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.

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.

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.

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.

What Is the Most Common Cause of Secondary Hypertension?: An Interdisciplinary Discussion.

PURPOSE OF REVIEW: Traditional statements in medical textbooks pointed that 90 to 95% of cases of hypertension is essential or primary. However, secondary hypertension seems to be common in those patients with resistant forms of hypertension. Appropriate investigation and treatment may have prognostic impact but frequently hypertension remission did not occur raising concerns about the real meaning of secondary hypertension. Here, we provided an interdisciplinary and critical discussion comprising an endocrinologist, a nephrologist, and a cardiologist with expertise in resistant hypertension. We reviewed the literature approaching each one of the recognizable cause of hypertension. RECENT FINDINGS: Recent studies pointed that the most common causes of secondary hypertension are those who overall responses to their treatments do not promote hypertension remission including obstructive sleep apnea (OSA), chronic kidney disease, renovascular hypertension and primary aldosteronism. The authors raised concerns regarding the lack of inclusion of obesity by several societies as a formal cause of hypertension considering not only the biologic plausibility but also the huge impact of weight loss therapies such as bariatric surgery on hypertension remission. In contrast, there is no discussion that a very rare condition-namely pheochromocytoma-is the most "typical" cause of hypertension by promoting hypertension remission in the majority of patients after surgical procedure. Hypertension is a complex condition with multiple environmental and genetics interactions. In clinical practice, it is challenging to prove causality in hypertension. Common conditions largely acceptable as causes of hypertension (OSA, chronic kidney disease, renovascular hypertension, and primary aldosteronism) frequently occur in a setting of an established hypertension background and therefore do not promote hypertension remission in a significant proportion of patients. If obesity becomes largely accepted by several societies as a secondary form of hypertension, this pandemic condition will be certainly the most common cause of hypertension.

Blood Pressure Increase in Hypertensive Individuals During Resistance Training Protocols With Equated Work to Rest Ratio.

Introduction: Despite growing evidence regarding the benefits of resistance training in hypertension, the large and abrupt rise of systolic blood pressure (SBP) observed during resistance exercise execution has resulted in concern about its safety. However, the manipulation of the resistance training protocol (RTP) organization, maintaining the work to rest ratio equated between protocols (W:R-equated), may reduce the SBP increase. Purpose: To compare cardiovascular responses during two W:R-equated RTPs (3 × 15:88 s vs. 9 × 5:22 s - sets × reps: rest between sets) performed in exercises for the lower and upper limbs. Methods: Twelve medicated hypertensives (48 ± 8 years) randomly performed two RTPs in the bilateral leg extension (BLE) and unilateral elbow flexion (UEF) exercises at 50% 1RM. Increases (Δ) of SBP, heart rate (HR) and rate pressure product (RPP) during the exercises were measured by photoplethysmography. Results: In both BLE and UEF exercises, Δ SBP was significantly greater during 3 × 15:88 s than 9 × 5:22 s (peak values: BLE = + 84 ± 39 vs. + 67 ± 20 mm Hg, and UEF = + 46 ± 25 vs. + 37 ± 18 mm Hg, respectively, both p < 0.05). ΔHR and ΔRPP were significantly higher in the 3 × 15:88 s than 9 × 5:22 s in BLE (peak values + 45 ± 17 vs. + 30 ± 8 bpm, and + 15,559 ± 5570 vs. + 10,483 ± 2614 mm Hg. bpm). Conclusion: In medicated hypertensives, a RTP combining more sets with less repetitions per set and shorter rest intervals between sets (i.e., 9 × 5:22 s) produced a smaller increase in cardiovascular load (ΔSBP, ΔHR and ΔRPP) during its execution than a protocol with fewer longer sets (i.e., 3 × 15:88 s).

KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear. OBJECTIVE: To determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA. METHODS: We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases. RESULTS: KCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004). CONCLUSION: The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.