Mon2 predicts poor outcome in ST-elevation myocardial infarction

J Intern Med. 2019 Mar;285(3):301-316. doi: 10.1111/joim.12847. Epub 2019 Jan 15.

Abstract

Aims: There are limited data on the role of human monocyte subsets in ST-elevation myocardial infarction (STEMI). The study aimed to establish the relationship between monocyte subsets, their phagocytic and nuclear factor κB (NFκB) activity and outcomes in STEMI.

Methods: Monocyte subsets and their phagocytic activity and intracellular levels of inhibitory κB kinase β (IKKβ, marker of NFκB activity) were measured by flow cytometry in 245 patients with STEMI, median follow-up of 46 months.

Results: Mon2 (CD14++CD16+CCR2+) counts were independently predictive of major adverse cardiovascular events (MACE) [4th quartile HR 3.42 (95% CI 1.43-8.16), P = 0.006 and 3rd quartile HR 2.88 (95% CI 1.19-7.00), P = 0.02 vs. 1st quartile]. Mon2 subset was the only subset associated with higher occurrence of heart failure (4th quartile vs. 1st quartile, sevenfold, P = 0.001 on univariate analysis; fivefold, P = 0.04 on multivariable analysis). On receiver operating characteristic, analysis including of Mon2 improved prognostic value of troponin T and creatine kinase for MACE and heart failure (HF). Higher intracellular Mon2 IKKβ levels were associated with 10-fold lower occurrence of HF on multivariable analysis (4th vs. 1st quartiles, P = 0.03). Abnormal Mon1 and Mon2 phagocytic capacities were related to HF development, but the association was dependent on the infarct size and other prognosticators. High Mon2 levels were associated with lower ejection fraction after STEMI onset (P = 0.001) and at 6-month follow-up (P < 0.001).

Conclusions: Abnormal Mon2 characteristics have a unique association with poor outcome in patients with STEMI. The relation of Mon2 with occurrence of HF is strongly and independently related to their functional status, which may have potential therapeutic implications.

Keywords: ejection fraction; monocyte subsets; myocardial infarction; phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Cell Count / methods
  • Correlation of Data
  • Female
  • Flow Cytometry
  • Heart Failure* / blood
  • Heart Failure* / diagnosis
  • Heart Failure* / etiology
  • Humans
  • I-kappa B Kinase* / analysis
  • I-kappa B Kinase* / metabolism
  • Male
  • Middle Aged
  • Monocytes* / classification
  • Monocytes* / physiology
  • NF-kappa B* / analysis
  • NF-kappa B* / metabolism
  • Outcome Assessment, Health Care
  • Phagocytosis
  • Prognosis
  • ST Elevation Myocardial Infarction* / blood
  • ST Elevation Myocardial Infarction* / complications
  • ST Elevation Myocardial Infarction* / diagnosis
  • Stroke Volume

Substances

  • Biomarkers
  • NF-kappa B
  • I-kappa B Kinase