The purpose of this research study is to investigate the role of chemical reactions, such as inflammation and oxidation, in the cause of cardiac dysfunction (the heart does not function properly). The investigators are interested in studying the various chemical pathways for cell damage to determine which are the most prevalent and/or most important. The investigators also want to determine whether waste products of oxidative damage or other chemicals can be monitored in the blood or urine and serve as an indication of the existence and severity of overall heart disease activity. The investigators further want to determine whether certain proteins, called enzymes, affect this cell damage, or whether the presence or absence of certain genes which create different forms of these enzymes correlate with the development of heart failure or cardiomyopathy (weakening of the heart muscle or a change in heart muscle structure) or other cardiovascular diseases.

This is a single-center study conducted at the Cleveland Clinic. The target population for this study is very broad and goes beyond any specific cohort or community. Participants will be mainly recruited from the greater Cleveland/Akron area, but any volunteer meeting the inclusion/exclusion criteria is eligible for participation.

The overall goal of the Cleveland Heart And Metabolic Prevention Study (CHAMPS) is to determine the role of nitrative stress in the development and progression of heart failure (HF) and left ventricular systolic dysfunction (LVSD). The investigators have previously developed and performed preliminary clinical validation studies on multiple specific molecular footprints of known pathways of nitric oxide (NO) pathobiology that affect substrate availability for NO production or generation of NO-derived oxidants as a result of nitrative stress. For each these molecular markers and indices, mechanistic links to cardiovascular diseases have been demonstrated. However, these processes may be differentially expressed in different proportions at different stages of LVSD/HF disease progression, and certainly may vary among different individuals. It is the investigators' hypothesis that the interplay of many of these processes contribute to development of subclinical myocardial dysfunction (SMD), and the progression to overt LVSD and HF.

In order to help determine the role of nitrative stress in the development and progression of heart failure and left ventricular systolic dysfunction study participants will receive many non-invasive, research only, procedures as well as a blood draw and urine collection. The procedures performed may include electrocardiogram (ECG), echocardiogram, carotid intima-medial thickness measurements, ankle-brachial index, bioelectrical impedance analysis, pulse wave velocity analysis, spirometry, exhaled nitric oxide analysis, and venous occlusion strain-gauge plethysmography. The specific tests performed on each participant will be at the description of the primary investigator and not all participants will receive all tests. All participants will have blood and urine collections and all participants will be asked to fill out questionnaires pertaining to family history, personal medical history and estimates of functional capacity.

Specific aims include:

Aim 1: To test the hypothesis that levels of specific nitric oxide (NO)-mediated processes are associated with the presence of SMD and LVSD/HF.

Aim 2: To test the hypothesis that levels of specific NO-mediated processes are associated with prospective risks for development of adverse cardiovascular events and overt HF in stable patients without LVSD/HF at baseline.

Inclusion Criteria:

• Either age 40 years or older OR age 18 years or older with a family history of heart failure or cardiac dysfunction (the heart does not function properly).
• Able and willing to consent to the study protocol, including an overnight (≥10 hour) fast.

Exclusion Criteria:

• Known history of heart failure or cardiomyopathy (LVSD, defined by left ventricular ejection fraction ≤45%) at the time of enrollment
• Major cardiovascular event (myocardial infarction, unstable angina, stroke, transient ischemic attack, pulmonary embolism), or major surgery <1 month of enrollment of present study (subject can be considered enrollment after 1 month if deemed clinically stable)
• Any hospitalization or emergency room visits for any cause <1 month of enrollment present study
• Known life expectancy <6 months at the time of enrollment.

Healthy volunteers