Sympathetic Activity and Cardiometabolic Complications

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Association Between Enhanced Sympathetic Activity and Cardiometabolic Complications: a Cross-sectional Study on Predictive Power of 24-hour Urinary Metanephrines (SYMPACT)

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

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Therapy with sulfasalazine Therapy with L-Dopa Therapy with sympathomimetic drugs or other vasopressors Alcohol abuse Cocaine abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure (SBP) | The value of urinary metanephrines will be evaluated as a possible predictor of systolic blood pressure values (mmHg) | At baseline | 
| Diastolic blood pressure (DBP) | The value of urinary metanephrines will be evaluated as a possible predictor of diastolic blood pressure values (mmHg) | At baseline | 
| Resting heart rate | The value of urinary metanephrines will be evaluated as a possible predictor of resting heart rate (bpm) | At baseline | 
| eGFR | The value of urinary metanephrines will be evaluated as a possible predictor of eGFR values (ml/min, as estimated by CKD-EPI formula) | At baseline | 
| Urinary albumin/creatinine ratio | The value of urinary metanephrines will be evaluated as a possible predictor of albumin/creatinine ratio values (mg/mmol) | At baseline | 
| Fasting glucose | The value of urinary metanephrines will be evaluated as a possible predictor of fasting glucose values (mg/dl) | At baseline | 
| Total cholesterol | The value of urinary metanephrines will be evaluated as a possible predictor of total cholesterol values (mg/dl) | At baseline | 
| HDL cholesterol | The value of urinary metanephrines will be evaluated as a possible predictor of HDL cholesterol values (mg/dl) | At baseline | 
| LDL cholesterol | The value of urinary metanephrines will be evaluated as a possible predictor of LDL cholesterol values (mg/dl, as estimated by Friedewald formula) | At baseline | 
| Triglycerides | The value of urinary metanephrines will be evaluated as a possible predictor of triglycerides values (mg/dl) | At baseline | 
| Body Mass Index (BMI) | The value of urinary metanephrines will be evaluated as a possible predictor of BMI values (kg/m2) | At baseline | 
| Cardiovascular risk as estimated by Framingham Risk Score (FRS) | 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 | At baseline | 
| Cardiovascular risk as estimated by Systematic COronary Risk Evaluation (SCORE) | 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 | At baseline | 
| Cardiovascular risk as estimated by Progetto Cuore Score (english translation: Heart Project Score) | 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 | At baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic Syndrome, Normetanephrine, Metanephrine, Sympathetic Nervous System, Cardiovascular System, Cardiometabolic Complications, Catecholamine; Overproduction, Catecholamine; Secretion, Hypertensive Heart Disease, Hypertensive Kidney Disease, Diabetes Mellitus, Type 2, Hypertension,Essential