Hormones and Sexual Function Predict Outcomes in Revascularized Men With Diabetes
Hormones and Sexual Function Predict Outcomes in Revascularized Men With Diabetes
The purpose of this study is to find out if androgen deficiency (low levels of testosterone,
 a male hormone produced by the sex glands) and erectile dysfunction (sexual dysfunction) will
 predict over time the development of a heart attack, stroke, or death in men with Diabetes
 Mellitus who have angiographically proven coronary artery disease (CAD) (≥50%) with or
 without percutaneous coronary intervention (PCI). A substudy aims to show the different
 factors and processes that may show a relationship between sexual function and levels of
 androgen in the body to heart disease.
Diabetes mellitus (DM) and multi-vessel coronary artery disease (CAD) entail significant risk
 for progression of cardiac morbidity and mortality. Compelling recent research points to
 biological pathways that link DM and CAD to androgen status and sexual function. We
 hypothesize that androgen deficiency (AD) and erectile dysfunction (ED) independently serve
 as sentinel indicators, predicting the future development of adverse cardiovascular and
 cerebrovascular events in men with diabetes following coronary revascularization.

 ED is emerging as a barometer of overall endothelial function. We hypothesize that as a
 consequence of this relationship, erectile dysfunction is predictive of cardiovascular
 outcomes in men with diabetes and CAD. We also propose that AD affects morbidity and
 mortality in men with DM and CAD by influencing presentation and progression of endothelial
 dysfunction as well as inflammation and hemostasis.

 We propose to investigate four specific aims using 1,143 diabetic men who have
 angiographically proven coronary artery disease (CAD) (≥50%) in at least one major epicardial
 vessel with or without percutaneous coronary intervention (PCI). Specific aims of this study
 are: 1) To determine whether androgen status at baseline independently predicts primary and
 secondary endpoints in men (n=1,143) with DM and CAD. 2) To determine whether erectile
 dysfunction at baseline independently predicts cardiovascular outcomes in men with DM and
 CAD. 3) To determine whether change of androgen status and sexual function over time
 independently predict cardiovascular outcomes in men with DM and CAD. 4) To demonstrate
 specific mediators and pathways that link sexual function and androgen status to
 cardiovascular disease.

 The primary endpoint is defined as the combined all-cause mortality, non-fatal myocardial
 infarction (MI), and stroke. Secondary endpoints include major adverse cardiovascular and
 cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at
 one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6
 months, 12 months, 18 months, 24 months, 30 months and 36 months following catheterization.
Inclusion Criteria:

 -  Male age [18-75 years];

 -  Type 2 Diabetes, defined according to the American Diabetes Association as history of:
 a) presence of classic symptoms of DM with unequivocal elevation of plasma glucose
 (2-hour post-prandial or random of >200 mg/dL (11mmol/L), b) fasting plasma glucose
 elevation on more than 1 occasion of at least 126 mg/dL (7mmol/L) or c) HA1C > 6.5,
 currently undergoing pharmacological or non-pharmacological treatment;

 -  Angiographically confirmed Coronary Artery Disease (≥50%) with or without PCI;

 -  Indication for revascularization based upon symptoms of angina and/or objective
 evidence of myocardial ischemia;

 -  Willingness to comply with all follow-up required study visits; and

 -  Signed and received copy of informed consent

 Exclusion Criteria:

 -  Severe congestive heart failure (class III or IV according to NYHA, or pulmonary
 edema) at the time of enrollment;

 -  Previous stroke within 6 months;

 -  Prior history of significant bleeding (within the previous 6 months) that might be
 expected to occur during PCI/DES related anticoagulation;

 -  Acute ST-elevation MI (Q-wave) within 72 hours prior to enrollment requiring
 revascularization;

 -  Abnormal creatine kinase (CK > 2x normal); or abnormal CK-MB levels at time of
 randomization;

 -  Contraindication to either CABG or PCI/DES because of a coexisting clinical
 condition];

 -  Significant leukopenia, neutropenia, thrombocytopenia, anemia, or known bleeding
 diathesis;

 -  Intolerance or contraindication to aspirin or both clopidogrel and ticlopidine;

 -  Dementia with a Mini Mental Status Examination (MMSE) score of <20;

 -  Extra-cardiac illness that is expected to limit survival to less than 5 years (e.g.
 oxygen-dependent chronic obstructive pulmonary disease, active hepatitis or
 significant hepatic failure, severe renal disease);

 -  Geographically inaccessible for follow-up visits required by protocol.

 -  Additional Ancillary Study Exclusions. Exclusion criteria that are unique to the
 proposed study are prior use of hormonal therapy (HRT) with testosterone in men at
 baseline and current use of sex-hormone antagonist medications at baseline.