Association between plasma desmosine, a marker of elastin degradation, and total atherosclerotic burden measured by whole body magnetic resonance angiography

Abstract

Abstract Background Elastin degradation has been implicated in the pathophysiology of vulnerable atherosclerotic plaque. Desmosine is the cross-link component in the elastin molecule and is exclusively released from mature elastin breakdown, thus has the potential to be a physiologically relevant biomarker of atherosclerosis. Objectives The aim of the present study was: 1. To investigate whether patients with known cardiovascular disease (CVD) have higher elastin degradation as indicated by plasma desmosine (pDES); 2. to determine the relationship between pDES and total atherosclerotic burden. Methods We measured pDES by a validated stable isotope dilution LC-MS/MS method1 in a total of 146 subjects from the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study2. (62% male, mean age 64±8 (SD) years). This included 62 patients with prior clinical diagnosis of CVD (including coronary artery disease (CAD), cerebrovascular disease and/or lower extremity arterial disease (LEAD)), and 84 patients without a clinical diagnosis of CVD. Total atherosclerotic burden was measured by whole body magnetic resonance angiography (WB-MRA). The WB-MRA data was divided into 31 anatomical arterial segments with each segment scored according to degree of luminal narrowing: 0 = no stenosis, 1 = <50% stenosis, 2 = 51–70% stenosis, 3 = 71–99% stenosis, 4 = vessel occlusion. The segment scores were summed and from this, a standardized atheroma score (SAS) was calculated by summing each individual segment's stenosis score, and divided by the number of diagnostic segments before dividing by 4 which is the maximum potential score. Relationship between SAS and pDES levels was investigated using multiple linear regression models Results pDES levels were significantly greater in patients with established clinical CVD compared to patients with no CVD (CVD patients, 0.56 (0.45–0.67) ng/mL; patients with no CVD, 0.47 (0.41–0.54)ng/mL; p=0.001). Median SAS for the study population was 4 (2–10). Overall pDES levels showed a strong correlation with SAS (r=0.44, p≤0.001). Univariable analysis suggested a significant association between pDES and whole-body atheroma score as measured by SAS. (β 29.31, p<0.001). This association persisted in the multivariable regression model adjusting for traditional cardiovascular risk factors including age, gender, BMI, systolic blood pressure, diabetes, smoking status and LDL. (adjusted β 18.75, p=0.004) Conclusion pDES levels are elevated in patients with clinical CVD when compared to those with no clinical history of CVD. pDES is also strongly associated with global atheroma burden. Overall, these findings support the role of pDES as a potential biomarker for atherosclerosis. Funding Acknowledgement Type of funding sources: None.