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

Jui-Tzu Huang; Shih-Hsien Sung; Chiao-Po Hsu; Chern-En Chiang; Wen-Chung Yu; Hao-Min Cheng; Cheng-Hsiung Huang

doi:10.3389/fcvm.2023.1226449

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

Front Cardiovasc Med. 2023 Dec 14:10:1226449. doi: 10.3389/fcvm.2023.1226449. eCollection 2023.

Authors

Jui-Tzu Huang¹, Shih-Hsien Sung^{1

2

3

4}, Chiao-Po Hsu^{3

5}, Chern-En Chiang^{3

4

6}, Wen-Chung Yu^{1

3

4}, Hao-Min Cheng^{3

4

7

8}, Cheng-Hsiung Huang^{3

5}

Affiliations

¹ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
² Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University College of Medicine, Taipei, Taiwan.
³ Cardiovascular Research Center, National Yang Ming Chiao Tung University College of Medicine, Taipei, Taiwan.
⁴ Department of Internal Medicine, National Yang Ming Chiao Tung University College of Medicine, Taipei, Taiwan.
⁵ Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
⁶ General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan.
⁷ Center for Evidence-Based Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁸ Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan.

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.

Keywords: MMP; TIMP-1; coronary artery disease; subclinical inflammation; ventricular remodeling.

Grants and funding

The study was supported by Taipei Veterans General Hospital (V104C-172, and V104E12-003-MY3, V108E-004-5, V109E-008-, V109C-134, V110C-131), Ministry of science and technology (MOST 104-2314-B-075-037, MOST 106-2314-B-075-047-MY2), and Ministry of Health and Welfare, Taiwan grant (MOHW109-TDU-B-211-114001, MOHW110-TDU-B-211-124001, MOHW111-TDU-B-211-134001), Ministry of Science and Technology, (MOST 111-2314-B-A49-010), National Science and Technology Council(NSTC 112-2314-B-A49-042, NSTC 112-2314-B-A49-074) and the National Death Registry.