Sympathetic Activity and Cardiometabolic Complications
- Conditions
- Catecholamine; OverproductionMetabolic SyndromeHypertensive Heart DiseaseHypertensive Kidney DiseaseDiabetes Mellitus, Type 2Catecholamine; SecretionHypertension,Essential
- Registration Number
- NCT04495231
- Lead Sponsor
- University of Turin, Italy
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1380
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Presence of type 2 diabetes mellitus At baseline The value of urinary metanephrines will be evaluated as a possible predictor of the presence of type 2 diabetes mellitus
Presence of metabolic syndrome At baseline The value of urinary metanephrines will be evaluated as a possible predictor of the presence of metabolic syndrome
Presence of chronic kidney disease At baseline The value of urinary metanephrines will be evaluated as a possible predictor of the presence of chronic kidney disease
Presence of left ventricular hypertrophy At baseline The value of urinary metanephrines will be evaluated as a possible predictor of the presence of left ventricular hypertrophy
- Secondary Outcome Measures
Name Time Method Body Mass Index (BMI) At baseline The value of urinary metanephrines will be evaluated as a possible predictor of BMI values (kg/m2)
Urinary albumin/creatinine ratio At baseline The value of urinary metanephrines will be evaluated as a possible predictor of albumin/creatinine ratio values (mg/mmol)
Total cholesterol At baseline The value of urinary metanephrines will be evaluated as a possible predictor of total cholesterol values (mg/dl)
LDL cholesterol At baseline The value of urinary metanephrines will be evaluated as a possible predictor of LDL cholesterol values (mg/dl, as estimated by Friedewald formula)
eGFR At baseline The value of urinary metanephrines will be evaluated as a possible predictor of eGFR values (ml/min, as estimated by CKD-EPI formula)
Fasting glucose At baseline The value of urinary metanephrines will be evaluated as a possible predictor of fasting glucose values (mg/dl)
Systolic blood pressure (SBP) At baseline The value of urinary metanephrines will be evaluated as a possible predictor of systolic blood pressure values (mmHg)
Triglycerides At baseline The value of urinary metanephrines will be evaluated as a possible predictor of triglycerides values (mg/dl)
Cardiovascular risk as estimated by Progetto Cuore Score (english translation: "Heart Project Score") At baseline 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
Diastolic blood pressure (DBP) At baseline The value of urinary metanephrines will be evaluated as a possible predictor of diastolic blood pressure values (mmHg)
Resting heart rate At baseline The value of urinary metanephrines will be evaluated as a possible predictor of resting heart rate (bpm)
HDL cholesterol At baseline The value of urinary metanephrines will be evaluated as a possible predictor of HDL cholesterol values (mg/dl)
Cardiovascular risk as estimated by Framingham Risk Score (FRS) At baseline 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
Cardiovascular risk as estimated by Systematic COronary Risk Evaluation (SCORE) At baseline 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
Trial Locations
- Locations (1)
Division of Endocrinology, Diabetology and Metabolism; University of Turin
🇮🇹Torino, Piemonte, Italy