Association of Urine Metanephrine Levels with CardiometaBolic Risk: An Observational Retrospective Study

Parasiliti-Caprino, Mirko; Obert, Chiara; Lopez, Chiara; Bollati, Martina; Bioletto, Fabio; Bima, Chiara; Egalini, Filippo; Berton, Alessandro Maria; Prencipe, Nunzia; Settanni, Fabio; Gasco, Valentina; Mengozzi, Giulio; Ghigo, Ezio; Maccario, Mauro

doi:10.3390/jcm10091967

Cited by 3 publications

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References 44 publications

(48 reference statements)

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“…Similarly, healthy subjects placed on a high phosphate diet showed an increase in urinary metanephrine and normetanephrine excretion [ 10 ]. Catecholamines are endogenous neurotransmitters and hormones derived from tyrosine metabolism, and are essential for maintenance of metabolic and cardiovascular homeostasis and for adaptation to stressors [ 40 , 41 ]. The most abundant catecholamines in circulation are norepinephrine, epinephrine, and dopamine [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Catecholamines have many cardiovascular and metabolic actions, including increasing the heart rate, blood pressure, myocardial contractility, and cardiac conduction velocity. The O -methylated metabolites of norepinephrine, epinephrine and dopamine are normetanephrine (NMN), metanephrine (MN), and methoxytyramine (MTY), respectively [ 41 ]. Metanephrine and normetanephrine are referred to as metanephrines.…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed that metanephrines can be used as markers of sympathetic activity [ 43 ]. Indeed, two independent studies have found a strong association between urinary metanephrine levels and systolic blood pressure in humans [ 41 , 44 ]. Therefore, the partially reversible increase in urinary excretion of catecholamines induced by the CPD in our study may contribute to increased arterial blood pressure and arterial stiffness, in addition to RAAS activation.…”

Section: Discussionmentioning

confidence: 99%

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Long-Term Excessive Dietary Phosphate Intake Increases Arterial Blood Pressure, Activates the Renin–Angiotensin–Aldosterone System, and Stimulates Sympathetic Tone in Mice

et al. 2022

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Increased dietary phosphate intake has been associated with severity of coronary artery disease, increased carotid intima–media thickness, left ventricular hypertrophy (LVH), and increased cardiovascular mortality and morbidity in individuals with normal renal function as well as in patients suffering from chronic kidney disease. However, the underlying mechanisms are still unclear. To further elucidate the cardiovascular sequelae of long-term elevated phosphate intake, we maintained male C57BL/6 mice on a calcium, phosphate, and lactose-enriched diet (CPD, 2% Ca, 1.25% P, 20% lactose) after weaning them for 14 months and compared them with age-matched male mice fed a normal mouse diet (ND, 1.0% Ca, 0.7% P). Notably, the CPD has a balanced calcium/phosphate ratio, allowing the effects of elevated dietary phosphate intake largely independent of changes in parathyroid hormone (PTH) to be investigated. In agreement with the rationale of this experiment, mice maintained on CPD for 14 months were characterized by unchanged serum PTH but showed elevated concentrations of circulating intact fibroblast growth factor-23 (FGF23) compared with mice on ND. Cardiovascular phenotyping did not provide evidence for LVH, as evidenced by unchanged LV chamber size, normal cardiomyocyte area, lack of fibrosis, and unchanged molecular markers of hypertrophy (Bnp) between the two groups. However, intra-arterial catheterization revealed increases in systolic pressure, mean arterial pressure, and pulse pressure in mice fed the CPD. Interestingly, chronically elevated dietary phosphate intake stimulated the renin–angiotensin–aldosterone system (RAAS) as evidenced by increased urinary aldosterone in animals fed the CPD, relative to the ND controls. Furthermore, the catecholamines epinephrine, norepinephrine, and dopamine as well as the catecholamine metabolites metanephrine. normetanephrine and methoxytyramine as measured by mass spectrometry were elevated in the urine of mice on CPD, relative to mice on the ND. These changes were partially reversed by switching 14-month-old mice on CPD back to ND for 2 weeks. In conclusion, our data suggest that excess dietary phosphate induces a rise in blood pressure independent of secondary hyperparathyroidism, and that this effect may be mediated through activation of the RAAS and stimulation of the sympathetic tone.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-Term Excessive Dietary Phosphate Intake Increases Arterial Blood Pressure, Activates the Renin–Angiotensin–Aldosterone System, and Stimulates Sympathetic Tone in Mice

et al. 2022

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A retrospective study on the association between urine metanephrines and cardiometabolic risk in patients with nonfunctioning adrenal incidentaloma

Parasiliti-Caprino

Lopez

Bollati

et al. 2022

Sci Rep

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Several studies argued that cardiovascular evaluation of patients with nonfunctioning adrenal incidentaloma is of particular importance. Therefore, we aimed to evaluate the possibility of stratifying the cardiometabolic risk using metanephrine levels in this setting of patients. A retrospective cross-sectional study was designed, collecting data of metanephrine values in 828 patients with nonfunctioning adrenal incidentaloma, referred to our Division within the University of Turin between 2007 and 2021. The univariate analysis showed associations between urine metanephrines and cardiometabolic variables/parameters, particularly considering the noradrenaline metabolite. At the univariate regression, normetanephrine was associated with metabolic syndrome (OR = 1.13, p = 0.002), hypertensive cardiomyopathy (OR = 1.09, p = 0.026), microalbuminuria (OR = 1.14, p = 0.024), and eGFR < 60 mL/min/1.73 m2 (OR = 1.11, p = 0.013), while metanephrine was associated with microalbuminuria (OR = 1.50, p = 0.008). At multivariate regression, considering all major cardiovascular risk factors as possible confounders, normetanephrine retained a significant association with metabolic syndrome (OR = 1.10, p = 0.037). Moreover, metanephrine retained a significant association with the presence of microalbuminuria (OR = 1.66, p = 0.003). The present study showed a further role for metanephrines in the cardiovascular risk stratification of patients with nonfunctioning adrenal incidentaloma. Individuals with high levels of these indirect markers of sympathetic activity should be carefully monitored and may benefit from an aggressive treatment to reduce their additional cardiometabolic burden.

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Hyperthyroidism in Graves Disease Causes Sleep Disorders Related to Sympathetic Hypertonia

Matsumoto

Izawa

Fukaya

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context It is well known that Graves’ disease (GD) causes sleep disorders (SD). However, the characteristics and associated factors of SD and its clinical course post-hyperthyroidism normalization remain unclear. Objective To clarify the characteristics and associated factors of subjective SD and its clinical course after GD treatment. Design, setting, and study participants From November 2017 to October 2020, we enrolled 72 participants (22 newly diagnosed with GD with untreated hyperthyroidism, 20 previously diagnosed with GD with normal thyroid function, and 30 normal controls) with no other underlying sleep disorder-related diseases. We compared the groups at enrollment and conducted prospective observations after 12 months of treatment on participants with newly diagnosed GD. Main outcome measures Differences and changes in the Pittsburgh Sleep Quality Index (PSQI) global and component sleep quality scores. Results PSQI global sleep quality scores (p = 0.036) and sleep disturbance scores (p = 0.011) were significantly different among the three groups, and were highest in the untreated hyperthyroidism group. Multiple regression analysis demonstrated that free thyroxine level, which was positively correlated with sympathetic tone (ST) as evaluated by pulse rate and urinary total metanephrines, was associated with poorer PSQI global sleep quality scores independently of other factors (p = 0.006). Prospective observation showed that PSQI global sleep quality scores (p = 0.018) and sleep disturbance scores (p = 0.011) significantly improved with thyroid function normalization and ST attenuation. Conclusions Hyperthyroidism caused by GD augmented ST and exacerbated subjective SD. Normalization of hyperthyroidism caused by GD improved subjective SD.

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Association of Urine Metanephrine Levels with CardiometaBolic Risk: An Observational Retrospective Study

Cited by 3 publications

References 44 publications

Long-Term Excessive Dietary Phosphate Intake Increases Arterial Blood Pressure, Activates the Renin–Angiotensin–Aldosterone System, and Stimulates Sympathetic Tone in Mice

Long-Term Excessive Dietary Phosphate Intake Increases Arterial Blood Pressure, Activates the Renin–Angiotensin–Aldosterone System, and Stimulates Sympathetic Tone in Mice

A retrospective study on the association between urine metanephrines and cardiometabolic risk in patients with nonfunctioning adrenal incidentaloma

Hyperthyroidism in Graves Disease Causes Sleep Disorders Related to Sympathetic Hypertonia

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