Kardiometaboolsed riskitegurid ja keha koostise muutused varase reumatoidartriidi haigetel

Väitekirja elektrooniline versioon ei sisalda publikatsiooneReumatoidartriit on põletikuline haigus, mida põeb ligi 1% täiskasvanutest. Tüüpiliselt on artriidist haaratud väikesed liigesed kätel ja jalgadel, need on turses ja valulikud. Liigesepõletik on reumatoidartriidi korral vaid jäämäe tipp, haigusest on haaratud kogu organism, sealjuures tekib põletik juba oluliselt enne esimeste haigusnähtude teket. Tänapäevane ravi võimaldab vältida varasemalt reumatoidartriidi paratamatuks tagajärjeks olnud liigesedeformatsioonide ja tõsiste liigeseväliste nähtude teket. Vaatamata ravi arengule on reumatoidartriiti põdevatel patsientidel endiselt lühem eluiga võrreldes tervetega, peamiselt on varane suremus põhjustatud sagedasemast ja ebatüüpilisest südame- veresoonkonna haiguse esinemisest. Üldrahvastikus on südame- veresoonkonna haiguste risk sageli seotud kõrgema kehakaaluga, reumatoidartriidi korral on leitud vastupidine seos- normkaalulistel on risk kõrgem kui ülekaalulistel. Tüüpilised rasvumisega seotud südame- veresoonkonna haiguste riskitegurid on kõrgvererõhktõbi, suhkruhaigus, kõrge kolesterooli ning triglütseriidide tase ja vöökoha rasvumine, mille koosesinemist nimetatakse metaboolseks sündroomiks. Metaboolse sündroomiga seostub lihaste ja teiste kudede madal tundlikkus veresuhkru taset reguleeriva hormooni- insuliini suhtes (insuliinresistentsus), mis veelgi suurendab veresoonkonna kahjustuse tõenäosust. Reumatoidartriidi üheks kaasnevaks nähuks on keha koostise muutus: rasvkoe osakaalu suurenemine ja lihaskoe vähenemine stabiilse kehakaalu juures. See fenomen, mida nimetatakse sarkopeeniliseks rasvumiseks, suurendab südamehaiguste riski enam kui tavapärane rasvumine. Enamik uuringuid südame- veresoonkonna haiguste riski mõjutavate tegurite ja keha koostise muutuste kohta reumatoidartriidi korral põhinevad kaua kestnud haigusega patsientide andmetel. Varasemalt mujal avaldatud uuringud annavad vihjeid selle kohta, et muutused võivad tekkida juba haiguse esimestel kuudel või isegi enne liigesepõletiku teket. Käesolev uurimistöö selgitab metaboolse sündroomi, insuliinresistentsuse ja keha rasv- lihaskoe osakaalu muutuste kujunemist esimestel kuudel pärast reumatoidartriidi kliinilist avaldumist. Lisaks otsisime haiguse ja eluviisiga seotud nähte, mis seletaksid keha koostise muutuste teket. Andmed põhinevad 92 varase reumatoidartriidiga patsiendi uurimisel, keskmiselt oli uuringute läbiviimise ajaks haiguse diagnoosimisest möödunud üks kuu. Võrdlesime saadud tulemusi Eesti üldrahvastiku andmetega, kaasates kontrollgrupina patsiendid perearstikeskuste nimistutest. Leidsime, et juba reumatoidartriidi esimestel kuudel on ainevahetuslike kõrgema südame- veresoonkonna haiguse riskiga seotud tegurite esinemissagedus kõrgem kui üldrahvastikus. Võrreldes andmeid kontrollgrupiga selgus, et hüpertensiooni, hüperglükeemiat ja metaboolset sündroomi esines oluliselt enam normkaalulistel reumatoidartriidiga patsientidel. Metaboolne sündroom oli 17% normaalkaalulistest artriidihaigetest ja vaid 2% kontrollgrupi samas kaalurühmas, ülekaaluliste/rasvunute seas olulist erinevust gruppide vahel esile ei tulnud. Reumatoidartiidiga patsientidel oli sagedamini kõrgenenud vererõhk, kuid vähesed nende hulgast kasutasid vererõhku alandavaid ravimeid. Perearstikeskusest juhuslikult valitud kõrgenenud vererõhuga patsientidest said ravi enam kui pooled, samas reumatoidartriidi haigetest vaid 31 protsenti. Saab järeldada, et ka varase artriidiga patsiente tuleks tihedamalt jälgida südame-veresoonkonna haiguse riskitegurite osas isegi sel juhul, kui nad on normkaalulised. Südame- veresoonkonna haiguse riski tõstvat madalat tundlikkust insuliini toimele esines varase reumatoidartriidiga haigetel ligi 5 korda enam kui kontrollgrupis. Insuliinresistentsust oli enam meestel ja nendel, kellel olid veres kõrgenenud põletikunäitajad. Leidsime, et nende muutuste teket ei saa ennustada kehamassiindeksi alusel, vaid vähenenud tundlikkus insuliini toime suhtes on seotud madala lihasmassiga. Erinevused kontrollgrupist keha rasv- ja lihaskoelises koostises oli täheldatavad enamikul varase reumatoidartriidiga patsientidest, neist 42% oli madal lihaskoe mass, 68% kõrge rasvkoe protsent ja 26% nii vähene lihaskude kui ka kõrge rasvkoe osakaal (sarkopeeniline rasvumine). Kõigest 16% reumatoidartriidi haigetest olid normaalse keha koostisega, samas tervete hulgas oli normaalse keha koostisega uuritavaid 43%. Lihasmassiga seotud tegurite osas leidsime olulisi erinevusi haigete ja kontrollgrupi vahel. Reumatoidartriidi grupis oli lihasmassi vähesus seotud kõrgema põletikunäitajate taseme, glükokortikoidhormoonide kasutamise ja madalama valgusisaldusega toidus. Kontrollgrupi hulgas olid olulisemad traditsioonilised lihasmassi mõjutajad nagu kõrgem vanus, vähesem liikumine ja suitsetamine. See uurimistöö näitas, et reumatoidartriidile omased kehakaalust sõltumatud eripärad südame veresoonkonna haiguste riskitegurite esinemises kujunevad juba varase haiguse korral. Nende ainevahetuslike muutustega tuleks arvestada hinnates südame- veresoonkonna haiguste riski reumatoidartriidiga patsientidel. Õigeaegne riskitegurite tuvastamine ja mõjutamine raviga võib aidata vähendada südamehaiguste tõenäosust ja vähendada enneaegset suremust reumatoidartriidi patsientide seas.Rheumatoid arthritis is a chronic progressive autoimmune disease that affects about 1% of population. The inflammatory process begins long time before the onset of symptoms of arthritis, damage to joints is only a tip of the iceberg, systemic inflammation has an effect on the whole body. Joint deformations and specific damage to internal organs is preventable with adequate treatment but people suffering from the disease are still at elevated risk of having cardiovascular disease and premature death as a consequence due to reasons not completely understood. In general population increased risk of cardiovascular disease is associated with overweight and obesity, in rheumatoid arthritis the opposite is evident- patients with higher body mass are at lower risk of getting heart disease. Obesity induced elevated cardiovascular risk is associated with metabolic disturbances. The co- occurrence of hypertension, diabetes, high cholesterol and triglyceride levels and abdominal obesity is called metabolic syndrome. The syndrome is associated with another important metabolic alteration called insulin resistance that presents as low sensitivity in muscle, fat and liver cells to insulin- a hormone responsible for regulation of blood sugar. In established rheumatoid arthritis a change in body composition called sarcopenic obesity (high fat percentage and low proportion of muscle tissue) has been described. This phenomenon increases the risk of cardiovascular disease at a higher extent than regular obesity. A change in body composition can be one of the reasons behind increased risk for heart disease in rheumatoid arthritis, metabolic disturbances caused by altered body composition can remain undetected on routine evaluation. Most of the previous studies looking into metabolic risk factors and body composition in rheumatoid arthritis have focused on data of patients with long disease duration. Some authors have hypothesized that the change in body composition may already start in the early or even preclinical stage of the disease. This study investigated the presence of metabolic syndrome, insulin resistance and changes in body composition in early rheumatoid arthritis. Additionally, we tried to find lifestyle and disease- associated factors explaining the development of body composition alterations. This project is based on a study of 92 patients with early rheumatoid arthritis with an average time from diagnosis one month. The data was compared to Estonian general population using patients from family doctors practice lists as control subjects. We found that metabolic factors associated with elevated cardiovascular risk can be detected in patients with rheumatoid arthritis in the first months after the disease onset. Normal weight patients with rheumatoid arthritis had hypertension, hyperglycemia and metabolic syndrome significantly more often than the control subjects with similar weight status, 17% of arthritis patients with normal weight had metabolic syndrome and only 2% of the controls. There was no difference between the groups in the presence of assessed cardiovascular risk factors or metabolic syndrome among overweight/obese subjects. Having rheumatoid arthritis was associated with higher blood pressure but only 31% of the rheumatoid patients with hypertension used anti-hypertensive medications, at the same time more than 50% of control subjects with hypertension received treatment. Low sensitivity to insulin was almost 5 times more common among arthritis patients. Insulin resistance was present more often in men and patients with high inflammatory markers. We found that insulin sensitivity could not be predicted by body mass index, reduced insulin sensitivity in rheumatoid arthritis group was associated with low lean mass. There was a significant difference in body fat and muscle composition between control subjects and early rheumatoid arthritis group. 42% of patients with arthritis had low muscle mass, 68% had high body fat percentage and 26% had both reduced muscle mass and excess fat (sarcopenic obesity). Only 16% of the patients did not have any abnormal components of body composition, at the same time 43% of the control subjects had healthy body composition with both normal fat percentage and muscle mass. Looking into the factors associated with low muscle mass we found a difference between rheumatoid arthritis and control group. In arthritis group low lean mass was associated with higher levels of inflammatory markers, glucocorticosteroid therapy and reduced protein intake in diet. In the control group the most important factors were older age, inactivity and smoking. Results of the study show that all patients with early rheumatoid arthritis should be screened for risk factors of cardiovascular disease regardless of their weight status. The development of metabolic risk factors in rheumatoid arthritis is independent of body weight and can appear in the initial stage of the disease. These differences should be taken into account when evaluating cardiovascular risk in patients with rheumatoid arthritis. Timely screening and treatment could postpone the progression of cardiovascular disease and avoid premature death.https://www.ester.ee/record=b534122

Reumatoidartriidi loomulik kulg

Reumatoidartriit (RA) on üldrahvastikus suhteliselt sage haigus, kus ebaadekvaatse ravi korral tekib inva-liidistumine, mis on tingitud nii liikumispuudest kui ka ekstra artikulaarsetest (liigesevälistest) tüsistustest. Artiklis kirjeldatud haigusjuht peegeldab RA kulgu haigel, kellel vähese ravisoostumuse ja puuduliku arstliku jälgimise tõttu on 23aastase kestusega haiguse jooksul tekkinud taaspöördumatud eluohtlikud tervisehäired. Eesti Arst 2007; 86 (1): 55–5

Autoimmuunhaigus kui kõrge kardiovaskulaarse riski marker

Autoimmuunsed reumaatilised haigused, nagu reumatoidartriit, võivad põhjustada kõigi südamestruktuuride häiret ja mõnelgi juhul võib südame kahjustus olla autoimmuunhaiguse (AIH) esmane manifestatsioon (1). Reumatoidartriit ei ole aga ainus ega kõige sagedasem põletikulise patofüsioloogiaga autoimmuunhaigus. Siinkohal võib näitena välja tuua sclerosis multiplex’i, psoriaasi või mõne muu sadadest teadaolevatest autoimmuunhaigustest, millest on mõjutatud 5–9% rahvastikust üle maailma. Üksikhaiguste panus kardiovaskulaarsesse (KV) riski või nende seos traditsiooniliste kardiovaskulaarse riski teguritega on endiselt arutelukohaks

Factors Associated with Low Lean Mass in Early Rheumatoid Arthritis: A Cross-Sectional Study

Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC-lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects—ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9–5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1–3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3–8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I. 1.002–1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002–1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96–0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4–9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24–4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment

Does Dietary Polyunsaturated Fatty Acid Intake Associate With Bone Mineral Density and Limb Structural Changes in Early Rheumatoid Arthritis?

Background: Rheumatoid arthritis (RA) is an inflammatory disease that can result in bone erosion, lean mass lowering, and increase of fat mass without changes in body weight. The dietary consumption of polyunsaturated fatty acids (PUFAs) has been assessed in many studies due to their potential anti-inflammatory effect. Aim: The aim of this research was to identify if dietary intake of PUFAs associates with bone mineral density (BMD) and limb structural changes in early rheumatoid arthritis (ERA) compared to a population-based control group. The study was conducted because previous results have been insufficient. Methods: The study group consisted of 83 ERA patients and 321 control subjects. A dual-energy X-Ray absorptiometry (DXA) machine was used to measure hip, lumbar spine, and radius BMD, as well as arm and leg fat, lean, and bone mass. Dietary habits and inflammatory markers were assessed to evaluate the effects to BMD and limb structural changes. Results: In ERA subjects, higher dietary consumption of PUFAs was associated with a decrease in arm fat mass (b −28.17, P  = .02) and possibly with higher lumbar BMD (b 0.008, P   =  .058). Limb bone and lean mass changes were not associated with dietary intake of PUFAs. Conclusion: Balanced nutrition is essential. Consuming PUFAs could be beneficial in ERA preventing structural changes to hands, but additional research is needed

Structural and Functional Changes of Hands and Legs in Early Rheumatoid Arthritis

Background and Objectives: The aim of this study was to assess if there are structural and functional changes of hands and legs already in early rheumatoid arthritis (ERA), compared with the population-based control group. Additionally, we aimed to identify if the changes are symmetrical in hands and legs and if there are factors that are associated with these changes. The study was conducted, and, thus far, the results have been controversial. Materials and Methods: The study group consisted of 83 consecutive patients with ERA and 321 control subjects. Dual-Energy X-Ray Absorptiometry (DXA) machine was used to measure bone, lean and fat mass. Inflammation and bone markers, smoking and nutritional habits were assessed, to evaluate the effects of different factors. The 30-Second Chair Stand Test (30-CST) and the Handgrip Strength Test (HST) were used to estimate muscle strength. Results: The presence of ERA was associated with lower arm, leg lean mass and higher fat mass of arm, compared with control subjects. ERA was also associated with lower mean handgrip in HST and worse muscle strength of legs in the 30-CST. Bone mass changes were not so evident both in arms and legs. Smoking habits did not seem to have relevant effect on bone mass, muscle structural and functional changes, both on hands and legs. In ERA, lean mass of arm and leg was negatively associated with C-reactive protein (CRP). The intake of proteins in ERA was not associated with lean mass changes both in hands and legs. Conclusions: Structural and functional changes of hands and legs are different in ERA. ERA patients had higher fat mass of arm, lower lean mass of arm and leg and, accordingly, decreased muscle function. The lowering of lean mass of arm and leg in ERA was associated with the elevation of CRP

Physical function measures and health-related quality of life in primary care medicine: cross-sectional study

Background . Health-related quality of life (HRQoL) is an important component of comprehensive management in primary care. Objectives. The purpose of this study was to investigate the relationships between physical performance measures and self-reported HRQoL and to fi nd optimal values of muscle function tests associated with lower HRQoL. Material and methods. From a single primary health care center patient list, 330 subjects were randomly selected. Information about the patient’s age, gender, body mass index and presence of self-reported chronic diseases was collected, as well as analyses for systemic infl ammation and vitamin D. Physical performance was measured by dominant hand grip strength (GS) and a 30-second chair stand test (30-CST). The physical (PCS) and mental (MCS) component scores of the Short-Form-36 Questionnaire (SF-36) were used to evaluate HRQoL. The predictive power of physical function measures were tested with multivariate linear regression analyses. Threshold values for physical function tests were calculated by receiver operating characteristic curves. Results . Multivariate analyses demonstrated that 30-CST was signifi cantly (p < 0.0001) associated with SF-36 summary scores for both genders. Males with 30-CST results under 7 stands and females with results of fewer than 13 stands were in the risk group for having the lowest PCS scores. Results in 30-CST under 12 stands in males and under 13 stands in females were associated with the lowest scores of MCS. Conclusions . 30-CST had the most expressed association with the outcomes of HRQoL in the Estonian population. Subjects with physical performance results under threshold values are at risk of lower HRQoL; therefore, 30-CST is a potential screening indicator for HRQoL assessment