Inflammation and Coronary Endothelial Function

This is an interventional other trial for Coronary Artery Disease Read More

Inclusion Criteria:

• Participants of either gender who are 21 years of age (no upper age limit),
• History of prior Myocardial Infarction (MI), coronary revascularization, or coronary angiography or Multidetector Computer Tomography (MDCT) demonstrating at least one coronary artery with >50% luminal stenosis and no plans for revascularization,
• Clinically stable for 3 months,
• Vascular inflammation based on elevated hsCRP (>2mg L-1), or a clinical diagnosis of diabetes mellitus or metabolic syndrome (metabolic syndrome is defined by three or more of the following): Abdominal obesity (waist circumference: Men>102 cm (>40 in), Women >88 cm (>35 in)), Serum triglycerides ≥150 mg/dL (or taking medication to treat high triglycerides), HDL cholesterol: Men<40 mg/dL, Women<50 mg/dL (or taking medication to treat low HDL cholesterol), High blood pressure: ≥130/≥85 mm Hg (or taking medication to treat high blood pressure), or Fasting glucose: ≥100 mg/dL (or taking medication to treat high fasting glucose).
• Abnormal Coronary Endothelial Function (CEF) (change in CSA during IHE of <0% of the resting value: by this we mean any decrease in CSA or no change (0%) from baseline during IHE),
• Permission of patient's clinical attending physician,
• Patients being treated with a statin.

Exclusion Criteria:

• Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent,
• Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips) or indwelling metallic projectiles,
• Acute coronary syndrome within the prior three months,
• Pregnant women,
• Contraindications to methotrexate or colchicine as outlined by the American College of Rheumatology; including active bacterial infection, tuberculosis, or herpes zoster infection, leukopenia (<4000/mm3), thrombocytopenia (<135,000/mm3), elevation in hepatic transaminases (>2x upper limit of normal), hepatitis B or C, moderate renal disease (estimated creatine clearance <45ml/min), or planned surgery,
• Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease,
• Interstitial lung disease or pulmonary fibrosis,
• HIV positive,
• Requirement for, or intolerance to, methotrexate or colchicine ,
• Intolerance to methotrexate, colchicine or folate,
• History of non-basal cell malignancy or treatment for lymphoproliferative disease in the past 5 years,
• Requirement for use of drugs that alter folate metabolism,
• History of alcohol abuse or unwillingness to limit consumption to < 4 drinks per week,
• Women of childbearing potential or intention to breastfeed.
• Men who plan to father children during the study period; men who have sexual intercourse with women of childbearing potential must agree to use a condom,
• Chronic use of oral or IV steroid therapy or other immunosuppressive or biologic response modifiers,
• History of chronic pericardial effusion, pleural effusion or ascites,
• New York Heart Association Class IV heart failure.