Sympathetic Activity and Cardiometabolic Complications

NCT04495231 | Completed DMC

• 1 other identifier: SympAct 1
• Study Type: observational
• Target: 1,380
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Catecholamine; Overproduction; Catecholamine; Secretion; Metabolic Syndrome; Hypertensive Heart Disease; Hypertensive Kidney Disease; Diabetes Mellitus, Type 2; Hypertension,Essential

Keywords

Normetanephrine; Metanephrine; Sympathetic Nervous System; Cardiovascular System; Cardiometabolic Complications; Catecholamine; Overproduction; Catecholamine; Secretion; Metabolic Syndrome; Hypertensive Heart Disease; Hypertensive Kidney Disease; Diabetes Mellitus, Type 2; Hypertension,Essential

Outcome Measures

Primary Outcomes (4)

• Presence of left ventricular hypertrophy

  The value of urinary metanephrines will be evaluated as a possible predictor of the presence of left ventricular hypertrophy

  At baseline

• Presence of chronic kidney disease

  The value of urinary metanephrines will be evaluated as a possible predictor of the presence of chronic kidney disease

  At baseline

• Presence of type 2 diabetes mellitus

  The value of urinary metanephrines will be evaluated as a possible predictor of the presence of type 2 diabetes mellitus

  At baseline

• Presence of metabolic syndrome

  The value of urinary metanephrines will be evaluated as a possible predictor of the presence of metabolic syndrome

  At baseline

Secondary Outcomes (14)

• Systolic blood pressure (SBP)

  At baseline

• Diastolic blood pressure (DBP)

  At baseline

• Resting heart rate

  At baseline

• eGFR

  At baseline

• Urinary albumin/creatinine ratio

  At baseline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients who performed a 24h urinary metanephrines assay at the laboratory of "City of Health and Science" hospital in Turin between 2007 and 2015, with availability of full clinical data due to hospitalization at the same hospital contextually to the dosage or within ± 6 months. Exclusion criteria are specified in the appropriate section.

You may qualify if:

• Measurement of 24h urinary metanephrines at the laboratory of "City of Health and Science" hospital in Turin between 2007 and 2015
• Availability of contextual clinical patient data as collected in prospective registries of Piedmont region

You may not qualify if:

• Diagnosis of pheochromocytoma or paraganglioma (at the time of urinary metanephrines collection or within the following 5 years)
• Diagnosis of other forms of secondary hypertension
• Previous cardiovascular or cerebrovascular event
• Chronic heart failure
• eGFR \< 50 ml/min (according to CKD-EPI)
• Liver cirrhosis
• Acute conditions and/or hospitalization in ICU (at the time of urinary metanephrines collection)
• Assumption of acetaminophen during the day before the 24-hour urine collection
• Therapy with labetalol
• Therapy with sotalol
• Therapy with alpha-methyldopa
• Therapy with MAO inhibitors
• Therapy with tricyclic antidepressants
• Therapy with buspirone
• Therapy with phenoxybenzamine

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (1)

Division of Endocrinology, Diabetology and Metabolism; University of Turin

Turin, Piedmont, 10126, Italy

Location

Related Publications (23)

• 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.

  PMID: 25304108 BACKGROUND

• 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.

  PMID: 25680900 BACKGROUND

• 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.

  PMID: 24694800 BACKGROUND

• 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.

  PMID: 24893135 BACKGROUND

• 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.

  PMID: 26619659 BACKGROUND

• 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.

  PMID: 25767284 BACKGROUND

• 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.

  PMID: 20226988 BACKGROUND

• 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.

  PMID: 1965656 BACKGROUND

• 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.

  PMID: 15317907 BACKGROUND

• 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.

  PMID: 25589262 BACKGROUND

• 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.

  PMID: 12649306 BACKGROUND

• 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.

  PMID: 7614812 BACKGROUND

• 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.

  PMID: 12953019 BACKGROUND

• 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.

  PMID: 25987662 BACKGROUND

• 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.

  PMID: 18803948 BACKGROUND

• 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.

  PMID: 9008251 BACKGROUND

• 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.

  PMID: 32132429 BACKGROUND

• 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.

  PMID: 17414649 BACKGROUND

• 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.

  PMID: 23271752 BACKGROUND

• 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.

  PMID: 12847071 BACKGROUND

• 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.

  PMID: 26376391 BACKGROUND

• 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.

  PMID: 4080953 BACKGROUND

• 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.

  PMID: 32247299 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Hypertensive Nephropathy; Diabetes Mellitus, Type 2; Essential Hypertension

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Mauro Maccario, MD

  Endocrinology, Diabetology and Metabolism; University of Turin

  PRINCIPAL INVESTIGATOR

• Ezio Ghigo, MD

  Endocrinology, Diabetology and Metabolism; University of Turin

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Professor

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 31, 2020
• Study Start: September 1, 2007
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2020
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)