Atherosclerosis in Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to investigate the link between rheumatoid arthritis and cardiovascular disease by studying inflammation, joint disease, cholesterol abnormalities, and endothelial function.

Detailed Description
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In the general population, individuals with elevated inflammatory markers (e.g. C-reactive protein, CRP) have increased cardiovascular disease. Patients with RA have chronic elevations in CRP and other inflammatory markers that are usually higher than the levels associated with increased cardiovascular risk in the general population. Indeed, RA patients have accelerated disease of their blood vessels, and increased cardiovascular death not explained by traditional cardiac risk factors but associated with chronic inflammation. However, the mechanisms by which inflammation leads to cardiovascular disease are not well characterized in RA. Moreover, current treatment strategies of RA largely target joint symptoms rather than inflammation, potentially leaving patients at increased risk for cardiovascular disease. Studies of markers that increase the risk of heart disease in the full spectrum of RA are missing. We hypothesize that inflammatory markers will be more strongly associated with abnormalities in blood vessels in RA patients than any clinical measure of disease activity. This hypothesis will be tested with a cross-sectional study of patients in the UCSF RA cohort. Aim 1 will characterize abnormal blood vessel changes across the spectrum of RA disease activity, specifically measuring ultrasound of the upper arm artery, markers of oxidative stress, and abnormalities in cholesterol proteins. Aim 2 will identify factors associated with these changes across the spectrum of RA disease activity, specifically focusing on the association between inflammatory markers, cholesterol, and blood vessel abnormalities.

Official Title
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Atherosclerosis in Rheumatoid Arthritis: Role of Inflammation, Lipoproteins, and Endothelial Dysfunction

Conditions
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Rheumatoid Arthritis, Endothelial Dysfunction

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA by ACR criteria Age 18-80 Enrolled in UCSF RA cohort already Exclusion Criteria: Diabetes (on meds or in medical history) Pregnant or Lactating Renal failure (Creatinine > 2mg/dL or on dialysis) History of MI or CAD History of ischemic CVA Symptomatic PVD Current uncontrolled hypertension (blood pressure > 160/100mmHg) Daily prednisone > 10mg daily Current smoker New BP med within 3 months New statin within 3 months Change in RA meds: new or increase in prednisone within 1 month, new TNF inhibitor within 2 months, titration of methotrexate, leflunomide or sulfasalazine within 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| rheumatoid arthritis subjects<br>60 subjects with rheumatoid arthritis, defined by American College of Rheumatology Criteria, enrolled in the UCSF RA cohort | |
| healthy controls<br>20 matched controls without rheumatoid arthritis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| flow mediated vasodilation of the brachial artery, measured by ultrasound |  | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulse wave velocity/arterial stiffness |  | day 1 | 
| lipid metabolism |  | day 1 | 
| pulse ampitude |  | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rheumatoid arthritis, endothelial dysfunction, lipoproteins, inflammation, oxidative stress, arterial stiffness