Targeting Inflammation Using Salsalate in CardioVascular Disease

Inclusion Criteria: Eligibility will be based upon the presence of established coronary artery disease including * previous myocardial infarction (≥6 months ago), or * previous coronary bypass surgery (\> 12 months ago), or * stable angina, or * significant non-calcified plaque in at least one coronary artery, or * abnormal exercise tolerance test or * an area of reversible ischemia on nuclear imaging study or pharmacologic stress, with subsequent revascularization, or angioplasty, or * abnormal exercise treadmill stress test with or without nuclear imaging or echocardiography with the following exclusions: Exclusions based on nuclear imaging: 1. Transient cavity dilation 2. More than one vascular territory involved with reversible defect (multiple defects) 3. Reversible defects involving the anterior wall, septum or apex (LAD territory) Exclusions based on echocardiography imaging: 1. More than one vascular territory involved with inducible wall motion abnormalities (multiple defects) 2. Inducible wall motion abnormalities involving the anterior wall, septum or apex (LAD territory) Subjects should be at list 6 months after a myocardial infarction and/or revascularization procedure to be eligible. In addition, subjects must be: 1. aged 21- 75 years inclusive, 2. BMI ≥ 27 kg/m2 and ≤ 35 kg/m2 if female and ≤ 40 kg/m2 if male (a BMI ≥24.5 for subjects from Asian origin) 3. on a stable dose of an HMG CoA reductase inhibitor (statin) for 1 month at screening or unable to tolerate a statin, 4. have normal renal function, (note estimated creatinine clearance calculated using Cockcroft-Gault (CG) equation ≥60 at screening \[eCrCLCG (ml/min) = \[(140 - age) x weight (kg)\]/\[SCr(mg/dl) x 72\] x \[0.85 if female\], 5. have liver function (ALT, AST) \< 3 times upper limits of normal), 6. normal thyroid function (on stable dose replacement therapy is acceptable), 7. if women are of child bearing potential they must have a pregnancy test prior to the CT angio and use contraception for the remainder of the study 8. patients with T2D must have a fasting glucose of ≤ 200 mg/dl at screening and cannot be treated with thiazolidinedione class agents or insulin or Extendin-4 (Byetta) therapy. Subjects must be willing to have at least three visits at the Beth Israel-Deaconess Medical Center/Joslin Diabetes Center with a baseline and a 30-month follow-up series of imaging studies including CT angiography of the coronary arteries and imaging of the aorta, abdominal adiposity and liver, and interim visit at 1 year. Exclusion Criteria: 1. Unstable angina (increase in frequency or severity of anginal episodes or development of chest pain at rest) 2. significant obstructive disease (≥ 70%) in left main coronary artery, ostial LAD or three-vessel disease by MDCTA 3. Significant heart failure (NYHA class III and IV) 4. Current atrial fibrillation or Wolf-Parkinson-White (WPW) syndrome 5. Allergy to beta-blocker in subjects with resting heart rate \> 65 bpm 6. Systolic blood pressure \> 160 mm Hg 7. Diastolic BP \> 100 mm Hg 8. Persons with allergies to contrast material 9. History of asthma if unable to tolerate beta blocker 10. Allergy to iodinated contrast material or shellfish 11. Allergy to nitroglycerin 12. BMI \> 35 kg/m2 if female and \> 40 kg/m2 if male 13. Body weight \> 350 lbs 14. Use of drugs for weight loss \[e.g. Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanolamine) or similar over-the counter medications\] within three months of screening 15. Surgery within 30 days of screening 16. History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV) 17. Poor mental function or history of dementia/ Alzheimer's Disease or on medications used for treatment of dementia \[e.g. Tacrine (Cognex), Rivastigmine (Exelon), Galantamine (Razadyne, Reminyl), Donepezil (Aricept), Memantine (Namenda)\] or any other reason to expect patient difficulty in complying with the requirements of the study 18. Medicine for erectile dysfunction within 72 hours prior to MDCTA 19. History of significant chronic rheumatologic or other chronic inflammatory disease (including foot ulcers) 20. Prior hemorrhagic stroke 21. persons with known aspirin allergy 22. Use of continuous oral corticosteroid treatment (more than 2 weeks), or patients requiring corticosteroids within 3 months 23. Anti-diabetic medication including thiazolidinedione (pioglitazone or rosiglitazone), or insulin or Extendin-4 (Byetta) 24. History of peptic ulcer or gastritis within 5 years 25. Positive stool guaiac 26. Hemoglobin 2 standard deviations below normal 27. Low platelet count (2 standard deviations below normal) 28. Known bleeding disorder 29. Coumadin (warfarin compounds) 30. History of type 1 diabetes and/or history of ketoacidosis 31. Daily use of NSAIDS (including salsalate) for arthritis 32. History of malignancy, except subjects who have been disease-free for greater than 5 years, or whose only malignancy has been basal or squamous cell skin carcinoma 33. History of drug or alcohol abuse, or current weekly alcohol consumption \>14 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol) 34. Use of probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other uricosuric agents 35. Chronic tinnitus.