<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03012022</url>
  </required_header>
  <id_info>
    <org_study_id>10-727</org_study_id>
    <secondary_id>1R01HL103931</secondary_id>
    <nct_id>NCT03012022</nct_id>
  </id_info>
  <brief_title>Cleveland Heart and Metabolic Prevention Study</brief_title>
  <acronym>CHAMPS</acronym>
  <official_title>Nitrative Stress in Heart Failure: The Cleveland Heart and Metabolic Prevention Study (CHAMPS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to investigate the role of chemical reactions, such as&#xD;
      inflammation and oxidation, in the cause of cardiac dysfunction (the heart does not function&#xD;
      properly). The investigators are interested in studying the various chemical pathways for&#xD;
      cell damage to determine which are the most prevalent and/or most important. The&#xD;
      investigators also want to determine whether waste products of oxidative damage or other&#xD;
      chemicals can be monitored in the blood or urine and serve as an indication of the existence&#xD;
      and severity of overall heart disease activity. The investigators further want to determine&#xD;
      whether certain proteins, called enzymes, affect this cell damage, or whether the presence or&#xD;
      absence of certain genes which create different forms of these enzymes correlate with the&#xD;
      development of heart failure or cardiomyopathy (weakening of the heart muscle or a change in&#xD;
      heart muscle structure) or other cardiovascular diseases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center study conducted at the Cleveland Clinic. The target population for&#xD;
      this study is very broad and goes beyond any specific cohort or community. Participants will&#xD;
      be mainly recruited from the greater Cleveland/Akron area, but any volunteer meeting the&#xD;
      inclusion/exclusion criteria is eligible for participation.&#xD;
&#xD;
      The overall goal of the Cleveland Heart And Metabolic Prevention Study (CHAMPS) is to&#xD;
      determine the role of nitrative stress in the development and progression of heart failure&#xD;
      (HF) and left ventricular systolic dysfunction (LVSD). The investigators have previously&#xD;
      developed and performed preliminary clinical validation studies on multiple specific&#xD;
      molecular footprints of known pathways of nitric oxide (NO) pathobiology that affect&#xD;
      substrate availability for NO production or generation of NO-derived oxidants as a result of&#xD;
      nitrative stress. For each these molecular markers and indices, mechanistic links to&#xD;
      cardiovascular diseases have been demonstrated. However, these processes may be&#xD;
      differentially expressed in different proportions at different stages of LVSD/HF disease&#xD;
      progression, and certainly may vary among different individuals. It is the investigators'&#xD;
      hypothesis that the interplay of many of these processes contribute to development of&#xD;
      subclinical myocardial dysfunction (SMD), and the progression to overt LVSD and HF.&#xD;
&#xD;
      In order to help determine the role of nitrative stress in the development and progression of&#xD;
      heart failure and left ventricular systolic dysfunction study participants will receive many&#xD;
      non-invasive, research only, procedures as well as a blood draw and urine collection. The&#xD;
      procedures performed may include electrocardiogram (ECG), echocardiogram, carotid&#xD;
      intima-medial thickness measurements, ankle-brachial index, bioelectrical impedance analysis,&#xD;
      pulse wave velocity analysis, spirometry, exhaled nitric oxide analysis, and venous occlusion&#xD;
      strain-gauge plethysmography. The specific tests performed on each participant will be at the&#xD;
      description of the primary investigator and not all participants will receive all tests. All&#xD;
      participants will have blood and urine collections and all participants will be asked to fill&#xD;
      out questionnaires pertaining to family history, personal medical history and estimates of&#xD;
      functional capacity.&#xD;
&#xD;
      Specific aims include:&#xD;
&#xD;
      Aim 1: To test the hypothesis that levels of specific nitric oxide (NO)-mediated processes&#xD;
      are associated with the presence of SMD and LVSD/HF.&#xD;
&#xD;
      Aim 2: To test the hypothesis that levels of specific NO-mediated processes are associated&#xD;
      with prospective risks for development of adverse cardiovascular events and overt HF in&#xD;
      stable patients without LVSD/HF at baseline.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 2010</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between metabolic and/or nitrative stress markers and predefined clinical endpoints</measure>
    <time_frame>10 years</time_frame>
    <description>Clinical endpoints include acute myocardial infarction, acute coronary syndrome, congestive heart failure, serious cardiac arrhythmia, peripheral vascular disease, cerebrovascular events and death. Events will be aggregated into a common category (e.g. MACE) for statistical analysis and reporting. These aggregated events data will then be correlated with each biomarker of interest.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determination of sub-clinical myocardial dysfunction by echocardiogram</measure>
    <time_frame>10 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between functional capacity, as measured by the Duke Activity Status Index (DASI) questionnaire, and markers of metabolic and nitrative stress</measure>
    <time_frame>10 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between functional capacity, as measured by the SF36 version 2 questionnaire, and markers of metabolic and nitrative stress</measure>
    <time_frame>10 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between functional capacity, as measured by DASI questionnaire, and markers of cardiac dysfunction</measure>
    <time_frame>10 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between functional capacity, as measured by SF36 version 2 questionnaire, and markers of cardiac dysfunction</measure>
    <time_frame>10 years</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1208</enrollment>
  <condition>Heart Failure Risk Factors in Healthy Individuals</condition>
  <arm_group>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <description>Volunteers without known cardiomyopathy or heart failure</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole Blood, Serum, Plasma, Red Blood Cells, Buffy Coat, Urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy volunteers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Either age 40 years or older OR age 18 years or older with a family history of heart&#xD;
             failure or cardiac dysfunction (the heart does not function properly).&#xD;
&#xD;
          -  Able and willing to consent to the study protocol, including an overnight (≥10 hour)&#xD;
             fast.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known history of heart failure or cardiomyopathy (LVSD, defined by left ventricular&#xD;
             ejection fraction ≤45%) at the time of enrollment&#xD;
&#xD;
          -  Major cardiovascular event (myocardial infarction, unstable angina, stroke, transient&#xD;
             ischemic attack, pulmonary embolism), or major surgery &lt;1 month of enrollment of&#xD;
             present study (subject can be considered enrollment after 1 month if deemed clinically&#xD;
             stable)&#xD;
&#xD;
          -  Any hospitalization or emergency room visits for any cause &lt;1 month of enrollment&#xD;
             present study&#xD;
&#xD;
          -  Known life expectancy &lt;6 months at the time of enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>W. H. Wilson Tang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Abu-Soud HM, Hazen SL. Nitric oxide is a physiological substrate for mammalian peroxidases. J Biol Chem. 2000 Dec 1;275(48):37524-32. doi: 10.1074/jbc.275.48.37524.</citation>
    <PMID>11090610</PMID>
  </reference>
  <reference>
    <citation>Shiva S, Wang X, Ringwood LA, Xu X, Yuditskaya S, Annavajjhala V, Miyajima H, Hogg N, Harris ZL, Gladwin MT. Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis. Nat Chem Biol. 2006 Sep;2(9):486-93. doi: 10.1038/nchembio813. Epub 2006 Aug 13.</citation>
    <PMID>16906150</PMID>
  </reference>
  <reference>
    <citation>Tang WH, Wang Z, Cho L, Brennan DM, Hazen SL. Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk. J Am Coll Cardiol. 2009 Jun 2;53(22):2061-7. doi: 10.1016/j.jacc.2009.02.036.</citation>
    <PMID>19477356</PMID>
  </reference>
  <reference>
    <citation>Mullens W, Abrahams Z, Francis GS, Sokos G, Starling RC, Young JB, Taylor DO, Tang WH. Usefulness of Isosorbide Dinitrate and Hydralazine as add-on therapy in patients discharged for advanced decompensated heart failure. Am J Cardiol. 2009 Apr 15;103(8):1113-9. doi: 10.1016/j.amjcard.2008.12.028. Epub 2009 Feb 21.</citation>
    <PMID>19361599</PMID>
  </reference>
  <reference>
    <citation>Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R Jr, Ferdinand K, Taylor M, Adams K, Sabolinski M, Worcel M, Cohn JN; African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004 Nov 11;351(20):2049-57. doi: 10.1056/NEJMoa042934. Epub 2004 Nov 8. Erratum In: N Engl J Med. 2005 Mar 24;352(12):1276.</citation>
    <PMID>15533851</PMID>
  </reference>
  <reference>
    <citation>Hare JM, Colucci WS. Role of nitric oxide in the regulation of myocardial function. Prog Cardiovasc Dis. 1995 Sep-Oct;38(2):155-66. doi: 10.1016/s0033-0620(05)80004-0.</citation>
    <PMID>7568904</PMID>
  </reference>
  <reference>
    <citation>Elahi MM, Naseem KM, Matata BM. Nitric oxide in blood. The nitrosative-oxidative disequilibrium hypothesis on the pathogenesis of cardiovascular disease. FEBS J. 2007 Feb;274(4):906-23. doi: 10.1111/j.1742-4658.2007.05660.x. Epub 2007 Jan 22.</citation>
    <PMID>17244198</PMID>
  </reference>
  <reference>
    <citation>Champion HC, Skaf MW, Hare JM. Role of nitric oxide in the pathophysiology of heart failure. Heart Fail Rev. 2003 Jan;8(1):35-46. doi: 10.1023/a:1022142904202.</citation>
    <PMID>12652158</PMID>
  </reference>
  <reference>
    <citation>Recchia FA. Role of nitric oxide in the regulation of substrate metabolism in heart failure. Heart Fail Rev. 2002 Apr;7(2):141-8. doi: 10.1023/a:1015324508556.</citation>
    <PMID>11988638</PMID>
  </reference>
  <reference>
    <citation>Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young JB, Taylor DO, Tang WH. Sodium nitroprusside for advanced low-output heart failure. J Am Coll Cardiol. 2008 Jul 15;52(3):200-7. doi: 10.1016/j.jacc.2008.02.083.</citation>
    <PMID>18617068</PMID>
  </reference>
  <reference>
    <citation>Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group. J Card Fail. 1999 Sep;5(3):178-87. doi: 10.1016/s1071-9164(99)90001-5.</citation>
    <PMID>10496190</PMID>
  </reference>
  <reference>
    <citation>Vanderheyden M, Bartunek J, Knaapen M, Kockx M, De Bruyne B, Goethals M. Hemodynamic effects of inducible nitric oxide synthase and nitrotyrosine generation in heart failure. J Heart Lung Transplant. 2004 Jun;23(6):723-8. doi: 10.1016/j.healun.2003.07.015.</citation>
    <PMID>15366433</PMID>
  </reference>
  <reference>
    <citation>Pacher P, Schulz R, Liaudet L, Szabo C. Nitrosative stress and pharmacological modulation of heart failure. Trends Pharmacol Sci. 2005 Jun;26(6):302-10. doi: 10.1016/j.tips.2005.04.003.</citation>
    <PMID>15925705</PMID>
  </reference>
  <reference>
    <citation>Reinartz M, Ding Z, Flogel U, Godecke A, Schrader J. Nitrosative stress leads to protein glutathiolation, increased s-nitrosation, and up-regulation of peroxiredoxins in the heart. J Biol Chem. 2008 Jun 20;283(25):17440-9. doi: 10.1074/jbc.M800126200. Epub 2008 Apr 21.</citation>
    <PMID>18426799</PMID>
  </reference>
  <reference>
    <citation>Ungvari Z, Gupte SA, Recchia FA, Batkai S, Pacher P. Role of oxidative-nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure. Curr Vasc Pharmacol. 2005 Jul;3(3):221-9. doi: 10.2174/1570161054368607.</citation>
    <PMID>16026319</PMID>
  </reference>
  <reference>
    <citation>Shishehbor MH, Aviles RJ, Brennan ML, Fu X, Goormastic M, Pearce GL, Gokce N, Keaney JF Jr, Penn MS, Sprecher DL, Vita JA, Hazen SL. Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. JAMA. 2003 Apr 2;289(13):1675-80. doi: 10.1001/jama.289.13.1675.</citation>
    <PMID>12672736</PMID>
  </reference>
  <reference>
    <citation>Shishehbor MH, Brennan ML, Aviles RJ, Fu X, Penn MS, Sprecher DL, Hazen SL. Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation. 2003 Jul 29;108(4):426-31. doi: 10.1161/01.CIR.0000080895.05158.8B. Epub 2003 Jul 14.</citation>
    <PMID>12860913</PMID>
  </reference>
  <reference>
    <citation>Hazen SL, Zhang R, Shen Z, Wu W, Podrez EA, MacPherson JC, Schmitt D, Mitra SN, Mukhopadhyay C, Chen Y, Cohen PA, Hoff HF, Abu-Soud HM. Formation of nitric oxide-derived oxidants by myeloperoxidase in monocytes: pathways for monocyte-mediated protein nitration and lipid peroxidation In vivo. Circ Res. 1999 Nov 12;85(10):950-8. doi: 10.1161/01.res.85.10.950.</citation>
    <PMID>10559142</PMID>
  </reference>
  <reference>
    <citation>Abu-Soud HM, Hazen SL. Nitric oxide modulates the catalytic activity of myeloperoxidase. J Biol Chem. 2000 Feb 25;275(8):5425-30. doi: 10.1074/jbc.275.8.5425.</citation>
    <PMID>10681518</PMID>
  </reference>
  <reference>
    <citation>Podrez EA, Schmitt D, Hoff HF, Hazen SL. Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro. J Clin Invest. 1999 Jun;103(11):1547-60. doi: 10.1172/JCI5549.</citation>
    <PMID>10359564</PMID>
  </reference>
  <reference>
    <citation>Parastatidis I, Thomson L, Fries DM, Moore RE, Tohyama J, Fu X, Hazen SL, Heijnen HF, Dennehy MK, Liebler DC, Rader DJ, Ischiropoulos H. Increased protein nitration burden in the atherosclerotic lesions and plasma of apolipoprotein A-I deficient mice. Circ Res. 2007 Aug 17;101(4):368-76. doi: 10.1161/CIRCRESAHA.107.157537. Epub 2007 Jul 5.</citation>
    <PMID>17615369</PMID>
  </reference>
  <reference>
    <citation>Leeuwenburgh C, Hardy MM, Hazen SL, Wagner P, Oh-ishi S, Steinbrecher UP, Heinecke JW. Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerotic intima. J Biol Chem. 1997 Jan 17;272(3):1433-6. doi: 10.1074/jbc.272.3.1433.</citation>
    <PMID>8999808</PMID>
  </reference>
  <reference>
    <citation>Zheng L, Nukuna B, Brennan ML, Sun M, Goormastic M, Settle M, Schmitt D, Fu X, Thomson L, Fox PL, Ischiropoulos H, Smith JD, Kinter M, Hazen SL. Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Invest. 2004 Aug;114(4):529-41. doi: 10.1172/JCI21109.</citation>
    <PMID>15314690</PMID>
  </reference>
  <reference>
    <citation>Wu Z, Wagner MA, Zheng L, Parks JS, Shy JM 3rd, Smith JD, Gogonea V, Hazen SL. The refined structure of nascent HDL reveals a key functional domain for particle maturation and dysfunction. Nat Struct Mol Biol. 2007 Sep;14(9):861-8. doi: 10.1038/nsmb1284. Epub 2007 Aug 5. Erratum In: Nat Struct Mol Biol. 2008 Jun;15(6):651. Nat Struct Mol Biol. 2008 Mar;15(3):330.</citation>
    <PMID>17676061</PMID>
  </reference>
  <reference>
    <citation>Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, Goormastic M, Pepoy ML, McErlean ES, Topol EJ, Nissen SE, Hazen SL. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med. 2003 Oct 23;349(17):1595-604. doi: 10.1056/NEJMoa035003.</citation>
    <PMID>14573731</PMID>
  </reference>
  <reference>
    <citation>Vita JA, Brennan ML, Gokce N, Mann SA, Goormastic M, Shishehbor MH, Penn MS, Keaney JF Jr, Hazen SL. Serum myeloperoxidase levels independently predict endothelial dysfunction in humans. Circulation. 2004 Aug 31;110(9):1134-9. doi: 10.1161/01.CIR.0000140262.20831.8F. Epub 2004 Aug 23.</citation>
    <PMID>15326065</PMID>
  </reference>
  <reference>
    <citation>Meuwese MC, Stroes ES, Hazen SL, van Miert JN, Kuivenhoven JA, Schaub RG, Wareham NJ, Luben R, Kastelein JJ, Khaw KT, Boekholdt SM. Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol. 2007 Jul 10;50(2):159-65. doi: 10.1016/j.jacc.2007.03.033. Epub 2007 Jun 21.</citation>
    <PMID>17616301</PMID>
  </reference>
  <reference>
    <citation>Tang WH, Tong W, Shrestha K, Wang Z, Levison BS, Delfraino B, Hu B, Troughton RW, Klein AL, Hazen SL. Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure. Eur Heart J. 2008 Oct;29(20):2506-13. doi: 10.1093/eurheartj/ehn360. Epub 2008 Aug 6.</citation>
    <PMID>18687662</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Wilson Tang</investigator_full_name>
    <investigator_title>Principal Investigator, Staff Cellular and Molecular Medicine and Cardiovascular Medicine, The Cleveland Clinic</investigator_title>
  </responsible_party>
  <keyword>Healthy Volunteers</keyword>
  <keyword>Congestive Heart Failure</keyword>
  <keyword>Cardiomyopathies</keyword>
  <keyword>Heart Failure</keyword>
  <keyword>Risk Factors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03012022
org study id: 10-727
secondary id: 1R01HL103931
nct id: NCT03012022
lead sponsor: 
collaborator: 
has dmc: No
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.
observational model: Other
time perspective: Prospective
measure: Correlation between metabolic and/or nitrative stress markers and predefined clinical endpoints
time frame: 10 years
description: Clinical endpoints include acute myocardial infarction, acute coronary syndrome, congestive heart failure, serious cardiac arrhythmia, peripheral vascular disease, cerebrovascular events and death. Events will be aggregated into a common category (e.g. MACE) for statistical analysis and reporting. These aggregated events data will then be correlated with each biomarker of interest.
measure: Determination of sub-clinical myocardial dysfunction by echocardiogram
time frame: 10 years
measure: Correlation between functional capacity, as measured by the Duke Activity Status Index (DASI) questionnaire, and markers of metabolic and nitrative stress
time frame: 10 years
measure: Correlation between functional capacity, as measured by the SF36 version 2 questionnaire, and markers of metabolic and nitrative stress
time frame: 10 years
measure: Correlation between functional capacity, as measured by DASI questionnaire, and markers of cardiac dysfunction
time frame: 10 years
measure: Correlation between functional capacity, as measured by SF36 version 2 questionnaire, and markers of cardiac dysfunction
time frame: 10 years
arm group label: Healthy Volunteers
description: Volunteers without known cardiomyopathy or heart failure
Whole Blood, Serum, Plasma, Red Blood Cells, Buffy Coat, Urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: W. H. Wilson Tang, MD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
citation: Abu-Soud HM, Hazen SL. Nitric oxide is a physiological substrate for mammalian peroxidases. J Biol Chem. 2000 Dec 1;275(48):37524-32. doi: 10.1074/jbc.275.48.37524.
PMID: 11090610
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responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Wilson Tang
investigator title: Principal Investigator, Staff Cellular and Molecular Medicine and Cardiovascular Medicine, The Cleveland Clinic
mesh term: Heart Failure
sharing ipd: No