Higher arterial stiffness and blunted vagal control of the heart in young women with compared to without a clinical diagnosis of PTSD.

PURPOSE: Young women are typically thought to be protected from cardiovascular disease (CVD) before menopause. However, posttraumatic stress disorder (PTSD) increases CVD risk in women by up to threefold. Data in predominantly male cohorts point to physiological mechanisms such as vascular and autonomic derangements as contributing to increased CVD risk. The purpose of the study reported here was to determine whether young women diagnosed with PTSD, compared to those without, present with arterial stiffness and impaired autonomic control of the heart. METHODS: A total of 73 healthy young women, ranging in age from 18 to 40 years, with a history of trauma exposure were included in this study, 32 with and 41 without a clinical PTSD diagnosis. We measured resting pulse wave velocity (PWV), central hemodynamics, augmentation pressure and augmentation index (AI) via pulse wave analysis using applanation tonometry. Heart rate variability was also assessed via peripheral arterial tone. RESULTS: In comparison to controls, women with PTSD showed higher central arterial pressure (mean ± standard deviation: systolic blood pressure 104 ± 8 vs. 97 ± 8 mmHg, p < 0.001; diastolic blood pressure 72 ± 7 vs. 67 ± 7 mmHg, p = 0.003), PWV (6 ± 0.3 vs. 5 ± 0.6 m/s, p < 0.001) and AI (22 ± 13 vs. 15 ± 12%, p = 0.007) but lower standard deviation of normal-to-normal intervals (SDNN; 44 ± 17 vs. 54 ± 18 ms, p = 0.005) and root mean square of successive differences between normal heartbeats (RMSSD; 37 ± 17 vs. 51 ± 22 ms, p = 0.002). CONCLUSION: PTSD in young women is associated with higher brachial and central pressures, increased arterial stiffness and blunted parasympathetic control of the heart. These findings illustrate potential mechanisms underlying high risk for CVD in young women with PTSD, suggesting possible treatment targets for this at-risk group.

Sleep disturbance and sympathetic neural reactivity in postmenopausal females.

Sleep disturbance, one of the most common menopausal symptoms, contributes to autonomic dysfunction and is linked to hypertension and cardiovascular risk. Longitudinal studies suggest that hyperreactivity of blood pressure (BP) to a stressor can predict the future development of hypertension. It remains unknown if postmenopausal females who experience sleep disturbance (SDG) demonstrate greater hemodynamic and sympathetic neural hyperreactivity to a stressor. We hypothesized that postmenopausal females with reported sleep disturbance would exhibit increased hemodynamic and sympathetic reactivity to a stressor compared with postmenopausal females without sleep disturbance (non-SDG). Fifty-five postmenopausal females (age, 62 ± 4 yr old; SDG, n = 36; non-SDG; n = 19) completed two study visits. The Menopause-Specific Quality of Life Questionnaire (MENQOL) was used to assess the presence of sleep disturbance (MENQOL sleep scale, ≥2 units). Beat-to-beat BP (finger plethysmography), heart rate (HR; electrocardiogram), and muscle sympathetic nerve activity (MSNA; microneurography; SDG, n = 25; non-SDG, n = 15) were continuously measured during a 10-min baseline and 2-min stressor (cold pressor test; CPT) in both groups. Menopause age and body mass index were similar between groups (P > 0.05). There were no differences between resting BP, HR, or MSNA (P > 0.05). HR and BP reactivity were not different between SDG and non-SDG (P > 0.05). In contrast, MSNA reactivity had a more rapid increase in the first 30 s of the CPT in the SDG (burst incidence, Δ10.2 ± 14.8 bursts/100 hb) compared with the non-SDG (burst incidence, Δ4.0 ± 14.8 bursts/100 hb, time × group, P = 0.011). Our results demonstrate a more rapid sympathetic neural reactivity to a CPT in postmenopausal females with perceived sleep disturbance, a finding that aligns with and advances recent evidence that sleep disturbance is associated with sympathetic neural hyperactivity in postmenopausal females.NEW & NOTEWORTHY This is the first study to demonstrate that muscle sympathetic nerve activity (MSNA) to a cold pressor test is augmented in postmenopausal females with perceived sleep disturbance. The more rapid increase in MSNA reactivity during the cold pressor test in the sleep disturbance group was present despite similar increases in the perceived pain levels between groups. Baseline MSNA burst incidence and burst frequency, as well as blood pressure and heart rate, were similar between the sleep disturbance and nonsleep disturbance groups.

Sex differences in Black Veterans with PTSD: women versus men have higher sympathetic activity, inflammation, and blunted cardiovagal baroreflex sensitivity.

PURPOSE: Post-traumatic stress disorder (PTSD) is associated with greater risk of incident hypertension and cardiovascular disease (CVD). Inflammation and autonomic derangements are suggested as contributing mechanisms. Women and Black adults have higher CVD risk associated with stress; however, whether there is a sex difference in autonomic and inflammatory mechanisms among Black individuals with PTSD is not known. We hypothesized that Black women with PTSD have higher inflammation, sympathetic nervous system (SNS) activity and impaired baroreflex sensitivity (BRS). METHODS: In 42 Black Veterans with PTSD (Women, N = 18 and Men, N = 24), we measured inflammatory biomarkers, continuous blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) at rest and during arterial BRS testing via the modified Oxford technique. RESULTS: Groups were matched for age and body mass index (BMI). Resting BP was similar between groups, but HR was higher (76 ± 12 vs. 68 ± 9 beats/min, p = 0.021) in women compared to men. Although women had lower PTSD symptoms severity (57 ± 17 vs. 68 ± 12 a.u.), resting MSNA (27 ± 13 vs. 16 ± 5 bursts/min, p = 0.003) was higher in women compared to men, respectively. Likewise, cardiovagal BRS was blunted (p = 0.002) in women (7.6 ± 4.3 ms/mmHg) compared to men (15.5 ± 8.4 ms/mmHg) while sympathetic BRS was not different between groups (p = 0.381). Black women also had higher (p = 0.020) plasma levels of interleukin-2 (IL-2). CONCLUSION: Black women with PTSD have higher resting HR and MSNA, greater impairment of cardiovagal BRS and possibly higher inflammation. These findings suggest a higher burden of autonomic and inflammatory derangements in Black women compared to Black men with PTSD.

A review of the historical use of sex as a biological variable in the American Journal of Physiology-Heart and Circulatory Physiology.

Despite National Institute of Health (NIH) mandates requiring sex as a biological variable (SABV), female underrepresentation persists in research, driving the American Journal of Physiology-Heart and Circulatory Physiology (Am J Physiol-Heart Circ) to publish SABV expectations in 2021. To determine progress within the Am J Physiol-Heart Circ, this mini-review evaluated SABV during the first 6 mo of each decade from 1980 to 2020, and 2019, to mitigate pandemic influence. Of the 1,205 articles published, 1,087 articles were included in this review (articles without original research subjects were excluded), of which 72.9% identified subjects. There were consistently fewer female human participants than males, except within 2019 (1980: females n = 3, males n = 5; 1990: females n = 70, males n = 199; 2000: females n = 305, males n = 355; 2010: females n = 186, males n = 472; 2019: females n = 1,695, males n = 1,550; 2020: females n = 1,157, males n = 1,222) and fewer female animals than males (1980: females n = 58, males n = 1,291; 1990: females n = 447, males n = 2,628; 2000: females n = 590, males n = 3,083; 2010: females n = 663, males n = 4,517; 2019: females n = 338, males n = 1,340; 2020: females n = 1,372, males n = 1,973). Only 16 (12.3%) articles including humans discussed SABV from 1980 to 2020. There are persistent SABV disparities within Am J Physiol-Heart Circ with some improvements in recent years. It is imperative that organizations such as the American Physiological Society and NIH foster an expectation of SABV as the norm, not the exception.

Sleep efficiency and PTSD symptom severity predict microvascular endothelial function and arterial stiffness in young, trauma-exposed women.

Posttraumatic stress disorder (PTSD) is linked to sleep disturbances and significantly higher risk of developing cardiovascular disease (CVD). Furthermore, vascular dysfunction and sleep are independently associated with CVD. Uncovering the link between PTSD symptom severity, sleep disturbances, and vascular function could shine a light on mechanisms of CVD risk in trauma-exposed young women. The purpose of the present study was to investigate the individual and combined effects of sleep efficiency and PTSD symptom severity on vascular function. We recruited 60 otherwise healthy women [age, 26 ± 7 yr and body mass index (BMI), 27.7 ± 6.5 kg/m2] who had been exposed to trauma. We objectively quantified sleep efficiency (SE) using actigraphy, microvascular endothelial function via Framingham reactive hyperemia index (fRHI), and arterial stiffness via pulse-wave velocity (PWV). PTSD symptom severity was assessed using the PTSD checklist for fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (PCL5). PWV was correlated with age (r = 0.490, P < 0.001) and BMI (r = 0.484, P < 0.001). In addition, fRHI was positively correlated with SE (r = 0.409, P = 0.001) and negatively correlated with PTSD symptoms (r = -0.382, P = 0.002). To explore the predictive value of SE and PTSD symptoms on PWV and fRHI, we conducted two multivariate linear regression models. The model predicting PWV was significant (R2 = 0.584, P < 0.001) with age, BMI, blood pressure, and SE emerging as predictors. Likewise, the model predicting fRHI was significant (R2 = 0.360, P < 0.001) with both PTSD symptoms and SE as significant predictors. Our results suggest that although PTSD symptoms mainly impact microvascular endothelial function, sleep efficiency is additionally associated with arterial stiffness in young trauma-exposed women, after controlling for age and BMI.NEW & NOTEWORTHY This is the first study to investigate the individual and combined impacts of objective sleep and PTSD symptoms severity on arterial stiffness and microvascular endothelial function in young premenopausal women. We report that in young trauma-exposed women, although low sleep efficiency is associated with overall vascular function (i.e., microvascular endothelial function and arterial stiffness), the severity of PTSD symptoms is specifically associated with microvascular endothelial function, after accounting for age and body mass index.

Vasomotor symptoms of menopause, autonomic dysfunction, and cardiovascular disease.

Cardiovascular disease (CVD), the leading cause of death among US adults, is more prevalent in menopausal females compared with age-matched males. Vasomotor symptoms of menopause (VMS; hot flashes/flushes and night sweats) are common among females undergoing menopausal transition and have been associated with elevated blood pressure (BP) and increased CVD risk. Autonomic dysregulation of BP has been posited as a contributing factor to the elevated CVD risk in menopausal females with VMS. This review includes 1) a brief overview of the relationship between VMS and CVD, 2) mechanisms of hot flushes and their potential impact on short- and long-term BP regulation, and 3) how the disruption of autonomic function associated with VMS might provide a mechanistic pathway to CVD development. Finally, this review will highlight knowledge gaps and future directions toward better understanding of hot flush physiology and VMS contributions to CVD.