TIMP-1 in the prognosis of patients who underwent coronary artery bypass surgery: a 12-year follow-up study.

Abstract

Introduction:

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been linked to clinical outcomes in patients with coronary artery disease (CAD). However, the prognostic value of TIMP-1 in patients with CAD who underwent coronary artery bypass grafting (CABG) has not been elucidated. We aimed to investigate the correlations of TIMP-1 with high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the long-term prognosis of consecutive patients who underwent CABG.

Methods:

A total of 234 patients (age: 70.4 ± 10.5 years, 84.6% men) with CAD who underwent CABG were prospectively enrolled. Preoperative levels of MMPs, TIMP-1, hs-CRP, and NT-proBNP were recorded. Major adverse cardiovascular events (MACE) were defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death.

Results:

During a median follow-up of 12.1 years, 120 deaths were recorded. The deceased were older, had more manifest acute coronary syndrome (ACS), a lower left ventricular ejection fraction (LVEF), and an estimated glomerular filtration rate (eGFR), but significantly higher MMP13, TIMP-1, hs-CRP, and NT-proBNP compared with the survivors. After adjusting for age, sex, manifest ACS, eGFR, LVEF, total cholesterol, and triglycerides, TIMP-1 (hazard ratio and 95% confidence intervals per SD: 1.506, 1.183-1.917), hs-CRP (1.349, 1.183-1.561), and NT-ProBNP (1.707, 1.326-2.199) were all independently associated with all-cause mortality. The mediation analysis revealed that the mortality risks of TIMP-1 were partially mediated by NT-proBNP (62.2%) and hs-CRP (25.3%). The associations of TIMP-1 with MACE were partially mediated by NT-proBNP (54.4%) but not hs-CRP.

Conclusions:

TIMP-1 was an independent predictor of long-term outcomes after CABG, with possible roles in subclinical inflammation and postoperative cardiac remodeling.

• Authors: Jui-Tzu Huang, Shih-Hsien Sung, Chiao-Po Hsu, Chern-En Chiang, Wen-Chung Yu, Hao-Min Cheng, Cheng-Hsiung Huang
• Journal: Frontiers in cardiovascular medicine (Front Cardiovasc Med) Vol. 10 Pg. 1226449 ( 2023) ISSN: 2297-055X [Print] Switzerland
• PMID: 38162139 (Publication Type: Journal Article)
• Copyright: © 2023 Huang, Sung, Hsu, Chiang, Yu, Cheng and Huang.