Angiotensin Inhibition Is Associated with Preservation of T-Cell and Monocyte Function and Decreases Multiple Organ Failure in Obese Trauma Patients

J Am Coll Surg. 2015 Aug;221(2):486-94.e4. doi: 10.1016/j.jamcollsurg.2015.03.051. Epub 2015 Apr 7.

Abstract

Background: Obese patients are more prone to post-injury multiple organ failure (MOF). Obesity pathophysiology includes an adipose-tissue-derived, renin-angiotensin-aldosterone system affecting inflammatory responses via leukocyte angiotensin receptors. We hypothesized that obese patients receiving pre-injury angiotensin-converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB) therapy would have decreased MOF and differences in immune cell frequencies.

Study design: We analyzed the Inflammation and the Host Response to Injury trauma-related database. Patients receiving pre-injury ACE or ARB were stratified as obese (BMI >30 kg/m(2)) or nonobese (BMI <30 kg/m(2)). Groups were age, sex, and Injury Severity Score matched against patients not receiving this therapy. Primary end points were Marshall Multiple Organ Dysfunction Score, Denver-2 Postinjury MOF Score, leukocyte markers on T cells, and monocytes measured by flow cytometry.

Results: We evaluated 1,932 patients. One hundred and ten were receiving pre-injury ACE/ARB; 94 patients had data available to calculate BMI. Obese patients receiving ACE/ARB showed maximum Marshall (5.83 ± 2.87) and Denver-2 (2.45 ± 2.32) scores similar to nonobese patients receiving or not receiving ACE/ARB, and obese patients not receiving ACE/ARB had significantly higher Marshall (6.49 ± 2.57; p = 0.009) and Denver-2 (3.33 ± 2.21; p = 0.006) scores. Leukocyte analysis suggested improved T-cell function and monocyte maturation in obese patients on ACE/ARB.

Conclusions: Obese patients receiving preinjury ACE/ARB therapy demonstrate post-injury MOF scores similar to nonobese patients; obese patients not receiving these medications have greater post-injury MOF. Leukocyte analysis demonstrates improved immune regulation. Modulation of the renin-angiotensin-aldosterone system pathway might represent a novel therapeutic target in severely injured obese patients.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Female
  • Flow Cytometry
  • Humans
  • Injury Severity Score
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / physiology
  • Multiple Organ Failure / etiology
  • Multiple Organ Failure / immunology
  • Multiple Organ Failure / prevention & control*
  • Obesity / complications*
  • Obesity / immunology
  • Patient Outcome Assessment
  • Retrospective Studies
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / physiology
  • Wounds and Injuries / complications*
  • Wounds and Injuries / immunology
  • Young Adult

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors