Normal Blood Pressure Response Research Articles

Blood pressure response to graded bicycle exercise in males and females across the age and fitness spectrum.

Blood pressure (BP) responses to exercise are frequently measured, with the concern that greater increases are a marker of disease. We sought to characterize the normal exercise BP response in healthy adults and its relationships with age, sex, and fitness. 589 participants (median age 46 [IQR 24-56] years, 81% male) underwent cardiopulmonary exercise testing with repeated, automated BP measures. An exaggerated maximal systolic BP (SBPmax) was defined from current guidelines as ≥210 mmHg in males and ≥190 mmHg in females. Individual linear regression analyses defined the relationship between BP and workload (SBP/W-slope and DBP/W-slope). Participants with or without an exaggerated SBPmax and above or below median SBP/W-slope were compared. An exaggerated SBPmax was found in 51% of males and 64% of females and was more prevalent in endurance-trained athletes (males 58%, females 72%, p<0.001). The mean SBP/W-slope was lower in males (0.24±0.10 mmHg/W) than females (0.27±0.12 mmHg/W), p=0.031. In both sexes, peak oxygen uptake (VO2peak) was inversely correlated with SBP/W-slope (p<0.01). Those with an exaggerated SBPmax and below-median SBP/W-slope were 10 years younger and had a 20% higher VO2peak, on average (p<0.001). A non-exaggerated SBPmax and above-median SBP/W-slope was observed in older individuals with the lowest VO2peak. In a large cohort of healthy individuals, an exaggerated SBPmax was common and associated with higher fitness. In contrast, higher SBP indexed to workload was associated with older age, lower fitness, and female sex. Thus, sex, age and fitness should be considered when evaluating BP response to exercise.

Usability of myocardial work parameters to demonstrate subclinical myocardial involvement in normotensive individuals with exaggerated hypertensive response in treadmill exercise testing.

Early determination of changes in myocardial functions is essential for the protection of cardiovascular diseases. This study aimed to evaluate myocardial work parameters in healthy individuals who developed an exaggerated hypertensive response during the treadmill exercise test procedure. The study included a total of 64 patients for whom an exercise electrocardiography test was planned for functional capacity evaluation. The study population was divided according to the presence of exaggerated hypertensive response to exercise (EBPRE) (SBP/DBP ≥210/105mmHg in males ≥190/105mmHg in females) and normal blood pressure response to exercise (NBPRE). Patients' echocardiographic evaluations were made at rest, and myocardial work parameters were calculated. There was no statistical difference between the groups (NBPRE vs. EBPRE, respectively) in terms of left ventricular 2,3 and 4 chamber strains and global longitudinal strain (GLS) values (-20.6±-2.3, -19.7±-1.9, p:.13; -21.3±-2.7, -21±-2.4, p:.68; -21.2±-2.2, -21.2±-2.3, p:.93; and -20.8±-1.5, -20.4±-1.5, p:.23, respectively). Global constrictive work (GCW), global waste work (GWW), and global work efficiency (GWE) were not statistically different between the two groups (2374±210, 2465±204, p:.10; 142±64, 127±42, p:.31; 94.3±2.5, 95.1±1.5, p:.18, respectively). In contrast, global work index (GWI) parameters were different between the two groups (2036±149, 2147±150, p<.001). The GWI was independently associated with EBPRE (odds ratio with 95% 3.32 (1.02-11.24), p=.03). The partial effect plots were used for GWI to predict EBPRE, according to the results, an increase in GWI predicts probability of exaggerated hypertensive response. In conclusion, Myocardial work analyses might be used to identify early signs of myocardial involvement in normotensive patients with EBPRE.

Exercise-induced Hypertension and Carotid Intima-media Thickness in Male Marathon Runners.

This study aimed to identify the relationship between exercise-induced hypertension and carotid artery intima-media thickness in long-distance runners. Sixty healthy male runners aged 40 to 60 years were assigned to the following three groups based on resting blood pressure and maximal systolic blood pressure during a maximal exercise test: normal blood pressure response, exercise-induced hypertension, and complex hypertension. An exaggerated systolic blood pressure response was defined as a maximal systolic blood pressure+≥+210 mmHg during the maximal exercise test, while carotid intima-media thickness was measured using B-mode ultrasonography. The carotid intima-media thickness mean values were the highest in the complex hypertension group (0.72±0.11 mm), followed by exercise-induced hypertension (0.62±0.12 mm) and normal blood pressure groups (0.55±0.13 mm), with a significant difference between the groups (p+<+0.002). In linear regression analysis, the mean intima-media thickness was independently associated with age (p=0.015) and maximal systolic blood pressure (p=0.046) but not with resting systolic blood pressure. These results suggest that exercise-induced hypertension is associated with carotid intima-media thickness, a surrogate marker of cardiovascular disease, in long-distance runners. Therefore, evaluating the blood pressure response during exercise is important for the early detection of potential cardiovascular disease risks in long-distance runners.

Hypertension, cardiovascular risk and exercise in middle-aged and elderly people: a narrative review

Hypertension (HTN) is widespread among middle-aged and elderly people, including those doing sports. For the first time in 2020, the European Society of Cardiology guidelines on sports cardiology and exercise in patients with cardiovascular disease included adult and elderly patients in a separate group. However, this is a heterogeneous category of patients, including everyone over 35 years of age. Therefore, admittance of athletes to training and competitions still remains at the discretion of physician.Aim. To assess the relationship and mutual influence of hypertension, other cardiovascular risk factors and sports in middle-aged and elderly people.Material and methods. Our narrative review is based on 50 articles published on Pubmed, Scopus, Web of Science and eLIBRARY.ru, selected using the keywords "veteran athletes", "arterial hypertension", "cardiovascular risk", "physical activity". Related papers over the past 5 years were evaluated.Results. Currently, there is a trend toward an increase in the number of veteran athletes whose problems are not reflected in guidelines on sports and exercise.Conclusion. In the future, large randomized studies are needed to assess the response of blood pressure (BP) to intense exercise, as well as to determine the normal BP response and clear strategy to manage this category of people, depending on the presence of hypertension.

Non-invasive Evaluation of Electromechanical Transmission in Patients with Hypertensive Response to Exercise Stress Test.

Excessive hypertensive response to exercise testing is associated with adverse cardiovascular events such as left ventricular hypertrophy and atrial fibrillation (AF). In this study, we examined the relationship between electromechanical delay and excessive hypertensive response to exercise testing. Twenty-five people who had a hypertensive response to the exercise stress test and 28 people who were similar in age and gender with a normal blood pressure response in the exercise stress test as the control group were included in the study. There was no statistical difference between the study groups in blood pressure holter values, conventional echocardiography findings, and exercise stress test findings. Lateral PA-TDI time (the time from the beginning of the P wave measured by tissue Doppler imaging to the beginning of the A' wave), left atrial electromechanical delay, and interatrial electromechanical delay were observed to be significantly longer in the hypertensive response group to exercise stress test compared with the control group (74.0±6.3 vs. 68.8±5.7, p=0.003; 24.7±7.0 vs. 19.6±7.1, p=0.013; 36.8±8.5 vs. 30.6±6.6, p=0.003, respectively). Early detection of electromechanical delay non-invasively may be useful in this patient group in predicting the development of new AF risk.

Influence of end-tidal CO2 on cerebral blood flow during orthostatic stress in controls and adults with myalgic encephalomyelitis/chronic fatigue syndrome.

Brain perfusion is sensitive to changes in CO2 levels (CO2 reactivity). Previously, we showed a pathological cerebral blood flow (CBF) reduction in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients during orthostatic stress. Limited data are available on the relation between CO2 and CBF changes in ME/CFS patients. Therefore, we studied this relation between ME/CFS patients and healthy controls (HC) during tilt testing. In this retrospective study, supine and end-tilt CBF, as measured by extracranial Doppler flow, were compared with PET CO2 data in female patients either with a normal heart rate and blood pressure (HR/BP) response or with postural orthostatic tachycardia syndrome (POTS), and in HC. Five hundred thirty-five female ME/CFS patients and 34 HC were included. Both in supine position and at end-tilt, there was a significant relation between CBF and PET CO2 in patients (p< 0.0001), without differences between patients with a normal HR/BP response and with POTS. The relations between the %CBF change and the PET CO2 reduction were both significant in patients and HC (p< 0.0001 and p= 0.0012, respectively). In a multiple regression analysis, the patient/HC status and PET CO2 predicted CBF. The contribution of the PET CO2 to CBF changes was limited, with low adjusted R2 values. In female ME/CFS patients, CO2 reactivity, as measured during orthostatic stress testing, is similar to that of HC and is independent of the type of hemodynamic abnormality. However, the influence of CO2 changes on CBF changes is modest in female ME/CFS patients.

Retrospective cohort study at two centers, systolic blood pressure response during exercise testing

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Palacky University Olomouc Faculty of Medicine Czechia. Introduction Measurement of blood pressure (BP) is a standard part of the exercise testing protocol in the general population and in athletes, however, we do not have a sufficient definition of normal and abnormal blood pressure response to exercise and we don´t know the prognostic impact of exercise systolic blood pressure. Purpose To present systolic blood pressure values during exercise in athletes examined by an exercise test. Methods Retrospective analysis of blood pressure response to exercise in a selected cohort of athletes who performed a bicycle ergometer exercise test at two centers. We excluded individuals with prevalent cardiovascular disease. An individual ramp protocol to maximum was used and blood pressure was measured by auscultation method. Resting BP and the highest systolic blood pressure during exercise (SPBmax), maximum heart rate (TF), and maximum workload were recorded for each individual. The SBP/Watt-slope and the SBP/Watt-ratio at peak exercise were calculated. The SBP/Watt-slope was calculated as the ratio of the difference in the rest SPB and peak SPB measurement over the increment of workload. The SBP/Watt-ratio at peak exercise was calculated as the ratio of peak SBD over the peak workload. Sex-specific mean values, standard deviations, and 5th, 25th, 75th and 95th percentiles were determined. Results Between the years 2015 and 2021, 14 702 individuals – 3821 females (27,2 %) and 10 251 males (72,8 %) – underwent the exercise test, with an average age of 19 years (±14). The average Body Mass Index (BMI) was 21,1. The average maximum heart rate achieved was 183/min (±16) and the average peak workload achieved was 3,9 W/kg regardless of gender. The following values were calculated for the whole cohort: peak SBP/Watt-ratio and SBP/Watt-slope. More detailed results are in Table 1. Sex-specific values can be seen in Table 2. Conclusion The values of BP response during exercise testing in our cohort are comparable to recently published data. These data can change the interpretation of SPB response to exercise in the future. There is also a strong need for further research-the multivariate analysis of factors associated with a higher blood pressure response to exercise and determination of sex and age-specific values.

A Review of Heart Rate and Blood Pressure Responses to Active Standing in Healthy Adults.

This review outlines the normal heart rate and blood pressure response to active standing, the physiological mechanisms governing these, and the effect of ageing on the responses. A literature search was conducted to identify articles investigating the normal heart rate and/or blood pressure response to standing. Heart rate when standing increases and then decreases and recovers to baseline. Blood pressure responses are inverse. Skeletal muscle contraction and the baroreceptor reflex drive this. With ageing, heart rate response attenuates and the initial blood pressure response increases. Normal heart rate and blood pressure responses are attributed to the baroreceptor reflex and skeletal muscle contraction. Decreased muscle strength and baroreceptor sensitivity are associated with ageing, suggesting a possible benefit in improving skeletal muscle strength to maintain an efficient response. Understanding these responses and their variation with ageing is clinically relevant and may be beneficial in improving rehabilitation outcomes.

Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration.

Background: Postural orthostatic tachycardia syndrome (POTS) has been described early after the onset of the COVID-19 infection, but also orthostatic hypotension (OH). In the present study, we hypothesized that orthostatic intolerance decreases over time. Methods: In 29 long-haul COVID-19 (LHC) patients, a tilt test was performed, including measurements of cerebral blood flow (CBF) by extracranial Doppler. The time interval between the onset of infection and the tilt test varied between 3 and 28 months. Results: In the first 12 months after the infection, 71% of the LHC patients showed POTS and after 24 months none of them. In the first 12 months, 29% of patients had a normal heart rate and blood pressure response (normHRBP) and after 24 months 75% (distribution of POTS, OH, and a normHRBP over time: p < 0.0001). Linear regression showed that, over time, there was a decrease in the abnormal CBF during the tilt (p = 0.024) but remained abnormal. Conclusion: In LHC patients, hemodynamic abnormalities of a tilt test change over time. Patients studied early after the onset of the disease mainly exhibit POTS, but patients studied later in the time course mainly show a normHRBP or OH. In addition, the abnormal CBF reduction improves over time, but CBF remains abnormal.

Is Exercise Blood Pressure Putting the Brake on Exercise Rehabilitation after Acute Type A Aortic Dissection Surgery?

(1) Background: Exercise is recommended to improve physical fitness in patients recovering from acute type A aortic dissection (ATAAD). However, surgery corrects the diseased blood vessels and reduces the risk of ATAAD, but it does not redefine a safe exercise blood pressure (BP) threshold. This review aimed to discuss whether the safe threshold of exercise BP can be upregulated after ATAAD surgery to increase exercise intensity with additional benefits. (2) Data sources: The PubMed databases were searched with the keywords “type A acute aortic dissection surgery”, “exercise”, “BP”, “stress”, and variations of these terms. (3) Study selection: Data from clinical trials, guidelines, and recent reviews were selected for review. (4) Results: Regular exercise can be considered a cardioprotective intervention for aortic dissection patients by attenuating hemodynamic responses at rest and during exercise. Previous studies have mainly focused on moderate-intensity aerobic exercise. In practice, the exercise systolic BP of some patients was higher than 160 mm Hg without adverse events, which indicates that the training intensity may be underestimated for patients after ATAAD surgery. Limited studies suggest a light-to-moderate resistance training for selected patients because it may cause a greater increase in BP. (5) Conclusions: Moderate-intensity continuous aerobic exercise supplemented by low-intensity resistance training is appropriate for cardiac rehabilitation after ATAAD surgery. The BP increase based on the normal exercise BP response, corresponding to the moderate-intensity is relatively safe. For high-risk post-ATAAD patients, considering the overall volume of training, personalizing the exercise regimen to remain within “safe” BP limits, and avoiding excessive fluctuations in BP should be the primary considerations for exercise training.

Cardiac baroreflex sensitivity and heart rate variability are lower in humans with high affinity hemoglobin compared to typical affinity hemoglobin

BackgroundHumans with high O2 affinity hemoglobin (HAH) have a markedly lower partial pressure of O2at which 50% of hemoglobin is saturated (P50) and a leftward shift of the oxy‐hemoglobin dissociation curve. Humans with HAH have attenuated heart rate responses during both acute and chronic hypoxic exposure relative to humans with typical P50. Despite the attenuated heart rate responses to hypoxia, there are typically no blood pressure differences found in humans with HAH relative to humans with typical P50. Due to the blunted heart rate and normal blood pressure responses to hypoxia in humans with HAH, this study aimed to investigate the impact of HAH on cardiac autonomic function during normoxia and hypoxia. We hypothesized that humans with HAH would have lower cardiac baroreflex sensitivity (cBRS) and heart rate variability (HRV) during normoxia and hypoxia relative to individuals with typical P50.MethodsNine humans with a HAH mutation (6 female, Age: 40±12yrs, P50: 16±1 mmHg) and 12 controls with typical affinity hemoglobin (6 female, Age: 40±10yrs, P50: 26±1 mmHg) laid supine for 10‐minutes prior to 20‐minutes of isocapnic hypoxia, titrated to reduce arterial O2 pressure to ~50 mmHg (Avg. FiO2 = 11.9±0.0%). Beat‐to‐beat arterial pressures (arterial catheter) and heart rate (electrocardiogram) were continuously recorded. Data were averaged in five‐minute segments starting with the last five minutes of supine normoxic rest. Spontaneous cBRS was quantified using the sequence method. HRV was measured in time and frequency domains. Standard deviation of the RR interval (SDRR) was calculated as the standard deviation of all RR intervals in a data segment. Low frequency (LF) HRV was calculated using Fast Fourier Transformation and assessed as absolute spectral intensity in the LF band (0.04‐0.15Hz).ResultsArterial oxygen (PaO2) and carbon dioxide (PaCO2) pressures were not different between humans with HAH and controls during normoxia or isocapnic hypoxia [PaO2: (HAH vs. Control): 48±3 vs. 47±2 mmHg, p=0.612; PaCO2: (HAH vs. Control): 40±3 vs. 39±1 mmHg, p=0.328] exposure. cBRS was lower in humans with HAH compared to controls in normoxia and throughout isocapnic hypoxia [normoxia (HAH vs. Control): 7±4 vs. 16±10 ms/mmHg; hypoxia minutes 15‐20 (HAH vs. Control): 4±3 vs. 14±11 ms/mmHg; Hb type, p=0.024]. Several metrics of HRV were lower in humans with HAH relative to control (SDRR: Hb type, p≤0.001; LF: Hb type, p=0.030) and HRV was blunted to a similar extent in both groups with hypoxia (SDRR: time effect, p=0.009).ConclusionThe findings of this study are twofold. Compared to controls, humans with HAH have: 1) attenuated cardiac baroreflex sensitivity and 2) lower heart rate variability in both normoxia and isocapnic hypoxia.

Association of orthostatic blood pressure response with incident heart failure: The Framingham Heart Study.

Orthostatic hypotension (OH) and hypertension (OHT) are aberrant blood pressure (BP) regulation conditions associated with higher cardiovascular disease risk. The relations of OH and OHT with heart failure (HF) risk in the community are unclear and there remains a paucity of data on the relations with HF subtypes [HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)]. Relate OH and OHT with HF risk and its subtypes. Prospective observational cohort. Community-based individuals in the Framingham Heart Study Original Cohort. 1,914 participants (mean age 72 years; 1159 women) attending examination cycle 17 (1981-1984) followed until December 31, 2017 for incident HF or death. OH or OHT, defined as a decrease or increase, respectively, of ≥20/10 mmHg in systolic/diastolic BP upon standing from supine position. At baseline, 1,241 participants had a normal BP response (749 women), 274 had OH (181 women), and 399 had OHT (229 women). Using Cox proportional hazards regression models, we related OH and OHT to risk of HF, HFrEF, and HFpEF compared to the absence of OH and OHT (reference), adjusting for age, sex, body mass index, systolic and diastolic BP, hypertension treatment, smoking, diabetes, and total cholesterol/high-density lipoprotein. On follow-up (median 13 years) we observed 492 HF events (292 in women; 134 HFrEF, 116 HFpEF, 242 HF indeterminate EF). Compared to the referent, participants with OH [n = 84/274 (31%) HF events] had a higher HF risk (Hazards Ratio [HR] 1.47, 95% CI 1.13-1.91). Moreover, OH was associated with a higher HFrEF risk (HR 2.21, 95% CI 1.34-3.67). OHT was not associated with HF risk. Orthostatic BP response may serve as an early marker of HF risk. Findings suggest shared pathophysiology of BP regulation and HF, including HFrEF.

Left Ventricular Apical Hypertrophic Cardiomyopathy After Heart Transplant: Case Report.

<h3>Background</h3> Apical hypertrophic cardiomyopathy (ApHCM) is a rare variant of HCM which predominantly involves the left ventricular apex, and therefore does not typically result in obstructive physiology. It has been infrequently reported in general, with a rarity in heart transplant patients, mostly due to a modest or delayed presentation with symptoms. We present a case of a heart transplant patient with a stable postoperative course who was incidentally found to have ApHCM during follow up non-invasive testing. <h3>Case presentation</h3> Patient is a 45-year-old gentleman with a history of cardiac transplantation in March 2013 for heart failure in the setting of arrhythmogenic right ventricular cardiomyopathy, on chronic dual immunosuppression therapy. He has maintained preserved allograft function with no treatable rejection. Mild donor-derived atherosclerotic disease was found on the first surveillance coronary angiogram with no progression over subsequent years. He has remained asymptomatic and extremely active. In September 2020, he underwent surveillance myocardial perfusion imaging, which showed a large area of moderately severe ischemia laterally extending from the mid ventricle to the apex, prompting coronary angiography which did not show significant epicardial coronary disease. A subsequent echocardiogram with contrast demonstrated normal biventricular function, with evidence of hypertrophy with classic spading of the apical myocardium, along with a corresponding reduction in longitudinal straining, consistent with ApHCM. Upon retrospective evaluation of prior echocardiograms, the finding was likely also present though less evident. Holter monitor detected no arrhythmia and treadmill exercise testing confirmed normal functional capacity, normal blood pressure response to exercise, and no arrhythmias.. Review of the details of the donor's death did not suggest cardiac etiology or arrhythmia. <h3>Conclusion</h3> In our literature search, we found only one similar presentation in a cardiac transplant patient with apical HCM. In general, familial ApHCM is known to follow an autosomal dominant inheritance, whereas sporadic forms are caused by acquired mutations of various sarcomeric and nonsarcomeric protein genes. Other associated factors include long-standing high-pressure states, as well as medications, with one case report suggesting a possible relation with tacrolimus. One literature review suggested a possible increase in mortality in ApHCM patients. Therefore, although it is usually a rare condition, pre and post transplant monitoring must take into account that this condition may clinically manifest post transplantation.

Blood Pressure and Heart Rate Responses to an Isokinetic Testing Protocol in Professional Soccer Players.

The aim of this study was to determine blood pressure (BP) and heart rate (HR) responses triggered during an isokinetic testing protocol in professional soccer players and compare cardiovascular parameters at completion of this isokinetic protocol with those during a treadmill test. Using purposive sampling, 63 professional soccer players were recruited. Cardiovascular responses were measured noninvasively during a bilateral testing protocol of knee flexion and extension. Treadmill ergospirometry following an incremental speed protocol was performed to analyze the same cardiovascular parameters at rest and at completion of this test. There were significant differences in diastolic blood pressure (DBP) and HR according to field position. The parameters presented high homogeneity at both competitive levels. Systolic blood pressure, mean arterial pressure, HR, and rate pressure product at completion of the treadmill test were significantly higher than those at completion of the isokinetic protocol. Intermittent isokinetic testing protocol of the knee triggers normal and safe BP and HR responses in healthy professional soccer players. The HR of the defenders was higher than those of the forwards and midfielders but was independent of the competitive level. The values of cardiovascular parameters at isokinetic protocol completion were lower than those during the treadmill test.

The higher resting heart rate in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients compared to healthy controls: relation with stroke volumes.

Introduction: In patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) a higher-than-normal resting heart rate has been reported in a number of studies. As heart rate is linked to stroke volume, the present study explored the relationship between the supine heart rate and stroke volume index in healthy controls and in ME/CFS patients. Moreover, as patients with a postural orthostatic tachycardia syndrome (POTS) during tilt testing, have a higher supine heart rate than patients with a normal heart rate and blood pressure response during tilting, these two patient groups were also compared. Methods and results: From a database of individuals who had undergone tilt-testing, including supine Doppler measurements for stroke volume index calculation, we selected ME/CFS patients and healthy controls without evidence of hypotension or syncope. 474 ME/CFS patients were analyzed, 314 with a normal heart rate and blood pressure response and 160 with POTS during tilt-testing, and 56 healthy controls. Resting stroke volume indices were similar between the 3 groups. All 3 groups had an inverse relation between the resting stroke volume index and resting heart rate (all p&lt;0.0001). The slope of the relation was not significantly different between the 3 groups. Using the upper limit of the 95% prediction interval for the heart rate of healthy controls, 46 (15%) of patients with a normal heart rate and blood pressure response had a resting heart rate above the upper limit, 248 (85%) a heart rate between the upper and lower limit. In 47 (29%) patients developing POTS the resting heart rate was above the upper limit, and in 113 (71%) patients within the upper limit and lower limit. This distribution was significantly different between the two patient groups (p=0.0001). Conclusion: Patients and healthy controls showed a significant and inverse relation between the SVI and heart rate at rest. Already at rest heart rate in patients developing POTS during tilt-testing were higher compared to the patients with a normal heart rate and blood pressure response per unit of SVI, but the heart rate of the majority of all patients fell within the limits of normal of healthy controls. The difference of patients with heart rate above the upper limit versus between the upper limit and lower limit deserves further investigation and may have therapeutic implications.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

Deconditioning does not explain orthostatic intolerance in ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome)

BackgroundOrthostatic intolerance (OI) is a frequent finding in individuals with myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS). Published studies have proposed that deconditioning is an important pathophysiological mechanism in various forms of OI, including postural orthostatic tachycardia syndrome (POTS), however conflicting opinions exist. Deconditioning can be classified objectively using the predicted peak oxygen consumption (VO2) values from cardiopulmonary exercise testing (CPET). Therefore, if deconditioning is an important contributor to OI symptomatology, one would expect a relation between the degree of reduction in peak VO2during CPET and the degree of reduction in CBF during head-up tilt testing (HUT).Methods and resultsIn 22 healthy controls and 199 ME/CFS patients were included. Deconditioning was classified by the CPET response as follows: %peak VO2 ≥ 85% = no deconditioning, %peak VO2 65–85% = mild deconditioning, and %peak VO2 < 65% = severe deconditioning. HC had higher oxygen consumption at the ventilatory threshold and at peak exercise as compared to ME/CFS patients (p ranging between 0.001 and < 0.0001). Although ME/CFS patients had significantly greater CBF reduction than HC (p < 0.0001), there were no differences in CBF reduction among ME/CFS patients with no, mild, or severe deconditioning. We classified the hemodynamic response to HUT into three categories: those with a normal heart rate and blood pressure response, postural orthostatic tachycardia syndrome, or orthostatic hypotension. No difference in the degree of CBF reduction was shown in those three groups.ConclusionThis study shows that in ME/CFS patients orthostatic intolerance is not caused by deconditioning as defined on cardiopulmonary exercise testing. An abnormal high decline in cerebral blood flow during orthostatic stress was present in all ME/CFS patients regardless of their %peak VO2 results on cardiopulmonary exercise testing.

Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients

ObjectiveOrthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients. Methods60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 min post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound). ResultsEnd-tilt cerebral blood flow reduction was −29 (6)%, improving to −16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥ 30 mmHg) versus hypocapnia (end-tidal PCO2 < 30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: −7 (2)%, moderate: −16 (3)%, and severe :-25 (4)% (p all < 0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients. ConclusionsDuring tilt testing, extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients. SignificanceThe finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients.

The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Joint Hypermobility Show Larger Cerebral Blood Flow Reductions during Orthostatic Stress Testing Than Patients without Hypermobility: A Case Control Study

Aims: An abnormal reduction in cerebral blood flow (CBF) during orthostatic stress is common in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition with more prevalent joint hypermobility than in the healthy population. As one of proposed underlying mechanisms of orthostatic intolerance in hypermobile patients is vessel laxity, reducing the normal return of blood to the heart during orthostatic stress, we hypothesized that the CBF reduction during tilt-testing would be larger in ME/CFS patients with joint hypermobility than in patients without hypermobility. Methods: In this case-control study, 100 female ME/CFS cases with joint hypermobility, who had undergone tilt-testing with CBF measurements, were compared to 100 female ME/CFS patients without joint hypermobility, matched by age and disease duration. Results: No differences in baseline characteristics were found between groups. The hypermobile patients had significantly more postural orthostatic tachycardia syndrome (POTS) during tilt testing than the non-hypermobile ones. Compared to supine CBF, the degree of CBF reduction during the tilt was significantly larger in hypermobile cases than in the non-hypermobile controls: -32 (6)% vs -23 (7)% (p&lt;0.0001) The larger CBF reduction in hypermobile patients was not only present in POTS patients: -33 (6)% vs -24 (4)%, but also in patients with a normal heart rate and blood pressure response to tilt testing: -31 (6)% vs -22 (9)%: (both p&lt;0.0001). Conclusions: ME/CFS patients with joint hypermobility syndromes have larger CBF reductions during orthostatic stress testing than patients without hypermobility. This larger CBF reduction is independent of the heart rate and blood pressure results of the orthostatic stress test.