Tag: arterial stiffness

Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2

Abstract:

Objective: COVID-19 survivors can experience lingering symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) that appear in different phenotypes, and its etiology remains elusive. We assessed the relationship of endothelial dysfunction with having COVID and PASC.

Methods: Data was collected from a prospectively enrolled cohort (n=379) of COVID-negative and COVID-positive participants with and without PASC. Primary outcomes, endothelial function (measured by reactive hyperemic index [RHI]), and arterial elasticity (measured by augmentation index standardized at 75 bpm [AI]), were measured using the FDA approved EndoPAT. Patient characteristics, labs, metabolic measures, markers of inflammation, and oxidized LDL (ox-LDL) were collected at each study visit, and PASC symptoms were categorized into 3 non-exclusive phenotypes: cardiopulmonary, neurocognitive, and general. COVID-negative controls were propensity score matched to COVID-negative-infected cases using the greedy nearest neighbor method.

Results: There were 14.3% of participants who were fully recovered COVID positive and 28.5% who were COVID positive with PASC, averaging 8.64 ± 6.26 total number of symptoms. The mean RHI was similar across the cohort and having COVID or PASC was not associated with endothelial function (P=0.33). Age (P<0.0001), female sex (P<0.0001), and CRP P=0.04) were positively associated with arterial stiffness, and COVID positive PASC positive with neurological and/or cardiopulmonary phenotypes had the worst arterial elasticity (highest AI). Values for AI (P=0.002) and ox-LDL (P<0.0001) were independently and positively associated with an increased likelihood of having PASC.

Conclusion: There is evidence of an independent association between PASC, ox-LDL, and arterial stiffness with neurological and/or cardiopulmonary phenotypes having the worst arterial elasticity. Future studies should continue investigating the role of oxidative stress in the pathophysiology of PASC.

Source: Zisis SN, Durieux JC, Mouchati C, Funderburg N, Ailstock K, Chong M, Labbato D, McComsey GA. Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2. Pathog Immun. 2023 Dec 20;8(2):1-15. doi: 10.20411/pai.v8i2.634. PMID: 38156116; PMCID: PMC10753933. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10753933/ (Full text)

Changes in the Allostatic Response to Whole-Body Cryotherapy and Static-Stretching Exercises in Chronic Fatigue Syndrome Patients vs. Healthy Individuals

Abstract:

This study represents a comparison of the functional interrelation of fatigue and cognitive, cardiovascular and autonomic nervous systems in a group of Chronic Fatigue Syndrome (CFS) patients compared with those in healthy individuals at different stages of analysis: at baseline and after changes induced by whole-body cryotherapy (WBC) combined with a static-stretching (SS) program. The study included 32 patients (Fukuda criteria) and 18 healthy controls. Fatigue, cognitive, cardiovascular and autonomic function and arterial stiffness were measured before and after 10 sessions of WBC with SS.

In the patients, a disturbance in homeostasis was observed. The network relationship based on differences before and after intervention showed comparatively higher stress and eccentricity in the CFS group: 50.9 ± 56.1 vs. 6.35 ± 8.72, p = 0.002, r = 0.28; and 4.8 ± 0.7 vs. 2.4 ± 1, p < 0.001, r = 0.46, respectively.

Before and after intervention, in the CFS group increased fatigue was related to baroreceptor function, and baroreceptor function was in turn related to aortic stiffness, but no such relationships were observed in the control group. Differences in the network structure underlying the interrelation among the four measured criteria were observed in both groups, before the intervention and after ten sessions of whole cryotherapy with a static stretching exercise.

Source: Kujawski S, Bach AM, Słomko J, Pheby DFH, Murovska M, Newton JL, Zalewski P. Changes in the Allostatic Response to Whole-Body Cryotherapy and Static-Stretching Exercises in Chronic Fatigue Syndrome Patients vs. Healthy Individuals. J Clin Med. 2021 Jun 25;10(13):2795. doi: 10.3390/jcm10132795. PMID: 34202023. https://pubmed.ncbi.nlm.nih.gov/34202023/

Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study

Abstract:

Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide.

Methods: This substudy to the open-label phase II trial “Cyclophosphamide in ME/CFS” included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18-65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30).

Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5-13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7-21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343-4,334) vs. healthy individuals 1,886 p.u. (range 808-8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls.

Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.

Source: Sørland K, Sandvik MK, Rekeland IG, Ribu L, Småstuen MC, Mella O, Fluge Ø. Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study. Front Med (Lausanne). 2021 Mar 22;8:642710. doi: 10.3389/fmed.2021.642710. PMID: 33829023; PMCID: PMC8019750. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019750/ (Full text)

Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Evidence is emerging that individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may suffer from chronic vascular dysfunction as a result of illness-related oxidative stress and vascular inflammation. The study aimed to examine the impact of maximal-intensity aerobic exercise on vascular function 48 and 72 h into recovery.

Methods: ME/CFS (n = 11) with gender and age-matched controls (n = 11) were randomly assigned to either a 48 h or 72 h protocol. Each participant had measures of brachial blood pressure, augmentation index (AIx75, standardized to 75 bpm) and carotid-radial pulse wave velocity (crPWV) taken. This was followed by a maximal incremental cycle exercise test. Resting measures were repeated 48 or 72 h later (depending on group allocation).

Results: No significant differences were found when ME/CFS were directly compared to controls at baseline. During recovery, the 48 h control group experienced a significant 7.2% reduction in AIx75 from baseline measures (p < 0.05), while the matched ME/CFS experienced no change in AIx75. The 72 h ME/CFS group experienced a non-significant increase of 1.4% from baseline measures. The 48 h and 72 h ME/CFS groups both experienced non-significant improvements in crPWV (0.56 ms−1 and 1.55 ms−1, respectively).

Conclusions: The findings suggest that those with ME/CFS may not experience exercise-induced vasodilation due to chronic vascular damage, which may be a contributor to the onset of post-exertional malaise (PEM).

Source: Bond J, Nielsen T, Hodges L. Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. International Journal of Environmental Research and Public Health. 2021; 18(5):2366. https://doi.org/10.3390/ijerph18052366 https://www.mdpi.com/1660-4601/18/5/2366/htm (Full text)

Autonomic Phenotypes in Chronic Fatigue Syndrome (CFS) Are Associated with Illness Severity: A Cluster Analysis

Abstract:

In this study we set out to define the characteristics of autonomic subgroups of patients with Chronic Fatigue Syndrome (CFS). The study included 131 patients with CFS (Fukuda criteria). Participants completed the following screening symptom assessment tools: Chalder Fatigue Scale, Fatigue Impact Scale, Fatigue Severity Scale, Epworth Sleepiness Scales, the self-reported Composite Autonomic Symptom Scale. Autonomic parameters were measured at rest with a Task Force Monitor (CNS Systems) and arterial stiffness using an Arteriograph (TensioMed Kft.).

Principal axis factor analysis yielded four factors: fatigue, subjective and objective autonomic dysfunction and arterial stiffness. Using cluster analyses, these factors were grouped in four autonomic profiles: 34% of patients had sympathetic symptoms with dysautonomia, 5% sympathetic alone, 21% parasympathetic and 40% had issues with sympathovagal balance.

Those with a sympathetic-dysautonomia phenotype were associated with more severe disease, reported greater subjective autonomic symptoms with sympathetic over-modulation and had the lowest quality of life. The highest quality of life was observed in the balance subtype where subjects were the youngest, had lower levels of fatigue and the lowest values for arterial stiffness. Future studies will aim to design autonomic profile-specific treatment interventions to determine links between autonomic phenotypes CFS and a specific treatment.

Source: Słomko J, Estévez-López F, Kujawski S, et al. Autonomic Phenotypes in Chronic Fatigue Syndrome (CFS) Are Associated with Illness Severity: A Cluster Analysis. J Clin Med. 2020;9(8):E2531. Published 2020 Aug 5. doi:10.3390/jcm9082531  https://www.mdpi.com/2077-0383/9/8/2531  (Full text)

Biochemical and vascular aspects of pediatric chronic fatigue syndrome

Abstract:

OBJECTIVE: To evaluate the biochemical and vascular aspects of pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

DESIGN: Cross-sectional clinical study.

SETTING: Tayside, Scotland, United Kingdom.

PARTICIPANTS: Twenty-five children with CFS/ME and 23 healthy children recruited from throughout the United Kingdom.

INTERVENTIONS: Participants underwent a full clinical examination to establish a diagnosis of CFS/ME and were asked to describe and score their CFS/ME symptoms. Biochemical markers were measured. Arterial wave reflection was estimated to assess systemic arterial stiffness.

MAIN OUTCOME MEASURES: Markers of oxidative stress and free radicals, C-reactive protein level, white blood cell apoptosis, and arterial wave reflection.

RESULTS: Children with CFS/ME had increased oxidative stress compared with control individuals (isoprostanes: 252.30 vs 215.60 pg/mL, P = .007; vitamin C, mean [SD]: 0.84 [0.26] vs 1.15 [0.28] mg/dL, P < .001; vitamin E, 8.72 [2.39] vs 10.94 [3.46] microg/mL, P = .01) and increased white blood cell apoptosis (neutrophils: 53.7% vs 35.7%, P = .005; lymphocytes: 40.1% vs 24.6%, P = .009). Arterial stiffness variables did not differ significantly between groups (mean augmentation index, -0.57% vs -0.47%, P = .09); however, the derived variables significantly correlated with total (r = 0.543, P = .02) and low-density lipoprotein (r = 0.631, P = .004) cholesterol in patients with CFS/ME but not in controls.

CONCLUSIONS: Biomedical anomalies seen in adults with CFS/ME-increased oxidative stress and increased white blood cell apoptosis-can also be observed in children with clinically diagnosed CFS/ME compared with matched controls. Unlike in their adult counterparts, however, arterial stiffness remained within the reference range in these pediatric patients.

Comment in: Chronic fatigue syndrome in adolescence: where to from here? [Arch Pediatr Adolesc Med. 2010]

 

Source: Kennedy G, Khan F, Hill A, Underwood C, Belch JJ. Biochemical and vascular aspects of pediatric chronic fatigue syndrome. Arch Pediatr Adolesc Med. 2010 Sep;164(9):817-23. doi: 10.1001/archpediatrics.2010.157. https://www.ncbi.nlm.nih.gov/pubmed/20819963

 

Low-grade inflammation and arterial wave reflection in patients with chronic fatigue syndrome

Abstract:

Some of the symptoms reported by people with CFS (chronic fatigue syndrome) are associated with various cardiovascular phenomena. Markers of cardiovascular risk, including inflammation and oxidative stress, have been demonstrated in some patients with CFS, but little is known about the relationship between these and prognostic indicators of cardiovascular risk in this patient group. In the present study, we investigated the relationship between inflammation and oxidative stress and augmentation index, a measure of arterial stiffness, in 41 well-characterized patients with CFS and in 30 healthy subjects.

AIx@75 (augmentation index normalized for a heart rate of 75 beats/min) was significantly greater in patients with CFS than in control subjects (22.5+/-1.7 compared with 13.3+/-2.3% respectively; P=0.002). Patients with CFS also had significantly increased levels of CRP (C-reactive protein) (2.58+/-2.91 compared with 1.07+/-2.16 mug/ml respectively; P<0.01) and 8-iso-prostaglandin F(2alpha) isoprostanes (470.7+/-250.9 compared with 331.1+/-97.6 pg/ml respectively; P<0.005). In patients with CFS, AIx@75 correlated significantly with logCRP (r=0.507, P=0.001), isoprostanes (r=0.366, P=0.026), oxidized LDL (low-density lipoprotein) (r=0.333, P=0.039) and systolic blood pressure (r=0.371, P=0.017). In a stepwise multiple regression model, including systolic and diastolic blood pressure, body mass index, CRP, tumour necrosis factor-alpha, interleukin-1, oxidized LDL, high-density lipoprotein-cholesterol levels, isoprostanes, age and gender, AIx@75 was independently associated with logCRP (beta=0.385, P=0.006), age (beta=0.363, P=0.022) and female gender (beta=0.302, P=0.03) in patients with CFS.

The combination of increased a, inflammation and oxidative stress may result in an increased risk of future cardiovascular events. Assessment of arterial wave reflection might be useful for determining cardiovascular risk in this patient group.

 

Source: Spence VA, Kennedy G, Belch JJ, Hill A, Khan F. Low-grade inflammation and arterial wave reflection in patients with chronic fatigue syndrome. Clin Sci (Lond). 2008 Apr;114(8):561-6. https://www.ncbi.nlm.nih.gov/pubmed/18031285

 

Evaluation of fatigue by using acceleration plethysmography

Abstract:

We evaluated the fatigue of patients with chronic fatigue syndrome by using acceleration plethysmography. The changes in the acceleration plethysmography were relatively dominant in the sympathetic nervous system from the viewpoint of the autonomic nervous system, and the fluctuation in the time-series data of the acceleration plethysmography was decreased from the viewpoint of chaos or complexity system. We found the relation between the level of fatigue and the changes in acceleration plethysmography. Therefore, the acceleration plethysmography might be useful for the evaluation of fatigue.

 

Source: Yamaguti K. Evaluation of fatigue by using acceleration plethysmography. Nihon Rinsho. 2007 Jun;65(6):1034-42. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561694

 

Is chronic fatigue syndrome a connective tissue disorder? A cross-sectional study in adolescents

Abstract:

OBJECTIVES: To investigate whether constitutional laxity of the connective tissues is more frequently present in adolescents with chronic fatigue syndrome (CFS) than in healthy controls. Increased joint hypermobility in patients with CFS has been previously described, as has lower blood pressure in fatigued individuals, which raises the question of whether constitutional laxity is a possible biological predisposing factor for CFS.

DESIGN: Cross-sectional study.

PARTICIPANTS: Thirty-two adolescents with CFS (according to the criteria of the Centers for Disease Control and Prevention) referred to a tertiary hospital and 167 healthy controls.

METHODS: The 32 adolescents with CFS were examined extensively regarding collagen-related parameters: joint mobility, blood pressure, arterial stiffness and arterial wall thickness, skin extensibility, and degradation products of collagen metabolism. Possible confounding factors (age, gender, height, weight, physical activity, muscle strength, diet, alcohol consumption, and cigarette smoking) were also measured. The results were compared with findings in 167 healthy adolescents who underwent the same examinations.

RESULTS: Joint mobility, Beighton score, and collagen biochemistry, all indicators of connective tissue abnormality, were equal for both groups. Systolic blood pressure, however, was remarkably lower in patients with CFS (117.3 vs. 129.7 mm Hg; adjusted difference: -13.5 mm Hg; 95% confidence interval [CI]: -19.1, -7.0). Skin extensibility was higher in adolescents with CFS (mean z score: 0.5 vs. 0.1 SD; adjusted difference: 0.3 SD; 95% CI: 0.1, 0.5). Arterial stiffness, expressed as common carotid distension, was lower in adolescents with CFS, indicating stiffer arteries (670 vs 820 mum; adjusted difference: -110 mum; 95% CI: -220, -10). All analyses were adjusted for age, gender, body mass index, and physical activity. Additionally, arterial stiffness was adjusted for lumen diameter and pulse pressure.

CONCLUSIONS: These findings do not consistently point in the same direction of an abnormality in connective tissue. Patients with CFS did have lower blood pressure and more extensible skin but lacked the most important parameter indicating constitutional laxity, ie, joint hypermobility. Moreover, the collagen metabolism measured by crosslinks and hydroxyproline in urine, mainly reflecting bone resorption, was not different. The unexpected finding of stiffer arteries in patients with CFS warrants additional investigation.

 

Source: van de Putte EM, Uiterwaal CS, Bots ML, Kuis W, Kimpen JL, Engelbert RH. Is chronic fatigue syndrome a connective tissue disorder? A cross-sectional study in adolescents. Pediatrics. 2005 Apr;115(4):e415-22. http://www.ncbi.nlm.nih.gov/pubmed/15805343