TY - JOUR
T1 - Angiotensin Inhibition is Associated with Preservation of T-Cell and Monocyte Function and Decreases Multiple Organ Failure in Obese Trauma Patients
AU - Winfield, Robert D.
AU - Southard, Robert E.
AU - Turnbull, Isaiah R.
AU - Bochicchio, Kelly
AU - Reese, Stacey
AU - Freeman, Bradley D.
AU - Bochicchio, Grant V.
N1 - Funding Information:
Support: The Glue Grant trauma-related database was supported by the Inflammation and the Host Response to Injury Large Scale Collaborative Research Program (Glue Grant U54 GM062119-7 ), awarded to Dr Ronald G Tompkins, Massachusetts General Hospital , by the National Institute of General Medical Sciences . The work represents a secondary use of this public database, and although the finished manuscript has been seen by the leadership of the Glue Grant, the conclusions and discussion are the authors and do not necessarily represent the views of either the Glue Grant, Massachusetts General Hospital, or the National Institute of General Medical Sciences.
Publisher Copyright:
© 2015 American College of Surgeons.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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/m2) or nonobese (BMI <30 kg/m2). 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.
AB - 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/m2) or nonobese (BMI <30 kg/m2). 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.
UR - http://www.scopus.com/inward/record.url?scp=84937724091&partnerID=8YFLogxK
U2 - 10.1016/j.jamcollsurg.2015.03.051
DO - 10.1016/j.jamcollsurg.2015.03.051
M3 - Article
C2 - 26141470
AN - SCOPUS:84937724091
SN - 1072-7515
VL - 221
SP - 486-494.e4
JO - Journal of the American College of Surgeons
JF - Journal of the American College of Surgeons
IS - 2
ER -