Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post‐traumatic stress disorder

Abstract

Key pointsr Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known.r Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients.r Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation.r Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients.Abstract Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD. Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress: combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD vs. Controls, MSNA (+8.2 ± 1.0 vs. +1.2 ± 1.3 bursts min -1 , P < 0.001) and heart rate responses (+3.2 ± 1.1 vs. −2.3 ± 1.0 beats min -1 , P = 0.003) were significantly augmented during VRCE. Similarly, in PTSD vs. Controls, MSNA (+21.0 ± 2.6 vs. +6.7 ± 1.5 bursts min -1 , P < 0.001) and diastolic BP responses (+6.3 ± 1.0 vs. +3.5 ± 1.0 mmHg, P = 0.011) were significantly augmented during MA but not during CPT (P = not significant). In the PTSD group, sympathetic BRS (-1.2 ± 0.2 vs. -2.0 ± 0.3 burst incidence mmHg and cardiovagal BRS (9.5 ± 1.4 vs. 23.6 ± 4.3 ms mmHg −1 , P = 0.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive-C-reactive protein levels compared to Controls (2.1 ± 0.4 vs. 1.0 ± 0.3 mg L −1 , P = 0.047). Augmented SNS and haemodynamic responses to mental stress, blunted BRS and inflammation may contribute to an increased CV risk in PTSD.

A comparison of physical comorbidities in patients with posttraumatic stress disorder developed after a terrorist attack or other traumatic event

“…Indeed, an increase in blood pressure values and arterial rigidity results from an inflammatory endothelial damage. Proinflammatory cytokines increase peripheral resistances, decrease vagal sensitivity, and induce SRAA dysfunction (Park et al, ).…”

Baroreflex‐mediated sympathetic overactivation induced by mental stress in post‐traumatic stress disorder depends on the type of stressor

“…Park et al . () also hypothesized that a baroreflex dysfunction might play a role in SNS overactivation during mental stress in PTSD subjects, increasing their risk of cardiovascular diseases and hypertension. In their study, for the first time, muscle sympathetic nerve activity (MSNA) was directly assessed in PTSD subjects during rest and mental stress conditions.…”

“…Additionally, Park et al . () assessed MSNA during a cold pressor test (CPT) that elicits a non‐baroreflex‐mediated SNS activation. The authors found that the increases in MSNA, blood pressure and heart rate were not different between PTSD and control subjects suggesting that the SNS overactivity in PTSD is restricted to mental stress conditions and, importantly, is baroreflex‐mediated.…”

“…Finally, Park et al . () found that baseline highly sensitivity C‐reactive protein (hsCRP) is increased in PTSD in comparison to control subjects, proposing that inflammation could be a potential mechanism leading to baroreflex dysfunction and increased SNS responses to mental stress.…”

“…The data presented by Park et al . () bring clear‐cut evidence that baroreflex dysfunction plays an important role in PTSD as in many other diseases where there is an autonomic imbalance. In PTSD, an impaired baroreflex seems to be triggering the overactivation of the SNS in response to mental stress, which in turn increases the risk of cardiovascular events and other diseases, such as hypertension.…”