Cardiac innervation by the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS) modulates the heart rate (HR) (chronotropic activity) and the contraction of the cardiac muscle (inotropic activity). The peripheral vasculature is controlled only by the SNS, which is responsible for peripheral vascular resistance. This also mediates the baroreceptor reflex (BR), which in turn mediates blood pressure (BP). Hypertension (HTN) and the autonomic nervous system (ANS) are closely related, such that derangements can lead to vasomotor impairments and several comorbidities, including obesity, hypertension, resistant hypertension, and chronic kidney disease. Autonomic dysfunction is also associated with functional and structural changes in target organs (heart, brain, kidneys, and blood vessels), increasing cardiovascular risk. Heart rate variability (HRV) is a method of assessing cardiac autonomic modulation. This tool has been used for clinical evaluation and to address the effect of therapeutic interventions. The present review aims (a) to approach the heart rate (HR) as a CV risk factor in hypertensive patients; (b) to analyze the heart rate variability (HRV) as a “tool” to estimate the individual risk stratum for Pre-HTN (P-HTN), Controlled-HTN (C-HTN), Resistant and Refractory HTN (R-HTN and Rf-HTN, respectively), and hypertensive patients with chronic renal disease (HTN+CKD).

RESUMENLa obesidad es una enfermedad crónica, considerada un factor de riesgo importante en el desarrollo de enfermedad coronaria, hipertensión, insuficiencia y fallo renal.La obesidad contribuye a la hipertensión por mecanismos tales como: resistencia insulínica e hiperinsulinemia, aumento de la actividad adrenérgica y de las concentraciones de aldosterona, retención de sodio y agua e incremento del gasto cardíaco, alteración de la función endotelial, a través de moléculas como leptina y adiponectina y factores genéticos. Quedan aún abiertas muchas vías de investigación.Los IECA y/o los ARA II son fármacos de primera elección por su efecto beneficioso sobre la resistencia insulínica y actividad simpática.Palabras clave. Hipertensión. Obesidad. Hiperinsulinemia. Sistema renina-angiotensina-aldosterona. Leptina. Adiponectina. ABSTRACTObesity is a chronic disease, considered to be an important risk factor in the development of coronary disease, hypertension, renal insufficiency and failure.Obesity contributes to hypertension by mechanisms such as: insulinic resistance and hyperinsulinaemia, increase of adrenergic activity and of concentrations of aldosterone, retention of sodium and water and increase of cardiac wear, alteration of the endothelial function, through molecules such as leptin and adiponectin and genetic factors. Many paths of research remain open.The angiotensin-converting-enzyme inhibitors (ACEI) and/or the angiotensin II receptor antagonists (ARA II) are first choice medicines because of their beneficial effect on insulinic resistance and sympathetic activity.

Objective: The different classes of drugs routinely used in anti-hypertensive therapy promote different effects on markers of arterial stiffness and, consequently, on the central blood pressure. Arterial stiffness is the main determinant for the increase of the central blood pressure and considered an important predictor for myocardial infarction, stroke and congestive heart failure. Objective: The objective of this study was to compare the effect on the systolic central blood pressure and arterial stiffness in resistant hypertensive patients submitted to sequential nephron blockade (SNB) against double blockade of the renin-angiotensin-aldosterone system (DBRAS) plus Bisoprolol. Design and method: Fifty-five resistant hypertensive patients were recruited in the Hypertension Outpatient Clinic of FAMERP, twenty-nine in the SNB group (18F/11 M) and twenty-six in the DBRAS group (22F/4 M). Central systolic blood pressure (cSBP), incrementing index (AI) and AI75 were measured with Omron HEM9000-A. (Japan). Results: The main result showed significant reduction of the central systolic blood pressure in patients submitted to sequential blockade nephron treatment when compared with the double blockade of the renin-angiotensin system plus Bisoprolol group (128.8 ± 22.1 vs. 117.4 ± 17.9 mmHg - P = 0.03). Figure 1 Conclusions: The sequential nephron blockade group, when compared with the double blockade of the renin-angiotensin-aldosterone system plus Bisoprolol, promotes significant higher reduction of the central systolic blood pressure in resistant hypertensive patients.

Objective: Resistant hypertension (RHTN) is a clinical entity, difficult to manage. To identify the contribution of the volume as well as the renin activity from the maintenance of blood pressure levels could individualize the treatment. Objectives : To demonstrate the efficacy of therapy of sequential nephron blocking (SNB) in relation to the double blockade of the renin-angiotensin system associated with beta-blockers (DBRAS) in patients with RHTN with > 85%-adherence rate after 20 weeks of treatment. Design and method: A prospective study was conducted, open, randomized, parallel comparison between two regimens for RHT: SNB versus DBRAS. SNB consists in a progressive increase of sodium depletion with thiazide, followed by a blockade of mineralocorticoid receptor, followed by progressive doses of loop diuretics and finally blocking sodium channels. DBRAS consists in reinforcing the effect of angiotensin receptor blocker (ARB) with an angiotensin converting enzyme inhibitors (ACEI), followed by betablockers to decrease the renin secretion. Seventy-two patients were randomized (35 to SNB 13 M/22F and 37 to RASDB 14 M/23F) coming from the tertiary outpatient clinic (HB-FAMERP). We used the criteria of the Brazilian VII Guidelines for Hypertension and V Guidelines for ABPM and HBPM. The BP was monitored with the SpaceLabs 90207. Results: Baseline clinical characteristics and laboratory parameters of the 72 RHTM randomized to SNB (n = 35) or DBRAS (n = 37) were similar across both study groups. At the end of the study, a significant reduction of the office pressure was observed (SBP and DBP) in both post-intervention groups (SNB group: initial SBP: 174.5 ± 21.08; final SBP: 127.0 ± 14.74; Initial DBP: 105.3 ± 15.5, final DBP: 78.11 ± 9.28 (p < 0.0001), RAASDB group: initial SBP: 178.4 ± 21.08, final SBP: 134.4 ± 23.25, initial DBP: 102.7 ± 11.07, final DBP: 77.33 ± 13.75 (p < 0.0001). No discontinuation due drug-related adverse events in both study groups. Conclusions: SNB and DBRAS associated with the beta-blocker in RHTN patients with full adherence to the treatment showed excellent therapeutic efficacy. However, the SNB group disclosed a greater absolute reduction of central blood pressure values.

Objective: Resistant hypertensive patients have a high prevalence of target organ damage. Increased central systolic blood pressure (cSBP) is more relevant than the peripheral one in these patients, because heart, brain and kidneys are directly exposed to high cSBP levels. Moreover, it is directly related to left ventricular hypertrophy, left atrial size, ischemic heart disease, brain injury, and kidney dysfunction. Currently, assessing cSBP and Augmentation Index (Aix) can be helpful to stratify cardiovascular risk and there is evidence that an improvement on cSBP leads to reduction of cardiovascular events and guides the antihypertensive treatment with drugs that more effective on cSBP reduction.An open prospective study was conducted, to identify markers associated with high cSBP values in resistant hypertensive patients on antihypertensive treatment. Design and method: Seventy-two hypertensive patients were recruited in the Hypertension Outpatient Clinic of FAMERP (44 women/ 28 men). Clinical characteristics and biochemical data collected are shown in the Table 1. The central systolic arterial pressure (cSBP) and the augmentation index (AIx) were measured using Tonometry HEM 9000-A validated OMRON equipment (JAPAN). Results: Multiple regression (cSBP) showed positive correlation between cSBP and brachial SBP (p = 0,0243) and microalbuminuria (p = 0,0325) and negative correlation with 24-h urinary sodium (p = 0,0277). Table2 and Figures. Conclusions: In Resistant hypertensive patientes the microalbuminuria can be useful as a marker to Increased central systolic blood pressure (cSBP)