Relation of baseline plasma MMP-1 levels to long-term all-cause mortality in patients with known or suspected coronary artery disease referred for coronary angiography. Issue 1 (March 2015)

• Record Type: Journal Article
• Authors: Cavusoglu, Erdal; Marmur, Jonathan D.; Hegde, Sudhanva; Yanamadala, Sunitha; Batuman, Olcay A.; Chopra, Vineet; Ay, Gonca; Eng, Calvin
• Is Part Of: Atherosclerosis. Volume 239:Issue 1(2015)
• Page Start: 268
• Page End: 275
• Publication Date: 2015-03
• Subjects: Matrix metalloproteinase 1 -- Biomarkers -- Acute coronary syndrome -- Prognosis -- Mortality; MMP-1 matrix metalloproteinase 1 -- GFR-MDRD estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula -- PAR1 protease-activated receptor-1 -- MI myocardial infarction -- NSTEMI non-ST-segment elevation MI -- STEMI ST-segment elevation MI -- ACS acute coronary syndrome -- CAD coronary artery disease -- CABG coronary artery bypass graft surgery -- CHF congestive heart failure -- LV left ventricular -- EF ejection fraction -- BMI body mass index -- hs-CRP high-sensitivity C-reactive protein -- TIMP-1 tissue inhibitor of matrix metalloproteinase 1 -- NT-proBNP N-terminal-pro-B-type natriuretic peptide -- MPO myeloperoxidase -- GDF-15 growth differentiation factor 15 -- RDW red blood cell distribution width -- ACE-I angiotensin converting enzyme inhibitor -- ARB angiotensin receptor blocker; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.01.003
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Objectives: To investigate the long-term prognostic significance of baseline plasma MMP-1 levels in a group of well-characterized male patients with known or suspected coronary artery disease, including those presenting with acute coronary syndrome. Background: MMP-1 is an interstitial collagenase that is considered the primary enzyme responsible for collagen degradation. In addition, MMP-1 can lead to platelet activation through the PAR1 pathway that is independent of thrombin. Methods: Baseline plasma MMP-1 levels were measured in 364 male patients who were referred for coronary angiography and followed prospectively for five years for the development of all-cause mortality. Results: After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, baseline plasma MMP-1 levels (analyzed as a continuous variable) were an independent predictor of all-cause mortality at 5 years (HR, 1.49; 95% CI, 1.23–1.80; P < 0.0001). Furthermore, in 3 additional multivariate models that included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, Cystatin C, hs-CRP, Myeloperoxidase, NT-proBNP, TIMP-1, Adiponectin, RDW, hemoglobin, and Erythropoietin), MMP-1 remained an independent predictor of all-cause mortality at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with acute coronary syndrome. Conclusions: Elevated levels of MMP-1 are associated with an increased risk of long-term all-cause mortality in patients with known or suspected coronary disease that is independent of a variety of clinical, angiographic, and laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy representing multiple different pathophysiologic processes. Highlights: MMP-1 is an interstitial collagenase that is considered the primary enzyme responsible for collagen degradation. MMP-1 can lead to platelet activation through the PAR1 pathway that is independent of thrombin. Elevated plasma levels of MMP-1 are an independent predictor of all-cause mortality in patients with known or suspected CAD.