Use of non-invasive respiratory supports in high-intensity internal medicine setting during the first two waves of the COVID-19 pandemic emergency in Italy: a multicenter, real-life experience.

During the first two waves of the COVID-19 emergency in Italy, internal medicine high-dependency wards (HDW) have been organized to manage patients with acute respiratory failure (ARF). There is heterogeneous evidence about the feasibility and outcomes of non-invasive respiratory supports (NIRS) in settings outside the intensive care unit (ICU), including in patients deemed not eligible for intubation (i.e., with do-not-intubate, DNI status). Few data are available about the different NIRS modalities applied to ARF patients in the newly assembled internal medicine HDW. The main aim of our study was to describe a real-life experience in this setting of cure, focusing on feasibility and outcomes. We retrospectively collected data from COVID-19 patients with ARF needing NIRS and admitted to internal medicine HDW. Patients were treated with different modalities, that is high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), or non-invasive mechanical ventilation (NIMV). Switching among different NIRS during the hospitalization and the success rate (weaning with the same NIRS) or failure (endotracheal intubation-ETI or in-hospital death) were recorded. Three hundred thirty four ARF patients (median age 74 years), of which 158 (54%) had a DNI status, were included. CPAP, NIMV, and HFNC's success rates were 54, 33, and 13%, respectively. Although DNI status was strongly associated with death (Gehan-Breslow-Wilcoxon test p < 0.001), an acceptable success rate was observed in these patients using CPAP (47%). Multivariate regression models showed older age (odds ratio-OR 4.74), chronic ischemic heart disease (OR 2.76), high respiratory rate after 24 h (OR 7.13), and suspected acute respiratory distress syndrome-ARDS (OR 21.1) as predictors of mortality risk or ETI. Our real-life experience shows that NIRS was feasible in internal medicine HDW with an acceptable success rate. Although DNI patients had a worse prognosis, the use of NIRS represented a reasonable chance of treatment.

Hypertensive emergencies and urgencies: a preliminary report of the ongoing Italian multicentric study ERIDANO.

Hypertensive urgencies (HU) and hypertensive emergencies (HE) are challenges for the Emergency Department (ED). A prospective multicentre study is ongoing to characterize patients with acute hypertensive disorders, prevalence of subclinical hypertension-mediated organ damage (HMOD), short- and long-term prognosis; this is a preliminary report. Patients admitted to the ED with symptomatic blood pressure (BP) ≥180/110 mmHg were enrolled. They were managed by ED personnel according to their clinical presentations. Subsequently they underwent clinical evaluation and subclinical HMOD assessment at a Hypertension Centre within 72 h from enrolment. 122 patients were included in this report. Mean age was 60.7±13.9 years, 52.5% were females. 18 (14.8%) patients were diagnosed with HE, 108 (88.5%) with HU. There were no differences in gender, BMI, and cardiovascular comorbidities between groups. At ED discharge, 66.7% and 93.6% (p = 0.003) of HE and HU patients, respectively, had BP < 180/110 mmHg. After 72 h, 34.4% of patients resulted normotensive; 35.2%, 22.1%, and 8.2% had hypertension grade 1, 2, and 3, respectively. Patients with uncontrolled BP at office evaluation had higher vascular HMOD (49.1 vs. 25.9%, p = 0.045). Cardiac (60 vs. 34%, p = 0.049), renal (27.8 vs. 9.6%, p = 0.010) and cerebral (100 vs. 21%, p < 0.001) HMOD was more frequent in HE compared to HU group. HE showed greater cardiac, renal, and cerebral subclinical HMOD, compared to HU. 72-hours BP control is not associated with different HMOD, except for vascular HMOD; therefore, proper comprehensive examination after discharge from the ED could provide added value in cardiovascular risk stratification of such patients. One third of patients with acute blood pressure rise evaluated to the ED resulted normotensive at office evaluation (<72 hours after discharge). Patients with hypertensive emergency showed greater cardiac, renal, and cerebral subclinical HMOD, compared to the patients with hypertensive urgency. BP: blood pressure; HMOD: hypertension-mediated organ damage; y.o.: years old; mo.: months.

Unattended versus Attended Blood Pressure Measurement: Relationship with Retinal Microcirculation.

Though the relationship between both "attended" and "unattended" BP and several forms of target organ damage have been evaluated, data on retinal arteriolar alterations are lacking. The aim of our study was to evaluate the relationship between "attended" or "unattended" BP values and retinal arteriolar changes in consecutive individuals undergoing a clinical evaluation and assessment of retinal fundus at an ESH Excellence Centre. An oscillometric device programmed to perform 3 BP measurements, at 1 min intervals and after 5 min of rest was used on all individuals to measure BP with the patient alone in the room ("unattended") or in the presence of the physician ("attended") in the same day in a random order. The retinal arteriole's wall thickness (WT) was measured automatically by a localization algorithm as the difference between external (ED) and internal diameter (ID) by adaptive optics (RTX-1, Imagine Eyes, Orsay, Francia). Media-to-lumen ratio (WLR) of the retinal arterioles and cross-sectional area (WCSA) of the vascular wall were calculated. Results: One-hundred-forty-two patients were examined (mean age 57 ± 12 yrs, 48% female, mean BMI 26 ± 4). Among them, 60% had hypertension (84% treated) and 11% had type 2 diabetes mellitus. Unattended systolic BP (SBP) was lower as compared to attended SBP (129 ± 14.8. vs. 122.1 ± 13.6 mmHg, p < 0.0001). WLR was similarly correlated with unattended and attended SBP (r = 0.281, p < 0.0001 and r = 0.382, p < 0.0001) and with unattended and attended diastolic BP (r = 0.34, p < 0.001 and r = 0.29, p < 0.0001). The differences between correlations were not statistically significant (Steiger's Z test). Conclusion: The measurement of "unattended" or "attended" BP provides different values, and unattended BP is lower as compared to attended BP. In this study a similar correlation was observed between attended and unattended BP values and structural changes of retinal arterioles.

Subclinical HMOD in Hypertension: Left Ventricular Diastolic Dysfunction.

Arterial hypertension represents an important risk factor for the development of cardiac, vascular and renal events, predisposing to heart failure, acute coronary syndromes, peripheral artery disease, stroke, and chronic renal disease. Arterial hypertension leads to the development of subclinical hypertension mediated organ damage (HMOD) which has prognostic relevance and may influence the choice of treatment options. Alterations of cardiac structure and function represent the more widely assessed form of HMOD. This manuscript will focus on the diagnostic opportunities, prognostic significance and treatment of diastolic dysfunction alterations.

Cardiovascular prognosis in patients admitted to an emergency department with hypertensive emergencies and urgencies.

BACKGROUND: At present, few data are available on the prognosis of hypertensive emergencies and urgencies admitted to emergency departments. AIM: The aim of our study was to evaluate the incidence of total and cardiovascular events during follow-up in hypertensive patients admitted to the emergency departments of Brescia Hospital (Northern Italy) with hypertensive emergencies or urgencies from 1 January to 31 December 2015. METHODS: Medical records of patients aged more than 18 years, admitted to the emergency department with SBP values at least 180 mmHg (SBP) and/or DBP values at least 120 mmHg (DBP) were collected and analysed (18% of patients were classified as 'hypertensive emergency' and 82% as 'hypertensive urgency'). Data in 895 patients (385 men and 510 women, mean age 70. 5 ±â€Š15 years) were analysed; the mean duration of follow-up after admission to the emergency department was 12 ±â€Š5 months. RESULTS: During the follow-up, 96 cardiovascular events (28 fatal) occurred (20 cardiac events, 30 cerebrovascular events, 26 hospital admission for heart failure, 20 cases of new onset kidney disease). In 40 patients (4.5%), a new episode of acute blood pressure rise with referral to the emergency department was recorded. Cardiovascular mortality and morbidity were greater in patients with a previous hypertensive emergency (14.5 vs. 4.5% in patients with hypertensive emergency and urgency, respectively, chi-square, P < 0.0001). Similar results were obtained when the occurrence of cerebrovascular or renal events were considered separately. CONCLUSION: Admission to the emergency department for hypertensive emergencies and urgencies identifies hypertensive patients at increased risk for fatal and nonfatal cardiovascular events. Our findings add some new finding suggesting that further research in this field should be improved aiming to define, prevent, treat and follow hypertensive urgencies and emergencies.

The Vobarno Study.

The Vobarno Study represents the first observational study aimed to assess in a general population sample the relationship between parameters of cardiac and vascular structure (and function) and blood pressure values, measured in the clinic and during the 24 hours. In the frame of The Vobarno Study blood samples for hematochemistry and DNA extraction, clinic and 24-hour blood pressure measurements, cardiac and carotid ultrasound, and aortic stiffness were measured in all subjects, living in a small town (Vobarno) between Brescia and the Garda Lake (Italy), and randomly selected from electoral roles. In this sample of a general population an extensive evaluation of organ damage, including left ventricular (LV) mass and hypertrophy, LV systolic function, left atrial dimensions and aortic root diameters, carotid intima media thickness (IMT) and carotid plaques, carotid and aortic stiffness were performed. In this study subjects were included in a long follow-up, lasting 25 years, and cardiovascular morbility and mortality were assessed up to 2019. This will allow to update the information related to cardiovascular morbidity and mortality in the study cohort. The present paper will report the results of some analyses performed, exploring epidemiological and clinical aspects of target organ damage.

Myocardial mechano-energetic efficiency in primary aldosteronism.

BACKGROUND: Available data indicate that patients with primary aldosteronism have an increased risk of cardiovascular events and cardiovascular risk seems to be, at least in part, independent of blood pressure (BP) values. Patients with primary aldosteronism have a greater prevalence of left ventricular (LV) hypertrophy and subtle alterations of ventricular function, which might contribute to the increase in cardiovascular risk. Recently, a noninvasive approach for the estimation of LV mechanical efficiency, obtained by echocardiography has been proposed. AIM OF THE STUDY: To evaluate the determinants of myocardial mechanoenergetic efficiency index (MEEi), in a large group of patients with primary aldosteronism (n = 99) and in a control group of essential hypertensive patients (n = 99) matched for age, sex and BP values. RESULTS: No differences between groups for age, sex, BMI, BP values, glucose, lipid profile and renal function were observed. LV mass index was greater in primary aldosteronism vs. essential hypertensive patients (46.0 ±â€Š16.7 vs. 36.9 ±â€Š8.6 g/m2, P < 0.001); also relative wall thickness was greater in primary aldosteronism (0.36 ±â€Š0.1 vs. 0.32 ±â€Š0.4, P < 0.001). Left atrial dimensions were significantly greater in primary aldosteronism. Ejection fraction was not different between groups, while endocardial and midwall fractional shortening were lower in primary aldosteronism vs. essential hypertensive patients (40 ±â€Š7 vs. 43 ±â€Š6, and 18 ±â€Š3 vs. 21 ±â€Š2, both P < 0.01). MEEi was lower in primary aldosteronism vs. essential hypertensive patients (0.44 ±â€Š0.14 vs. 0.52 ±â€Š0.10 ml/s per g, P < 0.01). A negative correlation was observed between MEEi and aldosterone levels (r = -0.203, P < 0.05) and aldosterone : renin ratio (P = -0.172, P < 0.05); the correlation remained significant after adjustment for possible confounders. CONCLUSION: In patients with primary aldosteronism myocardial MEEi is lower as compared with essential hypertensive patients. A reduced MEEi may reflect an impairment of production and utilization of energy in the myocardium, which could lead to the occurrence of cardiovascular complications and therefore these findings may contribute to explain the increased risk of cardiovascular events in patients with primary aldosteronism.

COVID-19 Pneumonia: Three Thoracic Complications in the Same Patient.

The most dreaded thoracic complications in patients with coronavirus disease 2019 (COVID-19) are acute pulmonary embolism and pulmonary fibrosis. Both the complications are associated with an increased risk of morbidity and mortality. While acute pulmonary embolism is not a rare finding in patients with COVID-19 pneumonia, the prevalence of pulmonary fibrosis remains unclear. Spontaneous pneumothorax is another possible complication in COVID-19 pneumonia, although its observation is rather uncommon. Herein, we present interesting computed tomography images of the first case of COVID-19 pneumonia that initially developed acute pulmonary embolism and subsequently showed progression toward pulmonary fibrosis and spontaneous pneumothorax.

Relationship between arterial stiffness and unattended or attended blood pressure values.

BACKGROUND AND METHOD: Measurement of 'unattended' blood pressure (BP) may reduce or eliminate the 'white-coat effect'. Despite the possible advantages of this approach for BP measurement, only few studies analysed the relationship between unattended BP and cardiovascular events or with hypertension-mediated organ damage (HMOD). The aim of our study was to evaluate the relationship between 'attended' or 'unattended' BP values and carotid-femoral pulse wave velocity (PWV) in 285 individuals undergoing a visit and assessment of arterial stiffness at an ESH Excellence Centre. Unattended BP (measured with the patient alone in the room, with an oscillometric device programmed to perform three BP measurements, at 1-min intervals, after 5 min) and attended BP were measured with the same device, on the same day of the measurement of PWV, in a random order. RESULTS: Mean age was 63 ±â€Š13 years, mean BMI 26 ±â€Š4, 47% were women, 76% had hypertension (55% treated). Systolic unattended BP was lower than attended SBP (124.4 ±â€Š14.3 vs. 130.9 ±â€Š16.1 mmHg). PWV was similarly correlated with attended and unattended SBP values (r = 0.428 and r = 0.404, P < 0.0001, respectively). No difference for the prediction of increased arterial stiffness was observed at receiver operator curves (ROCs) analysis [attended SBP area under the curve (AUC) 0.665, 95% confidence interval (95% CI) 0.607-0.720 vs. unattended SBP: AUC 0.651, 95% CI 0.593-0.706, P for the comparison = ns]. CONCLUSION: Attended and unattended BP values are similarly correlated with PWV, the gold standard measure of arterial stiffness. These findings may provide further information on the clinical value of unattended BP.

Hypertensive emergencies and urgencies: a single-centre experience in Northern Italy 2008-2015.

BACKGROUND: An increasing attention is given to emergency departments (EDs) admissions for an acute and severe rise in blood pressure (BP). Data on epidemiology and treatment of hypertensive emergencies and urgencies admitted to ED are still limited. The aim of our study was to evaluate the prevalence, clinical presentation and treatment of patients admitted for hypertensive emergencies or hypertensive urgencies. METHODS: Medical records of consecutive patients aged at least 18 years, admitted to the ED of the Spedali Civili in Brescia in 2008 and in 2015 and presenting with SBP at least 180 mmHg and/or DBP at least 120 mmHg were prospectively collected and analysed. RESULTS: The prevalence of patients admitted with acute BP rise was 2.0% (n = 1551, age 70 ±â€Š14 years) in 2008 and 1.75% (n = 1214, age 69.7 ±â€Š15 years) in 2015. According to the clinical presentation and the presence of acute organ damage, patients were defined hypertensive emergencies (20.4 and 15.4%, respectively, in 2008 and 2015) or as hypertensive urgencies (79.6 and 84.5%, respectively, in 2008 and 2015). SBP and DBP values were higher in patients with emergencies than in those with urgencies (BP 193 ±â€Š15/102 ±â€Š15 vs. 189 ±â€Š13/96 ±â€Š13 mmHg in 2008 and 192 ±â€Š17/98 ±â€Š15 vs. 189 ±â€Š12/94 ±â€Š15 mmHg in 2015, P < 0.001 for both).Among hypertensive emergencies, the different forms of organ damage were 25% acute coronary syndromes and 1% aortic dissection in both periods, 34 and 38% acute heart failure, 40 and 37% stroke. CONCLUSION: Admission to the ED for hypertensive emergencies and hypertensive urgencies is still high. Diagnosis and treatment are still not appropriate and require the rapid application of recently published guidelines.

Cardiovascular target organ damage in premenopausal systemic lupus erythematosus patients and in controls: Are there any differences?

OBJECTIVE: to analyze the presence of cardiac and vascular preclinical damage in premenopausal women with systemic lupus erythematosus (SLE) and controls, matched for demographic characteristics and for other cardiovascular risk factors. METHODS: 33 women (mean age 32 ± 7 years) with SLE clinically stable (SLEDAI Score 2.5 ± +1.5) and 33 controls, matched (MC) for sex, age, body mass index (BMI), clinic blood pressure (BP) and antihypertensive treatment (if present) underwent: 24-h BP monitoring, echocardiography with tissue Doppler analysis for left ventricular (LV) structure, systolic and diastolic function, echo-tracking carotid ultrasound for intima-media thickness (IMT) and carotid distensibility measurement, and pulse wave velocity measurement for aortic stiffness (PWV). RESULTS: by definition no difference was observed for age, sex, BMI and clinic BP values; Framingham risk score was low in SLE and MC (1.3 ± 2.7 vs 1.5 ± 2.3%, p = ns). 24-h BP was similar in SLE and in MC. Systolic function parameters, including LV longitudinal systolic function, an early index of LV systolic dysfunction, were reduced in SLE as compared to MC. Carotid IMT and carotid and aortic stiffness parameters were not different in SLE and MC. At multivariate regression analysis, PWV was independently associated with LV mass in controls and with the steroid weekly dose in SLE patients. CONCLUSIONS: in young patients with SLE and low activity index of the disease, we did not observe significant vascular alterations as compared to controls with similar CV risk. The early LV systolic impairment observed in SLE patients needs confirmation.

Vascular Aging and Disease of the Small Vessels.

Cardiovascular events are the consequence of vascular damage at both the macro and microcirculatory level. The relationship between large stiffening artery and microvascular disease may be bidirectional, since wave reflection from microvascular sites could increase systolic blood pressure and pulse pressure, while transmission of increased arterial pulsatility to microvessels could represent a mechanism of damage. Hypertension and aging share similar mechanisms of vascular dysfunction. In fact, vascular remodelling, endothelial dysfunction and vascular stiffness are common features in hypertension and aging. Structural and functional changes in small arteries occur during normal and accelerated aging, possibly triggered by hypertension. A cross-talk may be present between large and small artery changes, interacting with pressure wave transmission and reflection, exaggerating cardiac, brain and kidney damage, and finally leading to cardiovascular and renal complications.

Unattended Versus Attended Blood Pressure Measurement.

It has been suggested that measurement of unattended or automated oscillatory blood pressure (BP) values may provide advantages over conventional BP measurement. Some international guidelines now suggest automated oscillatory BP as the preferred approach for measuring BP. Data on the relationship between automated oscillatory BP and cardiovascular events are much less solid as compared to those obtained with the standard approach; preliminary data suggested that automated oscillatory BP might be more strictly correlated with organ damage. The aim of our study was to evaluate the relationship between attended or unattended BP and organ damage in 564 subjects undergoing an echocardiogram and carotid ultrasound at an European Society of Hypertension Excellence Center.Both unattended BP (patient alone in the room, an oscillometric device programmed to perform 3 BP measurements, at 1-minute intervals, after 5 minutes) and attended BP were measured with the same device, on the same day of the ultrasonographic examination, in random order. In 564 patients (age 61±15 years, 41% female 78% hypertensives) systolic unattended BP was lower as compared with attended BP (128.0±15.5 versus 134.5±19.9 mm Hg). Left ventricular mass index was similarly correlated with attended and unattended systolic BP ( r=0.205 and r=0.194, respectively). Carotid intima-media thickness was also significantly correlated with both attended and unattended systolic BP (mean max intima-media thickness: r=0.206 and r=0.194, respectively, P<0.0001). The differences between correlations were not statistically significant. Our results suggest that attended and unattended BP values are similarly related with hypertensive organ damage.

Changes in left ventricular geometry during antihypertensive treatment.

The reduction of echocardiographic left ventricular (LV) mass and the change toward a less concentric geometry during antihypertensive treatment are independently associated with a better prognosis. Blood pressure-lowering treatment may reduce cardiac hypertrophy, although different effect on changes of LV mass have been reported among antihypertensive drug classes, while changes in echocardiographic evaluated LV geometry have not been systemically evaluated. It is not yet clear whether antihypertensive drugs may influence LV geometry. Our aim was to compare the effects of diuretics (D), beta-blockers (BB), calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACE-I), and angiotensin receptor blockers (ARBS) on relative wall thickness (RWT) in patients with hypertension on the basis of prospective, randomized comparative studies. METHODS: MEDLINE, and the ISI Web of Sciences were searched for randomized clinical trials evaluating LV mass and geometry at baseline and end follow-up. We have performed a pooled pairwise comparisons of the effect of the 5 major drug classes on relative wall thickness changes, and of each drug class versus other classes statistically combined. RESULTS: We selected 53 publications involving 7684 patients. A significant correlation was observed between percent changes from baseline to end of treatment in LV mass and those in systolic BP (r = 0.44, p < 0.001). Reduction of LV mass was significantly greater with CCB than with BB (P <  0.02) without other significant differences between drug classes. Percent changes in RWT were related to percent changes in LV mass/LVmass index (r = 0.68, p = 0.016) and of SBP (r = 0.64 p < 0.033). RWT decreased during treatment with all classes of drugs, except the combination of BB and D; the decrease of RWT was less with diuretics and sympatholytic drugs. CONCLUSIONS: In studies evaluating the effect of different classes of antihypertensive drugs on LV mass, the reduction of relative wall thickness seems to be less during treatment with diuretics.

Therapeutic Approach to Hypertensive Emergencies: Hemorrhagic Stroke.

Arterial hypertension represents the most important risk factor for ischemic and haemorrhagic stroke, and an acute hypertensive response is often observed in patients with intracranial haemorrhage (ICH). Available data indicate that the vast majority (> 70%) of patient with acute ICH have a systolic BP above 140 mmHg at the time of presentation in the ED; about 20% have SBP values above 180 mmHg. Severe BP elevation in the presence of ICH represents a hypertensive emergency, and worsening of clinical conditions is not infrequent in the first hours after admission; an aggressive early management is therefore required for these patients. Despite this, appropriate management of BP in acute ICH is still controversial, due to the complex issues involved, and the heterogeneous results obtained in clinical trials. This article will review the available evidence supporting acute BP reduction in acute ICH.

Definitions and Epidemiological Aspects of Hypertensive Urgencies and Emergencies.

Acute blood pressure (BP) elevation represents a frequent reason of concern for clinicians in everyday clinical practice. The terms "hypertensive emergencies" and "hypertensive urgencies" may be used in order to better define the so called "hypertensive crises". A hypertensive emergency may be defined as a condition characterized by an acute and severe elevation of blood pressure (BP) associated to a new onset or worsening organ damage (OD). A hypertensive urgency may be defined as a condition characterized by an isolated elevation of BP values without evidence of acute hypertensive OD. This article will review the definition, the prevalence, and the prognostic implications of hypertensive emergencies and urgencies.

Hypertension and Organ Damage in Women.

An adequate cardiovascular (CV) prevention strategy in women should consider the acknowledgement of sex-specific risk factors, such as hypertension in pregnancy, the concomitant presence of autoimmune diseases and the benefit of evaluating subclinical organ damage and treating hypertension. In accordance to current guidelines, the diagnostic approach does not differ between men and women, although the cardiac response to pressure overload may suggest greater sensitivity in women, and may vary according to age, ethnic background and obesity, that potentiates the effect of hypertension on left ventricular (LV) hypertrophy. Several studies have observed peculiar abnormalities in LV systolic and diastolic function according to gender. The possible mechanisms that influence a different cardiac adaptation to chronic pressure overload in men and women are not fully understood, although hormonal status, and in particular the lack of estrogen effects after menopause may contribute to the cardiovascular adaptation response to increased afterload. The increase in LV mass in response to chronic pressure overload is associated with higher LV ejection fraction in women than in men and LV torsion is maintained with aging in women but not in men. Interstitial fibrosis may reduce circumferential shortening and early diastolic strain rate, in the presence of a preserved ejection fraction in women, favoring the development of heart failure with preserved ejection fraction. Changes in aortic stiffness with aging may influence cardiac structural and functional changes. Isolated systolic hypertension reflects an increase in aortic stiffness, is frequent in women and may be associated to a greater development of concentric LVH. The regression of hypertensive LVH is more difficult in women, and residual hypertrophy is more common in women than in men despite effective antihypertensive treatment and blood pressure control. Carotid atherosclerosis has been extensively investigated in men and women, showing that women usually develop carotid plaques after menopause, with smaller and less unstable plaques; however large and/or a hypoechogenic plaques are more strictly related to cerebrovascular events in women than in men. More advanced abnormalities in the subcutaneous microcirculation have been recently observed, and well translate in the evidence of more prevalent coronary microcirculation involvement in women ischemic heart disease. The prevalence of albuminuria and of reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73) are respectively lower and higher in postmenopausal women than in men. Experimental data suggest the possible involvement of renin-angiotensin-aldosterone system and of T regulatory lymphocytes to this regard.