Inflammation and Coronary Endothelial Function

The investigators are studying whether anti-inflammatory agents can improve abnormal coronary artery function in patients with coronary artery disease (CAD) and abnormal coronary artery endothelial function.

Sometimes, in patients with coronary artery disease (CAD), even though blood pressure is controlled, the patients are on cholesterol medication, not smoking, eating properly and have normal levels of physical activity; the investigators still see development of new blockages, progression of existing blockages, and sometimes even clinical events like heart attacks and strokes. Therefore, the investigators are always trying to find additional ways to decrease the progression of existing blockages and to prevent new ones.

What the investigators are studying in this program is the function of the coronary arteries and in particular the inner lining of the arteries called the endothelium. It has several important functions; one of them is that under conditions of stress it releases a substance called nitric oxide which increases the size of the artery and increases blood flow. When it is not functioning normally the artery does not increase as much and blood flow does not increase during stress.

The investigators study coronary artery function with magnetic resonance imaging, or MRI. MRI is a method of obtaining images of what is happening inside the body. MRI does not involve radiation, x-ray, and injection of contrast. The investigators can measure flow in the artery and the dimension of the artery at rest and with a handgrip stress and learn the extent to which the artery dilates and flow increases with the stress. The investigators believe that inflammation can interfere with normal function and that by decreasing inflammation abnormal endothelial function may be improved.

Methotrexate and colchicine are anti-inflammatory agents approved by the Food and Drug Administration (FDA) to treat arthritis and some other conditions. These drugs are not approved for use to suppress inflammation in patients with coronary artery disease and improve coronary artery endothelial function. The FDA is allowing the use of methotrexate, colchicine and/or their combination in this research study.

This study will involve 24 weeks of anti-inflammatory drugs and 3 Magnetic Resonance Imaging (MRI) scans of the heart and other study procedures.

Eligibility Criteria:
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.