Background: Modifiable cardiovascular risk factors (MCRFs), such as those related to aerobic capacity, muscle strength, physical activity, and body composition, have been poorly studied in Takayasu arteritis (TAK). Therefore, the aim of the study was to investigate MCRFs and their relationships with disease status and comorbidities among patients with TAK. Methods: A multicenter cross-sectional study was conducted between 2019 and 2020, in which 20 adult women with TAK were compared with 16 healthy controls matched by gender, age, and body mass index. The following parameters were analyzed: aerobic capacity by cardiopulmonary test; muscle function by timed-stands test, timed up- and-go test, and handgrip test; muscle strength by one-repetition maximum test and handgrip test; body composition by densitometry; physical activity and metabolic equivalent by IPAQ, quality of life by HAQ and SF-36; disease activity by ITAS2010 and NIH score; and presence of comorbidities. Results: Patients with TAK had a mean age of 41.5 (38.0–46.3) years, disease duration of 16.0 (9.5–20.0) years, and a mean BMI of 27.7±4.5 kg/m . Three out of the 20 patients with TAK had active disease. Regarding comorbidities, 16 patients had systemic arterial hypertension, 11 had dyslipidemia, and two had type 2 diabetes mellitus, while the control group had no comorbidities. TAK had a significant reduction in aerobic capacity (absolute and relative VO peak), muscle strength in the lower limbs, increased visceral adipose tissue, waist-to-hip ratio, reduced walking capacity, decreased weekly metabolic equivalent, and quality of life (P< 0.05) as compared to controls. However, there were no correlations between these MCRFs parameters and disease activity. Conclusions: TAK show impairment in MCRFs; therefore, strategies able to improve MCRF should be considered in this disease. Keywords: Aerobic capacity, Cardiovascular diseases, Muscle strength, Vasculitis Introduction Patients with TAK have a high prevalence of cardio- Takayasu arteritis (TAK) is a primary systemic vasculitis vascular disease (CVD) and its risk factors. Additionally, characterized mainly by large-diameter vessels involvement, 60–70% of patients present dyslipidemia [3, 4]. During such as the aorta and major branches. Epidemiological follow-up, approximately 85% of patients developed studies have shown that the disease mainly affects women systemic arterial hypertension [5, 6], and an increased under the age of 40 years of age [1, 2]. prevalence of metabolic syndrome in TAK ; altogether, these factors may lead to increased morbidity * Correspondence: email@example.com and mortality in TAK. Division of Rheumatology, Faculdade de Medicina FMUSP, Universidade de CVD risk factors, morbidity, and mortality rate can be Sao Paulo, Sao Paulo, Brazil divided into modifiable and non-modifiable. Modifiable Full list of author information is available at the end of the article cardiovascular risk factors (MCRFs) include impairment © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Santos et al. Advances in Rheumatology (2021) 61:1 Page 2 of 9 in aerobic capacity [7, 8], muscle strength [9, 10], phys- gender, and body mass index (BMI) to patients with ical activity levels [11, 12], and body composition , TAK. The following data were collected: among others. MCRFs may be relevant for predicting traditional CVD risk factors in healthy individuals and – Demographic data: age and ethnicity; those patients with rheumatic diseases. – Quality of life: Health Assessment Questionnaire Furthermore, MCRFs are closely interconnected, and (HAQ) , Short Form Health Survey (SF-36)  the alteration of one of the factors may worsen one or – Clinical data: age at disease diagnosis, duration of more other factors. Moreover, they seem to have addi- disease, the Edinburgh Claudication Questionnaire tive responses in morbidity and mortality [14, 15]. How- (ECQ) , Walking Impairment Questionnaire ever, few studies have currently analyzed MCRF (WIQ) , Indian Takayasu’s Arteritis Activity parameters in patients with TAK [16, 17]. Score (ITAS2010) ; For example, reduced aerobic capacity has been de- – Laboratory data: serum levels of C-reactive protein scribed in several systemic autoimmune diseases [18– (CRP) and an erythrocyte sedimentation rate (ESR), 20]. This reduction is accompanied by a decline in phys- total cholesterol, high-density lipoprotein (HDL), ical capacity, muscle strength, and physical activity, low-density lipoprotein (LDL), triglycerides; which can worse body composition, increase fatigue, and – Pharmacological therapy: previous and current predispose to a higher prevalence of CVD and its risk (glucocorticoids, immunosuppressive, factors in rheumatic diseases [19, 21]. immunomodulator and/or immunobiologicals Oliveira et al.  showed that patients with TAK had drugs); reduced aerobic capacity. However, the authors did not – Disease activity: ITAS 2010 , and National evaluate other MCRFs, such as visceral adipose tissue Institute of Health (NIH) score  (only in TAK); and the waist and hip index, which are relevant CVD – Comorbidities and their risk factors for CVD: type 2 risk factors [3–6]. In addition, limitations may exist in diabetes mellitus was defined when the fasting the analysis of its findings regarding aerobic capacity, glycemic test ≥ 126 mg/dL and/or the result of the strength, and muscle function, due to the size of your oral glucose tolerance test ≥ 200 mg/dL ; sample. systemic arterial hypertension was considered when Therefore, the aim of this study was to evaluate blood pressure had systolic values ≥ 130 mmHg and/ MCRFs and their relations with the disease status and or diastolic values ≥ 85 mmHg ; dyslipidemia comorbidities in patients with TAK. was defined when total plasma cholesterol ≥ 200 mg/dL, HDL-cholesterol ≤ 50 mg/dL, LDL- cholesterol ≥ 130 mg/dL and/or triglycerides ≥ 150 Patients and methods mg/dL ; or previously medical diagnosis and This is a multicenter cross-sectional study, conducted drug treatment for these comorbidities. between 2019 and 2020, in which adult women with – Vascular images taken routinely and recently in the TAK. Patients had an age between 18 and 50 years and outpatient clinic (< 6 months after the inclusion of fulfilled at least three of the six items of classification patients in the present study): data referring to criteria for TAK . The study was approved by the vascular lesions in the aorta and the major branches local ethics committee and registered with ClinicalTrials (magnetic resonance-angiography and/or computed (#NCT03750929). tomography-angiography) (only in TAK). The following exclusion criteria were adopted: patients with severe or decompensated diseases (e.g., endocrino- Physical activity level and weekly caloric expenditure pathies) that could interfere with the results interpret- These parameters were obtained from the International ation and the physical testing safety; presence or history Physical Activity Questionnaire (IPAQ, short version of critical/symptomatic aortic stenosis, congestive heart eight), translated into Portuguese and validated for the failure, arrhythmias or electrocardiographic changes in Brazilian population . the ST segment, coronary artery disease; presence or his- tory of peripheral atherosclerosis disease; sciatica or Anthropometry and body composition neurogenic claudication; with impaired walking (osteoar- The following parameters were collected: body mass ticular disorders in limbs), precluding exercise testing; (using a digital scale), height (using stadiometer), hip, pregnancy or lactation; and smoking in the previous 6 waist and abdominal circumference, BMI, and waist-to- months of the study. hip ratio. Dual X-ray absorptiometry was used to assess Interviews were conducted with eligible TAK patients, body composition, including lean mass, fat mass, and and medical records were systematically reviewed. In the visceral adipose tissue, through iDXA equipment (GE control group, the volunteers were matched for age, Lunar Medical Systems, Madison, WI). Santos et al. Advances in Rheumatology (2021) 61:1 Page 3 of 9 Aerobic capacity with the GraphPad Prism® software, version 6.01 for A treadmill cardiopulmonary test was conducted. The Windows (San Diego, California, USA). test was carried out according to the previous descrip- tion . Results One hundred eight patients with TAK were interviewed. Muscle strength Of these patients, 56 did not meet the inclusion criteria, Maximum repetition test (1RM) was performed to deter- and 32 refused to participate for various personal rea- mine muscle strength. The 1RM test was performed sons (e.g., lack of time, a long distance from home, and using the bench press and the 45° leg press. A lack of interest); therefore, 20 patients were included in familiarization trial was carried out, and it was followed the study (Fig. 1). by a 48 h-interval, followed by two tests performed on TAK and 16 CTR were comparable regarding age, eth- non-consecutive days, in which reproducibility was ac- nicity distribution, and BMI parameters (Table 1). There cepted as soon as the coefficient of variation was < 0.5%. no evidence of any chronic disease and comorbidities in The warm-up consisted of eight repetitions at 50% of the CTR group (Table 2). 1RM with an interval of 2 min of rest. After that, three Half of the patients with TAK had a type V angio- repetitions were performed at 70% of 1RM between 3- graphic classification by Hata et al. , followed by four min intervals. To determine the 1RM, five attempts were type III patients, three type IV patients, two type IIb pa- made, and the highest recorded value was regarded as tients, and one type I patient (Table 1). the maximum load. The interval between each attempt Regarding the drug treatment, only two patients were was 3 min . treated with prednisone at the time of data collection (doses were 10 mg/day and 5 mg/day over the past 3 Muscle function months). Eleven (55.0%) patients used one or more im- Timed-Stands test (TST) , and Timed Up-and-Go munosuppressive and/or immunobiological drugs: six (TUG) test  were applied beyond the handgrip test used methotrexate, two azathioprine, and one lefluno- . We performed a familiarization that was preceded mide. Moreover, two patients were treated with inflixi- by at least 48 h of interval before the tests. The coeffi- mab, and one was treated with tocilizumab. Moreover, cient of variation for all tests was < 0.5%. according to the ITAS2010 and NIH questionnaires, As a control group (CTR), healthy volunteers were three (15.0%) patients were classified as presenting active matched for age, gender, and BMI to patients with TAK. disease (Table 1). In addition, individuals in the CTR group had no sys- Systemic arterial hypertension and claudication of temic autoimmune diseases and were not smokers in the lower limbs were respectively present in 80.0 and 65.0% previous 6 months of the study. of patients with TAK, and two patients had type 2 dia- betes mellitus. In addition, 11 (55.0%) of the patients had dyslipidemia under treatment, with two (10.0%) pa- Statistical analysis tients having diabetes mellitus. No individuals from the Data distribution was evaluated using the Shapiro-Wilk CTR group had systemic arterial hypertension, dyslipid- test. Data with normal distribution were expressed as emia, limb claudication or type 2 diabetes mellitus, and mean ± standard deviation, while data with asymmetric none of them used any type of medication other than distribution were expressed as the median and the inter- contraceptives. No smokers were reported in the TAK quartile range (25–75%). The existence of differences be- and control groups (Table 2). tween quantitative variables and normal distribution was In the treadmill cardiopulmonary test, there were no analyzed using the Student’s t-test. For the quantitative differences between the TAK and CTR groups with re- variables with asymmetric distribution, the Mann- spect to estimated maximum heart rate, anaerobic Whitney U test was used. The categorical data were threshold, respiratory compensation point, and time-to- expressed as a percentage (%), and the differences were exhaustion (Table 3). analyzed using Fisher’s exact test. The correlation be- However, in comparison with the CTR group, patients tween variables with symmetric distribution was ana- achieved a lower maximum heart rate during the test, as lyzed using the Pearson correlation coefficient, while well as a significant decrease in the absolute and relative that with asymmetric distribution was analyzed using VO peak (Table 3). the Spearman coefficient ρ . Furthermore, the corre- Five out of 20 patients with TAK were excluded due lations were classified as poor (< 0.3), fair (0.3–0.5), to possible cardiopulmonary diseases; therefore, 15 pa- moderately strong (0.6–0.8), and very strong (> 0.8) . tients participated in muscle strength and function tests The differences were considered statistically significant (Table 3). when values of P < 0.05. The analyzes were performed Santos et al. Advances in Rheumatology (2021) 61:1 Page 4 of 9 Fig. 1 Study flowchart. Legends: Control group; TAK: Takayasu arteritis Regarding muscle strength, the TAK group did not significant impairment, in terms of functional capacity, show significant reductions in the muscle strength of the physical function, pain, general health, and mental upper limbs, assessed via the bench press. However, health. In the walking impairment questionnaire (WIQ), compared to the CTR group, a significant decrease in compared to CTR, patients showed a reduction in all the the strength of the lower limbs, assessed via leg press, variables evaluated (P < 0.05) (Table 4). was found in the TAK group (Table 3). Regarding the level of physical activity assessed The TST, TUG, and handgrip strength in both hands through the IPAQ, 14 (60%) patients in the TAK group were similar between the TAK and CTR groups (Table 3). had lower levels of physical activity than CTR. In the Concerning the CTR group, patients with TAK presented TAK group, six (30%) patients had moderate physical ac- a significant reduction in the ability to perform activities tivity levels, with no difference compared to CTR, and of daily living, assessed using the HAQ questionnaire none of the patients was classified as having a high level (Table 4). of physical activity. Additionally, in comparison with In the domains of the SF-36 questionnaire, in com- CTR, the weekly caloric expenditure values of the TAK parison with the CTR, the TAK group showed more group were lower (Table 4). In comparison with the CTR group, the body compos- ition and anthropometric measurements were similar Table 1 General features of patients with Takayasu arteritis between the TAK and CTR groups (Table 5), except for N=20 the higher volume and mass of visceral adipose tissue, Age (years) 41.5 (38.0–46.3) and the waist-hip ratio in patients with TAK. Based on reduced responses in both lower limb Caucasian ethnicity 11 (55.0) strength and aerobic capacity, we investigated possible Disease duration (years) 16.0 (9.5–20.0) correlations between these two variables and variables Angiographic classification related to functional capacity. However, no correlations Hata I 1 (5.0) were found between any of the evaluated variables Hata IIa 0 (Table 6). Hata IIb 2 (10.0) Discussion Hata III 4 (20.0) The present study showed patients with TAK present Hata IV 3 (15.0) worse MCRF than controls. Moreover, the patients Hata V 10 (50.0) showed impaired walking capacity and increased visceral Disease activity - NIH 3 (15.0) adipose tissue and waist-to-hip ratio. However, no corre- Disease activity - ITAS2010 3 (15.0) lations were observed between MCRF parameters or dis- Erythrocyte sedimentation rate (mm/1st hour) 12.0 (9.5–21.5) ease activity. Despite being a rare disease, this study evaluated a C-reactive protein (mg/L) 3.4 (0.9–6.8) sample of patients with well-characterized TAK, which Data are presented in median (25–75%) or percentage (%) ITAS2010 Indian Takayasu Activity Index, NIH National Institute of Health score were compared with well-matched healthy individuals. Santos et al. Advances in Rheumatology (2021) 61:1 Page 5 of 9 Table 2 Comorbidities and traditional risk factors for cardiovascular diseases TAK (n=20) CTR (n=16) P value SAH or drug treatment 16 (80) ── Dyslipidemia or drug treatment 11 (55) ── Type 2 diabetes mellitus or drug treatment 2 (10) ── Smoker ── ─ Total cholesterol (mg/dL) 167.0 (143.5–188.5) 177.0 (148.0–208.0) 0.335 HDL-cholesterol (mg/dL) 60.0 (48.5–74.0) 50.0 (48.0–81.0) 0.899 LDL-cholesterol (mg/dL) 93.0 (78.5–107.0) 109.0 (109.0–120.0) 0.089 Triglycerides (mg/dL) 100.0 (74.5–114.5) 83.0 (53.0–87.0) 0.279 Fasting glucose test (mg/dL) 83.5 (80.25–92.0) 85.0 (81.0–89.0) 0.832 Data are presented as median (25–75%) or percentage (%) CTR Control group, SAH Systemic arterial hypertension, TAK Takayasu arteritis Furthermore, the demographic, clinical, and laboratory Even with rigorous selection criteria, it was necessary to data, as well as imaging conditions, pharmacological exclude five out of 20 TAK patients who had already been treatment, comorbidities, and disease status of patients recruited to the study. The exclusion of these patients was with TAK were comprehensively described. due to arrhythmias, severe systemic arterial hypertension, In the present study, only women were selected due to or decompensated increase in heart rate observed during the higher prevalence of this gender in TAK [1, 2]. Indi- maximum stress in the cardiopulmonary test. Hence, we viduals over 50 years of age were excluded to minimize were unable to proceed with a cardiopulmonary test the inclusion of individuals with comorbidities inherent protocol. Therefore, these patients were excluded from in older age groups, as well as patients with atheroscler- muscle strength and function tests because they may pose osis and peripheral arterial disease , or other vascu- a risk to personal safety and health. litis such as giant cell arteritis . The inclusion of A large gap exists in the literature regarding the as- such group of patients would have undermined the ac- sessment of MCRFs in TAK, specifically in the assess- curacy of the diagnosis and symptoms. ment of VO peak. However, our study obtained Table 3 Parameters of aerobic capacity, strength and functional capacity of patients with Takayasu arteritis and the control group TAK (n=20) CTR (n=16) P value Aerobic capacity Estimated maximum heart rate (bpm) 180.5±7.2 180.2±6.1 0.907 Maximum heart rate in test (bpm) 149.3±15.7 172.9±18.2 0.002 Anaerobic threshold (min) 4.5±1.6 3.8±0.6 0.111 Respiratory compensation point (min) 7.7±1,9 7.9±1,7 0.730 Time-to-exhaustion (min) 10.7±2.6 10.5±2.3 0.847 VO peak relative (mL/kg/min) 17.4±4.6 26.3±8.0 0.004 VO peak absolute (L/min) 1.2±0.3 1.6±0.4 0.007 Muscle strength and function Bench press 1RM (kg) 25.3±4.3 28.0±5.4 0.311 Leg press 1RM 45° (kg) 122.7±35.9 174.2±37.3 0.018 Handgrip test Right (kg) 28.4±5.4 30.0±5.4 0.543 Left (kg) 26.1±5.7 28.5±5.2 0.378 Timed-Stands test (reps) 15.5±2.4 18.8±3.4 0.068 Timed Up and Go test (s) 6.7±0.6 6.3±0.5 0.199 Data are presented as mean ± standard deviation CTR Control group, RM Repetition maximum, TAK Takayasu arteritis, VO Volume of oxygen uptake 2 Santos et al. Advances in Rheumatology (2021) 61:1 Page 6 of 9 Table 4 Ability to perform activities of daily living, quality of life and level of physical activity of patients with Takayasu arteritis and the control group TAK (n=20) CTR (n=16) P value HAQ (0.00–3.00) 0.56 (0.12–0.87) 0.00 (0.00–0.00) < 0.001 SF-36 (0–100) Functional Capacity 62.5 (46.2–88.7) 100.0 (95.0–100.0) < 0.001 Physical function 50.0 (0.0–100.0) 100.0 (100.0–100.0) 0.008 Pain 41.0 (34.2–63.5) 84.0 (69.2–100.0) < 0.001 General health 61.0 (43.2–80.7) 92.0 (79.5–97.7) < 0.001 Vitality 55.0 (35.0–72.5) 77.5 (55.0–85.0) 0.066 Social aspects 88.0 (66.0–100.0) 100.0 (84.7–100.0) 0.194 Emotional aspects 100.0 (33.0–100.0) 100.0 (67.0–100.0) 0.195 Mental health 60.0 (53.0–84.0) 82.0 (75.0–97.0) 0.034 WIQ (0–100) Walking distance 68.0 (37.3–100.0) 100.0 (100.0–100.0) < 0.001 Walking speed 64.1 (38.6–79.9) 100.0 (97.3–100.0) < 0.001 Ability to climb stairs 58.3 (42.7–85.4) 100.0 (96.7–100.0) < 0.001 Overall score 64.4 (42.4–86.9) 100.0 (88.9–100.0) < 0.001 IPAQ-SF (%) Low 14 (60.0) 3 (18.7) 0.013 Moderate 6 (30.0) 9 (56.2) 0.080 High 0 2 (12.5) – METs per week 453.0 (240.0–751.7) 1693 (1089.0–2206.0) < 0.001 Data are presented as median (25–75%) or percentage (%) CTR Control group, HAQ Health Assessment Questionnaire, IPAQ-SF International Physical Activity Questionnaire Short Version, METs Metabolic equivalent, SF-36 Short Form Health Survey, TAK Takayasu arteritis, WIQ Walking Impairment Questionnaire Table 6 Correlation between functional variables, lower limb strength and peak relative VO of patients with Takayasu arteritis TAK (n=15) rho/r P value Table 5 Body composition of patients with Takayasu arteritis Lower limb strength (leg press) and the control group HAQ −0.291 0.293 TAK (n=20) CTR (n=16) P value WIQ - Overall score 0.069 0.806 Body mass (kg) 69.8±13.7 67.1±13.3 0.564 SF36 - Functional capacity 0.171 0.543 Height (cm) 158.3±6.1 159.7±6.7 0.508 SF36 - Physical aspect −0.057 0.838 Body mass index (kg/m2) 27.7±4.5 26.2±3.8 0.264 IPAQ-SF - METs 0.295 0.285 Fat body mass (kg) 29.4±9.4 26.0±11.5 0.347 VO peak relative (mL/kg/min) 0.024 0.933 Lean body mass (kg) 38.0±5.3 40.5±7.1 0.255 VO2 peak relative (mL/kg/min) Bone mineral content (kg) 2.3±0.3 2.3±0.4 0.580 HAQ 0.158 0.517 Visceral adipose tissue (cm ) 804.0±432.5 506.4±307.8 0.022 WIQ - Overall score −0.193 0.427 Visceral adipose tissue (g) 760,1±408,7 477,8±290,3 0.021 SF36 - Functional capacity −0.122 0.619 Abdominal circumference (cm) 91.6±10.7 85.5±7.7 0.172 SF36 - Physical aspect −0.114 0.641 Waist circumference (cm) 83.5±9.7 77.4±5.8 0.100 IPAQ-SF - METs −0.051 0.835 Hip circumference (cm) 104.3±11.0 104.8±8.0 0.919 Lower limb strength (leg press) 0.024 0.933 Waist-hip ratio 0.8±0.1 0.7±0.0 0.016 HAQ Health Assessment Questionnaire, IPAQ-SF International Physical Activity Data are presented as mean ± standard deviation Questionnaire Short Version, METs Metabolic equivalent, SF-36 Short Form CTR Control group, TAK Takayasu arteritis Health Survey, TAK Takayasu arteritis, VO Volume of oxygen 2 Santos et al. Advances in Rheumatology (2021) 61:1 Page 7 of 9 results similar to cardiopulmonary treadmill test by Importantly, muscle weakness is a strong and inde- Oliveira et al.  Lanzi et al.  evaluated (even pendent risk factor for all-cause morbidity and mortality though indirectly) the 6-min walk test, finding low in some populations [9, 10, 48, 49]. values. However, they did not use a control group A critical factor in our results is the reduction in the and employed one “gold standard” test, making com- total level of weekly caloric expenditure and physical activ- parisons difficult. ity. As seen in other rheumatic diseases, the reduction Furthermore, as seen in ANCA-associated vasculitis may be associated with a worsening of quality of life .  and other rheumatic diseases [20, 21], our patients Similar to Margiotta et al.’s study of paitents with sys- showed a significant reduction in maximum oxygen con- temic lupus erythematosus, our TAK patients presented low sumption; that is, a reduction in the capacity to absorb, levels and intensities of physical activity that did not meet transport, and use oxygen . This reduction and poor the recommendations of the World Health Organization test performance can be attributed to two main pur- (i.e., at least 150 min per week of moderate-intensity physical ported mechanisms: activity or 75 min of vigorous-intensity activity) . Similar to outcomes in the healthy population, physical a) Impairment of the cardiopulmonary system is inactivity may worsen the health of patients with rheum- expected for this population with major atic diseases, which may lead to higher risk of CVD and cardiovascular impairments, such as stenosis or comorbidities and increase the number and length of occlusion of the branches of the aorta, valve hospital stays . problems, etc. Far from our findings, Akar et al.  demonstrated b) The presence of vascular claudication may impair no differences in body composition in patients with physical performance, imposing the same daily rheumatoid arthritis, with the exception of bone mass living limitation as a peripheral arterial disease . density. Ours results found TAK patients showed a Difficulty in walking produces even more impaired significant increase in waist-to-hip ratio and visceral adi- aerobic capacity, creating a vicious circle of reduced pose tissue compared to controls, signaling an impair- VO peak and inactivity, as seen in peripheral ment of body composition in this population. arterial disease . However, patients with rheumatic diseases who present worse body composition, specifically adipose tis- Although the disease pathogenesis is distinct, the walk- sue, show an association with greater inflammation, dis- ing capacity of TAK patients is hindered, which occurs ease activity, glucocorticoid use, and disease severity, but similarly topatientswithperipheralarterial disease . mainly increased cardiovascular risk, as seen in systemic Moreover, patients with TAK also had a reduction lupus erythematosus . in functional capacity, physical strength, pain, and Adipose tissue has long been related to morbidity and general and mental health, demonstrating this disease mortality. In addition to this traditional relationship, an- leads to impairments in multiple aspects of quality of other important link is adipose tissue’s pro-inflammatory life. nature, where adipokines are linked to immune response Similarly, the patients had impairments in daily living, through their link with cytokines that lead to the inflam- as pointed out in the HAQ questionnaire. These findings matory process in rheumatic diseases, such as interleukin- corroborate other studies that assessed quality of life 6 and tumor necrosis factor-alpha . The result is the using the SF-36 and HAQ questionnaires, where a wors- hypothetical maintenance of vicious circle of inflammation ening was found in all domains that demonstrated a in rheumatic diseases, which can favor the process of ath- worsening of quality of life in general when compared to erosclerosis, cardiovascular risk, and mortality in this healthy controls [46, 47]. population . Another important aspect is the association between In addition, BMI should not be the sole parameter to remission and improved quality of life. In our study, only assess by which to assess boody composition in TAK. In 15% of patients had disease activity demonstrating re- our study, the BIM parameter was shown to be inaccur- gardless of activity the disease seems to deteriorate pa- ate, as it was in other populations, for evaluating adipose tients’ quality of life . tissue and obesity . As found in our patients, muscle strength is reduced Traditionally, patients with TAK have a higher risk of due to other chronic diseases [48, 49], resulting in a sig- developing CVD and a greater presence of its risk fac- nificant decrease in functional capacity and quality of tors. A series of studies corroborate our findings, as they life. Our data are similar to outocmes found in ANCA- observed the increase in systemic arterial hypertension associated vasculitis, demonstrating a possible associ- and dyslipidemia in TAK [4, 6]. ation between reduced strength and worsened quality of Markers such as LDL, total cholesterol, triglycerides life in vasculitis patients . were close to or within the normal range compared to Santos et al. Advances in Rheumatology (2021) 61:1 Page 8 of 9 healthy subjects, as shown in our study. These findings Ethics approval and consent to participate The study was approved by the local ethics committee (CAAE: make it difficult to assess possible long-term risks, prob- 89386618.0.0000.0068) and all participants signed the informed consent form. ably due to previous treatment of lipoproteins in patients with TAK. Consent for publication Not applicable. The focus of this study is to assess the MCRFs, which corroborate the higher risk of morbidity and mortality Competing interests [7–15, 59]. In our study, we found that most of the fac- All authors declare that they have no conflicts of interest. tors studied were deteriorating in TAK patients, such as Author details reduced aerobic capacity, decreased muscle strength, re- Division of Rheumatology, Faculdade de Medicina FMUSP, Universidade de duced physical activity, low intensity of physical activity, Sao Paulo, Sao Paulo, Brazil. Division of Rheumatology, Universidade Federal and increased visceral adipose tissue. de São Paulo (UNIFESP), Sao Paulo, Brazil. As demonstrated by Crump et al. [14, 15], even though Received: 28 July 2020 Accepted: 22 December 2020 the analysis of these factors was conducted in studies in- cluding most men, the sum of these MCRFs seem to represent an aggravated risk, with a 2.5-fold increase in References 1. Lupi-Herrera E, Sanchez-Torres G, Marcushamer J, et al. Takayasu’s arteritis. CVD. Clinical study of 107 cases. Am Heart J. 1977;93:94–103. 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JAMA. 2009;301:2024–35. ment of several MCRFs. These patients require strategies 9. Artero EG, Lee DC, Lavie CJ, et al. Effects of muscular strength on that will help change the MCFR, in order to reduce cardiovascular risk factors and prognosis. J Cardiopulm Rehabil Prev. 2012; morbi-mortality and improve the quality of life. 32:351–8. 10. Katzmarzyk PT, Craig CL. Musculoskeletal fitness and risk of mortality. Med Abbreviations Sci Sports Exerc. 2002;34:740–4. BMI: Body mass index; CRP: C-reactive protein; CTR: Control group; 11. Kubota Y, Evenson KR, MacLehose RF, et al. Physical activity and lifetime risk CVD: Cardiovascular disease; ECQ: Edinburgh Claudication Questionnaire; of cardiovascular disease and cancer. Med Sci Sports Exerc. 2017;49:1599– ESR: Erythrocyte sedimentation rate; HAQ: Health Assessment Questionnaire; 605. HDL: High-density lipoprotein; IPAQ: International Physical Activity 12. Arem H, Moore SC, Patel A, et al. Leisure time physical activity and Questionnaire; ITAS: Indian Takayasu’s Arteritis Activity Score; LDL: Low- mortality: a detailed pooled analysis of the dose-response relationship. density lipoprotein; MCRFs: Modifiable cardiovascular risk factors; JAMA Int Med. 2015;175:959–67. NIH: National Institute of Health; RM: Maximum repetition test; SF: Short 13. Britton KA, Massaro JM, Murabito JM, et al. Body fat distribution, incident Form; TAK: Takayasu arteritis; TST: Timed-Stands test; TUG: Timed Up-and-Go; cardiovascular disease, cancer, and all-cause mortality. J Am Coll Cardiol. WIQ: Walking Impairment Questionnaire 2013;62:921–5. 14. Crump C, Sundquist J, Winkleby MA, et al. Aerobic fitness, muscular strength Acknowledgments and obesity in relation to risk of heart failure. Heart. 2017;103:1780–7. Not applicable. 15. Crump C, Sundquist J, Winkleby MA, et al. Interactive effects of aerobic fitness, strength, and obesity on mortality in men. 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Advances in Rheumatology – Springer Journals
Published: Jan 8, 2021