<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/NCT04495231</url>
  </required_header>
  <id_info>
    <org_study_id>SympAct 1</org_study_id>
    <nct_id>NCT04495231</nct_id>
  </id_info>
  <brief_title>Sympathetic Activity and Cardiometabolic Complications</brief_title>
  <acronym>SYMPACT</acronym>
  <official_title>Association Between Enhanced Sympathetic Activity and Cardiometabolic Complications: a Cross-sectional Study on Predictive Power of 24-hour Urinary Metanephrines (SYMPACT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Turin, Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Turin, Italy</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recent studies on catecholamine physiology have shown a direct correlation with arterial&#xD;
      hypertension, overcoming the exclusive role in the diagnosis and follow-up of chromaffin&#xD;
      tumors.&#xD;
&#xD;
      Nevertheless, in literature, few studies explore and reveal the utility of testing&#xD;
      metanephrines for the evaluation of sympathetic activity and its associated cardiometabolic&#xD;
      complications in patients with essential hypertension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Catecholamines (noradrenaline, adrenaline and dopamine) are adaptive and maladaptive stress&#xD;
      hormones.&#xD;
&#xD;
      In the classic &quot;fight or flight&quot; mechanism, they activate behavioral and physiological&#xD;
      processes that facilitate the overcoming of stress; for instance, challenged by a physical&#xD;
      stressor, an organism responds to the threat either fighting and prevailing or accepting&#xD;
      defeat and fleeing in avoidance.&#xD;
&#xD;
      In the pathological context, an excessive catecholamine secretion is typical of the&#xD;
      chromaffin tissue tumors, determining a clinical picture characterized by blood pressure&#xD;
      elevation, tachycardia, anxiety, pallor, sweating and headache.&#xD;
&#xD;
      COMT enzyme catalyzes the O-methylation of the 3-hydroxyl group of catecholamines. The&#xD;
      O-methylated derivatives of noradrenaline, adrenaline and dopamine are normetanephrine,&#xD;
      metanephrine and 3-methoxytyramine, respectively. The term &quot;metanephrines&quot; is generally used&#xD;
      to collectively refer to the first two compounds.&#xD;
&#xD;
      Compared to catecholamines, metanephrines are characterized by longer half-life and more&#xD;
      stable levels over time. Their superior accuracy for the diagnosis and follow-up of&#xD;
      pheochromocytoma and paraganglioma (PPGL) has been widely proved.&#xD;
&#xD;
      Excluding patients with PPGL, however, metanephrines can be more broadly considered as&#xD;
      reliable markers of the whole sympathetic system activity; therefore, their levels may be&#xD;
      hypothesized to be associated to a higher rate of concurrent cardiometabolic complications&#xD;
      and, if so, could be useful for the stratification of cardiovascular risk.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2007</start_date>
  <completion_date type="Actual">July 1, 2020</completion_date>
  <primary_completion_date type="Actual">July 1, 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Presence of left ventricular hypertrophy</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of the presence of left ventricular hypertrophy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of chronic kidney disease</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of the presence of chronic kidney disease</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of type 2 diabetes mellitus</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of the presence of type 2 diabetes mellitus</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of metabolic syndrome</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of the presence of metabolic syndrome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Systolic blood pressure (SBP)</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of systolic blood pressure values (mmHg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diastolic blood pressure (DBP)</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of diastolic blood pressure values (mmHg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resting heart rate</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of resting heart rate (bpm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of eGFR values (ml/min, as estimated by CKD-EPI formula)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary albumin/creatinine ratio</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of albumin/creatinine ratio values (mg/mmol)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting glucose</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of fasting glucose values (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cholesterol</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of total cholesterol values (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HDL cholesterol</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of HDL cholesterol values (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LDL cholesterol</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of LDL cholesterol values (mg/dl, as estimated by Friedewald formula)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Triglycerides</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of triglycerides values (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index (BMI)</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of BMI values (kg/m2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular risk as estimated by Framingham Risk Score (FRS)</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of cardiovascular risk as estimated by FRS; FRS is expressed as a percentage, with higher values indicating higher risk; patients in which the risk estimation is not applicable will be excluded from the analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular risk as estimated by Systematic COronary Risk Evaluation (SCORE)</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of cardiovascular risk as estimated by SCORE; SCORE is expressed as a percentage, with higher values indicating higher risk; patients in which the risk estimation is not applicable will be excluded from the analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular risk as estimated by Progetto Cuore Score (english translation: &quot;Heart Project Score&quot;)</measure>
    <time_frame>At baseline</time_frame>
    <description>The value of urinary metanephrines will be evaluated as a possible predictor of cardiovascular risk as estimated by Progetto Cuore Score; Progetto Cuore Score is expressed as a percentage, with higher values indicating higher risk; patients in which the risk estimation is not applicable will be excluded from the analysis</description>
  </secondary_outcome>
  <enrollment type="Actual">1380</enrollment>
  <condition>Catecholamine; Overproduction</condition>
  <condition>Catecholamine; Secretion</condition>
  <condition>Metabolic Syndrome</condition>
  <condition>Hypertensive Heart Disease</condition>
  <condition>Hypertensive Kidney Disease</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Hypertension,Essential</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All patients who performed a 24h urinary metanephrines assay at the laboratory of &quot;City of&#xD;
        Health and Science&quot; hospital in Turin between 2007 and 2015, with availability of full&#xD;
        clinical data due to hospitalization at the same hospital contextually to the dosage or&#xD;
        within ± 6 months. Exclusion criteria are specified in the appropriate section.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Measurement of 24h urinary metanephrines at the laboratory of &quot;City of Health and&#xD;
             Science&quot; hospital in Turin between 2007 and 2015&#xD;
&#xD;
          -  Availability of contextual clinical patient data as collected in prospective&#xD;
             registries of Piedmont region&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of pheochromocytoma or paraganglioma (at the time of urinary metanephrines&#xD;
             collection or within the following 5 years)&#xD;
&#xD;
          -  Diagnosis of other forms of secondary hypertension&#xD;
&#xD;
          -  Previous cardiovascular or cerebrovascular event&#xD;
&#xD;
          -  Chronic heart failure&#xD;
&#xD;
          -  eGFR &lt; 50 ml/min (according to CKD-EPI)&#xD;
&#xD;
          -  Liver cirrhosis&#xD;
&#xD;
          -  Acute conditions and/or hospitalization in ICU (at the time of urinary metanephrines&#xD;
             collection)&#xD;
&#xD;
          -  Assumption of acetaminophen during the day before the 24-hour urine collection&#xD;
&#xD;
          -  Therapy with labetalol&#xD;
&#xD;
          -  Therapy with sotalol&#xD;
&#xD;
          -  Therapy with alpha-methyldopa&#xD;
&#xD;
          -  Therapy with MAO inhibitors&#xD;
&#xD;
          -  Therapy with tricyclic antidepressants&#xD;
&#xD;
          -  Therapy with buspirone&#xD;
&#xD;
          -  Therapy with phenoxybenzamine&#xD;
&#xD;
          -  Therapy with sulfasalazine&#xD;
&#xD;
          -  Therapy with L-Dopa&#xD;
&#xD;
          -  Therapy with sympathomimetic drugs or other vasopressors&#xD;
&#xD;
          -  Alcohol abuse&#xD;
&#xD;
          -  Cocaine abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mauro Maccario, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Endocrinology, Diabetology and Metabolism; University of Turin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ezio Ghigo, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Endocrinology, Diabetology and Metabolism; University of Turin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Endocrinology, Diabetology and Metabolism; University of Turin</name>
      <address>
        <city>Torino</city>
        <state>Piemonte</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Ton QV, Hammes SR. Recent insights on circulating catecholamines in hypertension. Curr Hypertens Rep. 2014 Dec;16(12):498. doi: 10.1007/s11906-014-0498-9.</citation>
    <PMID>25304108</PMID>
  </reference>
  <reference>
    <citation>Esler M. The sympathetic nervous system in hypertension: back to the future? Curr Hypertens Rep. 2015 Feb;17(2):11. doi: 10.1007/s11906-014-0519-8.</citation>
    <PMID>25680900</PMID>
  </reference>
  <reference>
    <citation>Coulson JM. The relationship between blood pressure variability and catecholamine metabolites: a pilot study. J Hum Hypertens. 2015 Jan;29(1):50-2. doi: 10.1038/jhh.2014.23. Epub 2014 Apr 3.</citation>
    <PMID>24694800</PMID>
  </reference>
  <reference>
    <citation>Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498. Erratum In: J Clin Endocrinol Metab. 2023 Apr 13;108(5):e200.</citation>
    <PMID>24893135</PMID>
  </reference>
  <reference>
    <citation>Okuyama Y, Sakata Y. [Device treatment approaches targeting the sympathetic nervous system in patients with resistant hypertension]. Nihon Rinsho. 2015 Nov;73(11):1857-63. Japanese.</citation>
    <PMID>26619659</PMID>
  </reference>
  <reference>
    <citation>Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension. Circ Res. 2015 Mar 13;116(6):976-90. doi: 10.1161/CIRCRESAHA.116.303604.</citation>
    <PMID>25767284</PMID>
  </reference>
  <reference>
    <citation>Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.</citation>
    <PMID>20226988</PMID>
  </reference>
  <reference>
    <citation>Esler M, Lambert G, Jennings G. Increased regional sympathetic nervous activity in human hypertension: causes and consequences. J Hypertens Suppl. 1990 Dec;8(7):S53-7.</citation>
    <PMID>1965656</PMID>
  </reference>
  <reference>
    <citation>Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004 Sep;56(3):331-49. doi: 10.1124/pr.56.3.1.</citation>
    <PMID>15317907</PMID>
  </reference>
  <reference>
    <citation>Tank AW, Lee Wong D. Peripheral and central effects of circulating catecholamines. Compr Physiol. 2015 Jan;5(1):1-15. doi: 10.1002/cphy.c140007.</citation>
    <PMID>25589262</PMID>
  </reference>
  <reference>
    <citation>Goldstein DS, Eisenhofer G, Kopin IJ. Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther. 2003 Jun;305(3):800-11. doi: 10.1124/jpet.103.049270. Epub 2003 Mar 20.</citation>
    <PMID>12649306</PMID>
  </reference>
  <reference>
    <citation>Eisenhofer G, Friberg P, Pacak K, Goldstein DS, Murphy DL, Tsigos C, Quyyumi AA, Brunner HG, Lenders JW. Plasma metadrenalines: do they provide useful information about sympatho-adrenal function and catecholamine metabolism? Clin Sci (Lond). 1995 May;88(5):533-42. doi: 10.1042/cs0880533.</citation>
    <PMID>7614812</PMID>
  </reference>
  <reference>
    <citation>Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension. 2003 Oct;42(4):474-80. doi: 10.1161/01.HYP.0000091371.53502.D3. Epub 2003 Sep 2.</citation>
    <PMID>12953019</PMID>
  </reference>
  <reference>
    <citation>Dudenbostel T, Acelajado MC, Pisoni R, Li P, Oparil S, Calhoun DA. Refractory Hypertension: Evidence of Heightened Sympathetic Activity as a Cause of Antihypertensive Treatment Failure. Hypertension. 2015 Jul;66(1):126-33. doi: 10.1161/HYPERTENSIONAHA.115.05449. Epub 2015 May 18.</citation>
    <PMID>25987662</PMID>
  </reference>
  <reference>
    <citation>Flaa A, Aksnes TA, Kjeldsen SE, Eide I, Rostrup M. Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study. Metabolism. 2008 Oct;57(10):1422-7. doi: 10.1016/j.metabol.2008.05.012.</citation>
    <PMID>18803948</PMID>
  </reference>
  <reference>
    <citation>Masuo K, Mikami H, Ogihara T, Tuck ML. Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population. Am J Hypertens. 1997 Jan;10(1):77-83. doi: 10.1016/s0895-7061(96)00303-2.</citation>
    <PMID>9008251</PMID>
  </reference>
  <reference>
    <citation>Quarti Trevano F, Dell'Oro R, Biffi A, Seravalle G, Corrao G, Mancia G, Grassi G. Sympathetic overdrive in the metabolic syndrome: meta-analysis of published studies. J Hypertens. 2020 Apr;38(4):565-572. doi: 10.1097/HJH.0000000000002288.</citation>
    <PMID>32132429</PMID>
  </reference>
  <reference>
    <citation>Mancia G, Bousquet P, Elghozi JL, Esler M, Grassi G, Julius S, Reid J, Van Zwieten PA. The sympathetic nervous system and the metabolic syndrome. J Hypertens. 2007 May;25(5):909-20. doi: 10.1097/HJH.0b013e328048d004.</citation>
    <PMID>17414649</PMID>
  </reference>
  <reference>
    <citation>Straznicky NE, Grima MT, Sari CI, Karapanagiotidis S, Wong C, Eikelis N, Richards KL, Lee G, Nestel PJ, Dixon JB, Lambert GW, Schlaich MP, Lambert EA. The relation of glucose metabolism to left ventricular mass and function and sympathetic nervous system activity in obese subjects with metabolic syndrome. J Clin Endocrinol Metab. 2013 Feb;98(2):E227-37. doi: 10.1210/jc.2012-3277. Epub 2012 Dec 27.</citation>
    <PMID>23271752</PMID>
  </reference>
  <reference>
    <citation>Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation. 2003 Aug 5;108(5):560-5. doi: 10.1161/01.CIR.0000081775.72651.B6. Epub 2003 Jul 7.</citation>
    <PMID>12847071</PMID>
  </reference>
  <reference>
    <citation>Wang W, Mu L, Su T, Ye L, Jiang Y, Jiang L, Zhou W. Plasma Metanephrines Are Associated With Glucose Metabolism in Patients With Essential Hypertension. Medicine (Baltimore). 2015 Sep;94(37):e1496. doi: 10.1097/MD.0000000000001496.</citation>
    <PMID>26376391</PMID>
  </reference>
  <reference>
    <citation>Brown MJ, Causon RC, Barnes VF, Brennan P, Barnes G, Greenberg G. Urinary catecholamines in essential hypertension: results of 24-hour urine catecholamine analyses from patients in the Medical Research Council trial for mild hypertension and from matched controls. Q J Med. 1985 Oct;57(222):637-51.</citation>
    <PMID>4080953</PMID>
  </reference>
  <reference>
    <citation>Zhou Y, Yuan J, Wang Y, Qiao S. Plasma metanephrins are associated with myocardial hypertrophy and cardiac diastolic function in patients with essential hypertension. Clin Invest Med. 2020 Apr 5;43(1):E22-E29. doi: 10.25011/cim.v43i1.33581.</citation>
    <PMID>32247299</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Turin, Italy</investigator_affiliation>
    <investigator_full_name>Mauro Maccario</investigator_full_name>
    <investigator_title>Medical Doctor, Professor</investigator_title>
  </responsible_party>
  <keyword>Normetanephrine</keyword>
  <keyword>Metanephrine</keyword>
  <keyword>Sympathetic Nervous System</keyword>
  <keyword>Cardiovascular System</keyword>
  <keyword>Cardiometabolic Complications</keyword>
  <keyword>Catecholamine; Overproduction</keyword>
  <keyword>Catecholamine; Secretion</keyword>
  <keyword>Metabolic Syndrome</keyword>
  <keyword>Hypertensive Heart Disease</keyword>
  <keyword>Hypertensive Kidney Disease</keyword>
  <keyword>Diabetes Mellitus, Type 2</keyword>
  <keyword>Hypertension,Essential</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Essential Hypertension</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</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/NCT04495231
org study id: SympAct 1
nct id: NCT04495231
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Recent studies on catecholamine physiology have shown a direct correlation with arterial
      hypertension, overcoming the exclusive role in the diagnosis and follow-up of chromaffin
      tumors.

      Nevertheless, in literature, few studies explore and reveal the utility of testing
      metanephrines for the evaluation of sympathetic activity and its associated cardiometabolic
      complications in patients with essential hypertension.
Catecholamines (noradrenaline, adrenaline and dopamine) are adaptive and maladaptive stress
      hormones.

      In the classic "fight or flight" mechanism, they activate behavioral and physiological
      processes that facilitate the overcoming of stress; for instance, challenged by a physical
      stressor, an organism responds to the threat either fighting and prevailing or accepting
      defeat and fleeing in avoidance.

      In the pathological context, an excessive catecholamine secretion is typical of the
      chromaffin tissue tumors, determining a clinical picture characterized by blood pressure
      elevation, tachycardia, anxiety, pallor, sweating and headache.

      COMT enzyme catalyzes the O-methylation of the 3-hydroxyl group of catecholamines. The
      O-methylated derivatives of noradrenaline, adrenaline and dopamine are normetanephrine,
      metanephrine and 3-methoxytyramine, respectively. The term "metanephrines" is generally used
      to collectively refer to the first two compounds.

      Compared to catecholamines, metanephrines are characterized by longer half-life and more
      stable levels over time. Their superior accuracy for the diagnosis and follow-up of
      pheochromocytoma and paraganglioma (PPGL) has been widely proved.

      Excluding patients with PPGL, however, metanephrines can be more broadly considered as
      reliable markers of the whole sympathetic system activity; therefore, their levels may be
      hypothesized to be associated to a higher rate of concurrent cardiometabolic complications
      and, if so, could be useful for the stratification of cardiovascular risk.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Presence of left ventricular hypertrophy
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of the presence of left ventricular hypertrophy
measure: Presence of chronic kidney disease
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of the presence of chronic kidney disease
measure: Presence of type 2 diabetes mellitus
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of the presence of type 2 diabetes mellitus
measure: Presence of metabolic syndrome
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of the presence of metabolic syndrome
measure: Systolic blood pressure (SBP)
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of systolic blood pressure values (mmHg)
measure: Diastolic blood pressure (DBP)
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of diastolic blood pressure values (mmHg)
measure: Resting heart rate
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of resting heart rate (bpm)
measure: eGFR
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of eGFR values (ml/min, as estimated by CKD-EPI formula)
measure: Urinary albumin/creatinine ratio
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of albumin/creatinine ratio values (mg/mmol)
measure: Fasting glucose
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of fasting glucose values (mg/dl)
measure: Total cholesterol
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of total cholesterol values (mg/dl)
measure: HDL cholesterol
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of HDL cholesterol values (mg/dl)
measure: LDL cholesterol
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of LDL cholesterol values (mg/dl, as estimated by Friedewald formula)
measure: Triglycerides
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of triglycerides values (mg/dl)
measure: Body Mass Index (BMI)
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of BMI values (kg/m2)
measure: Cardiovascular risk as estimated by Framingham Risk Score (FRS)
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of cardiovascular risk as estimated by FRS; FRS is expressed as a percentage, with higher values indicating higher risk; patients in which the risk estimation is not applicable will be excluded from the analysis
measure: Cardiovascular risk as estimated by Systematic COronary Risk Evaluation (SCORE)
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of cardiovascular risk as estimated by SCORE; SCORE is expressed as a percentage, with higher values indicating higher risk; patients in which the risk estimation is not applicable will be excluded from the analysis
measure: Cardiovascular risk as estimated by Progetto Cuore Score (english translation: "Heart Project Score")
time frame: At baseline
description: The value of urinary metanephrines will be evaluated as a possible predictor of cardiovascular risk as estimated by Progetto Cuore Score; Progetto Cuore Score is expressed as a percentage, with higher values indicating higher risk; patients in which the risk estimation is not applicable will be excluded from the analysis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mauro Maccario, MD
role: Principal Investigator
affiliation: Endocrinology, Diabetology and Metabolism; University of Turin
last name: Ezio Ghigo, MD
role: Study Chair
affiliation: Endocrinology, Diabetology and Metabolism; University of Turin
facility: 
country: Italy
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PMID: 32247299
responsible party type: Principal Investigator
investigator affiliation: University of Turin, Italy
investigator full name: Mauro Maccario
investigator title: Medical Doctor, Professor
mesh term: Kidney Diseases
mesh term: Hypertension
mesh term: Heart Diseases
mesh term: Essential Hypertension
mesh term: Diabetes Mellitus
mesh term: Metabolic Syndrome
mesh term: Diabetes Mellitus, Type 2
sharing ipd: No