title: Angiotensin Inhibition Is Associated with Preservation of T-Cell and Monocyte Function and Decreases Multiple Organ Failure in Obese Trauma Patients.
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.
  
  
  METHODS
  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.
authors.affiliation: Section of Acute and Critical Care Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO. Electronic address: winfieldr@wustl.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Winfield
authors.affiliation: Section of Acute and Critical Care Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Southard
authors.affiliation: Section of Acute and Critical Care Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Isaiah R
authors.initials: IR
authors.lastname: Turnbull
authors.affiliation: Section of Acute and Critical Care Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Kelly
authors.initials: K
authors.lastname: Bochicchio
authors.affiliation: Section of Acute and Critical Care Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Stacey
authors.initials: S
authors.lastname: Reese
authors.affiliation: Section of Acute and Critical Care Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Freeman
authors.affiliation: Section of Acute and Critical Care Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO.
authors.forename: Grant V
authors.initials: GV
authors.lastname: Bochicchio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009102:Multiple Organ Failure / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications* / Q000276:immunology; D063868:Patient Outcome Assessment; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014947:Wounds and Injuries / Q000150:complications* / Q000276:immunology; D055815:Young Adult
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors