Preliminary Study Mechanisms Of Atherosclerosis Artery Premature Patients With Rheumatoid Arthritis

BackgroundPatients with RA are characterized by high incidence and early onset of atherosclerosis related diseases. Cardiovascular mortality is an important cause of death in RA. Currently, the pathogenesises of atherosclerosis include inflammation, endothelial dysfunction and abnormalites of arterial structure and function. RA is a systemic inflammation disease. The progression of atherosclerosis may mediatd through inflammation process in RA.PWV, which reflects arterial stiffness and function, is an effective non-invasive means to detect the subclinical pathological changes of atherosclerosis, and is widely used to assess cardiovascular risk and prognosis. ADMA is a competitive inhibitor of endothelial nitric oxide synthase. ADMA inhibits the synthesis of nitric oxide, causes endothelial dysfunction, and probably participates in the development and progression of atherosclerosis. ADMA reflects endothelial function. MMP-9and TIMP-1co-regulate metabolism of connective tissue. MMP-9can degrade extracellular matrix, resulting smooth muscle cell migration and leukocyte invasion, thus promoting the processes of atherosclerosis. Elevated level of MMP-9may indicate increased risk of cardiovascular events.This study investigates the changes and correlations of PWV, ADMA and MMP-9in RA patients, in order to explore the mechanisms of early-onset of atherosclerosis in RA patients.Objectives1. Investigate the differences of clinical manifestations and biochemical indicators in RA patients and control populations;2. Investigate the differences of endothelial function and arterial function in RA patients and control populations;3. Investigate the differences of serum level of MMP-9and MMP-9/TIMP-I ratio in RA patients and control populations.Methods1. Outpatients diagnosis of RA in the rheumatology department of PUMCH fromDecember2011to May2012are enrolled in the study group. The subjects of control group are selected from the non-RA population that underwent physical examination in PUMCH from June2010to July2010;2. Automated arterial pulse detector is used to measure brachial-ankle PWV, which reflects arterial stiffness and function;3. High performance liquid chromatography-tandem mass spectrometry is used to measure serum level of ADMA, which reflects endothelial function;4. Double-antibody sandwich enzyme-linked immunosorbent assay is used to measure serum level of MMP-9and TIMP-1;Results1. Totally39cases of RA patients and39cases of controls are respectively enrolled in the study group and control group. There are no obvious differences in demographic characteristics and comorbidities between two groups. The HDL-C level of RA patients is significantly decreased, while the inflammartory markers of RA patients are significantly increased;2. The PWV and ADMA level of RA patients are significantly higher than that of control group. PWV and ADMA have a significant correlation;3. RA, advanced age and smoking are independent predictors of elevated ADMA;4. Advanced age and hypertension are independent predictors of elevated PWV;5. Advanced age, smoking, ESR≥20mm/h and DAS28score>6.6are the main risk factors for significant elevated ADMA in RA patients;6. Advanced age, hypertension, hsCRP≥7.0mg/L and DAS28score>5.15are the main risk factors for significant elevated ADMA in RA patients;7. ADMA is an independent predictor of PWV in RA patients;8. The MMP-9level and MMP-9/TIMP-1ratio of RA patients are significantly increased and are significantly correlates with inflammatory markers and disease activity, but not with PWV, ADMA and cardiovascular disease.Conclusion1. Endotherial and arterial dysfunction are possible mechanisms of early-onset of atherosclerosis in RA patients, in which inflammatory activation play an important role;2. In the inflammatory activation process of RA patients, circulating MMP-9elevatioon and MMP-9/TIMP-I imbalance are not necessarily linked with early-onset of atherosclerosis.