Cardiac Biomarkers, Mortality, and Post-Traumatic Stress Disorder in Military Veterans

Study Questions:

Post-traumatic stress disorder (PTSD) is a risk factor for morbidity and mortality. What is the relationship between PTSD and abnormal cardiovascular biomarkers on mortality in military veterans?

Methods:

Eight hundred ninety-one patients presenting for routine echocardiography were enrolled. Baseline clinical data and serum samples for biomarker measurement were obtained, and echocardiography was performed at the time of enrollment. Patients were followed for up to 7.5 years for the endpoint of all-cause mortality.

Results:

Ninety-one patients had PTSD at the time of enrollment. There was no difference at baseline in those with and without PTSD for the following: coronary artery disease, blood pressure, hypertension, smoking, or left ventricular (LV) end-diastolic size. However, PTSD patients had smaller LV end-systolic diameters, higher LV ejection fraction (EF) (63% vs. 60%, p = 0.01), and less arrhythmia (17% vs. 27%, p = 0.03) and heart failure (15% vs. 27%, p = 0.016). There were 33 deaths in patients with PTSD and 221 deaths in those without PTSD. Patients with PTSD had a trend toward worse survival on Kaplan-Meier analysis (p = 0.057). Among patients with elevated B-type natriuretic peptide (BNP) (>60 pg/ml), those with PTSD had significantly increased mortality (p = 0.024). Among patients with PTSD, midregional proadrenomedullin (MR-proADM), creatinine, and C-terminal proendothelin-1 were significant univariate predictors of mortality. In a multivariate model, PTSD, BNP, and MR-proADM were independent predictors of mortality. In patients with PTSD, MR-proADM was a significant independent predictor of mortality after adjusting for BNP, cardiovascular risk factors, cancer, and sleep apnea. Adding MR-proADM to clinical predictors of mortality increased the C-statistic from 0.572 to 0.697 (p = 0.007).

Conclusions:

The authors concluded that this study demonstrates an association among PTSD, abnormal cardiac biomarker levels, and increased mortality.

Perspective:

Adrenomedullin, whose precursor is MR-proADM, is a vasodilatory peptide that is indicative of sympathetic activation, and both are elevated in congestive heart failure. The improvement in the C-statistic by adding MR-proADM to clinical predictors of mortality is unusually robust. If the results can be validated, PTSD patients with an elevated MR-proADM may benefit from medical and psychiatric care directed at chronic inappropriate sympathetic activation.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Hypertension, Smoking, Sleep Apnea

Keywords: Coronary Artery Disease, Kaplan-Meier Estimate, Neoplasms, Morbidity, Endothelin-1, Risk Factors, Creatinine, Sleep Apnea Syndromes, Adrenomedullin, Smoking, Stress Disorders, Post-Traumatic, Biological Markers, Protein Precursors, Heart Failure, Peptide Fragments, Military Personnel, Hypertension, Natriuretic Peptide, Brain, Echocardiography


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