Cleveland Heart and Metabolic Prevention Study

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.