Cardiorespiratory Fitness Is Associated With Better Cardiometabolic Health and Lower PTSD Severity in Post-9/11 Veterans

Abstract

Introduction

Post-traumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular and metabolic diseases and physical inactivity. Cardiorespiratory fitness (CRF), which is modifiable by physical activity, is a strong independent predictor of cardiometabolic health. However, the relationship between CRF and cardiometabolic health in veterans with PTSD is unknown. Thus, this study aimed to explore the cross-sectional relationships among CRF, indices of cardiometabolic health (ie, HbA1c, blood lipids, blood pressure, waist-hip ratio, and body mass index), and PTSD severity in veterans with PTSD.

Materials and Methods

This study was approved by the local Institutional Review Board. All participants were informed of the study risks and provided consent prior to participation. Participants (n = 13) completed a cardiopulmonary exercise test, a fasting blood draw, and the Clinician Administered PTSD Scale. Correlations between CRF and cardiometabolic health were examined with Spearman’s rank correlations, and differences in PTSD symptom severity were explored as a function of CRF (ie, low-to-moderate vs. high CRF), using multiple linear regression.

Results

Peak oxygen uptake (O_2peak) was correlated with high-density lipoproteins rho = 0.60, P = 0.04 and diastolic blood pressure rho = −0.56, P = 0.05. Ventilatory threshold was correlated with HbA1c rho = −0.61, P = 0.03 and diastolic blood pressure rho = −0.56, P = 0.05. Higher CRF was associated with lower total PTSD severity standardized β = −0.84, P = 0.01, adjusted R² = 0.47, total Cluster C symptoms (avoidance/numbing) β = −0.71, P = 0.02, adjusted R² = 0.49, and total Cluster D symptoms (hyperarousal) β = −0.89, P = 0.01, adjusted R² = 0.41, while adjusting for age and smoking status.

Conclusions

These preliminary findings suggest that CRF and by proxy physical activity may be important factors in understanding the increased risk of cardiovascular and metabolic disease associated with PTSD.

Introduction

Post-traumatic stress disorder (PTSD) is a psychological disorder that occurs in some individuals who have experienced a traumatic event. PTSD is characterized by several distinct symptom clusters: re-experiencing symptoms (eg, intrusive memories), avoidance of reminders of the traumatic event, persistent negative changes in mood and cognitions, and increased arousal and reactivity.¹ PTSD also has profound negative impacts on physical health, such as an increased risk of cardiovascular and metabolic diseases.²

There are a number of factors associated with PTSD that may increase this risk, including obesity, hypertension, dyslipidemia and autonomic and immune dysfunction (eg, chronic increases in catecholamines and proinflammatory cytokines).³ Lifestyle choices also play an important role. Specifically, PTSD is consistently associated with decreases in physical activity,⁴ which in turn can lead to the development of cardiovascular and metabolic diseases.⁵ Cardiorespiratory fitness (CRF) is a strong independent risk factor for cardiovascular and metabolic diseases, and it is modifiable through physical activity (eg, aerobic exercise).⁶

Early studies suggest that exercise may reduce PTSD symptom severity as a standalone intervention⁷ or when paired with prolonged-exposure therapy or “care as usual.”⁸ Despite these encouraging findings, the relationship between CRF and PTSD remains unclear. For instance, a recent review of physical fitness and PTSD reported mixed results.⁹ However, fitness outcomes (eg, CRF or muscular strength), and methods (eg, with or without metabolic data) varied greatly across studies. Additionally, many studies in the field have relied exclusively on self-report measures of PTSD rather than a diagnostic interview and/or have included participants with subclinical levels of PTSD.⁸

Overall, studies examining CRF or other measures of physical fitness in individuals with PTSD are scarce, and the previously discussed methodological factors make accurately describing the relationships between CRF, cardiometabolic health, and PTSD difficult. A better understanding of the link between PTSD and biomarkers for cardiovascular and metabolic diseases—two of the leading causes of death in the world¹⁰—will inform the development of targeted exercise interventions for people living with PTSD. Thus, the purpose of this study was to: (1) examine the cross-sectional relationship(s) between CRF and indices of cardiometabolic health in individuals with PTSD and (2) explore potential associations between CRF and PTSD symptom severity. We hypothesized that (1) higher levels of CRF would be associated with better cardiometabolic health in individuals with PTSD and (2) individuals with greater CRF would have significantly lower PTSD symptom severity than those who were less aerobically fit.

Methods

Design and Procedure

This study was approved by the local Institutional Review Board. All participants were informed of the study risks and provided consent prior to participation. Participants were approached during the 1-year follow-up visit at the Translational Research Center for TBI and Stress Disorders (TRACTS) and invited to participate in a cardiopulmonary exercise testing (CPX) in addition to the standard TRACTS battery of assessments. All data were collected between September 2015 and December 2016.

Participants

Participants were military veterans recruited from TRACTS (see Table I for participant characteristics). TRACTS is a longitudinal cohort study of post-9/11 military service members and veterans that examines many aspects of physical and mental health. Participation in TRACTS includes an extensive battery of psychological testing, neuroimaging, and numerous physiological measures. A detailed description the TRACTS cohort is discussed elsewhere.¹¹ For the present study, we included veterans who met current diagnostic criteria for PTSD and excluded anyone with contraindications to CPX, such as unstable angina or respiratory failure. A total of 42 veterans agreed to participate in a CPX, during their 1-year follow-up visit for TRACTS. Of these, 16 did not show for their session, 1 was excluded for medical reasons, 3 were excluded for an invalid CPX, and 9 were excluded because they did not have PTSD, leaving a final sample size of n = 13.

Table I.

Sample Characteristics

	CRF Study (n = 13)	TRACTS (n = 115)
	n (%)	n (%)
Gender (male)	13 (100)	101 (87.8)
Race (White)	9 (69.2)	86 (74.8)
Military branch
Army	4 (30.8)	29 (25.2)
Navy	1 (7.7)	4 (3.5)
Marines	2 (15.4)	21 (18.3)
Air Force	0 (0)	2 (1.7)
National Guard/Reserves	6 (46.2)	58 (50.4)
Current smoker	4 (30.8)	31 (27.0)
Lifetime traumatic brain injury	9 (69.2)	86 (74.8)
Co-morbid mental disorder
Mood disorder	4 (30.8)	47 (40.9)
Anxiety disorder	1 (7.7)	35 (30.4)
Substance use disorder	1 (7.7)	32 (27.8)
	Mean (SD)	Mean (SD)
Age	35.3 (8.1)	35.0 (9.6)
Body mass index	28.7 (3.5)	29.1 (4.7)
Waist-hip ratio	0.92 (0.06)	0.90 (0.08)
Total cholesterol	191.8 (30.2)	188.6 (37.8)
High-density lipoproteins	43.0 (7.1)	48.7 (14.4)
Low-density lipoproteins	121.7 (28.2)	117.6 (33.2)
Triglycerides	148.5 (79.5)	144.0 (107.4)
HbA1c	5.5 (0.25)	5.5 (0.31)
Resting heart rate	78.6 (11.3)	NA
Resting systolic blood pressure	115.7 (12.8)	121.0 (13.9)
Resting diastolic blood pressure	79.8 (8.1)	77.8 (10.1)
O2peak (mL/kg/min)	37.7 (6.7)	NA
VT (mL/kg/min)	27.7 (6.5)	NA
CAPS total score	62.8 (18.5)	70.0 (10.1)
Re-experiencing	15.2 (6.3)	18.4 (7.5)
Avoidance/numbing	25.5 (9.5)	27.8 (9.6)
Hyperarousal	22.0 (6.8)	23.8 (6.7)

NA = not available

Measures

PTSD Symptoms and Diagnosis

The Clinician Administered PTSD Scale (CAPS) for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV was used to determine if participants met diagnostic criteria for current (ie, past month) PTSD.¹² DSM-IV criteria were used to diagnose PTSD because enrollment in the TRACTS longitudinal cohort study began in 2010, prior to the release of the updated DSM-5 criteria. There is strong correspondence between the CAPS for the DSM-IV and DSM-5 in military Veterans.¹³ The CAPS for the DSM-IV is a structured interview that rates the frequency and intensity of symptoms relating to each of the PTSD symptom clusters (ie, Criterion B: re-experiencing, Criterion C: avoidance/numbing, and Criterion D: hyperarousal) as described in the DSM-IV.¹⁴ PTSD symptom severity can be reported by individual symptom cluster or as a total severity score. Valid total CAPS scores range from 0 to 136 with higher scores indicating worse PTSD severity. The CAPS has excellent psychometric properties and is considered the gold standard for PTSD diagnosis.¹⁵

CRF Assessment

Oxygen uptake at peak exercise (O_2peak; mL/kg/min) and ventilatory threshold (VT; mL/kg/min) was measured with CPX.¹⁶ A standard treadmill Bruce protocol was followed.¹⁷ Blood pressure and electrocardiographic data were monitored throughout the test for safety, and all tests were performed under the supervision of a physician.

Indices of Cardiometabolic Health

Height, weight, waist and hip circumferences, and blood pressure were measured, and body mass index (BMI) and waist-hip ratio were calculated. Participants contributed a fasting blood sample upon arrival at testing, usually before 7:30 am. From this specimen, glycated hemoglobin (HbA1c) and a full lipid panel, including total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides were measured as indicators of cardiovascular and metabolic health.

Statistical Analysis

To address the first hypothesis, we examined potential associations between CRF and cardiometabolic health using Spearman’s rank correlations. Spearman’s rank correlations were used to reduce the effects of potential outliers. To test our second hypothesis, a multiple linear regression analysis was used to assess the contribution of CRF (ie, high vs. low-to-moderate CRF) to CAPS total score (to reflect PTSD symptom severity). We operationalized high and low-to-moderate CRF as a % O_2peak at VT of ≥70% and <70%, respectively. Prior research has demonstrated that the VT occurs below 70% of O_2peak for most untrained individuals and can increase to >70% of O_2peak in trained individuals.¹⁸ Participant age and smoking status were modeled as covariates, as they are known to independently effect O_2peak regardless of training status,^19,20 and cigarette smoking is further associated with greater PTSD severity.²¹ Additionally, separate regression analyses were conducted to explore the relationship between CRF and each of the individual PTSD symptom clusters, using the same independent variables as above. For these exploratory analyses, a square root transformation of the symptom cluster severity score was applied to meet the assumptions of linearity and normality of residuals. Additionally, no model exceeded a variance inflation factor of 2 verifying that multicollinearity was not present. The threshold for statistical significance was set at P < 0.05, and all analyses were conducted using IBM SPSS 25.

Results

Sample Characteristics

Descriptive characteristics of the TRACTS sample and the subsample used in this study can be referenced in Table I.

CRF Is Associated With Indices of Cardiometabolic Health in Veterans With PTSD

A full bivariate correlation matrix of CRF and indices of cardiometabolic health can be referenced in Supplementary Table S1. Regarding CRF, O_2peak was moderately and significantly correlated with HDLs (rho = 0.60, P = 0.04) and diastolic blood pressure (rho = −0.56, P = 0.05). VT was moderately and significantly correlated with HbA1c (rho = −0.61, P = 0.03) and diastolic blood pressure (rho = −0.56, P = 0.05). While nonsignificant, O_2peak was moderately correlated with BMI (rho = −0.54, P = 0.06) and HbA1c (rho = −0.54, P = 0.06). Similarly, there were nonsignificant moderate correlations observed between VT and systolic blood pressure (rho = −0.53, P = 0.07) and HDL (rho = 0.48, P = 0.11), respectively.

CRF Is Associated With PTSD Symptom Severity

Veterans with high CRF had significantly lower total PTSD severity than those with low-to-moderate CRF (mean total CAPS 52.6 (SD = 14.9) vs. 74.7 (SD = 15.9), respectively). The multiple linear regression model for total CAPS severity score is presented in Table II. The results indicate that CRF is significantly associated with total PTSD symptom severity (β = −0.84, P = 0.01), while adjusting for age and smoking status. Similarly, the exploratory analyses of the individual PTSD symptom clusters revealed that high CRF was significantly associated with lower avoidance/numbing (β = −0.71, P = 0.02) and hyperarousal symptom clusters (β = −0.89, P = 0.01), while adjusting for age and smoking status. However, CRF was not significantly associated with the re-experiencing symptom cluster (β = 0.13, P = 0.20).

Table II.

Multiple Linear Regression of PTSD Severity and CRF

Variable	B	SE	β	t	P	Adjusted R2
Total CAPS Score						0.47
Age	0.91	0.60	0.40	1.5	.16
Smoking status	12.1	8.15	0.32	1.5	.17
CRF	−29.9	9.35	−0.84	−3.2	.01*
Re-experiencing						0.19
Age	0.01	0.03	0.13	0.4	.71
Smoking status	0.78	0.44	0.47	1.8	.11
CRF	−0.69	0.50	0.13	−1.4	.20
Avoidance/numbing						0.49
Age	0.04	0.03	0.33	1.3	.23
Smoking status	0.98	0.42	0.49	2.3	.04*
CRF	−1.34	0.48	−0.71	−2.8	.02*
Hyperarousal						0.41
Age	0.05	0.02	0.55	2.0	.08
Smoking status	−0.39	0.34	−0.26	−1.2	.28
CRF	−1.25	0.38	−0.89	−3.3	.01*

Note. N = 13. B and standardized β coefficients reflect square root transformed data for the re-experiencing, avoidance/numbing, and hyperarousal symptom clusters.

^*Significance at P < .05.

Discussion

This study sought to examine the cross-sectional relationship between CRF, indices of cardiometabolic health, and PTSD symptom severity in post-9/11 military veterans diagnosed with PTSD. The results indicate that greater CRF as measured by cardiopulmonary exercise test is significantly associated with better cardiometabolic health (eg, lower HbA1c and blood pressure and higher HDLs). Importantly, this study also demonstrated that those with high CRF had significantly lower PTSD symptom severity, relative to low and moderately fit individuals. To our knowledge, this is the first study demonstrating that CRF is associated with both cardiometabolic health and PTSD severity in post-9/11 Veterans with PTSD.

The observed associations between CRF and cardiometabolic health were anticipated. CRF is a well-known and strong predictor of cardiovascular disease in non-Veteran samples without PTSD.⁶ However, these findings are particularly important when taken in the context of a diagnosis of PTSD. Specifically, PTSD is a significant risk factor for cardiovascular and metabolic disease.² PTSD has also been linked to low exercise participation in Veterans²¹ and non-Veterans.⁴ CRF is modifiable by regular exercise.²² As such, CRF and by proxy exercise may be important factors in the relationship between PTSD and negative physical health outcomes, such as cardiovascular disease and diabetes.

In addition to cardiometabolic health, CRF also appears to be connected to symptom severity in PTSD. Specifically, participants with the highest CRF (i.e., % O_2peak at VT ≥ 70%) reported the least severe PTSD. Our results further indicate that the avoidance/numbing and hyperarousal symptom clusters were primarily responsible for these observed differences in PTSD symptom severity as a function of CRF. These findings help to clarify prior research,^7,23 suggesting that exercise participation has the strongest effects on the PTSD avoidance/numbing and hyperarousal symptoms.

This study used cross-sectional data, as such, it is not possible to determine causality. For instance, it is possible that the participants with high CRF have lower PTSD symptom severity because they are more physically active, as some studies have shown that exercise has a therapeutic effect on PTSD.⁸ Alternatively, it is also possible that individuals with severe PTSD are more isolated and avoid public spaces, such as parks or recreation centers, and are consequently less physically fit. Both situations are plausible, highlighting the need for further longitudinal research. This is particularly true for studies interested in understanding the link between PTSD and cardiovascular and metabolic diseases, which to date have largely overlooked the role of CRF.⁹

Other limitations to this study include the relatively small sample size, lack of a comparison group (eg, trauma exposed individuals without PTSD), and a sample consisting only of male military veterans. This consequently limits statistical power and generalizability and prohibits any tests of mediation and/or moderation between CRF, cardiometabolic health, and PTSD symptom severity. Additionally, given that combat-related TBI is a strong predictor of PTSD severity in military veterans,²⁴ it is possible that combat-related TBI or combat blast exposure (eg, improvised explosive devices) may moderate the association between CRF and PTSD. There was a high rate of TBI (69%) and blast exposure (85%) in this sample; however, we did not have the power to examine these factors as moderators and should be explored in future studies.

Despite these limitations, this study had specific strengths as well, including the use of methodologically rigorous assessments, such as objectively measuring indices of cardiometabolic health, and assessing CRF with a CPX in lieu of estimating CRF using biometrics or predicting CRF with a submaximal test. Similarly, PTSD symptom severity and diagnosis were assessed with the CAPS, the gold standard diagnostic interview for PTSD, as opposed to self-report. Considering these strengths and the dearth of research examining CRF and cardiometabolic health in individuals with PTSD, this study fills an important gap and contributes to our understanding of the relationship between PTSD and cardiometabolic health.

In sum, this study demonstrates that greater CRF is associated with better cardiometabolic health and lower PTSD symptom severity in male Veterans with PTSD. Given the increased risk of negative cardiometabolic outcomes associated with PTSD, this study further underscores the importance of measuring CRF in this population, as CRF is often overlooked despite being a modifiable risk factor for cardiovascular and metabolic diseases. However, these findings are cross-sectional and preliminary, adding to a relatively small number of studies examining physical fitness and PTSD. Larger fully powered studies are needed to expand this work beyond parallel associations by examining the longitudinal direct and indirect relationships between CRF, PTSD, and cardiometabolic health in diverse populations.

Funding

This work was supported by the TRACTS National Network Research Center for TBI research (RM; B3001-C) from the U.S. Department of Veterans Affairs Rehabilitation Research and Development Service, the National Institute of Mental Health (JWW; 5T32MH019836–16), National Institute on Aging of the National Institutes of Health (SMH; R21AG056921), and the Boston University Spivack Emerging Leaders in Neurosciences Award (SMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the National Institutes of Health.