Post-dynamic, isometric and combined resistance exercise responses in medicated hypertensive men.

This study investigated the effects of dynamic resistance exercise (DRE), isometric handgrip exercise (IHE) and combined resistance exercise (DRE+IHE) on post-exercise hypotension (PEH) and its hemodynamic, autonomic, and vascular mechanisms. For that, 70 medicated hypertensives men (52 ± 8 years) were randomly allocated to perform one of the following interventions: DRE (3 sets, 8 exercises, 50% of 1RM), IHE (4 sets, 2 min, 30% of MVC), CRE (DRE+IHE) and control (CON, seated rest). Before and after the interventions, blood pressure (BP), systemic hemodynamics, cardiovascular autonomic modulation and brachial vascular parameters were evaluated. After the DRE and CRE, systolic and mean BP decreased (SBP = -7 ± 6 and -8 ± 8 mmHg; MBP -4 ± 5 and -5 ± 5 mmHg, respectively, all P < 0.05), vascular conductance increased (+ 0.47 ± 0.61 and +0.40 ± 0.47 ml.min-1.mmHg-1, respectively, both P < 0.05) and baroreflex sensitivity decreased (-0.15 ± 0.38 and -0.29 ± 0.47 ms/mmHg, respectively, both P < 0.05) in comparison to pre-exercise values. No variable presented any significant change after IHE. The responses observed after CRE were similar to DRE and significantly different from CON and IHE. In conclusion, DRE, but not IHE, elicits PEH, which happens concomitantly to skeletal muscle vasodilation and decreased baroreflex sensitivity. Moreover, adding IHE to DRE does not potentiate PEH and neither changes its mechanisms.Clinical Trial Registration: Data from this study derived from an ongoing longitudinal clinical trial approved by the Institution's Ethics Committee of Human Research (process 2.870.688) and registered at the Brazilian Clinical Trials (RBR-4fgknb) at http://www.ensaiosclinicos.gov.br .

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

Efficacy of Oral Furosemide Test for Primary Aldosteronism Diagnosis.

Context: Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved. Objective: To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis. Methods: We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA. Results: The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test. Conclusion: The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation.

Can blood pressure decrease after maximal exercise test predict the blood pressure lowering effect of aerobic training in treated hypertensive men?

The acute decrease in blood pressure (BP) observed after a session of exercise (called post-exercise hypotension) has been proposed as a tool to predict the chronic reduction in BP induced by aerobic training. Therefore, this study investigated whether post-exercise hypotension observed after a maximal exercise test is associated to the BP-lowering effect of aerobic training in treated hypertensives. Thirty hypertensive men (50 ± 8 years) who were under consistent anti-hypertensive treatment underwent a maximal exercise test (15 watts/min until exhaustion), and post-exercise hypotension was determined by the difference between BP measured before and at 30 min after the test. Subsequently, the patients underwent 10 weeks of aerobic training (3 times/week, 45 min/session at moderate intensity), and the BP-lowering effect of training was assessed by the difference in BP measured before and after the training period. Pearson correlations were employed to evaluate the associations. Post-maximal exercise test hypotension was observed for systolic and mean BPs (-8 ± 6 and -2 ± 4 mmHg, all P < 0.05). Aerobic training reduced clinic systolic/diastolic BPs (-5 ± 6/-2 ± 3 mmHg, both P < 0.05) as well as awake and 24 h mean BPs (-2 ± 6 and -2 ± 5 mmHg, all P < 0.05). No significant correlation was detected between post-exercise hypotension and the BP-lowering effect of training either for clinic or ambulatory BPs (r values ranging from 0.00 to 0.32, all p > 0.05). Post-exercise hypotension assessed 30 min after a maximal exercise test cannot be used to predict the BP-lowering effect of aerobic training in treated hypertensive men.

Obstructive sleep apnea and hypertension-mediated organ damage in nonresistant and resistant hypertension.

The potential role of obstructive sleep apnea (OSA) in hypertension-mediated organ damage (HMOD) may be influenced by the presence of resistant hypertension (RH). Herein, we enrolled patients with hypertension from a tertiary center for clinical evaluation and performed a sleep study to identify OSA (apnea-hypopnea index ≥15 events/h) and a blinded analysis of four standard HMOD parameters (left ventricular hypertrophy [LVH], increased arterial stiffness [≥10 m/s], presence of retinopathy, and nephropathy). RH was diagnosed based on uncontrolled blood pressure (BP) (≥140/90 mmHg) despite concurrent use of at least three antihypertensive drug classes or controlled BP with concurrent use of ≥4 antihypertensive drug classes at optimal doses. To avoid the white-coat effect, ambulatory BP monitoring was performed to confirm RH diagnosis. One-hundred patients were included in the analysis (mean age: 54 ± 8 years, 65% females, body mass index: 30.4 ± 4.5 kg/m²). OSA was detected in 52% of patients. Among patients with non-RH (n = 53), the presence of OSA (52.8%) was not associated with an increased frequency of HMOD. Conversely, among patients with RH, OSA (51.1%) was associated with a higher incidence of LVH (RH-OSA,61%; RH + OSA,87%; p = 0.049). Logistic regression analysis using the total sample revealed that RH (OR:7.89; 95% CI:2.18-28.52; p = 0.002), systolic BP (OR:1.04; 95% CI:1.00-1.07; p = 0.042) and OSA (OR:4.31; 95% CI:1.14-16.34; p = 0.032) were independently associated with LVH. No significant association was observed between OSA and arterial stiffness, retinopathy, or nephropathy. In conclusion, OSA is independently associated with LVH in RH, suggesting a potential role of OSA in RH prognosis.

Effects of dynamic, isometric and combined resistance training on blood pressure and its mechanisms in hypertensive men.

Although dynamic resistance training (DRT) and isometric handgrip training (IHT) may decrease blood pressure (BP) in hypertensives, the effects of these types of training have not been directly compared, and a possible additive effect of combining IHT to DRT (combined resistance training-CRT), has not been investigated. Thus, this study compared the effects of DRT, IHT and CRT on BP, systemic hemodynamics, vascular function, and cardiovascular autonomic modulation. Sixty-two middle-aged men with treated hypertension were randomly allocated among four groups: DRT (8 exercises, 50% of 1RM, 3 sets until moderate fatigue), IHT (30% of MVC, 4 sets of 2 min), CRT (DRT + IHT) and control (CON - stretching). In all groups, the interventions were administered 3 times/week for 10 weeks. Pre- and post-interventions, BP, systemic hemodynamics, vascular function and cardiovascular autonomic modulation were assessed. ANOVAs and ANCOVAs adjusted for pre-intervention values were employed for analysis. Systolic BP decreased similarly with DRT and CRT (125 ± 11 vs. 119 ± 12 and 128 ± 12 vs. 119 ± 12 mmHg, respectively; P < 0.05), while peak blood flow during reactive hyperaemia (a marker of microvascular function) increased similarly in these groups (774 ± 377 vs. 1067 ± 461 and 654 ± 321 vs. 954 ± 464 mL/min, respectively, P < 0.05). DRT and CRT did not change systemic hemodynamics, flow-mediated dilation, and cardiovascular autonomic modulation. In addition, none of the variables were changed by IHT. In conclusion, DRT, but not IHT, improved BP and microvascular function in treated hypertensive men. CRT did not have any additional effect in comparison with DRT alone.

Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening.

CONTEXT: Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. OBJECTIVE: To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. METHODS: A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. RESULTS: The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. CONCLUSION: Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

Directly observed therapy for resistant/refractory hypertension diagnosis and blood pressure control.

OBJECTIVE: To test the impact of directly observed therapy (DOT) at hospital for checking not only adherence/diagnosis in patients with resistant (RHTN) and refractory (RefHTN) hypertension but also blood pressure (BP) control after hospital discharge. METHODS: During 2 years, Brazilian patients with clinical suspicion of RHTN/RefHTN after several attempts (≥3) to control BP in the outpatient setting were invited to perform DOT (including low-sodium diet and supervised medications intake) at the hospital. RHTN and RefHTN were categorised using standard definitions. After hospital discharge, we evaluated the BP values and the number of antihypertensive drugs prescribed by physicians who were not involved with the investigation. RESULTS: We studied 83 patients clinically suspected for RHTN (31%) and RefHTN (69%) (mean age: 53 years; 76% female; systolic BP 177±28 mm Hg and diastolic BP 106±21 mm Hg; number of antihypertensive drugs: 5.3±1.3). DOT confirmed RHTN in 77%, whereas RefHTN was confirmed in only 32.5%. The number of antihypertensive drugs reduced to 4.5±1.3 and systolic/diastolic BP at hospital discharge reduced to 131±17 mm Hg/80±12 mm Hg. After hospital discharge, systolic BP remained significantly lower than the last outpatient visit prehospital admission (delta changes (95% CI): 1 month: -25.7 (-33.8 to -17.6) mm Hg; 7 months: -27.3 (-35.5 to -19.1) mm Hg) despite fewer number of antihypertensive classes (1 month: -1.01 (-1.36 to -0.67); 7 months: -0.77 (-1.11 to -0.42)). Similar reductions were observed for diastolic BP. CONCLUSIONS: DOT at hospital is helpful not only in confirming/excluding RHTN/RefHTN phenotypes, but also in improving BP values and BP control and in reducing the need for antihypertensive drugs after hospital discharge.

Evaluation of central venous catheter and other risk factors for mortality in chronic hemodialysis patients with COVID-19 in Brazil.

PURPOSE: Hemodialysis patients with COVID-19 are at increased risk of death. We aimed to describe the characteristics of a cohort of Brazilian hemodialysis patients with COVID-19 and assess their mortality rate and risk factors for death. METHODS: Retrospective cohort study of 741 Brazilian hemodialysis patients with confirmed COVID-19 from Feb-Dec/2020, of 52 dialysis centers of the country. We analyzed comorbid conditions, sociodemographic factors, and dialysis-related parameters. To detect risk factors for mortality in hemodialysis patients, we performed multivariable Cox proportional hazard regression analysis. Survival was analyzed by Kaplan-Meier. RESULTS: From 9877 hemodialysis patients, 741 were diagnosed with COVID-19. Mean age was 57 ± 16 years, 61% were male, and 51% white. The most frequent symptoms were fever (54.1%), cough (50.9%), and dyspnea (37.2%); 14.2% were asymptomatic. There were 139 deaths (18.8%), with 66% within the disease's first 15 days. 333 patients (44.9%) required hospitalization, and 211 (28.5%) were admitted to an intensive care unit. The cumulative probability of survival at 90 days of diagnosis was 79% (95% CI 76-82%). In the fully adjusted multivariate model, the risk factors significantly associated with death were diabetes mellitus (HR 1.52, 95% CI 1.05-2.19, P = 0.026), use of a central venous catheter (CVC) (HR 1.79, 95% CI 1.22-2.64, P = 0.003), age (HR 1.03, 95% CI 1.01-1.04, P < 0.001), and origin from the North vs. Southeast region (HR 2.60, 95% CI 1.01-6.68, P = 0.047). CONCLUSIONS: Hemodialysis patients using a CVC as the vascular access, aside from diabetic and elderly ones, should be closely monitored due to their high risk of death in the course of the COVID-19.

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic.

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Comparison of morning versus evening aerobic-exercise training on heart rate recovery in treated hypertensive men: a randomized controlled trial.

Heart rate recovery (HRR) is a marker of cardiac autonomic regulation and an independent predictor of mortality. Aerobic-exercise training conducted in the evening (evening training) produces greater improvement in resting cardiac autonomic control in hypertensives than morning training, suggesting it may also result in a faster autonomic restoration postexercise. This study compared the effects of morning training and evening training on HRR in treated hypertensive men. Forty-nine treated hypertensive men were randomly allocated into three groups: morning training, evening training and control. Training was conducted three times/week for 10 weeks. Training groups cycled (45 min, moderate intensity) while control group stretched (30 min). In the initial and final assessments of the study, HRR60s and HRR300s were evaluated during the active recovery (30 W) from cardiopulmonary exercise tests (CPET) conducted in the morning and evening. Between-within ANOVAs were applied (P ≤ 0.05). Only evening training increased HRR60s and HRR300 differently from control after morning CPET (+4 ± 5 and +7 ± 8 bpm, respectively, P < 0.05) and only evening training increased HRR300s differently from morning training and control after evening CPET (+8 ± 6 bpm, P < 0.05). Evening training improves HRR in treated hypertensive men, suggesting that this time of day is better for eliciting cardiac autonomic improvements via aerobic training in hypertensives.

Obstructive sleep apnea and ambulatory blood pressure monitoring: current evidence and research gaps.

Obstructive Sleep Apnea (OSA) is a common condition characterized by intermittent collapse of the upper airway during sleep, resulting in partial (hypopnoeas) and total obstructions (apneas). These respiratory events observed in OSA may trigger multiple pathways involved in the blood pressure (BP) instability during the night and potentially influencing daytime BP as well (carry-over effects). This review provides an update about the impact of OSA and its treatments on 24-h BP control. Overall, there is growing evidence suggest that OSA is associated with higher frequency of nondipping BP pattern and nocturnal hypertension in a dose-dependent manner. The presence of nondiping BP (especially the reverse pattern) is independently associated with OSA regardless of sleep-related symptoms suggesting a potential tool for screening OSA in patients with clinical indication for performing ABPM. Beyond dipping BP, preliminary evidence associated OSA with white-coat effect and higher frequency of masked hypertension and BP variability than the control group (no OSA). Unfortunately, most of the evidence on the evidence addressing the impact of OSA treatment on BP was limited to office measurements. In the last years, data from observational and randomized studies pointed that CPAP is able to promote 24-h BP decrease especially in patients with resistant and refractory hypertension. A randomized trial suggests that CPAP is able to decrease the rate of masked hypertension as compared to no treatment in patients with severe OSA. Interestingly, nondipping BP is a good predictor of BP response to CPAP making ABPM an interesting tool for better OSA management.

Association of Sodium with Obstructive Sleep Apnea. The ELSA-Brasil Study.

Rationale: Excessive sodium may have a role in the pathogenesis of obstructive sleep apnea (OSA) for patients with hypervolemic conditions, but it is unclear whether this is valid for all patients with OSA, including those with no significant comorbidities.Objectives: To test the association of urinary sodium and OSA in a large sample of participants from the ELSA-Brasil (Estudo Longitudinal de Saúde do Adulto-Brasil) Study. In addition, we stratified the analysis participants according to the presence of hypertension.Methods: In this cross-sectional study, OSA was defined by an apnea-hypopnea index ≥15 events/h. A validated 12-hour urine collection as representative of the 24-hour period was obtained from all participants to measure sodium excretion. We performed a logistic regression analysis to test the association of urinary sodium excretion with OSA (dependent variable) adjusting for age, sex, race and income, glomerular filtration rate, diabetes, physical activity, and antihypertensive classes related to sodium excretion. To address potential residual factors that may influence sodium excretion, we performed additional analysis replacing sodium excretion for salt intake (food frequency questionnaire) using the same models.Results: We studied 1,946 participants (age 49 ± 8 yr; 43.4% men). A third of them had OSA. Compared with those with no OSA, participants with OSA presented with higher sodium excretion (1.66 [1.19-2.29] vs. 1.99 [1.44-2.69] g/12 h; P < 0.001). After adjustments for confounding factors, we found no overall significant associations of sodium excretion with OSA (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.97-1.23; P = 0.150). Regardless of the OSA status, the sodium excretion was higher in hypertensive than in normotensive participants (1.93 [1.35-2.64] vs. 1.71 [1.22-2.37] g/12 h). An independent association of sodium excretion with OSA was observed in patients with hypertension only (OR, 1.326; 95% CI, 1.067-1.648; P = 0.011), but the interaction of urinary sodium with hypertension was not significant (P = 0.37). The analysis of salt intake revealed consistent findings.Conclusions: The potential role of sodium in the pathogenesis of OSA seems to be modest and limited for those with higher salt intake and, consequently, higher fluid retention such as observed in patients with hypertension.

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.