rheumatoid arthritis ( ra ) is a chronic , inflammatory , multisystemic autoimmune disorder 
 that affects ( mostly ) diarthrodial joints1 .
it is associated with an increased morbidity and mortality due to 
 cardiovascular disease ( cvd ) ; however , the reason for the increased risk of cvd is not 
 explained by traditional risk factors2 , 3 . in several studies ,
positive correlations 
 have been shown between the increased disease activity in ra and increased erythrocyte 
 sedimentation rate ( esr)4 , severe 
 extra - articular manifestations5 , 
 rheumatoid factor seropositivity6 , 
 elevated c - reactive protein levels ( crp)6 , 7 , and cardiovascular mortality .
the presence of inflammation leads to endothelial activation and dysfunction , and this is 
 regarded as the primary finding of atherosclerosis8 , 
 9 .
subclinical atherosclerosis and 
 vascular structure are measured through a noninvasive method of carotid intima - media 
 thickness ( cimt ) measurements in patients with ra10 .
in addition to predicting the presence of local atheroma , the 
 findings of cimt can reveal possible damage to the arterial system11 .
recent studies have shown increased cimt scores in ra 
 patients in contrast to healthy controls12 , 13 . in ra , radiographic assessment of joint damage is the most widely accepted standard for 
 following the course of the disease14 .
ra 
 is more severe , progressive , and destructive during the early stage15 , and although inflammation has a negative impact on 
 functional capacity in early ra , increased erosion and joint destruction become more 
 pronounced at the further established stages16 .
this joint destruction increases the health assessment 
 questionnaire ( haq ) scores of established ra patients16 ; however , it has been clearly indicated that the real marker of the 
 increment in haq score in established ra patients is the disease activity score ( das)17 . in several studies , the joint destruction 
 of ra patients has been measured using the van der heijde modification of the sharp method 
 ( mtts)18 , 19 .
inflammation in ra patients leads to joint destruction and subclinical atherosclerosis , and 
 the presence of elevated joint destruction can be a preclinical condition for cardiovascular 
 risk detection .
based on the relationships of inflammation and rheumatoid arthritis with the 
 atherosclerosis and joint destruction mentioned above , no research study has been performed , 
 as of yet , to clarify this issue .
we , herein , aimed to investigate the potential 
 relationship between joint destruction and carotid intima - media thickness .
thirty - four ra patients ( 10m/24f ) admitted to the physical medicine and rehabilitation 
 outpatient clinic at harran university school of medicine , fulfilling the american college 
 of rheumatology criteria20 for the 
 diagnosis of ra , were consecutively enrolled in our cross - sectional study .
thirty - one 
 healthy controls matched for age , sex , and bmi were recruited from the staff of the same 
 hospital .
the research protocol was approved by the ethics committee of the harran 
 university school of medicine , and written informed consent was obtained from all subjects . 

patients with any other inflammatory diseases , coronary arterial disease , liver disease , 
 neoplastic disease , diabetes mellitus , hypertension , renal failure , history of stroke , or 
 iron deficiency anemia were excluded from the study .
each patient s disease activity was measured using the disease activity score for 28 joints 
 with the erythrocyte sedimentation rate ( das28esr)21 , and a visual analog scale ( vas010 cm ) was used to 
 measure pain .
the disability of the ra patients was measured using the health assessment 
 questionnaire ( haq ) index , which ranges from 0 to 3 . the patients fasting total cholesterol , high - density lipoprotein ( hdl ) , low - density 
 lipoprotein ( ldl ) , triglycerides , esr , and crp concentrations were measured in the 
 morning .
the patients x - ray images were scored according to the modified sharp / van der heijde 
 method by consensus of the readers : one experienced musculoskeletal radiologist and two 
 clinical researchers .
the maximum erosion score is 160 for the hand and 120 for the feet ; 
 the maximum score for joint space narrowing is 120 for the hands and 48 for the feet , 
 resulting in a maximum total score of 44822 .
the images were obtained using a high - resolution doppler ultrasound ( mylab twice ; esaote , 
 genoa , italy ) with a 12  mhz linear - array transducer , and the cimt was automatically measured 
 with software .
the patients were examined in a supine position at 3045 degrees opposite the 
 direction of neck extension .
the cca , ica , and eca carotid bulbs were morphologically 
 evaluated with all visual segments at the axial level , and the cimt was measured at the 
 posterior wall when they were clearly visible in the longitudinal plane at 11.5  cm proximal 
 to the distal carotid bulbs . intima - media thickness ( imt )
was measured as the distance from 
 the leading edge of the first echogenic line to that of the second echogenic line .
the first 
 line represents the lumen - intima interface , and the second line the collagen - containing 
 upper layer of the tunica adventitia .
all of the sonographic examinations were performed by the same examiner , who was 
 unaware of the subjects clinical status throughout the study .
statistical analyses were carried out using spss 18.0 for windows ( pasw statistics for 
 windows , spss inc . , chicago , il , usa ) , and between group comparisons were made using 
 independent sample t - tests .
pearson correlation tests were used to determine the 
 relationships between the variables , and multivariate linear regression analyses were 
 performed to identify independent predictors of cimt .
all demographic and quantitative data 
 are expressed as the mean  standard deviation ( sd ) .
differences with p values < 0.05 
 were considered to be statistically significant , and all results are expressed with a 95% 
 confidence interval .
demographic and clinical data of the patients and healthy controls are shown in table 1table 1 . demographic and clinical data of patients and healthy controls ( mean 
 sd)patientsn=34controlsn=31age ( years)40.558.0038.836.21male / female ( number)10/248/23bmi ( kg / m)24.841.8924.671.86disease duration ( months)63.6169.13painvas ( 010 cm)6.792.25sjc281.141.70tjc287.764.43das28esr4.891.22haq1.890.77esr ( mm)33.9422.028.933.45*crp ( mg / dl)1.502.560.330.13**rf ( iu / ml)47.7623.23total cholesterol ( mg / dl)167.4934.68152.8033.28ldl cholesterol ( mg / dl)109.6931.7097.4123.04hdl cholesterol ( mg / dl)46.829.5041.775.21**triglyceride ( mg / dl)120.6150.75123.1943.91tc / hdl3.691.003.680.80 * p<0.001 ; * * p<0.05 .
bmi , body mass index ; crp , c reactive protein ; das , 
 disease activity score ; esr , erythrocyte sedimentation rate ; haq , health assessment 
 questionnaire ; hdl , high density lipoprotein ; ldl , low - density lipoprotein ; rf , 
 rheumatoid factor ; sjc , swollen joints count ; tc , total cholesterol ; tjc , tender 
 joints count ; vas , visual analog scale ; tmss , total modified sharp score .
there was no significant difference in terms of age , gender , and bmi between 
 the patients and the controls .
the hdl levels of the patients were significantly higher than 
 in the controls , and the esr and crp levels of the ra patients , right cimt , left cimt , and 
 mean cimt scores were significantly elevated .
the cimt of the patients and controls and 
 the  mtts of the patients are shown in table 
 2table 2 .
common carotid artery imts and total modified sharp score ( mean sd)patientsn=34controlsn=31right cimt0.590.130.500.06**left cimt0.610.150.490.06*mean cimt0.600.140.490.06*tmss66.1730.79 * p<0.001 ; * * p<0.05 .
cimt , common carotid artery intima - media thickness ; tmss , 
 total modified sharp score .
bmi , body mass index ; crp , c reactive protein ; das , 
 disease activity score ; esr , erythrocyte sedimentation rate ; haq , health assessment 
 questionnaire ; hdl , high density lipoprotein ; ldl , low - density lipoprotein ; rf , 
 rheumatoid factor ; sjc , swollen joints count ; tc , total cholesterol ; tjc , tender 
 joints count ; vas , visual analog scale ; tmss , total modified sharp score * p<0.001 ; * * p<0.05 .
cimt , common carotid artery intima - media thickness ; tmss , 
 total modified sharp score positive correlation was detected between the mean cimt score and age , and the crp levels , 
 ldl concentration and triglycerides level were positively correlated . in the regression 
 model in which the mean cimt was the independent variable and age , crp , ldl , and tg were the 
 dependent variables , age was found to be an independent predictor of cimt .
to the best of our knowledge , this is the first study to evaluate the relationship of cimt 
 and joint destruction with rheumatoid arthritis , and the main findings of the present study 
 were that : ( i ) that contrary to our hypothesis ,  mtss and cimt were not significantly 
 associated and ( ii ) that the cimt scores were positively correlated with age , crp levels , 
 ldl concentration , and triglycerides level .
radiographic follow - up is one of the most widely accepted methods of monitoring disease 
 progression in ra patients .
additionally ,  mtss as a radiographic measure evidently shows the 
 effectiveness of medical options18 , 19 .
it has also been proven that  mtss is 
 associated with impaired hand function and elevated haq scores in ra patients23 .
these findings presumably differ from the 
 cvd risk in the radiographic progression . in our study ,
similarly , veselinovic et al . determined that their ra patients 
 cimt scores were significantly higher than in the controls , and the brachial artery 
 flow - mediated vasodilatation values were lower , which was attributed to the development of 
 endothelial dysfunction and accelerated atherosclerosis13 .
adhikari et al . also studied early ra patients , and they reported 
 the same findings as previous researchers12 . according to the eular guidelines for cardiovascular risk management , low hdl levels with 
 increased ldl and tg levels are a predictor of cvd in the general population24 .
furthermore , if the score model is used , 
 increased tc / hdl levels could be an additional prognostic indicator in terms of cv 
 risks25 . in our study ,
the hdl levels 
 of the patients were significantly higher than in the controls ; however , the ldl , tg , and 
 tc / hdl levels were not significantly different between the groups .
these findings show that 
 endothelial dysfunction and atherosclerosis in ra patients are seen at the early stages of 
 ra and that existing data about the general population are not sufficient to evaluate ra 
 patients .
previously , the relationships between cimt scores and cardiac events ( myocardial 
 infarction , angina pectoris , and coronary revascularization ) , cerebrovascular events ( stroke 
 or transient ischemic attacks ) , and hypertension were evidently shown26 , 27 . moreover , the 
 cimt findings were worse , despite treatment with disease modifying drugs and biological 
 agents like anti - tnf inhibitors28 , 29 . in order to determine the potential factors affecting cimt in patients with ra ,
for that 
 reason , age was found to be the only independent predictor of cimt in multivariate 
 regression analysis . in parallel with our findings ,
one study has revealed increased cimt 
 scores with older ages30 . additionally , 
 we detected a positive correlation between crp and cimt among the controls , but the 
 regression analysis excluded crp as an independent predictor . unlike our results , 
 gonzalez - gay et al .
evidently proved that there is a positive association between the 
 maximum crp and cimt scores31 ( table 3table 3 .
the relationship between patients mean cimt score and demographic , clinical , 
 and laboratory characteristicspearsonscoefficientb regression coefficientage ( years)0.628 * 0.499**disease duration ( months)1.000painvas0.201sjc280.307tjc280.021das28esr0.249haq0.246esr0.261crp0.429**0.277rf0.115total cholesterol0.083ldl
cholesterol0.387**0.102hdl cholesterol0.265triglyceride0.4100.061tc / hdl0.252tmss0.164 * p<0.001 ; * * p<0.05 . from multiple lineer regression analysis ; 
 bmi , body mass index ; crp , c - reactive protein ; das , disease activity score ; esr , 
 erythrocyte sedimentation rate ; haq , health assessment questionnaire ; hdl , 
 high - density lipoprotein ; ldl , low - density lipoprotein ; rf , rheumatoid factor ; sjc , 
 swollen joints count ; tc , total cholesterol ; tjc , tender joints count ; vas , visual 
 analog scale ; tmss , total modified sharp score ) .
* p<0.001 ; * * p<0.05 . from multiple lineer regression analysis ; 
 bmi , body mass index ; crp , c - reactive protein ; das , disease activity score ; esr , 
 erythrocyte sedimentation rate ; haq , health assessment questionnaire ; hdl , 
 high - density lipoprotein ; ldl , low - density lipoprotein ; rf , rheumatoid factor ; sjc , 
 swollen joints count ; tc , total cholesterol ; tjc , tender joints count ; vas , visual 
 analog scale ; tmss , total modified sharp score the limitations of our study include a cross - sectional design and a small sample size . 
 despite the fact that our patients were not classified in terms of disease duration , we have 
 tried to minimize the potential negative factors that may affect cimt measurements . in conclusion , patients suffering from ra require close monitoring for cardiovascular 
 risks , and the comorbidity of age - related cardiovascular disease should not be overlooked . 

although we could not detect a positive relationship between cimt and  mtss , further 
 large - scale , multicenter , prospective studies are needed to clarify this issue .
   [ purpose ] the purpose of this study was to investigate the possible relationship between 
 joint destruction and carotid intima - media thickness in patients with rheumatoid 
 arthritis . 
 [ subjects and methods ] thirty - four ra patients and 31 healthy controls were 
 enrolled in this study . 
 the disease activity for 28 joints was recorded for each patient 
 using the erythrocyte sedimentation rate ( das28esr ) , a visual analog scale 
 ( vas010 cm ) , and a disability index , the health assessment questionnaire 
 ( haq ) . 
 x - ray imagesof the patients were scored according to the modified sharp / van der 
 heijde method , and the common carotid intimal medial thickness ( cimt ) was automatically 
 measured with software using high - resolution doppler ultrasound . [ results ] contrary to our 
 hypothesis , the modified total sharp score ( mtss ) and cimt were not significantly 
 associated . the erythrocyte sedimentation rate ( esr ) and c - reactive protein ( crp ) levels 
 of the ra patients and the right cimt , left cimt , and mean cimt scores were significantly 
 elevated . 
 positive correlation was detected between the mean cimt score and age , crp 
 levels , ldl concentration and triglycerides ( tg ) level . in the regression model , where the 
 mean cimt was the independent variable and age , crp , ldl , and tg were dependent variables , 
 age was found to be an independent predictor of cimt . [ conclusions ] patients suffering 
 from ra require close monitoring for cardiovascular risks , and the comorbidity of 
 age - related cardiovascular disease should not be overlooked . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION