Severe Combat Trauma Closely Tied to CAD, Hypertension, Diabetes Risks

Deborah Brauser

November 02, 2015

TRAVIS AFB, CA — War veterans with severe combat injuries are at risk of developing chronic diseases, such as coronary artery disease (CAD), chronic kidney disease (CKD), and diabetes mellitus, suggests new research[1]. And the worse the severity, the higher the health risks.

In fact, a retrospective analysis of nearly 4000 US military personnel who were critically wounded in Iraq or Afghanistan showed that each 5-point increase on an injury-severity score was associated with a 15% increase in CKD, a 13% increase in CAD or diabetes, and a 6% increase in hypertension.

In addition, those who had acute kidney injury (AKI) after a combat trauma had a 66% increased adjusted risk of developing comorbid hypertension and a 479% increased rate of having comorbid CKD.

"I thought we'd find these associations, but what surprised me was the consistency of the response. [Injury-severity score] ISS was associated with all four of the outcomes examined," lead author Dr Ian J Stewart (David Grant Medical Center, Travis Air Force Base, CA) told heartwire from Medscape.

"These are somewhat preliminary findings, but it sheds the first light on something that is a problem and something that deserves much further study."

The findings were published online November 2, 2015 in Circulation.

Service Member Questions

"I've taken care of wounded service members both in Afghanistan and back in the United States," said Stewart. "But the questions that came to mind were: what happens to these patients long term? What will they experience down the line? And can we make interventions in the short term, around the time of injury, and in the long term to mitigate these consequences?"

The investigators assessed data on 3846 men and women who were wounded with a physical injury severe enough to require intensive-care-unit admission while deployed in Iraq or Afghanistan between February 2002 and February 2011. Follow-ups occurred until January 2013, with 45 deaths occurring during this period.

A high injury-severity score "was associated with an increased incidence rate of developing each outcome independent of the risk of death, even after adjustment for age, race, [mean arterial blood pressure] MAP, heart rate, presence of burn injury, and AKI," report the researchers.

Incidence Rate Increases for Each 5-Point Increment in Severity Score

Factor Hazard ratio (95% CI) P
CAD 1.13 (1.03–1.25) 0.01
Hypertension 1.06 (1.02–1.09) 0.003
Diabetes 1.13 (1.04–1.23) 0.003
CKD 1.15 (1.04–1.27) 0.007

The adjusted hazard ratio (HR) for hypertension for those with AKI was 1.66 (95% CI 1.28–2.14, P<0.001), whereas the HR for CKD was 4.79 (95% CI 2.53–9.08, P<0.001).

There wasn't a significant association between AKI and CAD after adjustments. "One of the limitations of our analysis is that these are mostly young patients. And when you're looking at coronary artery disease, that's something that usually occurs over a long period," said Stewart. "It's possible we didn't have enough time in our study to look at that outcome."

Significant associations that were found included a higher rate of hypertension in black vs white service personnel (HR 1.69, P<0.001); and age was significantly associated with hypertension, CAD, and diabetes (HR 1.05, 1.07, and 1.08, respectively; all, P<0.001).

"When compared with historical data," the overall rates of the chronic disease were much higher than expected, write the investigators. "These findings could have profound implications for both those wounded in combat and for federal health systems."

They note that possible mechanisms for the associations could be related to proinflammatory cytokines, which have been linked to the conditions studied. "One hypothesis for our findings is that combat injury, which increases the inflammatory response, initiates a cascade that predisposes to a wide variety of chronic medical conditions," they write.

Or it could be that posttraumatic stress disorder (PTSD) "modulates this effect either directly via an inflammatory response or indirectly via weight gain and substance abuse" or that the severe functioning limitations of these injured veterans may affect outcomes, note the researchers.

"This study was meant to lay the groundwork for future work," said Stewart, adding that in future research they'd like to get a larger subset of patients, follow them for a longer period of time, and possibly include assessments of PTSD.

For now, "the number-one take-away for clinicians is to recognize that it's possible that if someone has had a combat injury, it could predispose them to a wide variety of chronic medical conditions," he said. "I'd say simple awareness is important."

The study was funded in part by a postdoctoral fellowship from the Oak Ridge Institute of Science and Education. The study authors report no relevant financial relationships.

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