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.

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

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.