Article

Impaired aerobic exercise capacity and cardiac autonomic control in primary antiphospholipid syndrome

If you want to read the PDF, try requesting it from the authors.

Abstract

Primary antiphospholipid syndrome (PAPS) is associated with increased risk of cardiovascular disease and mortality. Aerobic capacity and cardiac autonomic control are also associated with these risks. The aim of our study was to assess aerobic capacity and cardiac autonomic control in PAPS patients. Thirteen women with PAPS and 13 healthy controls matched for age, gender, and body mass index were enrolled for the study. Both groups were sedentary and were not under chronotropic, antidepressants and hypolipemiant drugs. All subjects performed a treadmill-graded maximal exercise. Aerobic capacity was assessed by peak oxygen uptake (VO2peak), time at anaerobic ventilatory threshold (VAT) and respiratory compensation point (RCP) and time-to-exhaustion, whereas cardiac autonomic control was assessed by chronotropic reserve (CR) and heart rate recovery at the first and second minutes after graded exercise (HRR1min and HRR2min, respectively). All aerobic capacity indexes were reduced more in PAPS patients than in healthy subjects: VO2peak (30.2 ± 4.7 vs 34.6 ± 4.3 ml.kg(-1).min(-1), p = 0.021), time at VAT (3.0 ± 1.5 vs 5.0 ± 2.0 min, p = 0.016), time at RCP (6.5 ± 2.0 vs 8.0 ± 2.0 min, p = 0.050), time-to-exhaustion (8.5 ± 2.0 vs 11.0 ± 2.5 min, p = 0.010). HRR1min (22 ± 9 vs 30 ± 7 bpm, p = 0.032) and HRR2min (33 ± 9 vs 46 ± 8 bpm, p = 0.002) were delayed in PAPS patients compared to healthy controls but CR was not significantly different (p = 0.272). In conclusion, an impaired aerobic capacity and cardiac autonomic control was identified in PAPS.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Although different in nature, most of the rheumatic diseases share a number of common clinical features, including hypoactivity, fatigue, muscle weakness, disability, and poor aerobic conditioning [1][2][3][4][5][6][7][8][9][10][11][12]. The accurate assessment of physical capacity parameters has been considered increasingly important to determine the impact of the disease or its treatment upon overall physical conditioning as well as to comprehensively evaluate the outcomes of clinical interventions in rheumatic diseases (e.g., exercise training and drug therapy) both in research and clinical setting. ...
... Physical functioning tests included timed-stands test (n = 895) and timed-up-and-go test (n = 896). SLE, systemic lupus erythematosus; PAPS, primary antiphospholipid antibody syndrome; cardiac disturbance, chest pain typical of angina induced or increased by exercise (n = 1; myositis); systolic blood pressure of more than 250 mmHg or diastolic of more than 120 mmHg (osteopenia/osteoporosis; n = 2); physical limitations, previous injury, weakness and/or insufficient range of motion; URTI, upper respiratory tract infection [26], and poor aerobic conditioning and exercise tolerance [9,24,25,[27][28][29][30][31]. Finally, maximal cardiopulmonary exercise tests have been shown to be effective in detecting exercise-induced changes in aerobic capacity in a number of rheumatic diseases [3,24,29,[32][33][34][35][36][37]. ...
Article
Full-text available
The purpose of the study was to report on the safety and feasibility of the application of maximal physical tests in a heterogeneous cohort of rheumatic patients. This is a 5-year retrospective descriptive report on the incidence of events associated with maximal physical testing from 536 patients, totalizing 5,910 tests. Tests were classified as cardiopulmonary, muscle strength, and physical functioning tests. Any adverse events during the tests and limiting factors incurring in tests cancellation were reported. Eighteen out of 641 cardiopulmonary exercise tests had an adverse occurrence, with cardiac disturbance (1.4 % of total tests) being the most prevalent. Moreover, 14 out of 641 tests were not feasible. Out of 3,478 tests comprising leg press, bench press, knee extension, and handgrip tests, 15 tests had an adverse event. The most common occurrence was joint pain (0.4 % of total tests), which was also the most frequent factor precluding testing (0.5 % of total tests). Forty-five out of 3,478 (1.3 %) of the tests were not feasible. There was a very low incidence of events (0.2 %) during the physical functioning tests. Joint pain was the only adverse event during the tests, whereas physical limitations were the most important barriers for the execution of the tests (1.1 % of total tests). The incidence of limiting events in this test was 1.6 % (n = 29). This report brings new data on the safety and feasibility of maximal physical testing in rheumatic patients. The physical tests described in this study may be applied for testing rheumatic patients both in research and clinical setting.
... Similar to the association with certain autoimmune diseases [8,9], autonomic dysfunction has been also reported to occur in the setting of APS [10][11][12]. By definition, autonomic disorders could be primary or secondary to chronic etiologies or acute trauma [13]. ...
Article
As part of the non-criteria clinical manifestations, postural orthostatic tachycardia syndrome (POTS), a multisystem autonomic dysfunction, can co-exist with antiphospholipid syndrome (APS). Several pieces of evidence hint on the autoimmune basis of POTS, and its possible association with several autoimmune diseases, including APS. Indeed, the evidence exists in the etiologies, symptomatology, and treatment options. Although infections, viral ones in particular, stress, and pregnancy are etiologies to both POTS and APS, the exact pathophysiological connection is still to be studied taking into consideration the activity of cytokines in both diseases. Nevertheless, certain immunomodulatory treatments used for the catastrophic or obstetrical forms of APS, such as intravenous immunoglobulins (IVIG) and steroids, have been also used for the treatment of POTS resistant to classical treatments. Therefore, our review aims to highlight the association between POTS and APS, shedding light on the common etiologies explaining the pathophysiology of the two disorders, the diagnostic approach to POTS as a possible clinical criterion of APS, and the treatment of APS in the context of treating POTS.
... Impaired aerobic capacity and muscle dysfunction are present in several autoimmune rheumatic diseases [11][12][13][14]. However, no study has evaluated these outcomes in patients with RP. ...
Article
Full-text available
Citation: De Oliveira DS, Dos Santos AM, Misse RG, De Souza JM, Shinjo SK, et al. (2020) Evaluation of aerobic capacity and muscle function in a case series of patients with relapsing polychondritis. Rheumatica Acta: Open Access 4(1): 007-010. Introduction Relapsing Polychondritis (RP) is a rare systemic immune-mediated disease characterized by recurrent episodes of infl ammation of cartilaginous and proteoglycan-rich tissues, resulting in progressive anatomical deformation and functional impairment of the involved structures [1]. Typical features include recurrent episodes of nasal and auricular chondritis, ocular infl ammation, and tracheobronchial tree involvement [2-5], which have high proteoglycan-rich structures [3]. The annual incidence of RP is 3.5 cases per million, and the disease affects predominantly female and white individuals [2-Abstract Background: To evaluate aerobic capacity and muscle function in patients with Relapsing Polychondritis (RP).
... Labile hypertension without associated renal disease was mentioned in early reports [4], but the first formal association of APS with dysfunction of the autonomic nervous system came in 1999 when Tsutsumi et al. reported reflex sympathetic dystrophy (now known as complex regional pain syndrome) in a patient with APS [5]. In 2012, Bilora et al. demonstrated abnormal autonomic function testing in APS patients without any other autoimmune or cardiovascular disease [6] and in 2013, Garcia et al. reported impaired cardiac autonomic control as well as impaired aerobic exercise capacity in APS patients [7]. In 2014, the association of a number of autonomic disorders in APS was reported, including postural Jill R. Schofield tachycardia syndrome, neurocardiogenic syncope, orthostatic hypotension, inappropriate sinus tachycardia, and complex regional pain syndrome [8]. ...
Article
Full-text available
Autonomic disorders have previously been described in association with the antiphospholipid syndrome. The present study aimed to determine the clinical phenotype of patients in whom autonomic dysfunction was the initial manifestation of the antiphospholipid syndrome and to evaluate for autonomic neuropathy in these patients. This was a retrospective study of 22 patients evaluated at the University of Colorado who were found to have a disorder of the autonomic nervous system as the initial manifestation of antiphospholipid syndrome. All patients had persistent antiphospholipid antibody positivity and all patients who underwent skin biopsy were found to have reduced sweat gland nerve fiber density suggestive of an autonomic neuropathy. All patients underwent an extensive evaluation to rule out other causes for their autonomic dysfunction. Patients presented with multiple different autonomic disorders, including postural tachycardia syndrome, gastrointestinal dysmotility, and complex regional pain syndrome. Despite most having low-titer IgM antiphospholipid antibodies, 13 of the 22 patients (59%) suffered one or more thrombotic event, but pregnancy morbidity was minimal. Prothrombin-associated antibodies were helpful in confirming the diagnosis of antiphospholipid syndrome. We conclude that autonomic neuropathy may occur in association with antiphospholipid antibodies and may be the initial manifestation of the syndrome. Increased awareness of this association is important, because it is associated with a significant thrombotic risk and a high degree of disability. In addition, anecdotal experience has suggested that antithrombotic therapy and intravenous immunoglobulin therapy may result in significant clinical improvement in these patients.
Article
A síndrome do anticorpo antifosfolípide (SAF) é uma doença autoimune caracterizada pela presença do anticorpo antifosfolípide (aPL) associada à trombose e/ou morbidade gestacional. O tratamento da síndrome, na presença de um evento trombótico, consiste na anticoagulação com antagonista de vitamina K (varfarina), sendo seu monitoramento necessário para que se evitem complicações como sangramento e novos eventos trombóticos. A checagem das interações medicamentosas e dietéticas minimiza os riscos do tratamento. O controle dos fatores de risco por meio de hábitos saudáveis é meta importante no tratamento, a fim de obter melhora na qualidade de vida bem como aumento de sobrevida do paciente. Unitermos: Dicas para pacientes. Dieta na síndrome do anticorpo antifosfolípide. Hábitos de vida. Interações. Varfarina.
Article
Systemic lupus erythematosus is a chronic, progressive, autoimmune disease that causes significant stress on patients. There is no specific instrument for assessing stress in Chinese systemic lupus erythematosus patients. The objective of this study was to test the reliability and validity of the 10-item Perceived Stress Scale in Chinese systemic lupus erythematosus patients. Validity evaluation included structural and construct validity (convergent and discriminant validity). Structural validity was assessed by exploratory factor analysis. Convergent validity was assessed by correlating the total score of the 10-item Perceived Stress Scale with the Patient Health Questionnaire-9, Self-Efficacy for Managing Chronic Disease 6-Item Scale, the Simplified Coping Style Questionnaire, and the Systemic Lupus Erythematosus Disease Activity Index. Discriminant validity was determined by the statistically significant differences in perceived stress scores among patients with different education levels and disease activity. Reliability was assessed by internal consistency and test-retest reliability. The test-retest reliability was measured at 1-week intervals. Exploratory factor analysis extracted two dimensions that explained 66.45% of the variation. Moderate-to-strong correlations were also found between the 10-item Perceived Stress Scale and the Patient Health Questionnaire-9, Self-Efficacy for Managing Chronic Disease 6-Item Scale, the Simplified Coping Style Questionnaire, and Systemic Lupus Erythematosus Disease Activity Index. Excellent test-retest reliability (intraclass correlation coefficient = 0.954) and internal consistency (Cronbach's alpha = 0.810) were demonstrated. In conclusion, the 10-item Perceived Stress Scale can be used to measure stress among Chinese systemic lupus erythematosus patients and serve as a basis for further research.
Conference Paper
Full-text available
Background Physical inactivity is a recognised major public health challenge. Antiphospholipid syndrome (APS) is associated with increased risk of cardiovascular morbidity and mortality.1 Physical activity levels of people with chronic illnesses are lower than those in the general adult population but there is currently no data on exercise participation in people with APS. Objectives To evaluate self-reported exercise participation in a cohort of adults with APS and associations with exercise self-efficacy and illness perception. Methods Two hundred and sixty-eight individuals with APS participated in the cross-sectional online survey (85% female, mean age 47±11 years, 59% primary APS). Frequency of exercise of at least 30 minutes with shortness of breath and sweating was self-reported. A regular exerciser was defined as exercise participation 1-2 times per week or more.2,3 Patient reported outcomes included the Brief Illness Perception Questionnaire (B-IPQ), Chronic Disease Self-Efficacy Exercise Scale, SF-36, American College of Rheumatology Patient Activity Level Assessment and questions relating to motivation and confidence in exercise participation. Bivariate correlation analysis was used to determine relationships between variables. Multiple regression analysis was conducted to identify factors associated with exercise participation. Results Regular exercise (≥1-2 times weekly) was reported by 143 (53.4%) patients while 47 (17.5%) of patients were inactive due to reduced function and APS. There was no significant difference in female:male ratio or age between regular exercisers and irregular/non-exercisers. Irregular/non-exercisers (37.2%) had significantly lower levels of exercise self-efficacy (p≤0.001); lower scores for SF36 physical function, role physical, bodily pain and social function (p≤0.001); and higher scores for B-IPQ consequences and identity (p≤0.01) compared to regular exercisers. Individuals who had a greater perceived influence of APS upon their life and who had a greater experience of severe symptoms as a result of APS were more likely to be irregular or non-exercisers. The linear regression analyses showed that exercise self-efficacy was the factor most associated with being a regular exerciser. Further, the SF36 physical function subscale and “confidence in maintaining an active lifestyle” were the two factors most associated with a higher level of exercise self-efficacy. Conclusions Physical activity is important in the management of cardiovascular morbidity and mortality in people with APS. Over a third of APS patients in this study were not regular exercisers. Perception of illness and exercise self-efficacy were shown to be key factors associated with participation in regular exercise. There is potential to develop interventions to enhance exercise self-efficacy and change illness perceptions that may increase exercise participation for people with APS. References Acknowledgements The Hughes Syndrome Foundation and the individuals who participated in the study. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1451
Article
Background Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder that has been shown to cause a large number of cardiac and neurological manifestations. Two recent studies have demonstrated abnormalities in cardiovascular autonomic function testing in APS patients without other cardiovascular or autoimmune disease. However, an association between autonomic disorders such as postural tachycardia syndrome and APS has not previously been described.Methods and resultsData were obtained by retrospective chart review. We identified 15 patients who have been diagnosed with APS and an autonomic disorder. The median age of the patients at the time of data analysis was 39 years. The autonomic disorders seen in these patients included postural tachycardia syndrome, neurocardiogenic syncope and orthostatic hypotension. The majority of patients (14/15) were female and the majority (14/15) had non-thrombotic neurological manifestations of APS, most commonly migraine, memory loss and balance disorder. Many also had livedo reticularis (11/15) and Raynaud's phenomenon (nine of 15). In some patients, the autonomic manifestations improved with anticoagulation and/or anti-platelet therapy; in others they did not. Two patients with postural tachycardia syndrome who failed to improve with the usual treatment of APS have been treated with intravenous immunoglobulin with significant improvement in their autonomic symptoms.Conclusion We believe that autonomic disorders in APS may represent an important clinical association with significant implications for treatment.
Article
Full-text available
the correlation between primary antiphospholipid syndrome (APS) and cardiovascular events is well known, but the correlation between APS and sudden death is not clear; it probably correlates with sympathetic alterations of the autonomic system. To compare the autonomic nervous system (ANS) in a group of subjects suffering from APS against that of a control group with no cardiovascular risk factors, matched for age, sex, and body mass index. An equal number (n = 31) of subjects with APS, and healthy controls, underwent autonomic evaluation: tilt test, deep breath, Valsalva maneuver, hand grip, lying-to-standing, Stroop, and sweat tests. Cases in the APS group were positive for the tilt test, relating to changes in respiratory rate intervals, by comparison with controls. Results of other tests were also altered significantly in APS cases, by comparison with controls. (The sweat and Stroop tests were only performed in 14 cases). Autonomic disease did not correlate with age, sex, history of disease, arterial or venous thrombosis, or antibody positivity; only their coagulation parameters correlated with autonomic dysfunction. Autonomic dysfunction in APS seems to correlate with coagulation parameters. APS patients should receive autonomic evaluation, to minimize the risks of fatal arrhythmias and sudden death.
Article
Full-text available
We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI). Fourteen women with FM (age: 46 ± 3 years; body mass index (BMI): 26.6 ± 1.4 kg/m2) and 14 gender-, BMI- (25.4 ± 1.3 kg/m2), and age-matched (age: 41 ± 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test. FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 ± 1 versus CTRL: 32 ± 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 ± 5 versus CTRL: 106.1 ± 6, P < 0.001), deltaHRR1 (24.5 ± 3 versus CTRL: 32.6 ± 2, P = 0.059) and deltaHRR2 (34.3 ± 4 versus CTRL: 50.8 ± 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM. Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality.
Article
Full-text available
The aim of this study was to evaluate heart rate variability (HRV) and heart rate recovery (HRR) in otherwise healthy ankylosing spondylitis (AS) patients and control subjects. A total of 28 patients with AS and 30 volunteers matched for age and sex were enrolled. All subjects underwent HRV analysis, exercise testing (ET), and transthoracic echocardiography. HRR indices were calculated by subtracting first, second, and third minute heart rates (HR) from the maximal HR. The AS and control groups were similar with respect to age (28.7 ± 5.7 vs. 29.3 ± 5.8 years), gender distribution [(male/female) 24/4 vs. 26/4], and left ventricular ejection fraction (LVEF) (63.8 ± 2.8% vs. 65.7 ± 3.6%). Mean HRR1 (24.8 ± 4.2 vs. 28.8 ± 5.5, P = 0.001) and HRR2 (42.0 ± 4.4 vs. 48.0 ± 6.3, P = 0.001) values were significantly higher in control group. SDNN, SDANN, RMSDD, and PNN50 significantly decreased; LF and LF/HF increased in AS patients compared with control subjects. Patients with AS has lower HRR and HRV indices with respect to normal subjects. Cardiac autonomic functions might be involved in AS patients even in patients without cardiac symptoms.
Article
Full-text available
The presence of antiphospholipid antibodies has been shown to be related to an increased risk of thrombotic events. In patients with definite antiphospholipid syndrome (APS), that is, those who have had thrombosis and at least two positive determinations of antiphospholipid antibodies, secondary thromboprophylaxis with long-term anticoagulation therapy results in a low rate of recurrent thrombotic events, ranging from 0.016 to 0.031 events per patient per year. Thrombotic complications are, however, the most common cause of death in APS. The mortality rate in a large European cohort of patients with APS during a 5-year study period was 5.3%, and up to 40% of the deaths in this cohort were attributed to severe thrombotic events such as myocardial infarction, stroke and pulmonary embolism. Catastrophic APS is an unusual form of the disease, being observed in less than 1% of reported cases of APS, which is associated with a much higher mortality rate than classical APS. The combined use of anticoagulation, corticosteroids, plasma exchange and intravenous immunoglobulin therapy could result in a dramatic reduction in mortality, by approximately 20%, in patients with catastrophic APS.
Article
Full-text available
The increase in heart rate that accompanies exercise is due in part to a reduction in vagal tone. Recovery of the heart rate immediately after exercise is a function of vagal reactivation. Because a generalized decrease in vagal activity is known to be a risk factor for death, we hypothesized that a delayed fall in the heart rate after exercise might be an important prognostic marker. For six years we followed 2428 consecutive adults (mean [+/-SD] age, 57+/-12 years; 63 percent men) without a history of heart failure or coronary revascularization and without pacemakers. The patients were undergoing symptom-limited exercise testing and single-photon-emission computed tomography with thallium scintigraphy for diagnostic purposes. The value for the recovery of heart rate was defined as the decrease in the heart rate from peak exercise to one minute after the cessation of exercise. An abnormal value for the recovery of heart rate was defined as a reduction of 12 beats per minute or less from the heart rate at peak exercise. There were 213 deaths from all causes. A total of 639 patients (26 percent) had abnormal values for heart-rate recovery. In univariate analyses, a low value for the recovery of heart rate was strongly predictive of death (relative risk, 4.0; 95 percent confidence interval, 3.0 to 5.2; P<0.001). After adjustments were made for age, sex, the use or nonuse of medications, the presence or absence of myocardial perfusion defects on thallium scintigraphy, standard cardiac risk factors, the resting heart rate, the change in heart rate during exercise, and workload achieved, a low value for heart-rate recovery remained predictive of death (adjusted relative risk, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001). A delayed decrease in the heart rate during the first minute after graded exercise, which may be a reflection of decreased vagal activity, is a powerful predictor of overall mortality, independent of workload, the presence or absence of myocardial perfusion defects, and changes in heart rate during exercise.
Article
Full-text available
New clinical, laboratory and experimental insights, since the 1999 publication of the Sapporo preliminary classification criteria for antiphospholipid syndrome (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh International Congress on antiphospholipid antibodies. In this document, we appraise the existing evidence on clinical and laboratory features of APS addressed during the forum. Based on this, we propose amendments to the Sapporo criteria. We also provide definitions on features of APS that were not included in the updated criteria.
Article
Full-text available
Fibromyalgia (FM) is a non-inflammatory rheumatologic disorder characterized by musculoskeletal pain, fatigue, depression, cognitive dysfunction and sleep disturbance. Research suggests that autonomic dysfunction may account for some of the symptomatology of FM. An open label trial of biofeedback training was conducted to manipulate suboptimal heart rate variability (HRV), a key marker of autonomic dysfunction. Twelve women ages 18-60 with FM completed 10 weekly sessions of HRV biofeedback. They were taught to breathe at their resonant frequency (RF) and asked to practice twice daily. At sessions 1, 10 and 3-month follow-up, physiological and questionnaire data were collected. There were clinically significant decreases in depression and pain and improvement in functioning from Session 1 to a 3-month follow-up. For depression, the improvement occurred by Session 10. HRV and blood pressure variability (BPV) increased during biofeedback tasks. HRV increased from Sessions 1-10, while BPV decreased from Session 1 to the 3 month follow-up. These data suggest that HRV biofeedback may be a useful treatment for FM, perhaps mediated by autonomic changes. While HRV effects were immediate, blood pressure, baroreflex, and therapeutic effects were delayed. This is consistent with data on the relationship among stress, HPA axis activity, and brain function.
Article
Objective. —To quantify the relation of cardiorespiratory fitness to cardiovascular disease (CVD) mortality and to all-cause mortality within strata of other personal characteristics that predispose to early mortality.
Article
To determine if there is a difference between autonomic cardiac control as measured by heart rate variability (HRV) in women with rheumatoid arthritis (RA) compared to a healthy control group. The RA group (45) and control group (39) were matched for age and body mass index (BMI). Three techniques were used: time domain, frequency domain and Poincarè plot analysis. All possible confounding factors were excluded and the test environment strictly regulated. Basal heart rate was significantly higher in the RA patients. In the supine position significant differences existed between RA patients and controls (P ≤ 0.01). Indicators of parasympathetic activity showed significantly lower variation in the RA group (root mean square of the standard deviation [RMSSD] = 14.70, percentage of successive normal-to-normal interval differences larger than 50 ms [pNN50] = 0.50, standard deviation [SD]1 = 10.50, high frequency [HF] (ms(2)) = 31) compared to controls (RMSSD = 29.40, pNN50 = 7.8, SD1 = 20.9, HF (ms(2)) = 141.00). Indicators of sympathetic variation were also significantly lower in RA patients (SD2 = 36.70, low frequency [LF] (ms(2)) = 65) compared to controls (SD2 = 49.50, LF (ms(2)) = 175). In the standing position eight variables indicated autonomic impairment by significant differences (P ≤ 0.01) between the groups. The response of the RA group to an orthostatic stressor showed less vagal withdrawal, (P-values for RMSSD = 0.038, pNN50 = 0.022, SD1 = 0.043 and HF [ms(2) ] = 0.008 respectively); and lower sympathetic response (P-values for SD2 = 0.001 and LF [ms(2) ] < 0.001) when compared to controls. An inability of the autonomic nervous system to efficiently compensate for internal and external environmental changes may predispose RA patients to arrhythmias, thereby increasing cardiovascular mortality. All three methods used showed the same outcome, implying decreased HRV and thus an increased risk for arrhythmias in RA patients. Evaluating the autonomic nervous system might be critical in planning management of RA patients.
Article
Although considerable epidemiologic and clinical evidence suggests that structured exercise, increased lifestyle activity, or both are cardioprotective, the absolute and relative risk of cardiovascular and musculoskeletal complications appear to increase transiently during vigorous physical activity. The estimated relative risk of exercise-related cardiac events ranges from 2.1 to 56 and is highest among habitually sedentary individuals with underlying cardiovascular disease who were performing unaccustomed vigorous physical exertion. Moreover, an estimated 7 million Americans receive medical attention for sports and recreation-related injuries each year. These risks, and their modulators, should be considered when endorsing strenuous leisure time or exercise interventions. If the current mantra "exercise is medicine" is embraced, underdosing and overdosing are possible. Thus, exercise may have a typical dose-response curve with a plateau in benefit or even adverse effects, in some individuals, at more extreme levels.
Article
Chronic inflammation is a common feature shared by several autoimmune rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis, and ankylosing spondylitis. Therefore, blocking or reducing inflammation is one of the major treatment strategies in these diseases. In this context, exercise training has emerged as a potential therapeutic tool in counteracting systemic inflammation, thereby leading to better clinical outcomes. The aims of this review are i) to provide a summary of the clinical effects of exercise training in selected autoimmune rheumatic diseases; and ii) to discuss the potential anti-inflammatory role of exercise training in autoimmune rheumatic diseases, stressing the gaps in literature and the clinical and scientific perspectives in the field.
Article
Patients with rheumatoid arthritis (RA) show lower cardiorespiratory fitness than normal subjects. This study was planned to investigate the pulmonary function tests (PFT), respiratory muscle strength and endurance, and aerobic capacity of patients with RA, as well as the relationship of these parameters to clinical and functional status. Twenty-five RA patients aged 25–71 (48.52 ± 14.09) and 21 control subjects aged 25–66 (45.67 ± 13.27) participated in the study. PFT, maximum volunteer ventilation, maximum inspiratory and maximum expiratory pressures and cardiorespiratory exercise tests were carried out in all subjects to evaluate the respiratory involvement, inspiratory and expiratory muscle strength and endurance, and aerobic capacity. Patients’ duration of disease, smoking and alcohol habits, duration of morning stiffness, visual analogue scale scores, ARA functional classifications and Ritchie articular indexes were recorded. All the patients and control subjects were non-exercising individuals. As a result, we found that RA patients have normal PFT but reduced respiratory muscle strength and endurance, and also reduced aerobic capacity compared to controls. According to this result, respiratory and aerobic exercises may be recommended to improve respiratory muscle strength and endurance and aerobic capacity in these patients.
Article
To evaluate the efficacy of a 3-month exercise training program in counteracting the chronotropic incompetence and delayed heart rate recovery in patients with systemic lupus erythematosus (SLE). A 12-week randomized trial was conducted. Twenty-four inactive SLE patients were randomly assigned into 2 groups: trained (T; n = 15, 3-month exercise program) and nontrained (NT; n = 13). A sex-, body mass index-, and age-matched healthy control (C) group (n = 8) also underwent the exercise program. Subjects were assessed at baseline and at 12 weeks after training. Main measurements included the chronotropic reserve (CR) and the heart rate (HR) recovery (ΔHRR) as defined by the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes after the exercise test. Neither the NT SLE patients nor the C group presented any change in the CR or in ΔHRR1 and ΔHRR2 (P > 0.05). The exercise training program was effective in promoting significant increases in CR (P = 0.007, effect size [ES] 1.15) and in ΔHRR1 and ΔHRR2 (P = 0.009, ES 1.12 and P = 0.002, ES 1.11, respectively) in the SLE T group when compared with the NT group. Moreover, the HR response in SLE patients after training achieved parameters comparable to the C group, as evidenced by the analysis of variance and by the Z score analysis (P > 0.05, T versus C). Systemic Lupus Erythematosus Disease Activity Index scores remained stable throughout the study. A 3-month exercise training program was safe and capable of reducing the chronotropic incompetence and the delayed ΔHRR observed in physically inactive SLE patients.
Article
This review gives an overview of the rehabilitation of autoimmune diseases. After general remarks on rehabilitation, the effects of acute and chronic exercises on inflammatory markers are summarized. Most of the available literature deals with rheumatoid arthritis (RA) and multiple sclerosis (MS), and therefore, rehabilitation of these diseases is described in more detail. Exercise is the main component in the rehabilitation of patients with RA and aims at increasing physical capacity, muscle strength, aerobic endurance, cardiovascular fitness and functional abilities, and helps to prevent secondary deconditioning due to reduced activity levels. Since MS causes a wide range of symptoms, the rehabilitation of these patients requires a multidisciplinary approach and encompasses physiotherapy, exercise therapy, hippotherapy, cognitive rehabilitation, psychological therapy, strategies to improve fatigue and coping programs. The ultimate goal of rehabilitation is to enable patients with chronic conditions to reach and maintain their optimal physical, sensory, intellectual, psychological and social functional levels, and to attain independence and self-determination as far as possible.
Article
Abnormal heart-rate (HR) response during or after a graded exercise test has been recognized as a strong and an independent predictor of all-cause mortality in healthy and diseased subjects. The purpose of the present study was to evaluate the HR response during exercise in women with systemic lupus erythematosus (SLE). In this case-control study, 22 women with SLE (age 29.5 ± 1.1 years) were compared with 20 gender-, BMI-, and age-matched healthy subjects (age 26.5 ± 1.4 years). A treadmill cardiorespiratory test was performed and HR response during exercise was evaluated by the chronotropic reserve (CR). HR recovery (ΔHRR) was defined as the difference between HR at peak exercise and at both first (ΔHRR1) and second (ΔHRR2) minutes after exercising. SLE patients presented lower peak VO(2) when compared with healthy subjects (27.6 ± 0.9 vs. 36.7 ± 1.1 ml/kg/min, p = 0.001, respectively). Additionally, SLE patients demonstrated lower CR (71.8 ± 2.4 vs. 98.2 ± 2.6%, p = 0.001), ΔHRR1 (22.1 ± 2.5 vs. 32.4 ± 2.2%, p = 0.004) and ΔHRR2 (39.1 ± 2.9 vs. 50.8 ± 2.5%, p = 0.001) than their healthy peers. In conclusion, SLE patients presented abnormal HR response to exercise, characterized by chronotropic incompetence and delayed ΔHRR.
Article
Chronotropic incompetence (CI), broadly defined as the inability of the heart to increase its rate commensurate with increased activity or demand, is common in patients with cardiovascular disease, produces exercise intolerance which impairs quality-of-life, and is an independent predictor of major adverse cardiovascular events and overall mortality. However, the importance of CI is under-appreciated and CI is often overlooked in clinical practice. This may be due partly due to multiple definitions, the confounding effects of aging, medications, and the need for formal exercise testing for definitive diagnosis. This review discusses the definition, mechanisms, diagnosis, and treatment of CI, with particular emphasis on its prominent role in HF. CI is common, can be diagnosed by objective, widely available, inexpensive methods, is potentially treatable, and its management can lead to significant improvements in exercise tolerance and quality-of-life.
Article
The antiphospholipid syndrome causes venous, arterial, and small-vessel thrombosis; pregnancy loss; and preterm delivery for patients with severe pre-eclampsia or placental insufficiency. Other clinical manifestations are cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, and cognitive impairment. Antiphospholipid antibodies promote activation of endothelial cells, monocytes, and platelets; and overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. Of the different antiphospholipid antibodies, lupus anticoagulant is the strongest predictor of features related to antiphospholipid syndrome. Therapy of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thromboprophylaxis is recommended in patients with systemic lupus erythematosus and probably in purely obstetric antiphospholipid syndrome. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin. Hydroxychloroquine is a potential additional treatment for this syndrome. Possible future therapies for non-pregnant patients with antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs.
Article
Because of the dynamic and complex nature of chronic pain, successful treatment usually requires addressing behavioral, cognitive, and affective processes. Many adjunctive interventions have been implemented in fibromyalgia (FM) treatment, but few are supported by controlled trials. Herein, some of the more commonly used nonpharmacologic interventions for FM are described and the evidence for efficacy is presented. Clinical observations and suggestions are also offered, including using the principles outlined in the acronym ExPRESS to organize a comprehensive nonpharmacologic pain management approach.
Article
Several studies have established that systemic sclerosis patients have a reduced exercise capacity when compared to healthy individuals. It is relevant to evaluate whether aerobic exercise in systemic sclerosis patients is a safe and effective intervention to improve aerobic capacity. Seven patients without pulmonary impairment and seven healthy controls were enrolled in an 8-week program consisting of moderate intensity aerobic exercise. Patients and controls had a significant improvement in peak oxygen consumption (19.72+/-3.51 vs. 22.27+/-2.53 and 22.94+/-4.70 vs. 24.55+/-3.00, respectively, p=0.006), but difference between groups was not statistically significant (p=0.149). This finding was reinforced by the fact that at the end of the study both groups were able to perform a significantly higher exercise intensity when compared to baseline, as measured by peak blood lactate (1.43+/-0.51 vs. 1.84+/-0.33 and 1.11+/-0.45 vs. 1.59+/-0.25, respectively, p=0.01). Patients improved the peak exercise oxygen saturation comparing to the baseline (84.14+/-9.86 vs. 90.29+/-5.09, p=0.048). Rodnan score was similar before and after the intervention (15.84+/-7.84 vs.12.71+/-4.31, p=0.0855). Digital ulcers and Raynaud's phenomenon remained stable. Our data support the notion that improving aerobic capacity is a feasible goal in systemic sclerosis management. The long term benefit of this intervention needs to be determined in large prospective studies.
Article
Heart rate recovery (HRR) is an important indicator of cardiovascular health. The purpose of the present investigation is to examine the influence of sex on the relationship between HRR and other markers of cardiovascular health. Two hundred and seventy-five apparently healthy subjects participated in this study. Subjects underwent cardiopulmonary exercise testing (outcome measures: VO(2max) and HRR 1 and 2 min into recovery), lipid analysis, measurement of resting systolic and diastolic blood pressure and measurement of aortic wave velocity (AWV in m/s) via magnetic resonance. HRR both at 1 min (HRR(1)) and at 2 min (HRR(2)) were higher in males. In general, the correlation between HRR(1) and other measures of interest was weaker than that found with HRR(2) in both male and female subjects. With respect to HRR(2), the relationship with other measures of interest was stronger in the female subgroup. Specific to arterial stiffness, the correlation between HRR(2) and AWV was -0.33 and -0.46 (P<0.001 for both) in male and female subgroups, respectively. The results of the present study indicate that both gender and the timing of HRR measurement influence its relationship with other important cardiovascular risk factors.
Article
Alterations in gas exchange were studied in man during exercise increasing in increments of 5 w each minute, to determine the noninvasive indicators of the onset of metabolic acidosis (anaerobic metabolism). Expired airflow and CO2 and O2 tensions at the mouth during the breath were continuously monitored with rapidly responding gas analyzers. These measurements were recorded directly as well as processed by a minicomputer, on line, to give minute ventilation (VE), CO2 production (VCO2), O2 consumption (VO2), and the gas exchange ratio (R), breath by breath. The anaerobic threshold (AT) could be identified by the point of nonlinear increase in VE, nonlinear increase in VCO2, an increase in end tidal O2 without a corresponding decrease in end tidal CO2, and an increase in R, as work rate was increased during an incremental exercise test. Of these measurements, R was found least sensitive. The AT was determined in 85 normal subjects between 7 and 91 yr of age, by these techniques. The lower limit of normal was 45 w (VO2 = 1 liter/min) while values for very fit normal adults were as high as 180 w. The patients studied with cardiac disease above functional class I have lower anaerobic thresholds than the least fit normal subjects. The 1 min incremental work rate test is associated with changes in gas exchange which can be used as sensitive on line indicators of the AT, thus bypassing the need for measuring arterial lactate or acid base parameters to indicate anaerobiosis.
Article
Resting heart rate is directly associated and maximal exercise-induced heart rate inversely associated with cardiovascular mortality, and therefore their difference might contain prognostic information from both variables. The comparative long-term prognostic values of maximal exercise-induced heart rate and of the difference between it and resting heart rate were studied in apparently healthy middle-aged men. Resting heart rate and maximal exercise-induced heart rate were measured, and their difference calculated, in 1960 apparently healthy men aged 40-59 years, and mortality was recorded over a period of 16 years. Conventional coronary risk factors were assessed at baseline. Both the difference between the two heart rates and the maximal exercise-induced heart rate were strongly, independently and inversely associated with cardiovascular mortality after adjustment for age, smoking, systolic blood pressure, lung function, glucose tolerance, serum cholesterol level, serum triglycerides level, physical fitness and exercise ECG findings. The adjusted relative risk of cardiovascular death in heart-rate difference quartiles 3 and 4 compared with that in quartile 1 (the lowest heart-rate difference quartile) was 0.54 (95% confidence interval 0.33-0.86; P = 0.009). The corresponding value for maximal exercise-induced heart rate was 0.56 (95% confidence interval 0.34-0.89; P = 0.018). Within the lowest heart-rate difference quartile, but not within the lowest maximal exercise-induced heart rate quartile, a further, strong, negative gradient in cardiovascular mortality was observed. In the high working capacity range, low heart-rate difference but not low maximal exercise-induced heart rate predicted very high cardiovascular disease mortality. Heart-rate difference and maximal exercise-induced heart rate were also inversely associated with non-cardiovascular disease mortality. Both heart-rate difference and maximal exercise-induced heart rate were strong, graded, long-term predictors of cardiovascular mortality among apparently healthy middle-aged men, independent of age, physical fitness and conventional coronary risk factors. However, low heart-rate difference was a better predictor than low maximal exercise-induced heart rate for recognizing individuals who were at particularly high risk of dying prematurely from cardiovascular diseases.
Article
Although heart rate variability (HRV) is altered in a variety of pathological conditions, the association of reduced HRV with risk for new cardiac events has not been studied in a large community-based population. The first 2 hours of ambulatory ECG recordings obtained on subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease or congestive heart failure were reprocessed to assess HRV. Five frequency-domain measures and three time-domain measures were obtained. The associations between HRV measures and the incidence of new cardiac events (angina pectroris, myocardial infarction, coronary heart disease death, or congestive heart failure) were assessed with proportional hazards regression analyses. There were 2501 eligible subjects with a mean age of 53 years. During a mean follow-up of 3.5 years, cardiac events occurred in 58 subjects. After adjustment for age, sex, cigarette smoking, diabetes, left ventricular hypertrophy, and other relevant risk factors, all HRV measures except the ratio of low-frequency to high-frequency power were significantly associated with risk for a cardiac event (P = .0016 to .0496). A one-standard deviation decrement in the standard deviation of total normal RR intervals (natural log transformed) was associated with a hazard ratio of 1.47 for new cardiac events (95% confidence interval of 1.16 to 1.86). The estimation of HRV by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional cardiovascular disease risk factors.
Article
Ankylosing spondylitis (AS) has been shown to produce exercise limitation and breathlessness. The purpose of this study was to investigate factors which may be responsible for limiting aerobic capacity in patients with AS. Twenty patients with no other cardio-respiratory disease performed integrative cardiopulmonary exercise testing (CPET). The results were compared to 20 age and gender matched healthy controls. Variables that might influence exercise tolerance, including pulmonary function tests (body plethysmography), respiratory muscle strength (MIP, MEP) and endurance (Tlim), AS severity assessment including chest expansion (CE), thoracolumber movement (TL), wall tragus distance and peripheral muscle strength assessed by maximum voluntary contraction of the knee extensors (Qds), hand grip strength and lean body mass (LBM), were measured in the patients with AS and used as explanatory variables against the peak V̇O2 achieved during CPET. AS subjects achieved a lower peak V̇O2 than controls (25·2 ± 1·4 vs. 33·1 ± 1·6 ml kg⁻¹min⁻¹, mean ± sem, P=0·001). When compared with controls, ventilatory response (V̇E/V̇CO2) in AS was elevated (P=0·01); however gas exchange indices, transcutaneous blood gases and breathing reserve were similar to controls. AS subjects developed a higher HR/V̇O2 response (P<0·01) on exertion but without associated abnormalities in ECG, blood pressure response or anaerobic threshold. The AS group experienced a greater degree of leg fatigue (P<0·01) than controls at peak exercise. Although the breathlessness scores (BS) were comparable to controls at peak exercise, the slopes of the relationship between BS and work rate (WR) [AS 0·054 (0·1), Controls 0·043 (0·06); P<0·05] and BS and % predicted oxygen uptake [AS 0·084 (0·18), Controls 0·045 (0·06); P<0·01] were steeper in the AS subjects. There was weak association between peak V̇O2 and vital capacity (r²% 12·0), MIP (11·8) but no association between Tlim, CE, Wall tragus distance or TL movement. The strongest association with aerobic capacity was between measurements of peripheral muscle strength (Qds; r=0·75; hand grip; r=0·47) accounting for 53% (P<0·001) and 23·5% (P<0·01) of the total variance in peak V̇O2, respectively. The addition of LBM to Qds in the regression model significantly improved the explained variance to 78·3% (P<0·001). This study shows that peripheral muscle function is the most important determinant of exercise intolerance in AS patients suggesting that deconditioning is the main factor in the production of the reduced aerobic capacity.
Article
Exercise tolerance is often reduced in patients with systemic lupus erythematosus (SLE). Mechanisms have been proposed but the underlying causes have not yet been elucidated. The study of pulmonary gas exchange during exercise may be helpful in revealing circulatory, ventilatory, and metabolic abnormalities. We hypothesized that in SLE, exercise aerobic capacity would be reduced due to chronic inactivity and poor muscle energetics. Thirteen women with SLE and low disease activity were studied; 5 age matched subjects served as controls. Clinical examination, chest radiography, electrocardiogram, and pulmonary function test were all normal. Subjects underwent 1 min incremental cycle ergometer exercise to exhaustion. Oxygen uptake (VO2), CO2 output (VCO2), minute ventilation (VE), heart rate (HR), and arterial O2 saturation were monitored. Anaerobic threshold (AT), VO2/HR, deltaVO2/deltaWatt, respiratory rate (RR), Ti/Ttot, VE/VCO2, and breathing reserve (BR) were computed. At rest, patients exhibited high VE, respiratory alkalosis, and a wide alveolar-arterial O2 gradient [(A - a)O2] during 50% O2 breathing. Other indexes of respiratory function were within the normal range. In the 6 patients with SLE where pulmonary artery systolic pressure at Doppler echocardiography was measurable, mean level was in the upper limits of normal. During exercise, maximal aerobic capacity was reduced in all patients (VO2 peak, 1098+/-74 vs. 2150+/-160 ml/min, p<0.01; AT, 36 +/-3 vs. 48+/-3% predicted VO2 max, p<0.05). Ventilation adjusted for the metabolic demand (VE/VCO2 at AT) was increased (31+/-1 vs. 24+/-1; p<0.05). A normal breathing pattern was observed during all tests. No patient stopped exercising because of ventilatory limitation (i.e., they had normal breathing reserve). Reduced muscle aerobic capacity is common in SLE and is most likely because of peripheral muscle deconditioning. Increased ventilatory demand, secondary to diffuse interstitial lung disease, is not a significant contributor to the reduction in exercise tolerance.
Article
The present aim is to investigate the relationships between aerobic capacity and disease activity, organ damage, health-related quality of life (HRQL) and physical activity in 34 women with systemic lupus erythematosus (SLE) with low-to-moderate disease activity and organ damage. Mean age was 51 (SD 10) years, disease duration 17 (SD 11) years. Aerobic capacity (maximal oxygen uptake/VO2 max) was measured with a bicycle ergometer exercise test. Overall disease activity was assessed with Systemic Lupus Activity Measure (SLAM) and the modified Systemic Lupus Erythematosus-Disease Activity Index (modified SLE-DAI), overall organ damage with the Systemic Lupus International Collaboration Clinics/American College of Rheumatology-Damage Index, [SLICC/(ACR)-DI], HRQL with the 36-item Short-form health-survey (SF-36) and physical activity with a self-assessed question. The women who were low-to-moderately physically active had 89-92% (P < or = 0.001) of VO2 max predicted for sedentary women. Maximal oxygen uptake (L/min, mL/min/kg) correlated to SF-36 physical function (rs = 0.49, rs = 0.72) (P < or = 0.01), but not (rs < or = 0.25) to other HRQL scales, overall disease activity or organ damage or physical activity. The correlation between aerobic capacity and physical function and the absence of correlation between aerobic capacity and physical activity, suggest a possible disease-related factor behind the low aerobic capacity. However, with no correlation between aerobic capacity and overall disease activity and organ damage, low physical activity may contribute to the low aerobic capacity in our sample.
Autonomic impairment in rheumatoid arthritis
  • Janse Van Rensburg
  • D C Ker
  • J A Grant
  • C C Fletcher
Janse van Rensburg DC, Ker JA, Grant CC, Fletcher L. Autonomic impairment in rheumatoid arthritis. Int J Rheum Dis 2012; 15: 419-426.