Arterial Stiffness Measured By Doppler Ultrasound And Its Application In The Assessment Of Cardiovascular Pathologies In Autoimmune Rheumatoid Diseases

Background and Objective1.There is a higher incidence of cardiovascular complications in patients with TAK,which has become the leading cause of premature death in patients with TAK.Studies have shown that a variety of autoimmune diseases,including TAK,all could develop atherosclerosis prematurely and show accelerated progression,so that patients with autoimmune diseases have higher cardiovascular morbidity and mortality.Therefore,the diagnosis and evaluation of premature atherosclerosis,especially the early non-invasive detection,is an urgent need for the prevention,treatment and reduction of mortality of TAK.Arterial stiffness?AS?is the earliest detectable index of arterial wall structural and functional abnormalities.Carotid-femoral pulse wave velocity?cfPWV?is the"gold standard"method for non-invasive evaluation of AS in human,and also acts as an independent predictor of cardiovascular events and all-cause mortality in general population and different patients.However,there are few studies on the evaluation of AS in TAK patients at home and abroad,and no study has been conducted on the evaluation of AS in TAK patients using Doppler ultrasound.Therefore,the purpose of this study was to measure the cfPWV of TAK patients in young women and to evaluate their AS using the ultrasound Doppler.The clinical utility and repeatability of Doppler measured cfPWV are also explored in this study.2.Rheumatoid arthritis?RA?,a rare idiopathic autoimmune disease,has a higher risk of developing cardiovascular disease than the normal population.In recent years,more and more studies have begun to focus on AS of RA patients.Previous studies showed that the aortic PWV?mainly covering the descending aorta and abdominal aorta?of RA patients was significantly increased compared with the control group.In addition,the study also found that brachial-ankle PWV?mainly covering the lower extremity artery?was significantly increased in RA patients.However,a meta-analysis in recent years showed that there was no significant increase in carotid PWV?mainly covering the upper extremity?,but it showed an increased trend.Therefore,AS in different regions was not equally damaged in RA,that is,RA can cause varying degrees of changes in AS in different regions of major arteries.These changes of AS in different regions may play different roles in the macrovascular disease of RA.However,there are very limited reports on the changes of AS in different regions of RA patients.No research has reported the effects of RA on different parts of AS of the same individual.The role of AS changes in different regions in the macroangiopathy is still unclear.Therefore,the purpose of this part of study is to explore whether RA has equal influence on AS in different regions,including central artery and peripheral arteries.This study is expected to find out which specific AS parameter can be better used for the early diagnosis of subclinical atherosclerosis and preliminarily determine the distribution of arterial vessels susceptible to RA damage.3.The accelerated progression of atherosclerosis in rheumatoid arthritis?RA?,is the leading cause of high rates of cardiovascular complications and mortality in such patients.Previous studies have confirmed a significant increase in AS in RA patients compared with healthy controls.Other studies have shown that significantly increased AS may be reversed by anti-inflammatory therapy.However,according to the current clinical observations,there is no unified conclusion on whether anti-inflammatory therapy can reverse the increase of AS in RA patients.Another part of the study found that increased AS was not associated with decreased treatment.Therefore,for the AS of RA patients,different anti-rheumatism drugs and different treatment strategies may have different effects.Methotrexate?MTX?combined with short-term glucocorticoid?GC?is the preferred treatment strategy recommended by the European Union of rheumatology and should be implemented immediately after the diagnosis of RA.However,so far,information about the effect of MTX combined with short-term GC therapy on AS in RA patients is extremely limited,although MTX appears to reduce cardiovascular complications and mortality in RA patients.Therefore,the purpose of this study was to explore the effect of MTX combined with short-term GC treatment on AS in patients with early RA at 6 months.4.Systemic lupus erythematosus?SLE?is an autoimmune disease mainly occurring in young women,involving multiple systems and organs.The high incidence of cardiovascular complications has become the leading cause of premature death in patients with SLE.The elasticity of the aorta can reflect the structural changes of the vessel wall independently of other traditional risk factors and predict future cardiovascular events.Subclinical atherosclerosis can be detected before endovascular mesangial thickening.Currently,carotid-femoral pulse wave velocity?carotid-femoral PWV?is the"gold standard"method for non-invasive evaluation of AS in human.In previous studies,we found and proposed another indicator of aorta whole AS,heart-femoral PWV,which can reflect the whole elastic information of aorta.However,as this indicator has not been used in previous studies,it is not clear whether it can also be used for the evaluation of macroangiopathy in SLE patients,as in the case of carotid-femoral PWV.Therefore,the purpose of this study is to use Doppler ultrasound to measure the carotid-femoral PWV and heart-femoral PWV in SLE patients,and to explore its clinical value in the evaluation of macroangiopathy in SLE patients.Methods1.A totle of 25 female TAK patients were included,all of whom were hospitalized for the first time in the rheumatology department of Tangdu Hospital of the Airforce Military Medical University.Meanwhile,25 control volunteers whose age,height and weight were strictly matched with the disease group were selected.All subjects were measured by ultrasonography with c-femoral PWV.The basic principle is:the flow velocity curve of the common carotid artery and the common femoral artery was recorded by using PW Doppler,and the slope method was used to determine the time delay between the start point of pulse wave and the top of the R wave of ECG.The spread distance was measured on the surface of the body,and the propagation distance divided by the time delay was used to calculate the neck-thigh PWV.The repeatability of c-femoral PWV measured by ultrasound Doppler was performed in 15 randomly selected cases of TAK and 15 controls.2.RA patients admitted to the department of rheumatology of Tangdu Hospital for the first time were studied in 45 cases,and a healthy control group of 45 patients with age,height and weight matching were included.PHILIPS IU22 ultrasound instrument?PHILIPS,Netherlands?,shallow linear array probe?L9-3?and frequency 3-9MHz were used.All subjects were measured for different parts of AS,and the evaluation indicators included:cardiac-carotid PWV,heart-femoral PWV,brachial-radial PWV,femoral-ankle PWV,and neck-femoral PWV.The measurement method of each index adopts ultrasonic Doppler method.3.This study included RA patients who were first hospitalized in rheumatology department of Tangdu Hospital of Air Force Military Medical University?Fourth Military Medical University?from April 2016 to April 2017.Inclusion criteria:28 joint disease activity score?DAS28ESR and DAS28CRP?based on ESR and CRP;According to the treatment program developed after admission,patients need to receive MTX and short-term GC treatment.The patient was not previously treated with any immunosuppressant and/or glucocorticoid;Duration of disease was less than 1 year;Age is more than 18 years old.The measurement of carotid-femoral PWV was performed by the same ultrasound surgeon before and after 6 months of treatment.Other indicators were collected or tested before and 6 months after treatment.4.A totle of 30 female SLE patients were included,all of whom were hospitalized patients with SLE who were first diagnosed and treated in the rheumatology department of Tangdu hospital.At the same time,30 control volunteers whose age,height and weight were strictly matched with the disease group were selected.All subjects were measured with PHILIPS IU22 ultrasound instrument?PHILIPS,Netherlands?,shallow linear array probe?L9-3?,and frequency 3-9MHz.The measurement indexes were carotid-femoral PWV and heart-femoral PWV in this study.Results1.The mean duration of disease in TAK patients was 14.6±8.2 months,ranging from3-36 months.There were no statistically significant differences in left ventricular systolic and diastolic functional indicators between TAK patients and healthy controls in age,height,weight,mean arterial pressure,diastolic blood pressure,heart rate,biochemical examination and routine echocardiography?P>0.1?.Carotid-femoral PWV in TAK patients was 8.37±2.23 m/s,and 6.46±1.15 m/s in the control group,which was statistically significant?P<0.001?.Systolic and pulse pressures in TAK patients were higher than those in the control group,and the PWV in the neck and thigh of TAK patients was still significantly higher than that in the control group?P<0.001?after correction of the multivariate regression analysis model.Spearman correlation analysis showed that there was no correlation between the measured value of PWV of the neck and the LVEF and the diastolic index?E/A,e/a?measured by echocardiography in TAK patients?both P>0.05?.There was no significant correlation between cervical-femoral PWV and biochemical markers in TAK patients?all P>0.05?.The coefficient of variation between and within the observer of carotid-femoral PWV measured by ultrasound Doppler was low,and the Bland-Altman analysis showed that the measurement repetition was good.2.There were no statistically significant differences in age,height,weight,systolic blood pressure,diastolic blood pressure and biochemical examination indicators?blood lipid and blood glucose?between RA patients and healthy control group?P>0.05?.Blood sedimentation?ESR?and C-reactive protein?CRP?were significantly increased in RA patients.Compared with the healthy control group,carotid-femoral PWV was significantly increased in RA patients?8.08±2.34 vs.6.84±1.82 m/s,P<0.05?.Heart-femoral PWV was also significantly increased?6.33±1.90 vs.5.23±1.21 m/s,P<0.05?.However,there was no significant difference between the brachial-radial PWV,heart-carotid PWV and femoral-ankle PWV compared with the healthy control group.3.In this study,41 RA patients were initially included.In the subsequent research process,11 patients were excluded due to the change of treatment plan,2 patients were withdrawn due to the treatment in the hospital,and 9 patients were unable to complete the whole study due to the loss of interview.After 6 months of MTX plus short-term GC treatment,no significant change in the measured value of c-femoral PWV was found in RA patients?8.31±1.92 vs 8.45±1.99m/s,P=0.7060?.After 6 months of treatment,11cases?57.9%?reached DAS-28 remission.However,in RA patients with DAS-28remission or without remission,there was no significant change in the measurement of carotid-femoral PWV.In this study,no significant changes in carotid-femoral PWV were observed before and after treatment in both female and male patients.After 6 months of MTX plus short-term GC treatment,DAS-28_ESR and DAS-28_CRP were significantly reduced in RA patients.Inflammatory markers,including ESR and CRP,declined significantly after treatment.After 6 months of treatment,only HDL cholesterol was significantly elevated.Other blood lipid indicators showed a trend of increase,but no statistical significance.4.Patients with SLE were 40.12±8.51 years old and had an average course of 10.11±7.91 months.There were no statistically significant differences in left ventricular systolic and diastolic functional indicators between SLE patients and healthy controls in age,height,weight,systolic,diastolic,biochemical,and conventional echocardiography?P>0.05?.The carotid-femoral PWV and heart-femoral PWV of the SLE patients were respectively 7.88±1.84 m/s,6.33±1.68 m/s,the carotid-femoral PWV and heart-femoral PWV of the control group were 6.71±0.78 m/s and 5.21±0.76 m/s.The difference between the two groups was statistically significant?P<0.01?.Pearson correlation analysis showed that,in both healthy control group and SLE patients,there was a good correlation between the measured value of heart-femoral PWV and that of carotid-femoral PWV?all P<0.0001?.Conclusions1.In patients with TAK,the degree of central arterial stiffness measured by ultrasound Doppler was significantly higher than that in normal people,indicating significant macroangiopathy in such patients,and this change was earlier than the damage of diastolic function.Carotid-femoral PWV measured by Doppler ultrasound provides a reliable method for clinical center arterial stiffness and cardiovascular risk assessment,and has important clinical significance for early intervention of cardiovascular diseases in TAK patients.2.In RA patients,macroangiopathy mainly focuses on the central aorta,while peripheral arteries are less affected by the disease.The evaluation of PWV in the Doppler area,especially the detection of aorta PWV,can provide a reliable method for the evaluation of the distribution and degree of major vascular damage in clinical RA.3.We have shown that 6-month MTX combined with short-term GC treatment can significantly reduce systemic inflammation and disease activity in patients with early RA,but has no significant effect on the increased AS in patients.4.Based on the aortic stiffness measured by ultrasound Doppler technique,carotid-femoral PWV and heart-femoral PWV were significantly increased in SLE patients,indicating a significantly increased risk of cardiovascular disease.Our results indicate that both carotid-femoral PWV and heart-femoral PWV can be used as the AS indicators to measure the whole aortic AS for clinical evaluation of macroangiopathy in SLE patients.