Role of cathepsin D activation in major adverse cardiovascular events and new-onset heart failure after STEMI

Herz. 2015 Sep;40(6):912-20. doi: 10.1007/s00059-015-4311-6. Epub 2015 Apr 25.

Abstract

Aim: Increased serum levels of the activated aspartic lysosomal endopeptidase cathepsin D (CatD) have been found in patients with acute myocardial infarction (AMI). However, to date there have been no analyses of clinical follow-up data measuring the enzyme course and its role in the development of post-MI heart failure. This study aimed to evaluate the role of serum CatD activity in the development of heart failure in patients with ST-segment elevation acute myocardial infarction (STEMI).

Patients and methods: Eighty-eight consecutive patients (79.5 % men, mean age 57.4 ± 10.2 years) with STEMI were included in this study. Serum CatD activity was measured directly after primary percutaneous coronary intervention (PCI), before discharge, and at the 6-month follow-up. Patients were monitored for major adverse cardiovascular events (MACE), defined as hospitalization due to cardiovascular causes, recurrent nonfatal myocardial infarction, unplanned PCI, new-onset heart failure, and cardiovascular mortality.

Results: Serum CatD activity was significantly higher in patients with AMI after PCI and during follow-up (FU) than that in age-matched controls (16.2 ± 7.5 and 29.8 ± 8.9 vs. 8.5 ± 4.2 RFU; p < 0.001 for each time point). At the 6-month follow-up, serum CatD activity in these patients was inversely related to new-onset cardiac dysfunction compared with patients with preserved and improved LVEF after treatment (23.1 ± 3.2 vs. 28.8 ± 7.0 and 29.7 ± 5.0 RFU respectively, p < 0.01). Patients suffering from MACE during a follow-up period of 6 months had lower serum levels of activated CatD than those without any MACE (23.8 ± 4.6 vs 29.6 ± 6.9 RFU; p < 0.001).

Conclusions: Serum CatD activity as a marker of healthy endogenous phagocytosis and remodeling was impaired in patients with new-onset cardiac dysfunction, and lower levels of serum CatD were associated with MACE at the 6-month post-MI follow-up.

Keywords: Cardiac remodeling; Heart failure; Myocardial infarction; Percutaneous coronary intervention; Serum cathepsin D activity.

Publication types

  • Clinical Trial

MeSH terms

  • Biomarkers / blood
  • Cathepsin D / blood*
  • Causality
  • Comorbidity
  • Death, Sudden, Cardiac / epidemiology
  • Enzyme Activation
  • Female
  • Heart Failure / blood*
  • Heart Failure / mortality*
  • Heart Failure / prevention & control
  • Hospitalization / statistics & numerical data
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / mortality
  • Myocardial Infarction / surgery*
  • Percutaneous Coronary Intervention / mortality*
  • Prognosis
  • Recurrence
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Survival Rate
  • Turkey / epidemiology

Substances

  • Biomarkers
  • CTSD protein, human
  • Cathepsin D