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.

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 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.

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.

Eight weeks of device-guided slow breathing decreases sympathetic nervous reactivity to stress in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by increased risk for developing hypertension and cardiovascular disease. We recently showed that device-guided slow breathing (DGB) acutely lowers blood pressure (BP) and muscle sympathetic activity (MSNA) and improves baroreflex sensitivity (BRS) in PTSD. The aim of this study was to assess the long-term benefits of DGB on autonomic function at rest and during stress. We hypothesized that long-term DGB improves arterial BRS and lowers BP and MSNA in PTSD. Twenty-five veterans with PTSD were studied and randomized to either 8 wk of daily DGB (n = 12) or 8 wk of sham device (Sham; n = 13). BP, heart rate (HR), and MSNA were measured at rest and during mental math. Arterial BRS was assessed using the modified Oxford technique. Resting MSNA, BP, and heart rate (HR) remained comparable before and after 8 wk in both groups (DGB and Sham). Likewise, the change in sympathetic and cardiovagal BRS was not different between the groups. Interestingly, DGB significantly decreased MSNA reactivity to mental math when expressed as burst frequency (P = 0.012) or burst incidence (P = 0.008) compared with Sham, suggesting a sustained effect of DGB on sympathetic reactivity to stress in PTSD. Contrary to our hypothesis, long-term DGB did not lower systolic BP, diastolic BP, or HR responses to stress compared with Sham. Likewise, pulse pressure reactivity after 8 wk (P = 0.121) was also comparable. In summary, these data suggest that long-term use of DGB may lead to a sustained dampening of sympathetic reactivity to mental stress in PTSD.

Symptom severity impacts sympathetic dysregulation and inflammation in post-traumatic stress disorder (PTSD).

Post-traumatic stress disorder (PTSD) is associated with a greater risk of incident hypertension and cardiovascular disease. Inflammation, impaired baroreflex sensitivity (BRS) decreased parasympathetic nervous system (PNS) and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Increasing severity of PTSD symptoms has been linked to greater cardiovascular risk; however, the impact of PTSD symptom severity on inflammation and autonomic control of blood pressure has not yet been explored. We hypothesized that increasing PTSD symptom severity is linked to higher inflammation, greater SNS activity, lower PNS reactivity and impaired BRS. Seventy Veterans participated in this study: 28 with severe PTSD ((Clinical Administered PTSD Scale (CAPS) > 60; S-PTSD), 16 with moderate PTSD (CAPS ≥ 45 ≤ 60; M-PTSD) and 26 Controls (CAPS < 45; NO-PTSD). We recorded continuous blood pressure (BP), heart rate (HR) via EKG, heart rate variability (HRV) markers reflecting PNS and muscle sympathetic nerve activity (MSNA) at rest, during arterial baroreflex sensitivity (BRS) testing via the modified Oxford technique, and during 3 min of mental stress via mental arithmetic. Blood samples were analyzed for 12 biomarkers of systemic and vascular inflammation. While BP was comparable between severity groups, HR tended to be higher (p = 0.055) in S-PTSD (76 ±â€¯2 beats/min) than in Controls (67 ±â€¯2 beats/min) but comparable to M-PTSD (70 ±â€¯3 beats/min). There were no differences in resting HRV and MSNA between groups; however, cardiovagal BRS was blunted (p = 0.021) in S-PTSD (10 ±â€¯1 ms/mmHg) compared to controls (16 ±â€¯3 ms/mmHg) but comparable to M-PTSD (12 ±â€¯2 ms/mmHg). Veterans in the S-PTSD group had a higher (p < 0.001) combined inflammatory score compared to both M-PTSD and NO-PTSD. Likewise, while mental stress induced similar SNS and cardiovascular responses between the groups, there was a greater reduction in HRV in S-PTSD compared to both M-PTSD and NO-PTSD. In summary, individuals with severe PTSD symptoms have higher inflammation, greater impairment of BRS, a trend towards higher resting HR and exaggerated PNS withdrawal at the onset of mental stress that may contribute to cardiovascular risk in severe PTSD.

Sex differences in post-traumatic stress disorder risk: autonomic control and inflammation.

AIM: Over 7 million U.S. adults and about 20% of the military population have post-traumatic stress disorder (PTSD), a debilitating condition that is independently linked to a significantly greater risk of developing cardiovascular disease (CVD). Women have twice the probability of developing PTSD after experiencing a traumatic event compared to men. Existing literatures have reported higher inflammation and autonomic dysfunction including impaired baroreflex sensitivity, increased sympathetic reactivity and decreased parasympathetic activity in PTSD. However, most of these findings stem from studies conducted predominantly in males. METHODS: We attempt in this narrative review to summarize the mixed literature available on sex differences in autonomic dysfunction and inflammation in PTSD, at rest and in response to stress in PTSD. RESULTS: This review reveals that there is a paucity of research exploring autonomic function in females with PTSD. Recent studies have included female participants without probing for sex differences. A small number of studies have been conducted exclusively in women. Available data suggest that sympathetic nervous system output tends to be heightened, while parasympathetic activity and arterial baroreflex sensitivity appear more blunted in females with PTSD. Although few studies have investigated sex differences in inflammation in PTSD, data within females suggest chronic increases in inflammation with PTSD. This autonomic dysregulation and inflammation have also been described in males with PTSD. CONCLUSION: In sum, given the inherent biological differences in CVD clinical presentation and characteristics between men and women, human and animal studies aiming at elucidating sex differences in the pathophysiology of PTSD are needed.

Sympathetic neural responsiveness to sleep deprivation in older adults: sex differences.

Our laboratory has previously reported that total sleep deprivation (TSD) modifies muscle sympathetic neural activity (MSNA) differently in young men and women. Because postmenopausal women are among the highest risk for hypertension, this study compares MSNA responses with TSD in older men and women. We hypothesized that TSD would alter MSNA in older adults, with greater sympathoexcitation in postmenopausal women. Twenty-seven participants (14 men and 13 women) between the ages of 55 and 75 yr were tested twice, once after 24-h TSD and once after normal sleep (randomized, crossover design). Our primary outcome measure of MSNA (microneurography) was successful across both conditions in 20 participants (10 men and 10 women). Secondary outcome measures included seated blood pressure, heart rate, and fasting plasma testosterone, estradiol, and progesterone. Age (60 ± 1 vs. 61 ± 2 yr) and BMI (27 ± 1 vs. 26 ± 1 kg/m2) were not different between groups. TSD increased systolic blood pressure in both men (124 ± 5 to 130 ± 4 mmHg) and women (107 ± 5 to 116 ± 4 mmHg), but the increases were not different between groups (condition, P = 0.014; condition × sex, P > 0.05). In contrast, TSD elicited divergent MSNA responses in older men and women. Specifically, MSNA burst frequency increased in postmenopausal women (28 ± 3 to 34 ± 3 burst/min), but not older men (38 ± 3 to 35 ± 3 bursts/min; condition × sex, P = 0.032). In conclusion, TSD elicited sympathoexcitation in postmenopausal women but not age-matched men. These findings provide new mechanistic insight into reported links between sleep deprivation and hypertension.NEW & NOTEWORTHY Epidemiological studies report that sleep deprivation is more strongly associated with hypertension in women than in men. In the present study, 24-h total sleep deprivation (TSD) increased blood pressure in postmenopausal women and age-matched men. In contrast, only women demonstrated increases in muscle sympathetic nerve activity after TSD. The sympathoexcitation observed in postmenopausal women suggests a potential contributing mechanism for epidemiological observations and advances our understanding of the complex relations between sleep, sex, and hypertension.

Vascular α1-adrenergic sensitivity is enhanced in chronic kidney disease.

Chronic kidney disease (CKD) is often complicated by difficult-to-control hypertension, in part due to chronic overactivation of the sympathetic nervous system (SNS). CKD patients also exhibit a greater increase in arterial blood pressure for a given increase in sympathetic nerve activation, suggesting an augmented vasoconstrictive response to SNS activation (i.e., neurovascular transduction). One potential mechanism of increased sympathetic neurovascular transduction is heightened sensitivity of the vascular α1-adrenergic receptors (α1ARs), the major effectors of vasoconstriction in response to norepinephrine release at the sympathetic nerve terminals. Therefore, we hypothesized that patients with CKD have increased vascular α1AR sensitivity. We studied 32 patients with CKD stages III and IV (age 59.9 ± 1.3 yr) and 19 age-matched controls (CON, age 63.2 ± 1.6 yr). Using a linear variable differential transformer (LVDT), we measured change in venoconstriction in response to exponentially increasing doses of the selective α1AR agonist phenylephrine (PE) administered sequentially into a dorsal hand vein. Individual semilogarithmic PE dose-response curves were constructed for each participant to determine the PE dose at which 50% of maximum venoconstriction occurred (ED50), reflecting α1AR sensitivity. In support of our hypothesis, CKD patients had a lower PE ED50 than CON (CKD = 2.23 ± 0.11 vs. CON = 2.63 ± 0.20, P = 0.023), demonstrating increased vascular α1AR sensitivity. Additionally, CKD patients had a greater venoconstrictive capacity to PE than CON (P = 0.015). Augmented α1AR sensitivity may contribute mechanistically to enhanced neurovascular transduction in CKD and may explain, in part, the greater blood pressure reactivity exhibited in these patients.

Functional sympatholysis is impaired in end-stage renal disease.

Patients with end-stage renal disease (ESRD) have decreased exercise capacity and exercise intolerance that contribute to cardiovascular risk. One potential mechanism underlying exercise intolerance in ESRD is impaired ability to oppose sympathetically mediated vasoconstriction within exercising skeletal muscle (i.e., functional sympatholysis, FS). We hypothesized that ESRD patients have impaired FS compared with healthy (CON) and hypertensive (HTN) controls and that impaired FS is related to circulating levels of the uremic toxin asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide synthase inhibitor. Near-infrared spectroscopy-derived oxygen tissue saturation index (TSI) of the forearm muscle was measured continuously in 33 participants (9 CON, 14 HTN, 10 ESRD) at rest and during low-dose (-20 mmHg) lower body negative pressure (LBNP), moderate rhythmic handgrip exercise, and LBNP with concomitant handgrip exercise (LBNP+handgrip). Resting muscle TSI was lower in ESRD than in CON and HTN groups (CON = 67.8 ± 1.9%, HTN = 67.2 ± 1.1%, ESRD = 62.7 ± 1.5%, P = 0.03). Whereas CON and HTN groups had an attenuation in sympathetically mediated reduction in TSI during LBNP + handgrip compared with LBNP alone (P ≤ 0.05), this response was not present in ESRD (P = 0.71), suggesting impaired FS. There was no difference in plasma [ADMA] between groups (CON = 0.47 ± 0.05 µmol/l, HTN = 0.42 ± 0.06 µmol/l, ESRD = 0.63 ± 0.14 µmol/l, P = 0.106) and no correlation between plasma [ADMA] and resting muscle TSI (P = 0.84) or FS (P = 0.75). Collectively, these findings suggest that ESRD patients have lower muscle perfusion at rest and impaired FS but that these derangements are not related to circulating [ADMA].

Metabolic acidosis augments exercise pressor responses in chronic kidney disease.

Chronic kidney disease (CKD) patients experience augmented blood pressure (BP) reactivity during exercise that is associated with an increased risk of cardiovascular mortality. Exaggerated exercise pressor responses in CKD are in part mediated by augmented sympathetic nerve activation due to heightened muscle mechanoreflex. One mechanism that may lead to sensitization of the muscle mechanoreflex in CKD is metabolic acidosis. We hypothesized that CKD patients with low serum [bicarbonate] would exhibit exaggerated increases in arterial BP, greater reductions in muscle interstitial pH, and fatigue earlier during exercise compared with CKD patients with normal serum bicarbonate concentration ([bicarbonate]). Eighteen CKD participants with normal serum [bicarbonate] (≥24 mmol/l, normal-bicarb) and 9 CKD participants with mild metabolic acidosis ([bicarbonate] range 20-22 mmol/l, low-bicarb) performed rhythmic handgrip (RHG) exercise to volitional fatigue at 40% of maximal voluntary contraction. BP, heart rate, and muscle interstitial pH using near infrared spectroscopy were measured continuously. While mean arterial pressure (MAP) increased with exercise in both groups (P ≤ 0.002), CKD with low-bicarb had an exaggerated MAP response compared with CKD with normal-bicarb (+5.9 ± 1.3 mmHg/30 s vs. +2.6 ± 0.5 mmHg/30 s, P = 0.01). The low-bicarb group reached exhaustion earlier than the normal-bicarb group (179 ± 21 vs. 279 ± 19 s, P = 0.003). There were no differences in the change in muscle interstitial pH during exercise between groups (P = 0.31). CKD patients with metabolic acidosis have augmented exercise-induced increases in BP and poorer exercise tolerance. There was no difference in change in muscle interstitial pH between groups, however, suggesting that augmented exercise BP responses in metabolic acidosis are not due to impaired muscle-buffering capacity.

Acute effects of device-guided slow breathing on sympathetic nerve activity and baroreflex sensitivity in posttraumatic stress disorder.

Patients with posttraumatic stress disorder (PTSD) have elevated sympathetic nervous system reactivity and impaired sympathetic and cardiovagal baroreflex sensitivity (BRS). Device-guided slow breathing (DGB) has been shown to lower blood pressure (BP) and sympathetic activity in other patient populations. We hypothesized that DGB acutely lowers BP, heart rate (HR), and improves BRS in PTSD. In 23 prehypertensive veterans with PTSD, we measured continuous BP, ECG, and muscle sympathetic nerve activity (MSNA) at rest and during 15 min of DGB at 5 breaths/min ( n = 13) or identical sham device breathing at normal rates of 14 breaths/min (sham; n = 10). Sympathetic and cardiovagal BRS was quantified using pharmacological manipulation of BP via the modified Oxford technique at baseline and during the last 5 min of DGB or sham. There was a significant reduction in systolic BP (by -9 ± 2 mmHg, P < 0.001), diastolic BP (by -3 ± 1 mmHg, P = 0.019), mean arterial pressure (by -4 ± 1 mmHg, P = 0.002), and MSNA burst frequency (by -7.8 ± 2.1 bursts/min, P = 0.004) with DGB but no significant change in HR ( P > 0.05). Within the sham group, there was no significant change in diastolic BP, mean arterial pressure, HR, or MSNA burst frequency, but there was a small but significant decrease in systolic BP ( P = 0.034) and MSNA burst incidence ( P = 0.033). Sympathetic BRS increased significantly in the DGB group (-1.08 ± 0.25 to -2.29 ± 0.24 bursts·100 heart beats-1·mmHg-1, P = 0.014) but decreased in the sham group (-1.58 ± 0.34 to -0.82 ± 0.28 bursts·100 heart beats-1·mmHg-1, P = 0.025) (time × device, P = 0.001). There was no significant difference in the change in cardiovagal BRS between the groups (time × device, P = 0.496). DGB acutely lowers BP and MSNA and improves sympathetic but not cardiovagal BRS in prehypertensive veterans with PTSD. NEW & NOTEWORTHY Posttraumatic stress disorder is characterized by augmented sympathetic reactivity, impaired baroreflex sensitivity, and an increased risk for developing hypertension and cardiovascular disease. This is the first study to examine the potential beneficial effects of device-guided slow breathing on hemodynamics, sympathetic activity, and arterial baroreflex sensitivity in prehypertensive veterans with posttraumatic stress disorder.

Elevated resting blood pressure augments autonomic imbalance in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by increased sympathetic nervous system (SNS) activity, blunted parasympathetic nervous system (PNS) activity, and impaired baroreflex sensitivity (BRS), which contribute to accelerated cardiovascular disease. Patients with PTSD also have chronic stress-related elevations in resting blood pressure (BP), often in the prehypertensive range; yet, it is unclear if elevated resting blood pressure (ERBP) augments these autonomic derangements in PTSD. We hypothesized that compared with normotensive PTSD (N-PTSD), those with ERBP (E-PTSD) have further increased SNS, decreased PNS activity, and impaired BRS at rest and exaggerated SNS reactivity, PNS withdrawal, and pressor responses during stress. In 16 E-PTSD and 17 matched N-PTSD, we measured continuous BP, ECG, muscle sympathetic nerve activity (MSNA), and heart rate variability (HRV) markers reflecting cardiac PNS activity [standard deviation of R-R intervals (SDNN), root mean square of differences in successive R-R intervals (RMSSD), and high frequency power (HF)] during 5 min of rest and 3 min of mental arithmetic. Resting MSNA ( P = 0.943), sympathetic BRS ( P = 0.189), and cardiovagal BRS ( P = 0.332) were similar between groups. However, baseline SDNN (56 ± 6 vs. 78 ± 8 ms, P = 0.019), RMSSD (39 ± 6 vs. 63 ± 9 ms, P = 0.018), and HF (378 ± 103 vs. 693 ± 92 ms2, P = 0.015) were lower in E-PTSD versus N-PTSD. During mental stress, the systolic blood pressure response ( P = 0.011) was augmented in E-PTSD. Although MSNA reactivity was not different ( P > 0.05), the E-PTSD group had an exaggerated reduction in HRV during mental stress ( P < 0.05). PTSD with ERBP have attenuated resting cardiac PNS activity, coupled with exaggerated BP reactivity and PNS withdrawal during stress.

Sympathetic neural reactivity to mental stress in offspring of hypertensive parents: 20 years revisited.

A number of recent studies have highlighted large interindividual variability of muscle sympathetic nerve activity (MSNA) responsiveness to mental stress in humans. The purpose of this study was to examine blood pressure (BP) and MSNA responsiveness to mental stress in a large and generalizable cohort of young adults with and without family history of hypertension (FHH). We hypothesized that subjects with FHH would demonstrate greater sympathoexcitation to mental stress than subjects without FHH. A total of 87 subjects (55 men and 32 women, 18-40 yr of age) from recently published (n = 45) and ongoing (n = 42) studies were examined; 57 subjects (19 with FHH and 38 without FHH) had complete MSNA recordings at baseline. Heart rate (HR), BP, and MSNA were recorded during 5 min of supine rest and 5 min of mental stress (mental arithmetic). Resting MSNA and HR were not statistically different between subjects with and without FHH (P > 0.05), whereas resting mean arterial pressure was higher in subjects with FHH (86 ± 2 vs. 80 ± 1 mmHg, P < 0.05). Mental stress increased MSNA in subjects with FHH (Δ5 ± 1 bursts/min), but not in subjects without FHH [Δ1 ± 1 burst/min, P < 0.01 (time × group)]. Mental stress increased mean arterial pressure (Δ12 ± 1 and Δ10 ± 1 mmHg, P < 0.001) and HR (Δ19 ± 2 and Δ16 ± 2 beats/min, P < 0.001) in subjects with and without FHH, but these increases were not different between groups [P ≥ 0.05 (time × group)]. MSNA and BP reactivity to mental stress were not correlated in either group. In conclusion, FHH was associated with heightened MSNA reactivity to mental stress, despite a dissociation between MSNA and BP responsiveness.

Positive airway pressure improves nocturnal beat-to-beat blood pressure surges in obesity hypoventilation syndrome with obstructive sleep apnea.

Positive airway pressure (PAP) treatment has been shown to have a modest effect on ambulatory blood pressure (BP) in patients with obstructive sleep apnea (OSA). However, there is a paucity of data on the effect of PAP therapy on rapid, yet significant, BP swings during sleep, particularly in obesity hypoventilation syndrome (OHS). The present study hypothesizes that PAP therapy will improve nocturnal BP on the first treatment night (titration PAP) in OHS patients with underlying OSA, and that these improvements will become more significant with 6 wk of PAP therapy. Seventeen adults (7 men, 10 women; age 50.4 ± 10.7 years, BMI 49.3 ± 2.4 kg/m(2)) with OHS and clinically diagnosed OSA participated in three overnight laboratory visits that included polysomnography and beat-to-beat BP monitoring via finger plethysmography. Six weeks of PAP therapy, but not titration PAP, lowered mean nocturnal BP. In contrast, when nocturnal beat-to-beat BPs were aggregated into bins consisting of at least three consecutive cardiac cycles with a >10 mmHg BP surge (i.e., Δ10-20, Δ20-30, Δ30-40, and Δ>40 mmHg), titration, and 6-wk PAP reduced the number of BP surges per hour (time × bin, P < 0.05). PAP adherence over the 6-wk period was significantly correlated to reductions in nocturnal systolic (r = 0.713, P = 0.001) and diastolic (r = 0.497, P = 0.043) BP surges. Despite these PAP-induced improvements in nocturnal beat-to-beat BP surges, 6 wk of PAP therapy did not alter daytime BP. In conclusion, PAP treatment reduces nocturnal beat-to-beat BP surges in OHS patients with underlying OSA, and this improvement in nocturnal BP regulation was greater in patients with higher PAP adherence.

Sympathetic neural reactivity to mental stress in humans: test-retest reproducibility.

Mental stress consistently increases arterial blood pressure, but this reliable pressor response is often associated with highly variable muscle sympathetic nerve activity (MSNA) responsiveness between individuals. Although MSNA has been shown to be reproducible within individuals at rest and during the cold pressor test (CPT), intraindividual reproducibility of MSNA responsiveness to mental stress has not been adequately explored. The purpose of this study was to examine MSNA reactivity to mental stress across three experimental sessions. Sixteen men and women (age 21 ± 1 yr) performed two experimental sessions within a single laboratory visit and a third experimental session 1 mo later. Each experimental session consisted of a mental stress trial via mental arithmetic and a CPT trial. Blood pressure, heart rate (HR), and MSNA were measured, and the consistencies of these variables were determined using intraclass correlation (Cronbach's α coefficient). MSNA, mean arterial pressure (MAP), and HR were highly reproducible across the baselines preceding mental stress (Cronbach's α ≥ 0.816, P ≤ 0.001) and CPT (Cronbach's α ≥ 0.782, P ≤ 0.001). Across the three mental stress trials, changes in MSNA (Cronbach's α = 0.875; P = 0.001), MAP (Cronbach's α = 0.749; P < 0.001), and HR (Cronbach's α = 0.919; P < 0.001) were reproducible. During CPT, changes in MSNA (Cronbach's α = 0.805; P = 0.008), MAP (Cronbach's α = 0.878; P < 0.001), and HR (Cronbach's α = 0.927; P < 0.001) remained consistent across the three sessions. In conclusion, our findings demonstrate that MSNA reactivity to mental stress is consistent within a single laboratory visit and across laboratory sessions conducted on separate days.

Blunted brachial blood flow velocity response to acute mental stress in PTSD females.

Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular disease (CVD) risk. Compared with males, females are twice as likely to develop PTSD after trauma exposure, and cardiovascular reactivity to stress is a known risk factor for CVD. We aimed to examine hemodynamic responses to acute mental stress in trauma-exposed females with and without a clinical diagnosis of PTSD. We hypothesized that females with PTSD would have higher heart rate (HR), blood pressure (BP), and lower blood flow velocity (BFV) responsiveness compared with controls. We enrolled 21 females with PTSD and 21 trauma-exposed controls. We continuously measured HR using a three-lead electrocardiogram, BP using finger plethysmography, and brachial BFV using Doppler ultrasound. All variables were recorded during 10 min of supine rest, 5 min of mental arithmetic, and 5 min of recovery. Females with PTSD were older, and had higher BMI and higher resting diastolic BP. Accordingly, age, BMI, and diastolic BP were covariates for all repeated measures analyses. Females with PTSD had a blunted brachial BFV response to mental stress (time × group, p = 0.005) compared with controls, suggesting greater vasoconstriction. HR and BP responses were comparable. In conclusion, our results suggest early impairment of vascular function in premenopausal females with PTSD.

The Role of Psychosocial Stress on Cardiovascular Disease in Women: JACC State-of-the-Art Review.

Psychosocial stress can affect cardiovascular health through multiple pathways. Certain stressors, such as socioeconomic disadvantage, childhood adversity, intimate partner violence, and caregiving stress, are especially common among women. The consequences of stress begin at a young age and persist throughout the life course. This is especially true for women, among whom the burden of negative psychosocial experiences tends to be larger in young age and midlife. Menarche, pregnancy, and menopause can further exacerbate stress in vulnerable women. Not only is psychosocial adversity prevalent in women, but it could have more pronounced consequences for cardiovascular risk among women than among men. These differential effects could reside in sex differences in responses to stress, combined with women's propensity toward vasomotor reactivity, microvascular dysfunction, and inflammation. The bulk of evidence suggests that targeting stress could be an important strategy for cardiovascular risk reduction in women.

Association between perimenopausal age and greater posttraumatic stress disorder and depression symptoms in trauma-exposed women.

OBJECTIVE: This study aimed to determine the relationship between stages of the menopause transition (premenopausal, perimenopausal, and postmenopausal) on symptoms of posttraumatic stress disorder (PTSD) and depression in trauma-exposed women. METHODS: A cross-sectional study conducted between 2005 and 2017 recruited and enrolled an urban community sample (n = 6,093) from nonpsychiatric medical clinic waiting rooms of Grady Memorial Hospital, a public safety net hospital in Atlanta, Georgia. Participants were female, 18 to 65 years old, and predominantly Black/African American. RESULTS: Of the 6,093 participants, 93.8% were Black/African American, 2.5% were White, and 3.8% were of all other races (Hispanic/Latino, Asian, multiracial). Participants younger than 40 years were categorized as premenopausal (n = 3,166), between 40 and 55 years of age were categorized as perimenopausal (n = 2,127), and older than 55 years were categorized as postmenopausal (n = 790). Menopause status was associated with total PTSD symptom severity ( F2,5416 = 9.61, P < 0.001), symptom severity within all three PTSD symptom clusters (avoidance/numbing symptoms: F2,5416 = 7.10, P < 0.001; intrusive symptoms: F2,5416 = 7.04, P < 0.001; hyperarousal symptoms: F2,5409 = 8.31, P < 0.001), and depression symptom severity ( F2,5148 = 11.4, P < 0.001). Compared with both premenopausal and postmenopausal women, perimenopausal women reported significantly worse total PTSD symptoms, symptoms in the hyperarousal cluster, and depressive symptoms. CONCLUSIONS: The current cross-sectional data show that symptoms of PTSD and depression in women are associated with reproductive age, such that perimenopausal women show higher symptom severity than premenopausal and postmenopausal women. Future longitudinal studies can reveal how changes in hormones over the course of the menopause transition impact the symptoms, neurobiology, and psychophysiology of PTSD.