Elastin degradation is associated with progressive aortic stiffening and all-cause mortality in predialysis chronic kidney disease

Smith, Edward R, Tomlinson, Laurie A, Ford, Martin L, McMahon, Lawrence P, Rajkumar, Chakravarthi and Holt, Stephen G (2012) Elastin degradation is associated with progressive aortic stiffening and all-cause mortality in predialysis chronic kidney disease. Hypertension, 59 (5). pp. 973-978. ISSN 1524-4563

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Abstract

In the large conduit arteries, elastin is important in maintaining vascular compliance. Studies in animal models suggest that elastin degradation may promote arteriosclerotic vascular changes. There is already a well-established link between aortic stiffening and mortality in the general population and in patients undergoing dialysis. Elastin degradation is mediated by several proteases, including matrix metalloproteinase 2 and cathepsin S. Elastin turnover may be inferred by measuring serum levels of elastin-derived peptides. We analyzed the serum concentration of these biomarkers, their endogenous inhibitors, and aortic pulse wave velocity in 200 patients with stages 3 and 4 chronic kidney disease and then serially in a subgroup of 65 patients over 36 months. Serum matrix metalloproteinase 2, cathepsin S, and elastin-derived peptide levels were independently associated with baseline aortic pulse wave velocity and changes in stiffness over the follow-up period. Higher matrix metalloproteinase 2 and elastin-derived peptide levels were also independently associated with preexisting cardiovascular disease. In multivariable Cox regression, higher serum elastin-derived peptide levels were independently associated with increased all-cause mortality (hazard ratio per SD increase=1.78; P=0.021). In predialysis chronic kidney disease, elastin degradation is an important determinant of arterial stiffness and is associated with all-cause mortality.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine > RC Internal medicine > RC0581 Specialties of internal medicine > RC0952 Geriatrics
Depositing User: Simone Breckell
Date Deposited: 30 Oct 2012 15:08
Last Modified: 30 Oct 2012 15:08
URI: http://sro.sussex.ac.uk/id/eprint/41693
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