Supine Rest Research Articles

Autonomic Testing in Collegiate Athletes Following SARS‐Cov‐2 Infection

To date, more than 46 million people in the United States have contracted the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes COVID‐19. Over 700 thousand total cases have been linked to American colleges and universities. Post‐acute sequelae of SARS‐CoV‐2 infection may affect varied systems. It was reported that sympathetic nerve activity following SARS‐CoV‐2 infection was elevated in young individuals. Cardiovascular autonomic function post‐acute SARS‐CoV‐2 infection in other populations such as athletes, however, has not been thoroughly investigated. Collegiate athletes are a unique population given that they might have a high level of physical fitness before the infection. The present study examined 16 collegiate athletes (12 men and 4 women, age: 20±1 yrs, height: 181±10 cm, weight: 81±18 kg) who were evaluated ~2 weeks after testing positive for SARS‐CoV‐2 by polymerase chain reaction assay. These subjects were asymptomatic or with mild/moderate symptoms during infection. None of the subjects had been hospitalized for COVID‐19 and all subjects were asymptomatic at the time of the study. Beat‐by‐beat blood pressure (BP) with Finometer, and heart rate (HR) from ECG were recorded during 10 minutes of supine rest, Valsalva maneuver, slow breathing (6 breaths/min), handgrip exercise, and 10 minutes of standing. BP, HR, heart rate variability (HRV), and cardiac baroreflex sensitivity (CBRS), and venous blood aldosterone and renin levels were analyzed. The vagal tone index from HRV in 3 of 16 athletes was lower than normative values. The responses in BP to Valsalva maneuver during phases IIa (i.e., “early”) and IIb (i.e., “late”) were mildly abnormal in 4 athletes and moderately abnormal in one athlete. The Valsalva ratio was below the normal range in 6 athletes. In response to slow breathing, the respiratory sinus arrhythmia amplitude was below the normal range in 3 athletes. In response to handgrip exercise, one athlete had an atypical response where BP decreased while HR was increased from baseline. Three of the subjects were unable to tolerate an orthostatic challenge for 10 minutes. Four out of 16 athletes had abnormally elevated renin activity and 1 out 16 elevated aldosterone levels. It is important to note that while several athletes had abnormal responses to the various autonomic tests, these abnormalities did not correlate with symptoms seen during the infection. Our data suggest that SARS‐CoV‐2 infection may reduce parasympathetic and increase sympathetic tone and may contribute to the autonomic disfunction associated in a subset of collegiate athletes even after recovering from COVID‐19. This study provides further evidence for potential long‐term cardiovascular autonomic effects of Covid‐19 infection even in healthy young trained athletes. Further studies with a larger patient population as well as suitable healthy control subjects are warranted.

The Influence of Self‐Reported and Actigraphy‐Derived Sleep Quality on Cardiometabolic Health in a Diverse Cohort of Healthy Adults

PurposeInsufficient sleep is associated with adverse cardiometabolic health (CMH) including high blood pressure (BP) and insulin resistance, which increases cardiovascular disease risk. However, there are limited data on insufficient sleep and CMH in healthy adults, particularly in diverse cohorts. Thus, we sought to examine associations between actigraphy‐derived sleep, self‐reported sleep quality, and CMH in healthy adults.Methods99 individuals (50 female, age: 26 ± 12yrs, BMI: 25.5 ± 4.1 kg/m2, resting BP: 108±11/ 65 ± 8 mmHg, mean ± SD) were included in this analysis. We assessed objective sleep quality, including sleep duration and efficiency using wrist‐worn Philips Actiwatch Spectrum PLUS monitors (8.4 ± 2.7 days). Self‐reported sleep was characterized using the Pittsburgh Sleep Quality Index (0 [better] to 21 [worse]) and an average weekly score to the question “how rested do you feel” (0 [better] to 4 [worse]). We combined all four sleep variables to create a multidimensional sleep score (0 [better] to 4 [worse]). Following ≥10‐minutes of supine rest, we assessed oscillometric brachial BP in triplicate. We assessed estimated central BP with pulse wave analysis and arterial stiffness via carotid‐femoral pulse wave velocity (cf‐PWV) with SphygmoCor. We evaluated endothelial function using brachial artery flow mediated dilation (FMD) via ultrasound. We are collected venous blood samples to calculate homeostatic model assessment of insulin resistance (HOMA‐IR) via blood glucose and insulin concentration. We performed stepwise regressions controlling for sex, race, age, and BMI (model 1) and with the addition of individual sleep metrics (model 2) or the multidimensional sleep score (model 3) to determine whether sleep was associated with measures of CMH.ResultsAdding independent sleep variables or composite sleep score did not improve model fit for brachial BP (e.g., systolic BP Model 1: R2= 0.301, p < 0.001, Model 3: R2= 0.262, p<0.001). The addition of sleep variables improved model fit for central BP (e.g., systolic BP Model 1: R2= 0.280, p < 0.001, Model 3: R2= 0.306, p <0.001) and cf‐PWV (Model 1: R2= 0.153 p < 0.001, Model 2: R2= 0.159, p = .014). Furthermore, the multidimensional sleep score was independently associated with central systolic BP (β± SE = ‐2.41 ± 0.961, p = 0.015) and central diastolic BP (β± SE = ‐1.97 ± 0.91, p = 0.035). Finally, the addition of the multidimensional sleep score improved model fit for FMD (Model 1: R2=0.113, p = 0.012, Model 3: R2= 0.132, p = 0.023) and HOMA‐IR (Model 1: R2= 0.229, p<0.001, Model 3: R2= 0.246, p <0.001).ConclusionOur preliminary data indicate that multidimensional sleep is independently associated with central BP and the addition of individual or multidimensional sleep adds upon the predictive value of sex, race age and BMI in predicting CMH in a diverse cohort of healthy adults.

Mental Stress Pressor Response and Post‐Stress Aortic Wave Reflection

Reactivity to mental stress has been linked to cardiovascular risk, and is shown to negatively influence aortic wave reflection for up to an hour after acute mental arithmetic. It has been postulated that sympathetic catecholamine release during the stressful task drives the sustained elevation in wave reflection. In the present study we sought to determine how muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) reactivity influence post mental stress aortic augmentation index (AIx). Twenty‐seven volunteers (25±1 years) with resting blood pressure ≥120/80 mmHg participated in the present study. Baseline pulse wave analysis and pulse wave velocity recordings were assessed on participants after 10 minutes of supine rest. Participants were then instrumented for measurements of MSNA (microneurography), beat‐to‐beat blood pressure (finger plethysmography), and heart rate (3‐lead ECG). Subsequently MSNA, blood pressure, and heart rate were measured during a 5‐minute baseline, 5‐minute mental stress task (serial subtraction), and 5‐minute recovery. Finally, aortic wave reflection (i.e. AIx) was reassessed 10 minutes after completion of mental stress. Statistical analyses included paired t‐tests to compare MSNA, MAP, heart rate (HR), and perceived stress during baseline and mental stress. We used standard multiple regression with change in AIx as the dependent variable and changes in MSNA, MAP, and perceived stress as the independent variables. Means were considered significantly different when p<0.05. The mental stress task significantly increased HR (Δ15±2 beats/minute), MAP (Δ14±1 mmHg), and perceived stress (Δ1.9±0.1 a.u.), while MSNA was not significantly increased. There was however a range of changes in MSNA from ‐13 to +20 bursts/minute. The change in MAP during mental stress was a significant predictor (ꞵ=0.47; p=0.03) of the change in AIx (post‐stress vs. baseline). Changes in MSNA and perceived stress were not predictors of mental stress‐related changes in AIx. Our results indicate that the aortic wave reflection responses to mental stress appear to be linked to the pressor response, but not sympathetic or perceived stress responses. This is novel preliminary data that suggests there may not be a direct link between sympathetic activation and aortic wave reflection following cognitive stress.

Spontaneous Cardiovagal Baroreflex Sensitivity in Females with Multiple Sclerosis

Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system that is known to disrupt autonomic function. Females with MS are at an increased risk of cardiovascular disease partly due to altered autonomic regulation of arterial blood pressure. Longitudinal data suggest that low spontaneous cardiovagal baroreflex sensitivity is a predictor of cardiovascular disease. Therefore, the purpose of this investigation is to test the hypothesis that spontaneous cardiovagal baroreflex sensitivity (cBRS) is less in females with MS compared to healthy controls. Electrocardiogram (ECG) and beat‐to‐beat blood pressure (Finometer) were continuously recorded during 10 minutes of quiet supine rest in 3 females with relapsing‐remitting MS (Expanded Disability Scale Score < 6.0) and 3 sex‐, age‐, height‐, weight‐ and race‐ matched healthy controls. Spontaneous cBRS was determined using the sequence method (CardioSeries v2.7). Spontaneous cBRS gain is calculated as the average slope of the relationship between R‐R interval and systolic blood pressure from individual sequences of 3 or more consecutive cardiac cycles where both variables are increasing (up‐up sequences) or decreasing (down‐down sequences). Females with MS had similar resting mean arterial pressures (P=0.55), systolic blood pressures (P=0.53) and heart rates (P=0.18) compared to healthy controls. Overall spontaneous cBRS gain was greater in females with MS compared to healthy controls (27.1 ± 6.3 ms/mmHg vs. 18.8 ± 1.1 ms/mmHg respectively; P=0.04). Spontaneous cBRS gain from up‐up sequences was also greater in females with MS compared to healthy controls (27.6 ± 5.1 ms/mmHg vs. 17.1 ± 2.1 ms/mmHg respectively; P=0.01). Spontaneous cBRS gain from down‐down sequences trended to be greater in females with MS compared to healthy controls but was not statistically significant (27.2 ± 7.8 ms/mmHg vs. 20.1 ± 2.4 ms/mmHg respectively; P=0.10). Counter to our hypothesis, these preliminary findings in a small sample suggest that females with MS have increased spontaneous cBRS compared to healthy controls. If this relationship continues with additional data collection, it may indicate that females with MS have enhanced cardiac responses to regulate arterial blood pressure.

Perceived Pain is Associated with Cardiovascular Responsiveness During Metaboreflex Activation in Apparently Healthy Young Males and Females

Stimuli that evoke pain stimulate the sympathetic nervous system leading to downstream vascular and hemodynamic adjustments. In clinical populations and older individuals, the perception of pain is associated with cardiovascular responses (e.g., heart rate, blood pressure, and arterial stiffness). However, there are extensive inter‐individual differences in the perception of pain, pain perception may be influenced by age, and it’s unclear if pain is associated with cardiovascular responses in younger adults.PURPOSETherefore, we sought to determine whether heart rate, blood pressure, and arterial stiffness responses to sympathoexcitatory stimuli were associated with perceived pain, in apparently healthy young adultsMETHODS17 young adults (21.6±3.9 yrs; BMI: 24.4±2.8 kg/m2;Mean±SD) participated in this investigation. Following 10‐min of supine rest, we measured heart rate (HR) and mean arterial pressure (MAP), via pulse wave analysis (PWA), and arterial stiffness via carotid‐femoral pulse wave velocity (cf‐PWV). Measures were obtained in duplicate then averaged for analysis. Participants then performed a 3‐min isometric handgrip exercise (HG) at 30% of maximum voluntary contraction, which was immediately followed by 3‐min of brachial cuff‐occlusion at 240mmHg. Perceived pain was assessed via visual analog scale (0‐10; 0=no pain, 10=most pain) at the first minute of each stimulus. HR and MAP were assessed at minute two and arterial stiffness was acquired in the final minute of each stimulus. Associations between perceived pain scores during HG and cuff‐occlusion with percent change in cardiovascular responses were assessed using Spearman’s correlations (α=0.05)RESULTSDuring HG, significant (P<0.01) increases in HR (pre: 63±6 vs. post: 78±11 bpm; 23±15 %), MAP (pre: 86±9 vs. post: 105±14 mmHg; 22±10 %), and cf‐PWV (pre: 6.5±1.7 vs. post: 7.2±1.0 m/s; 13±26 %) were observed. During cuff‐occlusion, relative to pre, significant (P<0.05) increases in MAP (post: 100±13 mmHg; 18±15%) and cf‐PWV (post: 7.2±1.4 m/s; 14±13%), but not (P>0.05) HR (post: 64±7 bpm; 7±6%) were observed. Perceived pain during cuff‐occlusion (3.73±1.79 A.U.) was significantly greater (P=0.01) than during HG (1.88±1.20 A.U.). While no relationships were observed between perceived pain and cardiovascular responsiveness during HG (P>0.05) with HR (r=0.28; P=0.28), BP (r=0.45; P=0.07), or cf‐PVW (r=0.28; P=0.28), perceived pain was associated with increases in BP (r=0.57; P=0.02) and cf‐PWV (r=0.55; P=0.02;), but not HR (r=0.19; P=0.47), during cuff‐occlusion.CONCLUSIONSWhile pain during HG was not associated with cardiovascular responses, significantly greater cuff‐occlusion evoked pain was associated with cardiovascular responsiveness. Our data suggests that the relation between perceived pain and cardiovascular responsiveness to sympathoexcitatory stimuli exists in younger adults, although additional data in larger cohorts and using varied stimuli are warranted.

Impact of Maternal Obesity on Resting Muscle Sympathetic Nerve Activity during Normotensive Pregnancy

Maternal obesity increases the risk of adverse pregnancy outcomes. The mechanisms that contribute to this elevated risk are unclear but may be related to overactivation of the sympathetic nervous system. Indeed, sympathetic activation during pregnancy is now regarded as a normal adaptation to maintain homeostasis. However, sympathetic overactivation is associated with gestational hypertensive disorders. It is unknown whether the health related problems linked to maternal obesity (i.e., inflammation, insulin resistance, dyslipidemia) results in sympathetic overactivation during pregnancy. We hypothesized that maternal obesity would induce greater increases in resting muscle sympathetic nerve activity (MSNA) during pregnancy when compared with normal‐weight women.Blood pressure (BP), heart rate and MSNA (microneurography) were recorded during 5 min of supine rest in 14 normal‐weight (Age 30±1.6 [SE] yrs; BMI 22.1±0.6 kg/m2) and 14 obese (Age 28±0.8 yrs; BMI 33.9±1.0 kg/m2) women during early pregnancy (5‐12 weeks), late pregnancy (32 to 34 weeks) and 6‐10 weeks postpartum.Gestational weight gain from early to late pregnancy was not significantly different between groups (11.8±0.9 kg vs. 9.2±2.1 kg, P=0.23). Resting MSNA burst frequency was not different between normal‐weight and obese groups during early pregnancy (17±3 bursts/min vs. 22±4 bursts/min, P=0.35) or postpartum (10±2 bursts/min vs. 8±2 bursts/min P=0.74) but was significantly greater in the obese group during late pregnancy (23±4 bursts/min vs. 35±4 bursts/min, Figure A, P=0.031). There were no significant changes in resting MSNA from early to late pregnancy in the normal‐weight group (P=0.67) whereas the obese group had significant increases in MSNA from early to late pregnancy (P=0.002). These findings were also apparent when MSNA was characterized as burst incidence and total activity (Figure B and C). Although still within the normotensive range, women with obesity had greater levels of systolic BP when compared with normal‐weight women across all time points (Figure D, group main effect P=0.002). Diastolic BP was lower during pregnancy when compared with postpartum and this was similar between groups (Figure E, gestation main effect P<0.001). Heart rate was greater during early pregnancy when compared with postpartum and increased similarly in both groups during late pregnancy (Figure F, gestation main effect P<0.001).These findings suggest that maternal obesity is associated with greater increases in sympathetic activation even during normotensive pregnancy and may play a role in the increased risk of adverse maternal and fetal outcomes in women with obesity.

Free Day, but Not Work Day, Sleep Duration Is Inversely Associated With Aortic Stiffness in Apparently Healthy Young Adults

Insufficiency or irregularity in sleep is associated with high blood pressure (BP) and aortic stiffness, both of which are independent predictors of all‐cause and cardiovascular mortality. The cardiovascular ramifications of short and irregular sleep are well documented in shift workers, but the health implications of possible differences between sleep duration on workdays (WD) and free days (FD) in non‐shift workers is less clear.PURPOSEWe sought to examine associations between WD and FD sleep duration, and then to inspect for relationships between WD and FD sleep duration, as well as the difference between WD and FD sleep duration (i.e., sleep irregularity), with BP and indices of arterial stiffness in apparently healthy young adults. We hypothesized 1) participants would sleep less on WD than FD, and 2) that participants with short WD sleep duration would exhibit higher BP and arterial stiffness, and 3) those with greater sleep irregularity would exhibit higher BP and arterial stiffness.METHODS16 apparently healthy young adults (21.8±4.0 yrs; 24.4±2.9 kg/m2; Mean±SD) participated in this study. All participants completed the Munich ChronoType Questionnaire to assess self‐described WD and FD sleep‐wake behavior. WD and FD sleep duration were determined, and sleep irregularity was quantified as the absolute value of the difference between WD and FD sleep duration. Following 10‐min of supine rest, we used an automated oscillometric device (SphygmoCor XCEL) to measure BP and augmentation index (AIx), an indirect measure of arterial stiffness. Aortic stiffness was then assessed using carotid‐femoral pulse wave velocity (cf‐PWV). WD and FD sleep duration were compared using a paired t‐test and associations between sleep with BP and indices of arterial stiffness were assessed using Pearson correlations, or the non‐parametric equivalent for sleep irregularity.RESULTSWD sleep duration was 492±85 min, FD sleep duration was 480±83 min, and sleep irregularity was 53±49 min. Systolic BP was 120±10 mmHg, diastolic BP was 68±7 mmHg, AIx was 10.9±9.8 %, and cf‐PWV was 5.8±0.7 m/s. WD sleep duration was significantly greater (P<0.01) than FD sleep duration, and WD sleep duration was not associated (P>0.05) with systolic BP (r=0.10), diastolic BP (r=0.10), AIx (r=0.07), or cf‐PWV (r=‐0.18). FD sleep duration was inversely correlated with cf‐PWV (r=‐0.65; P=0.01), but was not associated (P>0.05) with systolic BP (r=‐0.12), diastolic BP (r =‐0.08), or AIx (r=0.25). Sleep irregularity was not associated (P>0.05) with systolic BP (r=0.37), diastolic BP (r=0.45), AIx (r=0.08), or cf‐PWV (r=0.14).CONCLUSIONSContrary to our hypothesis, FD, but not WD, sleep duration was associated with aortic stiffness in apparently healthy young adults. Average sleep duration of our cohort exceeded the recommended minimum of 7 hours per night and sleep irregularity was small (i.e., <60 min on average), thus potentially masking elevations in BP and arterial stiffness seen with short and/or irregular sleep such as in shift workers.

Middle Cerebral Artery Pulsatility Index is Elevated in Chronic Kidney Disease

IntroductionCKD patients exhibit an increased risk of cerebrovascular disease such as stroke, transient ischemic attacks, and cerebral small vessel disease. One mechanism that may contribute to this risk is increased cerebrovascular stiffness and augmented pulsatility of blood flow into the cerebral microcirculation. Middle cerebral artery pulsatility index (MCA PI) provides an indirect measure of cerebrovascular stiffness and can be measured with transcranial Doppler (TCD) ultrasonography. Prior work suggests that MCA PI is elevated in CKD patients following stroke, but it remains unclear if MCA PI is elevated in CKD patients without a history of cerebrovascular disease. Moreover, whether MCA PI correlates with central (aortic) arterial stiffness in CKD remains unknown. We hypothesized that MCA PI would be elevated in CKD patients stages III‐IV compared to controls without CKD matched for age, race, sex, diabetes and hypertension. Furthermore, we hypothesized that MCA PI would correlate with central arterial stiffness and estimated glomerular filtration rate (eGFR) in CKD.Methods13 CKD participants stages III‐IV (mean eGFR=38±3 ml/min/1.73m2) and 10 controls without CKD (age=60±2y) underwent measurement of middle cerebral artery blood velocity via TCD during 5 minutes of seated rest. MCA PI was averaged over the 5 minute period and calculated as MCA PI = (peak systolic blood velocity – diastolic blood velocity)/(mean blood velocity). In CKD, central arterial stiffness was measured via carotid‐femoral pulse wave velocity (cfPWV) after 5 minutes of supine rest. MCA PI was compared between CKD vs CON via 2‐tailed, independent sample T‐tests and the relationships between MCA PI, cfPWV, and eGFR CKD were examined via linear regression.ResultsMCA PI was elevated in CKD compared to CON (0.91±0.06 vs 0.73±.04, P=0.04) and was associated with cfPWV (R=0.72, P=0.01). However, we observed no relationship between MCA PI and eGFR in CKD (P=0.83).DiscussionIn support of our hypothesis, MCA was elevated in CKD compared to controls and was associated with central arterial stiffness. These findings suggest that cerebrovascular stiffness is elevated in CKD patients without a history of cerebrovascular disease, and that MCA PI correlates with central arterial stiffness in CKD. Increases in cerebrovascular stiffness and subsequent flow pulsatility may comprise one mechanism of cerebrovascular disease risk in CKD. Future work should clarify the relationship between MCA PI and severity of renal disease in a larger cohort, and examine the prognostic value of MCA PI as a predictor of future cerebrovascular disease burden in CKD.

Stroke volume variation as an index of fluid responsiveness can be impaired by mental stress.

Cardiac stroke volume variation (SVV) measurement is one of the techniques to detect fluid-responsive hypovolemia in patients under mechanical ventilation. There is an ongoing effort to apply SVV for this purpose also in conscious patients. However, the effect of mental stress often occurring in conscious patients as a potential confounding factor on SVV is not known. The aim of our study was to compare effect of simulated hypovolemia and mental stress on SVV in healthy volunteers in the context of potential confounders - breathing pattern, respiratory sinus arrhythmia magnitude and sex. We examined 102 young healthy volunteers (58 females), mean age 18.6 years. Finger arterial blood pressure was recorded by volume-clamp photoplethysmographic method (Finometer Pro, FMS, Amsterdam, Netherland). From the blood pressure curve, a built in ModelFlow algorithm calculated stroke volume values (SV) for each heartbeat. Respiratory volume was recorded using calibrated respiratory inductive plethysmography (RespiTrace, NIMS, Miami Beach, FL, USA). During four phases of examination protocol (supine rest, head-up tilt (HUT), supine recovery, mental arithmetic task (MA)) we analyzed SVV related to respiratory activity. While during HUT we found an expected increase in SVV together with mean SV decrease, SVV significantly decreased during MA. The observed changes during MA could be attributed to an increased respiratory rate and/or decreased respiratory sinus arrhythmia. Sex related differences in SVV responses to HUT and MA were observed. We conclude that mental stress together with respiratory sinus arrhythmia and respiratory pattern changes can significantly influence SVV as a potential index of fluid responsiveness in conscious patients.

Assessing Cardiac Recovery for Decommissioning of LVAD Support: Structure versus Function

<h3>Introduction</h3> Recovery of left ventricular (LV) function during LVAD support occurs in only 1-3% of patients. Assessment for recovery and LVAD removal is desirable given the risks of infection, stroke, and device malfunction. This case of a patient with an LVAD, with recovered LV systolic function but abnormal exercise hemodynamics, illustrates the potential utility of right heart catheterization studies for clinical decisions. <h3>Case Report</h3> A 35-year-old man presented with cardiogenic shock after a late-presentation ST elevation myocardial infarction, requiring short-term veno-arterial extracorporeal membrane oxygenation post-angioplasty. Then, a HeartMate II LVAD was inserted. Four months after implantation, the patient was well (NYHA I). Serial echocardiography demonstrated recovery of LVEF to 50-55% by 7 months. Repeated hemodynamic assessments were performed over 11 months. Hemodynamics were recorded at supine rest with baseline LVAD speed, with speed reduced to the equivalent of unsupported (8000 rpm) and then during cycle ergometer exercise at a constant work rate (Table). Between baseline and unsupported speeds, minimal change in the mixed venous O2 saturation and smaller increases in mean pulmonary arterial wedge pressure (mPAWP) and mean pulmonary artery pressures (mPAP) were noted during the 3rd and 4th studies. However, during exercise, the patient displayed persistently limited increases in cardiac output (CO) and the relationship between PAWP and CO (∆PAWP/∆CO) was persistently elevated above 2 mmHg/L/min. As such, the patient was listed for transplant rather than explanted. <h3>Summary</h3> Although echocardiographic imaging showed recovery of LV systolic function, exercise at unsupported speed was associated with abnormal ∆PAWP/∆CO, prompting concern of recurrent symptomatic heart failure if the LVAD was explanted. This case illustrates ongoing efforts to evaluate appropriate structural and functional markers of myocardial recovery to support decisions regarding LVAD explantation.

420 Comparison of Statin Use to Non-Use on Cerebral Blood Flow Velocity in Older Adults at Risk for Alzheimers Disease: Data from a Phase II Multisite Clinical Trial

OBJECTIVES/GOALS: Reduced cerebral blood flow (CBF) along with vascular risk factors (e.g., dyslipidemia) are prevalent in Alzheimers disease (AD) and related dementias. Statins are one of the most effective pharmacologic treatments for vascular risk reduction, which may contribute to CBF in individuals with an increased risk for AD. METHODS/STUDY POPULATION: Cross-sectional analysis of 212 older adults with a family history of dementia. Heart rate via electrocardiogram, mean arterial pressure (MAP) via brachial sphygmomanometers, end-tidal CO2 via capnograph, and CBF velocity at the middle cerebral artery (MCAv) via transcranial Doppler ultrasound were collected following 20-minutes of supine rest. Mean MCAv (cm/s) was measured within each cardiac cycle and averaged over an 8-minute duration. Cerebrovascular conductance was calculated by dividing mean MCAv by MAP. Pulsatility Index was calculated by subtracting systolic MCAv from diastolic MCAv and then dividing by mean MCAv. RESULTS/ANTICIPATED RESULTS: 125 females (68 ± 6 years; 49 statin) and 87 males (70 ± 6 years; 47 statin) were included in analyses. There were no significant differences between heart rate, MAP, or end-tidal CO2 between statin and non-statin users. After controlling for age, sex, and low-density and high-density lipoprotein, statin use did not significantly contribute to MCAv (p = 0.09). However, statin use did significantly contribute to cerebrovascular conductance (MCAv/MAP; p = 0.03) as well as Pulsatility Index (assessment of cerebral health, p &lt; 0.01). DISCUSSION/SIGNIFICANCE: Our findings suggest statin use significantly and positively contributes to resting cerebral blood flow velocity and cerebrovascular health. Further investigation is warranted into statin interventions with other components of cerebrovascular function, as differences may have implications for brain health and disease pathogenesis.

Physiological assessment of orthostatic intolerance in chronic fatigue syndrome

BackgroundOrthostatic intolerance-OI is common in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-ME/CFS. We used a 10-min passive vertical lean test as orthostatic challenge-OC and measured changes in vitals and end tidal CO2 (eTCO2). An abnormal physiologic response to OC was identified in 60% of the 63 patients evaluated from one to three times over several years. Hypocapnia, either resting or induced by OC, was the most frequent abnormality, followed by postural orthostatic tachycardia.ObjectiveEvaluate the physiologic response of patients with ME/CFS to a standardized OC.DesignRespiratory and heart rate, blood pressure and eTCO2 were recorded twice at the end of 10-min supine rest and then every minute during the 10-min lean. Hypocapnia was eTCO2 ≤ 32 mmHg. Orthostatic tachycardia was heart rate increase ≥ 30 beats per minute compared with resting or ≥ 120 BPM. Orthostatic hypotension was decreased systolic pressure ≥ 20 mmHg from baseline. Tachypnea was respiratory rate of ≥ 20 breaths per minute—either supine or leaning. Questionnaire data on symptom severity, quality of life and mood were collected at visit #2.Patients63 consecutive patients fulfilling the 1994 case definition for CFS underwent lean testing at first visit and then annually at visit 2 (n = 48) and 3 (n = 29).MeasuresSupine hypocapnia; orthostatic tachycardia, hypocapnia or hypotension.ResultsThe majority of ME/CFS patients (60.3%, 38/63) had an abnormality detected during a lean test at any visit (51%, 50% and 45% at visits 1, 2 and 3, respectively). Hypocapnia at rest or induced by OC was more common and more likely to persist than postural orthostatic tachycardia. Anxiety scores did not differ between those with and without hypocapnia.ConclusionsThe 10-min lean test is useful in evaluation of OI in patients with ME/CFS. The most frequent abnormality, hypocapnia, would be missed without capnography.

Validity and reliability of different smartphones applications to measure HRV during short and ultra-short measurements in elite athletes

Background and objectiveHeart rate variability (HRV) has been proposed as a useful marker that can show the performance adaptation and optimize the training process in elite athletes. The development of wearable technology permits the measurement of this marker through smartphone applications. The purpose of this study is to assess the validity and reliability of short and ultra-short HRV measurements in elite cyclists using different smartphone applications. MethodTwenty-six professional cyclists were measured at rest in supine and in seated positions through the simultaneous use of an electrocardiogram and two different smartphone applications that implement different technologies to measure HRV: Elite HRV (with a chest strap) and Welltory (photoplethysmography). Level of significance was set at p < 0.05. ResultsCompared to an electrocardiogram, Elite HRV and Welltory showed no differences neither in supine nor in seated positions (p > 0.05) and they showed very strong to almost perfect correlation levels (r = 0.77 to 0.94). Furthermore, no differences were found between short (5 min) and ultra-short (1 min) length measurements. Intraclass correlation coefficient showed good to excellent reliability and the standard error of measurement remained lower than 6%. ConclusionBoth smartphone applications can be implemented to monitor HRV using short- and ultra-short length measurements in elite endurance athletes.

Effect of yoga nidra on the brain activity in individuals with migraine

Background: Migraine is a frequent neurological problem that carries the largest burden in terms of years spent disabled among neurological conditions. The conventional management has not been able to successfully treat migraine and hence, there was a need for combating these disorders through conventional therapies like yoga with an evidence-based approach. As there are only few evidence in this aspect, this research aims at finding evidence for yoga and naturopathy on migraine. Materials and Methods: Participants (n = 60) were randomly allocated into two groups, control group (n = 30) and intervention group (n = 30). The intervention group received Yoga Nidra and the control group was given supine rest (Rest without conscious awareness). The electroencephalogram data were recorded both at baseline and postintervention for both groups. The data were analyzed using SPSS version 20.0 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp), and the results were tabulated. Results: The results of the current study showed increased frequency in alpha waves in the interventional group compared to the control group. The control group showed no significant changes in the brain activity. Conclusion: The results indicate that Yoga Nidra induces relaxation through enhanced alpha waves. This shows that Yoga Nidra helps in parasympathetic dominance and hence decreases sympathetic activation. Hence, this study suggests that Yoga Nidra could be used as an effective tool in combating stress and neuropsychiatric symptoms in migraine patients.

Effect of Electrical Muscle Stimulation on Vascular Endothelial Function during Prolonged Sitting.

While prolonged sedentary behaviors (SBs) increase cardiovascular disease (CVD) risk, interrupting prolonged sitting (PS) with frequent light exercise reduces arterial functional decline. Skeletal muscle electrical stimulation (EMS) enhances peripheral circulation through passive muscle contraction, suggesting that EMS reduces CVD risk by providing an alternative to active exercise for prolonged SBs. This study aimed to investigate the effects of EMS to skeletal muscles during PS on the endothelial function of the brachial artery (BA). Study participants included 12 healthy adult men who were subjected to 15 min of supine rest, followed by 1 h of PS only (control [CON] trial), or 20 min of EMS to the lower extremities at 50% of the maximum tolerance intensity during PS (EMS trial). Flow-mediated dilation (FMD) of the BA was measured before and 30 min after PS, and normalized FMD (nFMD) was calculated. The nFMD of the CON trial significantly decreased 30 min after PS completion (6.21% ± 1.13%) compared with that before PS (7.26% ± 0.73%), and there was no significant change in the EMS trial before and after PS. The EMS trial showed a significant increase in the nFMD 30 min after PS completion (1.14 ± 0.77) compared with that before PS (0.84 ± 0.43). However, no significant difference was observed in the CON trials. Passive contraction of the lower extremity muscles by EMS increases BA nFMD, suggesting that prolonged sedentary lower extremity EMS use may reduce the risk of vascular endothelial dysfunction.

Electrocardiographic Abnormalities in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Objective: The objective of this article was to determine the frequency of different electrocardiographic (ECG) abnormalities in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Design: This is a cross-sectional study.Place and duration: The study was conducted at the medicine department at Civil Hospital Karachi, Pakistan, between November 2018 and May 2019.Method: Both female and male participants aged 18-60 years with acute exacerbation of COPD (as per the operational definition) for more than three days who did not receive any treatment for exacerbation were included in the study. Twelve-lead ECG was recorded (Schiller AG, Baar, Switzerland) for 10 minutes after the supine rest, with a 50 mm/s of paper speed, 10 mm/mV of gain, and filter default settings.Results: In total, 140 participants (male: n = 124 [88.6%] and female: n = 16 [11.4%]) were included the research. The mean age of the participants was 40.43 ± 11.51 years. In terms of severity, 46 (32.95) patients presented with mild, 46 (32.9%) with moderate, and 48 (34.4%) with severe exacerbation. Moreover, 33 (23.65%) participants had ECG abnormalities, i.e., 13 (9.3%) patients presented with right atrial enlargement, and eight (5.7%) with right ventricular hypertrophy. Patients with a longer smoking duration (years) were likely to present with ECG abnormalities.Conclusion: Patients with COPD who had severe acute exacerbation and a long smoking duration have a high prevalence of ECG abnormalities. Hence, ECG may be a valuable tool for detecting ischemic abnormalities among patients with COPD, independent of previously known heart disease, in clinical settings.

Effects of statins on cerebral blood velocity in older adults at risk for Alzheimer’s disease: Data from a phase II multisite clinical trial

Reduced cerebral blood flow (CBF) along with vascular risk factors (e.g., dyslipidemia) are prevalent in Alzheimer's disease (AD) and related dementias. Considering the lack of disease-modifying therapies, targeting modifiable vascular risk factors is imperative. Statins are one of the most effective pharmacologic treatments for vascular risk reduction, which may increase CBF in individuals with an increased risk for AD. Despite widespread statin use in both sexes, sex specific statin effects on CBF is not completely understood. Cross-sectional analysis of 194 older adults with a family history of dementia. Heart rate via electrocardiogram, mean arterial pressure (MAP) via plethysmograph, end-tidal CO2 via capnograph, and CBF velocity at the middle cerebral artery (MCAv) via transcranial Doppler ultrasound were collected following 20-minutes of supine rest. Mean MCAv (cm/s) was measured within each cardiac cycle and averaged over an 8-minute duration. 114 females (68 ± 5 years; 49 statin) and 80 males (70 ± 6 years; 46 statin) were included in analyses. There were no significant differences between vasodilator medication use, heart rate, end-tidal CO2 , or MAP between sexes. MCAv was significantly higher in females compared to males. There was a significant interaction effect between statin use and sex (p = 0.03). Post-hoc analyses suggest that the female statin group had significantly higher MCAv than female non-statin group (59.0 ± 12.1 vs. 52.7 ± 12.1; p = 0.02) and female statin group had significantly higher MCAv than male statin group (59.0 ± 12.1 vs. 47.5 ± 10.4 cm/s; p < 0.001). Males were significantly older than females; however, we report that age was not a significant covariate in the model. Our findings suggest a sex specific statin effect on MCAv, with females having had a significantly higher MCAv from statin use. Further investigation is warranted into other components of cerebrovascular function, as differences between sexes may have implications for brain health and disease pathogenesis.

78 HIGHER NEUROVASCULAR SIGNAL ENTROPY IS ASSOCIATED WITH ACCELERATED BRAIN AGEING

Abstract Background Often chronological age is not the most accurate marker of an individual’s health status since ageing is a heterogeneous process across individuals. Machine learning can be used to quantify the relationship between structural brain MRI data and chronological age, to estimate an individual’s ‘brain age’, which, when subtracted from chronological age, provides a brain predicted-age difference score (BrainPAD) [1]. BrainPAD reflects the biological ageing of the brain. Increased complexity in neurovascular signals has been shown to be associated with poorer cognitive performance and physical frailty [2]. The aim of this study was to investigate associations between the complexity of frontal-lobe oxygenation (tissue saturation index (TSI)) data and BrainPAD in a cohort of older community-dwelling adults. Methods To calculate BrainPAD, machine learning was applied to 1,359 T1-weighted MRI brain scans from various open-access repositories, and this model was subsequently applied to MRI data acquired from the study cohort. TSI was non-invasively measured in the left frontal lobe using near-infrared spectroscopy. TSI data were acquired continuously during five minutes of supine rest and the last minute was utilized in this analysis. The complexity of TSI signals was quantified using sample entropy (SampEn). Multivariable linear regression was employed, controlling for age, sex, education, antihypertensive medications, diabetes, cardiovascular conditions, smoking, alcohol, depression, BMI, physical activity, and blood pressure. Results Complete data were available for 397 individuals (age: 67.9 ± 7.7 years; 53.7% female). An increase in TSI SampEn of 0.1 was associated with an increase in BrainPAD of 0.9 years (P = 0.007, 95%CIs: 0.3 to 1.6). Similar results were found with and without the inclusion of chronological age in the models. Conclusion This study reports significant associations between higher complexity in peripherally measured frontal lobe oxygenation concentration and accelerated brain ageing.

Cardiac-vascular-respiratory coupling analysis during 6-degree head-down tilt microgravity analogue

In the study, quantitative analysis was done to identify the interaction among cardiac, vascular and respiratory signals for 6-degree head-down tilt (HDT) microgravity analogue. This HDT shifts the blood volume towards the thoracic cavity of the human body. The linear and non-linear domain analyses are based on coherence techniques that are used to analyse these cardiovascular responses. But they lack to measure the information flow and coupling changes that occurred during HDT. The present study applied an information domain approach for the investigation of non-linear causality to the heart rate variability, systolic blood pressure and respiration measured during HDT. It was hypothesized that the HDT will demonstrate alteration in cardiac, vascular and respiratory parameters. Twenty healthy subjects were inspected each for 10 min at supine rest and HDT. The responses were significant for cardiac and vascular but not for the respiratory system during HDT. It was observed that during HDT, the parasympathetic nervous system activated and increased the effect of vascular on the cardiac. The effect of respiration on either vascular or cardiac was not significant, therefore the variation and coupling observed in the vascular and cardiac systems are solely because of HDT. The results of this study support the hypothesis and revealed that the HDT altered the autonomic function parameters. It can be concluded that the HDT increases the parasympathetic activity and cardiovascular interaction as well as confirmed the usefulness of conditional entropy for coupling analysis.

Intake Duration of Anthocyanin-Rich New Zealand Blackcurrant Extract Affects Cardiovascular Responses during Moderate-Intensity Walking But Not at Rest

We examined effects of intake duration of New Zealand blackcurrant (NZBC) extract on cardiovascular responses during supine rest and moderate-intensity walking. Recreationally active men (n = 15, age: 24 ± 6 yr, BMI: 24.7 ± 4.3 kg·m−2) volunteered in a randomized, cross-over design. One metabolic equivalent (1-MET) was measured (3.97 ± 0.66 mL·kg−1·min−1) and an incremental walking test was performed to individualize speed at 4 (n = 3) or 5 (n = 12) METs for the 30-min walk (5.7 ± 0.7 km·hr−1). NZBC extract (210 mg of anthocyanins) was taken with breakfast for 7 and 14 days, with a 14-days washout. The final dose was ingested 2-hr before recording of the cardiovascular responses (Portapres Model-2). At rest, %changes at 7- and 14-days intake were observed for stroke volume (+6.8% (trend), p = 0.065; +8.5%, p = 0.012), cardiac output (+10.1%, p = 0.007; +8.5%, p = 0.013), total peripheral resistance (−12.0%, p = 0.004; −13.1%, p = 0.011), diastolic (−5.7%, p = 0.045; −9.7%, p = 0.015) and mean arterial pressure (−4.4%, p = 0.040; −7.2%, p = 0.029), but without intake duration effect. During walking, %changes at 7- and 14-days intake were observed for stroke volume (+7.7% (trend), p = 0.063; +9.9%, p = 0.006), cardiac output (+8.7%, p = 0.037; +10.1%, p = 0.007), diastolic blood pressure (−6.2%, p = 0.042; −10.6%, p = 0.001), and total peripheral resistance (−9.6%, p = 0.042; −13.5%, p = 0.005) but without intake duration effect. During walking, %changes at 14-days were observed only for mean arterial pressure (−6.4%, p = 0.018) and arterio-venous oxygen difference (−7.9%, p = 0.019). NZBC extract affects cardiovascular responses at rest and during moderate-intensity exercise with 7- and 14-day intake. Only during moderate-intensity exercise, a longer intake of NZBC extract was required for an effect on some cardiovascular responses.