Self-Reported Social Determinants of Health and Area-Level Social Vulnerability.

Importance: Many health care systems are investing resources in identifying social determinants of health (SDoH) needs and facilitating interventions among the populations they serve. Because self-reported SDoH information is lacking, area-level measures are often used to estimate needs and direct resources. Objective: To describe the large-scale deployment of SDoH assessments by a health system and determine the extent to which self-reported SDoH needs identified therein are associated with census tract-level social vulnerability measured using the Social Vulnerability Index (SVI). Design, Setting, and Participants: This cross-sectional study assessed SDoH needs between January 1, 2020, and April 30, 2023, in both payer and clinical care settings. Modalities included telephonic outreach, face-to-face clinical interactions, self-entry into a tablet or kiosk, and web-based survey tools. Participants included individuals who responded to the assessment and had sufficient information for census tract identification. Respondents included both Highmark Health Plan members and nonmembers. Health plan members responded to the assessment through health plan programs or platforms, and both members and nonmembers responded to assessments during inpatient or outpatient encounters with the affiliated health system. Main Outcomes and Measures: Overall and domain-specific SDoH needs self-reported through assessments, and severity and complexity of needs identified. Residential social vulnerability measures included overall SVI and the 4 conceptual themes comprising overall SVI. Results: In total, 841 874 assessments were recorded for 401 697 individuals (55.1% women; median [IQR] age, 55 [41-70] years). Social determinants of health needs were identified in 120 769 assessments (14.3%). Across all SDoH domains, increasing SVI was associated with a higher positivity rate (eg, 11.2% of those residing in the lowest-risk SVI quintile reported a need compared with 22.7% among those residing in the highest-risk quintile). Associations varied by SDoH domain and SVI theme. After adjusting for demographic and screening characteristics, odds of positive screening among those residing in the highest-risk SVI quintile were 1.74 (95% CI, 1.62-1.86) to 3.73 (95% CI, 3.48-4.00) times the odds among those residing in lowest risk quintile. Conclusions and Relevance: In this cross-sectional study, the overall level of SDoH needs generally corresponded to area-level vulnerability. Some SDoH domains appeared far more sensitive to community characteristics than others. Notably, even among individuals from the highest-risk areas, the positive screening rate was roughly 1 in 4. These findings underscore the importance of individual-level SDoH data for service provision planning and health services research.

Effects of Acute Hyperoxia on Autonomic Function and Coronary Tone in Patients with Peripheral Artery Disease.

Numerous studies have shown that oxidative stress plays an important role in peripheral artery disease (PAD). Prior reports suggested autonomic dysfunction in PAD. We hypothesized that responses of the autonomic nervous system and coronary tone would be impaired in patients with PAD during exposure to acute hyperoxia, an oxidative stressor. In 20 PAD patients and 16 healthy, sex and age-matched controls, beat-by-beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 minutes during room air breathing and 5 minutes of hyperoxia. Cardiovagal baroreflex sensitivity and HR variability (HRV) were evaluated as measures of autonomic function. Transthoracic coronary echocardiography was used to assess peak coronary blood flow velocity (CBV) in the left anterior descending coronary artery. Cardiaovagal baroreflex sensitivity at rest was lower in PAD than in healthy controls. Hyperoxia raised BP solely in the patients with PAD, with no change observed in healthy controls. Hyperoxia induced an increase in cardiac parasympathetic activity assessed by the high-frequency component of HRV in healthy controls but not in PAD. Indices of parasympathetic activity were lower in PAD than in healthy controls throughout the trial as well as during hyperoxia. Hyperoxia induced coronary vasoconstriction in both groups, while the coronary perfusion time fraction was lower in PAD than in healthy controls. These results suggest that the response in parasympathetic activity to hyperoxia (i.e., oxidative stress) is blunted and the coronary perfusion time is shorter in PAD patients.

Glucose metabolism and autonomic function in healthy individuals and patients with type 2 diabetes mellitus at rest and during exercise.

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P = 0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R = -0.45, P = 0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P < 0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R = 0.69, P < 0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM.

HeartWare Left Ventricular Assist Device Exercise Hemodynamics With Speed Adjustment Based on Left Ventricular Filling Pressures.

Functional capacity remains limited in heart failure patients with left ventricular assist devices (LVADs) due to fixed pump speed and inability to offload the left ventricle adequately. We hypothesized that manually adjusting LVAD speed during exercise based on pulmonary capillary wedge pressures would increase total cardiac output and maximal oxygen consumption. Two participants with a HeartWare LVAD underwent an invasive ramp study at rest followed by an invasive cardiopulmonary stress test exercising in two randomized phases: fixed speed and adjusted speed. In the latter phase, speed was adjusted every 1 minute during exercise at ±20 rpm/1 mm Hg change from baseline pulmonary capillary wedge pressure. There was no difference in maximal oxygen consumption between the two phases, with a modest increase in total cardiac output during speed adjustment. Filling pressures were initially controlled during speed adjustment until speed was capped at 4,000 rpm, at which point filling pressures increased. Blood pressure was variable. The pressure across the head of the pump (ΔP) was higher with speed adjustment. Contrary to our hypothesis, LVAD speed adjustment during exercise did not improve total cardiac output and functional capacity. This variable response may be attributed to the native cardiac reserve and baroreceptor response; however, additional studies are needed.

Urban vs. rural differences in psychiatric diagnoses, symptom severity, and functioning in a psychiatric sample.

OBJECTIVE: Identifying whether certain groups of people experience elevated rates or severities of psychiatric symptoms provides information to guide healthcare allocation. People living in urban areas have higher rates of some psychiatric disorders relative to people living in rural settings, however, it is unclear if psychiatric severity is more elevated in urban vs. rural settings. This study investigates the urban vs. rural differences in rates of psychiatric disorders and severity of psychiatric symptoms. METHOD: A cohort of patients (63% women, 85% White) presenting to an outpatient psychiatric treatment center in the U.S. completed patient-reported outcomes at all clinic visits as part of standard care. Rurality was determined by municipality population density. Sociodemographic characteristics, psychiatric diagnoses, trauma exposure, psychiatric symptom severity, functioning, and suicidality were compared by rural vs. urban municipality. RESULTS: There were virtually no differences between patients living in rural vs. urban municipalities on rates of psychiatric disorders, severity of psychiatric symptoms, functional impairment, and suicidality (ps≥.09). The only difference was that patients living in rural municipalities had higher exposure to serious accidents than patients living in urban municipalities (p < .01); exposure to nine other traumatic events did not differ between groups (p≥.07). CONCLUSIONS: People living in urban and rural municipalities have a similar need for mental health treatment. Access to care may be one explanatory factor for the occasional rural-urban differences in rates of psychiatric disorders. In other words, if people living in rural areas can access care, their symptom presentations appear unlikely to differ from those of people living in urban areas.

Association between diseases of despair and atherosclerotic cardiovascular disease among insured adults in the USA: a retrospective cohort study from 2017 to 2021.

OBJECTIVES: To assess associations between diseases of despair (DoD) and incident atherosclerotic cardiovascular disease (ASCVD) among insured adults in the USA. DESIGN: Retrospective cohort study. SETTING: Highmark insurance claims data in the USA from 2017 to 2021. PARTICIPANTS: Adults with at least 10 months of continuous insurance enrolment, no record of ASCVD in the 2016 baseline year and no missing data on study variables. PRIMARY AND SECONDARY OUTCOME MEASURES: Cox proportional hazard regression was used to calculate crude and adjusted hazard ratios (HR) and 95% confidence intervals (CI) to assess risk of ASCVD (composite of ischaemic cardiomyopathy, non-fatal ischaemic stroke, peripheral arterial disease or non-fatal acute myocardial infarction) by baseline DoD overall, and by the component conditions comprising DoD (alcohol-related disorders, substance-related disorders, suicidality) individually and in combination. RESULTS: The DoD-exposed group had an age-adjusted rate of 20.5 ASCVD events per 1000 person-years, compared with 11.7 among the unexposed. In adjusted models, overall DoD was associated with increased risk of incident ASCVD (HR 1.42, 95% CI 1.36 to 1.47). Individually and in combination, component conditions of DoD were associated with higher risk for ASCVD relative to no DoD. Substance-related disorders were associated with 50% higher risk of incident ASCVD (HR 1.5, 95% CI 1.41 to 1.59), alcohol-related disorders and suicidality/intentional self-harm were associated with 33% and 30% higher risk, respectively (HR 1.33, 95% CI 1.26 to 1.41; HR 1.30, 95% CI 1.11 to 1.52). Co-occurring DoD components conferred higher risk still. The highest risk combination was substance-related disorders+suicidality (HR 2.01, 95% CI 1.44 to 2.82). CONCLUSIONS: Among this cohort of insured adults, documented DoD was associated with increased ASCVD risk. Further research to understand and address cardiovascular disease prevention in those with DoD could reduce costs, morbidity and mortality. Further examination of overlapping structural factors that may be contributing to concurrent rises in ASCVD and DoD in the USA is needed.

Autonomic and vascular function testing in collegiate athletes following SARS-CoV-2 infection: an exploratory study.

Introduction: Recent studies suggest that SARS-CoV-2 infection alters autonomic and vascular function in young, otherwise healthy, adults. However, whether these alterations exist in young competitive athletes remains unknown. This study aimed to assess the effects of COVID-19 on cardiac autonomic control and vascular function in collegiate athletes who tested positive for COVID-19, acknowledging the limitations imposed by the early stages of the pandemic. Methods: Sixteen collegiate athletes from various sports underwent a battery of commonly used autonomic and vascular function tests (23 ± 9, range: 12-44 days post-infection). Additionally, data from 26 healthy control participants were included. Results: In response to the Valsalva maneuver, nine athletes had a reduced early phase II blood pressure response and/or reduced Valsalva ratio. A depressed respiratory sinus arrhythmia amplitude was observed in three athletes. Three athletes became presyncopal during standing and did not complete the 10-min orthostatic challenge. Brachial artery flow-mediated dilation, when allometrically scaled to account for differences in baseline diameter, was not different between athletes and controls (10.0% ± 3.5% vs. 7.1% ± 2.4%, p = 0.058). Additionally, no differences were observed between groups when FMD responses were normalized by shear rate (athletes: 0.055% ± 0.026%/s-1, controls: 0.068% ± 0.049%/s-1, p = 0.40). Discussion: Few atypical and borderline responses to autonomic function tests were observed in athletes following an acute SARS-CoV-2 infection. The most meaningful autonomic abnormality being the failure of three athletes to complete a 10-min orthostatic challenge. These findings suggest that some athletes may develop mild alterations in autonomic function in the weeks after developing COVID-19, while vascular function is not significantly impaired.

Aortic blood pressure and pulse wave indices responses to exercise in peripheral artery disease.

Peripheral artery disease (PAD) refers to obstructed blood flow in peripheral arteries typically due to atherosclerotic plaques. How PAD alters aortic blood pressure and pressure wave propagation during exercise is unclear. Thus, this study examined central blood pressure responses to plantar flexion exercise by investigating aortic pulse wave properties in PAD. Thirteen subjects with PAD and 13 healthy [age-, sex-, body mass index (BMI) matched] subjects performed rhythmic plantar flexion for 14 min or until fatigue (20 contractions/min; started at 2 kg with 1 kg/min increment up to 12 kg). Brachial (oscillometric cuff) and radial (SphygmoCor) blood pressure and derived-aortic waveforms were analyzed during supine rest and plantar flexion exercise. At rest, baseline augmentation index (P = 0.0263) and cardiac wasted energy (P = 0.0321) were greater in PAD due to earlier arrival of the reflected wave (P = 0.0289). During exercise, aortic blood pressure (aMAP) and aortic pulse pressure showed significant interaction effects (P = 0.0041 and P = 0.0109, respectively). In particular, PAD had a greater aMAP increase at peak exercise (P = 0.0147). Moreover, the tension time index was greater during exercise in PAD (P = 0.0173), especially at peak exercise (P = 0.0173), whereas the diastolic time index (P = 0.0685) was not different between the two groups. Hence, during exercise, the subendocardial viability ratio was lower in PAD (P = 0.0164), especially at peak exercise (P = 0.0164). The results suggest that in PAD, the aortic blood pressure responses and myocardial oxygen demand during exercise are increased compared with healthy controls.

Effect of Cyclooxygenase Inhibition on Peripheral Venous Distension Reflex in Healthy Humans.

BACKGROUND: Peripheral venous distension evokes a pressor reflex (venous distension reflex). Afferent group III and IV nerves innervating veins are suggested as the afferent arm of the venous distension reflex. Prostaglandins stimulate/sensitize group III/IV nerves. We hypothesized that inhibition of prostaglandin synthesis by local cyclooxygenase blockade would attenuate the muscle sympathetic nerve activity (MSNA) and blood pressure responses to venous distension. METHODS: Nineteen healthy volunteers (age, 27±5 years) participated in the study with 2 visits. To induce venous distension, a volume of solution (saline alone or 9 mg ketorolac tromethamine in saline) was infused into the vein in the antecubital fossa of an arterially occluded forearm. During the procedure, beat-by-beat heart rate, blood pressure and MSNA were recorded simultaneously. The vein size was measured with ultrasound. RESULTS: In both visits, the venous distension procedure significantly increased blood pressure, heart rate, and MSNA (all, P<0.05). The increase in mean arterial pressure and MSNA in the ketorolac visit was significantly lower than in the control visit (∆ mean arterial pressure, 7.0±6.2 versus 13.8±7.7 mm Hg; ∆MSNA, 6.0±7.1 versus 14.8±7.7 bursts/min; both, P<0.05). The increase in vein size induced by the infusion was not different between visits. CONCLUSIONS: The presented data show that cyclooxygenase blockade attenuates the responses in MSNA and blood pressure to peripheral venous distension reflex. The results suggest that cyclooxygenase products play a key role in evoking afferent activation responsible for the venous distension reflex.

Rapid adjustments to autonomic control of cardiac rhythm at the onset of isometric exercise in healthy young adults.

Sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) influences on cardiac rhythm at the onset of exercise, a time of rapid autonomic adjustments, are clinically important areas of investigation. Continuous wavelet transform (CWT) involves time-frequency-based heart rate variability (HRV) analysis allowing investigation of autonomic influences on cardiac rhythm during short durations of exercise. Therefore, the purpose of this study was to characterize SNS and PNS influences on cardiac rhythm at the onset of isometric exercise in healthy young adults. CWT analysis was retrospectively applied to R-R interval data (electrocardiogram) previously collected from 14 healthy young adults (26 ± 2 years) who performed 30-s, one-legged, isometric, calf exercise at 70% maximal voluntary contraction (MVC; 70% MVC trial) or rested (0% MVC trial). Absolute and normalized low-frequency (aLF, nLF; 0.04-0.15 Hz) and high-frequency (aHF, nHF; 0.15-0.4 Hz) bands and LF/HF were used to analyze one 30-s baseline period and six 5-s time windows during the 30-s exercise (70% MVC) or rest (0% MVC). Statistical analysis involved two-way analysis of variance with post-hoc analysis. aHF, aLF, LF/HF, nHF, and nLF displayed a trial-time interaction (all p ≤ 0.027). In the 70% compared to the 0% MVC trial, aHF and nHF were lower after 5-30 s (all p ≤ 0.040), aLF was lower after 20-30 s (all p ≤ 0.011) and LF/HF and nLF were higher after 5-20 s (all p ≤ 0.045). These results indicate the reduction of the PNS influence on cardiac rhythm begins sooner than the augmentation of the SNS influence at the onset of isometric exercise in healthy young adults.

Gardening Is Associated With Better Cardiovascular Health Status Among Older Adults in the United States: Analysis of the 2019 Behavioral Risk Factor Surveillance System Survey.

BACKGROUND: Gardening benefits health in older adults, but previous studies have limited generalizability or do not adequately adjust for sociodemographic factors or physical activity (PA). OBJECTIVE: We examined health outcomes, fruits and vegetables (F&V) intake, and 10-year mortality risk among gardeners and exercisers compared with nonexercisers. DESIGN: Cross-sectional data of noninstitutionalized US adults in the 2019 Behavioral Risk Factor Surveillance System was collected via landline and cellular phone survey. PARTICIPANTS/SETTING: Adults 65 years and older reporting any PA (n = 146,047) were grouped as gardeners, exercisers, or nonexercisers. MAIN OUTCOME MEASURES: Outcomes included cardiovascular disease (CVD) risk factors, mental and physical health, F&V intake, and 10-year mortality risk. STATISTICAL ANALYSES: Summary statistics were calculated and adjusted logistic regression models were conducted to calculate adjusted odds ratios (aORs) and 95% CIs, accounting for the complex survey design. RESULTS: The sample included gardeners (10.2%), exercisers (60.0%), and nonexercisers (30.8%). Gardeners, compared with nonexercisers, had significantly lower odds of reporting all studied health outcomes and higher odds of consuming 5 or more F&V per day (CVD: aOR 0.60, 95% CI 0.53 to 0.68; stroke: aOR 0.55, 95% CI 0.47 to 0.64; heart attack: aOR 0.63, 95% CI 0.55 to 0.73, high cholesterol: aOR 0.86, 95% CI 0.79 to 0.93; high blood pressure: aOR 0.74, 95% CI 0.68 to 0.81; diabetes: aOR 0.51, 95% CI 0.46 to 0.56; body mass index ≥25: aOR 0.74, 95% CI 0.68 to 0.80; poor mental health status: aOR 0.50, 95% CI 0.43 to 0.59; poor physical health status: aOR 0.35, 95% CI 0.31 to 0.39; 5 or more F&V per day: aOR 1.56, 95% CI 1.40 to 1.57; high 10-year mortality risk: aOR 0.39, 95% CI 0.36 to 0.42). Male and female gardeners had significantly lower odds of reporting diabetes even when compared with exercisers. CONCLUSIONS: Among adults 65 years and older, gardening is associated with better CVD health status, including lower odds of diabetes. Future longitudinal or interventional studies are warranted to determine whether promoting gardening activities can be a CVD risk reduction strategy.

Repeated warm water baths decrease sympathetic activity in humans.

Acute whole body heat stress evokes sympathetic activation. However, the chronic effects of repeated moderate heat exposure (RMHE) on muscle sympathetic nerve activity (MSNA) in healthy individuals remain unclear. We performed RMHE with 4 wk (5 days/wk) of warm baths (∼40°C, for 30 min) in nine healthy older (59 ± 2 yr) volunteers. Hemodynamic variables and MSNA were examined before, 1 day after, and 1 wk following 4 wk of RMHE in a laboratory at ∼23°C. Cold pressor test (CPT) and handgrip (HG) exercise were performed during the tests. Under normothermic condition, the resting MSNA burst rate (prior, post, post 1-wk: 31.6 ± 2.0, 25.2 ± 2.0, and 27.7 ± 1.7 bursts/min; P < 0.001) and burst incidence (P < 0.001) significantly decreased after RMHE. Moreover, the resting heart rate significantly decreased after RMHE (62 ± 2, 60 ± 2, and 58 ± 2 beats/min, P = 0.031). The sensitivity of baroreflex control of MSNA and heart rate were not altered by RMHE, although the operating points were reset. The MSNA and hemodynamic responses (i.e., changes) to handgrip exercise or cold pressor test were not significantly altered. These data suggest that the RMHE evoked by warm baths decreases resting sympathetic activity and heart rate, which can be considered beneficial effects. The mechanism(s) should be examined in future studies.NEW & NOTEWORTHY To our knowledge, this is the first study to observe the effects of repeated warm baths on sympathetic nerve activity during rest and stress in healthy middle age and older individuals. The data suggest that the repeated warm baths decreased resting sympathetic activity and heart rate, which can be considered beneficial effects. This study also provides the first evidence that the repeated warm baths did not alter the baroreflex sensitivity and the sympathetic responses to stress.

Multiple Laser Doppler Flowmetry Probes Increase the Reproducibility of Skin Blood Flow Measurements.

Cutaneous microcirculatory perfusion is commonly measured using laser Doppler flowmetry (LDF) probes, which provide a continuous, non-invasive quantification of skin blood flow (SkBF). However, inhomogeneities in the skin's microvasculature density contribute to a decrease in reproducibility whenever an LDF probe is removed and replaced, as is the case during pre- and post-intervention or between-day measurements. Therefore, this study aimed to determine whether increasing the total number of individual LDF probes in a localized area improves the reproducibility of the measurement. Seven laser Doppler probes were secured in a custom-made acrylic holder designed to attach to the skin's surface easily. SkBF, local skin temperature (Tsk), and blood pressure (BP) were assessed in 11 participants (6 M, 5 F, 42 ± 15 years). SkBF and Tsk were measured from the dorsal forearm (arm trial) for 5 min. Next, the multi-laser device was moved to the lateral side of the calf (leg trial), and measurements were obtained for 5 min. Each arm and leg trial was cyclically repeated three times, and all trials were separated by intermissions lasting 10-15 min. The average SkBF and the cutaneous vascular conductance (CVC) from all possible LDF probe combinations were not statistically different across the three arm and leg trials. Two-way mixed-effects models with absolute agreement were used to compute the intraclass correlation coefficient (ICC) for CVC, and the minimum ICC increased with the addition of LDF probes. The ICC of the average CVC from seven LDF probes was 0.96 between the arm trials and 0.91 between the leg trials, which suggests that there is excellent reliability and little difference between trials following the removal and replacement of the device. Moreover, all individual ICC values from ≥3 LDF probe combinations were greater than 0.70 (i.e., good reliability). These data suggest that SkBF measurements with multiple laser Doppler probes in a custom-made holder have excellent reproducibility after replacing the probes within the same participant. Therefore, this application could provide more reproducible assessments between repeated measurements (e.g., before and after exercise or clinical procedures) where the LDF probes must be removed and replaced within the same location.

Baroreflex responses to limb venous distension in humans.

The venous distension reflex (VDR) is a pressor response evoked by peripheral venous distension and accompanied by increased muscle sympathetic nerve activity (MSNA). The effects of venous distension on the baroreflex, an important modulator of blood pressure (BP), have not been examined. The purpose of this study was to examine the effect of the VDR on baroreflex sensitivity (BRS). We hypothesized that the VDR will increase the sympathetic BRS (SBRS). Beat-by-beat heart rate (HR), BP, and MSNA were recorded in 16 female and 19 male young healthy subjects. To induce venous distension, normal saline equivalent to 5% of the forearm volume was infused into the veins of the occluded forearm. SBRS was assessed from the relationship between diastolic BP and MSNA during spontaneous BP variations. Cardiovagal BRS (CBRS) was assessed with the sequence technique. Venous distension evoked significant increases in BP and MSNA. Compared with baseline, during the maximal VDR response period, SBRS was significantly increased (-3.1 ± 1.5 to -4.5 ± 1.6 bursts·100 heartbeats-1·mmHg-1, P < 0.01) and CBRS was significantly decreased (16.6 ± 5.4 to 13.8 ± 6.1 ms·mmHg-1, P < 0.01). No sex differences were observed in the effect of the VDR on SBRS or CBRS. These results indicate that in addition to its pressor effect, the VDR altered both SBRS and CBRS. We speculate that these changes in baroreflex function contribute to the modulation of MSNA and BP during limb venous distension.

Acute effects of sublingual nitroglycerin on cardiovagal and sympathetic baroreflex sensitivity.

The effects of nitroglycerin (glyceryl trinitrate, GTN) on baroreflex sensitivity (BRS) are incompletely understood. Moreover, there are no reports evaluating the acute responses in both the sympathetic BRS (SBRS) and the cardiovagal BRS (CBRS) to the administration of sublingual GTN. We hypothesized that sublingual GTN modulates both CBRS and SBRS. In 10 healthy subjects, beat-to-beat heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated from the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. These variables were assessed during baseline, during 3rd-6th min (post A), and 7th-10th min (post B) after GTN administration. Two min after GTN administration, MSNA increased significantly and remained significantly elevated during recording. Compared with baseline, CBRS decreased significantly (post A: 12.9 ± 1.6 to 7.1 ± 1.0 ms/mmHg, P < 0.05), whereas SBRS increased significantly (post A: 0.8 ± 0.2 to 1.5 ± 0.2 units·beat-1·mmHg-1, P < 0.05) with an upward shift of the operating point. There were no differences in these variables between posts A and B. A clinical dose of GTN increased MSNA rapidly through effects on both CBRS and SBRS. These effects should be kept in mind when nitrates are used to clinically treat chest pain and acute coronary syndromes and used as vasodilators in experimental settings.

Perceptions of Diseases of Despair by Members of Rural and Urban High-Prevalence Communities: A Qualitative Study.

Importance: Diseases of despair (ie, mortality or morbidity from suicidality, drug abuse, and alcoholism) were first characterized as increasing in rural White working-class populations in midlife with low educational attainment and associated with long-term economic decline. Excess mortality now appears to be associated with working-class citizens across demographic and geographic boundaries, but no known qualitative studies have engaged residents of rural and urban locales with high prevalence of diseases of despair to learn their perspectives. Objective: To explore perceptions about despair-related illness and potential intervention strategies among diverse community members residing in discrete rural and urban hotspots. Design, Setting, and Participants: In this qualitative study, high-prevalence hotspots for diseases of despair were identified from health insurance claims data in Central Pennsylvania. Four focus groups were conducted with 60 community members in organizations and coalitions from 3 census block group hotspot clusters in the health system between September 2019 and January 2020. Focus groups explored awareness and beliefs about causation and potential intervention strategies. Main Outcomes and Measures: A descriptive phenomenological approach was applied to thematic analysis, and a preliminary conceptual model was constructed to describe how various factors may be associated with perpetuating despair and with public health. Results: In total, 60 adult community members participated in 4 focus groups (44 women, 16 men; 40 White non-Hispanic, 17 Black, and 3 Hispanic/Latino members). Three focus groups with 43 members were held in rural areas with high prevalence of diseases of despair, and 1 focus group with 17 members in a high-prevalence urban area. Four themes emerged with respect to awareness and believed causation of despair-related illness, and participants identified common associated factors, including financial distress, lack of critical infrastructure and social services, deteriorating sense of community, and family fragmentation. Intervention strategies focused around 2 themes: (1) building resilience to despair through better community and organizational coordination and peer support at the local level and (2) encouraging broader state investments in social services and infrastructure to mitigate despair-related illness. Conclusions and Relevance: In this qualitative study, rural and urban community members identified common factors associated with diseases of despair, highlighting the association between long-term political and economic decline and public health and a need for both community- and state-level solutions to address despair. Health care systems participating in addressing community health needs may improve processes to screen for despair (eg, social history taking) and codesign primary, secondary, and tertiary interventions aimed at addressing factors associated with distress. Such actions have taken on greater urgency with the COVID-19 pandemic.

Diffusion tensor imaging indices of acute muscle damage are augmented after exercise in peripheral arterial disease.

PURPOSE: Although it is known that peripheral arterial disease (PAD) is associated with chronic myopathies, the acute muscular responses to exercise in this population are less clear. This study used diffusion tensor imaging (DTI) to compare acute exercise-related muscle damage between PAD patients and healthy controls. METHODS: Eight PAD patients and seven healthy controls performed graded plantar flexion in the bore of a 3T MRI scanner. Exercise began at 2 kg and increased by 2 kg every 2 min until failure, or completion of 10 min of exercise. DTI images were acquired from the lower leg pre- and post-exercise, and were analyzed for mean diffusivity, fractional anisotropy (FA), and eigenvalues 1-3 (λ1-3) of the medial gastrocnemius (MG) and tibialis anterior (TA). RESULTS: Results indicated a significant leg by time interaction for mean diffusivity, explained by a significantly greater increase in diffusivity of the MG in the most affected legs of PAD patients (11.1 × 10-4 ± 0.5 × 10-4 mm2/s vs. 12.7 × 10-4 ± 1.2 × 10-4 mm2/s at pre and post, respectively, P = 0.02) compared to healthy control subjects (10.8 × 10-4 ± 0.3 × 10-4 mm2/s vs. 11.2 × 10-4 ± 0.5 × 10-4 mm2/s at pre and post, respectively, P = 1.0). No significant differences were observed for the TA, or λ1-3 (all P ≥ 0.06). Moreover, no reciprocal changes were observed for FA in either group (all P ≥ 0.29). CONCLUSION: These data suggest that calf muscle diffusivity increases more in PAD patients compared to controls after exercise. These findings are consistent with the notion that acute exercise results in increased muscle damage in PAD.

Sympathetic activation due to limb venous distension is preserved during muscle metaboreceptor stimulation.

Venous saline infusions in an arterially occluded forearm evoke reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans (venous distension reflex). It is unclear if the inputs from metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) would modify the venous distension reflex. We hypothesized that muscle metaboreceptor stimulation might augment the venous distension reflex. BP (Finapres), heart rate (ECG), and MSNA (microneurography) were assessed in 18 young healthy subjects. In trial A, saline (5% forearm volume) was infused into the veins of an arterially occluded arm (nonhandgrip trial). In trial B, subjects performed 2-min static handgrip followed by postexercise circulatory occlusion (PECO) of the arm. During PECO, saline was infused into the veins of the arm (handgrip trial). In trial A, the infusion increased MSNA and BP as expected (both P < 0.001). In trial B, handgrip significantly raised MSNA, BP, and venous lactic acid concentrations. Venous saline infusion during PECO further raised MSNA and BP (both P < 0.001). The changes in MSNA (Δ8.6 ± 1.5 to Δ10.6 ± 1.8 bursts/min, P = 0.258) and mean arterial pressure (P = 0.844) evoked by the infusion during PECO were not significantly different from those in the nonhandgrip trial. These observations indicate that venous distension reflex responses are preserved during sympathetic activation mediated by the muscle metaboreflex.

Moderate whole body heating attenuates the exercise pressor reflex responses in older humans.

Prior reports show that whole body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole body heating (WBH; e.g., increase in internal temperature Tcore of ∼0.4°C-0.5°C) or limb heating on sympathetic and cardiovascular responses to exercise in older healthy humans remain unclear. We examined the muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and heart rate (HR) in 14 older (62 ± 2 yr) healthy subjects during fatiguing isometric handgrip exercise and postexercise circulatory occlusion (PECO). The protocol was performed under normothermic, moderate WBH, and local limb (i.e., forearm) heating conditions during three visits. During the mild WBH stage (increase in Tcore of <0.3°C), HR increased, whereas BP and MSNA decreased from baseline. Under the moderate WBH condition (increase in Tcore of ∼0.4°C), BP decreased, HR increased, and MSNA was unchanged from baseline. Compared with the normothermic trial, the absolute MAP during fatiguing exercise and PECO was lower during the WBH trial. Moreover, MSNA and MAP responses (i.e., changes) to fatiguing exercise were also less than those seen during the normothermic trial. Limb heating induced a similar increase in forearm muscle temperature to that seen in the WBH trial (∼0.7°C-1.5°C). Limb heating did not alter resting MAP, HR, or MSNA. The MSNA and hemodynamic responses to exercise in the limb heating trial were not different from those in the normothermic trial. These data suggest that moderate WBH attenuates MSNA and BP responses to exercise in older healthy humans.

Renal medullary oxygenation decreases with lower body negative pressure in healthy young adults.

One in three Americans suffer from kidney diseases such as chronic kidney disease, and one of the etiologies is suggested to be long-term renal hypoxia. Interestingly, sympathetic nervous system activation evokes a renal vasoconstrictor effect that may limit oxygen delivery to the kidney. In this report, we sought to determine if sympathetic activation evoked by lower body negative pressure (LBNP) would decrease cortical and medullary oxygenation in humans. LBNP was activated in a graded fashion (LBNP; -10, -20, and -30 mmHg), as renal oxygenation was measured (T2*, blood oxygen level dependent, BOLD MRI; n = 8). At a separate time, renal blood flow velocity (RBV) to the kidney was measured (n = 13) as LBNP was instituted. LBNP significantly reduced RBV (P = 0.041) at -30 mmHg of LBNP (Δ-8.17 ± 3.75 cm/s). Moreover, both renal medullary and cortical T2* were reduced with the graded LBNP application (main effect for the level of LBNP P = 0.0008). During recovery, RBV rapidly returned to baseline, whereas medullary T2* remained depressed into the first minute of recovery. In conclusion, sympathetic activation reduces renal blood flow and leads to a significant decrease in oxygenation in the renal cortex and medulla.NEW & NOTEWORTHY In healthy young adults, increased sympathetic activation induced by lower body negative pressure, led to a decrease in renal cortical and medullary oxygenation measured by T2*, a noninvasive magnetic resonance derived index of deoxyhemoglobin levels. In this study, we observed a significant decrease in renal cortical and medullary oxygenation with LBNP as well as an increase in renal vasoconstriction. We speculate that sympathetic renal vasoconstriction led to a significant reduction in tissue oxygenation by limiting oxygen delivery to the renal medulla.