to 54 mm, 0.47±0.22 ng/mL; and <35 mm, 0.34±0.16 ng/mL (Kruskal‐Wallis test).

Figure 3

Serial plot of mean plasma desmosine (pDES) over the 24‐month follow‐up period, stratified by baseline desmosine. Points represent mean plasma desmosine in each group (stratified by baseline desmosine levels). Error bars represent 95% CIs.

Figure 4

Kaplan‐Meier curve for emergency abdominal aortic aneurysm events based on the optimal cutoff for plasma desmosine (log‐rank P<0.001).

Figure 5

Desmosine is released into the circulation only when there is breakdown of mature elastin within the aortic vessel wall. Increased plasma desmosine reflects a loss of aortic structural integrity and is associated with increased abdominal aortic aneurysm (AAA) size and AAA events.