Fabio de Souza

Efficacy of Spironolactone Therapy in Patients With True Resistant Hypertension

The role of spironolactone in resistant hypertension management is unclear. The aim of this prospective trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring. A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after a median interval of 7 months. Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration, and multivariate analysis adjusted for age, sex, and number of antihypertensive drugs to assess the predictors of blood pressure fall. There were mean reductions of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; P<0.001). Office systolic blood pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled ambulatory blood pressure was reached in 48% of patients. Factors associated with better response were higher waist circumference, lower aortic pulse wave velocity, and lower serum potassium. No association with plasma aldosterone or aldosterone:renin ratio was found. Adverse effects were observed in 13 patients (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect. In conclusion, spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure, especially in those with abdominal obesity and lower arterial stiffness. Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended.

Effects of Continuous Positive Airway Pressure Treatment on Clinic and Ambulatory Blood Pressures in Patients With Obstructive Sleep Apnea and Resistant Hypertension: A Randomized Controlled Trial

The effect of continuous positive airway pressure (CPAP) on blood pressures (BPs) in patients with resistant hypertension and obstructive sleep apnea is not established. We aimed to evaluate it in a randomized controlled clinical trial, with blinded assessment of outcomes. Four hundred thirty-four resistant hypertensive patients were screened and 117 patients with moderate/severe obstructive sleep apnea, defined by an apnea–hypopnea index ≥15 per hour, were randomized to 6-month CPAP treatment (57 patients) or no therapy (60 patients), while maintaining antihypertensive treatment. Clinic and 24-hour ambulatory BPs were obtained before and after 6-month treatment. Primary outcomes were changes in clinic and ambulatory BPs and in nocturnal BP fall patterns. Intention-to-treat and per-protocol (limited to those with uncontrolled ambulatory BPs) analyses were performed. Patients had mean (SD) 24-hour BP of 129(16)/75(12) mm Hg, and 59% had uncontrolled ambulatory BPs. Mean apnea–hypopnea index was 41 per hour and 58.5% had severe obstructive sleep apnea. On intention-to-treat analysis, there was no significant difference in any BP change, neither in nocturnal BP fall, between CPAP and control groups. The best effect of CPAP was on night-time systolic blood pressure in per-protocol analysis, with greater reduction of 4.7 mm Hg (95% confidence interval, −11.3 to +3.1 mm Hg; P=0.24) and an increase in nocturnal BP fall of 2.2% (95% confidence interval, −1.6% to +5.8%; P=0.25), in comparison with control group. In conclusion, CPAP treatment had no significant effect on clinic and ambulatory BPs in patients with resistant hypertension and moderate/severe obstructive sleep apnea, although a beneficial effect on night-time systolic blood pressure and on nocturnal BP fall might exist in patients with uncontrolled ambulatory BP levels.

Appropriate Time Interval to Repeat Ambulatory Blood Pressure Monitoring in Patients With White-Coat Resistant Hypertension

Resistant hypertension is defined as uncontrolled office blood pressure, despite the use of ≥3 antihypertensive drugs. Ambulatory blood pressure monitoring (ABPM) is mandatory to diagnose 2 different groups, those with true and white-coat resistant hypertension. Patients are found to change categories between controlled/uncontrolled ambulatory pressures without changing their office blood pressures. In this way, ABPM should be periodically repeated. The aim of this study was to evaluate the most appropriate time interval to repeat ABPM to assure sustained blood pressure control in patients with white-coat resistant hypertension. This prospective study enrolled 198 patients (69% women; mean age: 68.9±9.9 years) diagnosed as white-coat resistant hypertension on ABPM. Patients were submitted to a second confirmatory examination 3 months later and repeated twice at 6-month intervals. Statistical analyses included Bland-Altman repeatability coefficients and multivariate logistic regression. Mean office blood pressure was 163±20/84±17 mm Hg, and mean 24-hour blood pressure was 118±8/66±7 mm Hg. White-coat resistant hypertension diagnosis presented a moderate reproducibility and was confirmed in 144 patients after 3 months. In the third and fourth ABPMs, 74% and 79% of patients sustained the diagnosis. In multivariate regression, a daytime systolic blood pressure ⩽115 mm Hg in the confirmatory ABPM triplicated the chance of white-coat resistant hypertension status persistence after 1 year. In conclusion, a confirmatory ABPM is necessary after 3 months of the first white-coat–resistant hypertension diagnosis, and the procedure should be repeated at 6-month intervals, except in patients with daytime systolic blood pressure ⩽115 mm Hg, in whom it may be repeated annually.

Diphosphine complexes of nickel: analogies in molecular structures and variety in crystalline arrangement

Abstract This work comprised the preparation of six complexes of Ni(II) and their study by spectroscopy and X-ray diffraction. These complexes are: [Ni(dppe)Cl2]CH2Cl2 (I), [Ni(dppen)Cl2] (II), [Ni(dppm)Br2]CH2Cl2 (III), [Ni(dppe)(NCS)2] (IV), [Ni(dppen)I2] (V), [Ni(dppp)Cl2]CH2Cl2 (VI), where dppe=1,2-bis(diphenylphosphine)ethane, dppen=cis-1,2-bis(diphenylphosphine)ethene, dppm=bis(diphenylphosphine)methane, dppp=1,3-bis(diphenylphosphine)propane. The structures of complexes III–VI are unknown in the literature. Although the molecular structures of the six complexes present many similarities, their crystalline arrangements vary considerably. This is a feature not presented hitherto in previous work involving complexes of this type. In addition, a systematic spectroscopic study was undertaken on all six complexes.

Prognostic factors in resistant hypertension: implications for cardiovascular risk stratification and therapeutic management.

Resistant hypertension (RH) is defined as uncontrolled office blood pressure (BP) in spite of the use of at least three antihypertensive medications. Although its condition has a high prevalence, it is still understudied, and its prognosis is not well established. Some prospective studies evaluated the prognostic value of ambulatory BP monitoring, ECG and renal parameters. They pointed out that ambulatory BPs are important predictors of cardiovascular morbidity and mortality, whereas office BP has no prognostic value. The diagnosis of true RH and the nondipping pattern are also valuable predictors of cardiovascular outcomes. Moreover, several ECG (prolonged ventricular repolarization, serial changes in the strain pattern and left ventricular hypertrophy) and renal parameters (albuminuria and reduced glomerular filtration rate) are also powerful cardiovascular risk markers in RH. These markers and others yet unexplored, such as arterial stiffness and serum biomarkers, may improve cardiovascular risk stratification in these very high-risk patients.

Effects of Continuous Positive Airway Pressure Treatment on Clinic and Ambulatory Blood Pressures in Patients With Obstructive Sleep Apnea and Resistant Hypertension

The effect of continuous positive airway pressure (CPAP) on blood pressures (BPs) in patients with resistant hypertension and obstructive sleep apnea is not established. We aimed to evaluate it in a randomized controlled clinical trial, with blinded assessment of outcomes. Four hundred thirty-four resistant hypertensive patients were screened and 117 patients with moderate/severe obstructive sleep apnea, defined by an apnea–hypopnea index ≥15 per hour, were randomized to 6-month CPAP treatment (57 patients) or no therapy (60 patients), while maintaining antihypertensive treatment. Clinic and 24-hour ambulatory BPs were obtained before and after 6-month treatment. Primary outcomes were changes in clinic and ambulatory BPs and in nocturnal BP fall patterns. Intention-to-treat and per-protocol (limited to those with uncontrolled ambulatory BPs) analyses were performed. Patients had mean (SD) 24-hour BP of 129(16)/75(12) mm Hg, and 59% had uncontrolled ambulatory BPs. Mean apnea–hypopnea index was 41 per hour and 58.5% had severe obstructive sleep apnea. On intention-to-treat analysis, there was no significant difference in any BP change, neither in nocturnal BP fall, between CPAP and control groups. The best effect of CPAP was on night-time systolic blood pressure in per-protocol analysis, with greater reduction of 4.7 mm Hg (95% confidence interval, −11.3 to +3.1 mm Hg; P=0.24) and an increase in nocturnal BP fall of 2.2% (95% confidence interval, −1.6% to +5.8%; P=0.25), in comparison with control group. In conclusion, CPAP treatment had no significant effect on clinic and ambulatory BPs in patients with resistant hypertension and moderate/severe obstructive sleep apnea, although a beneficial effect on night-time systolic blood pressure and on nocturnal BP fall might exist in patients with uncontrolled ambulatory BP levels.

Effects of continuous positive airway pressure treatment on aldosterone excretion in patients with obstructive sleep apnoea and resistant hypertension: a randomized controlled trial.

Objective: Aldosterone excess has been equally associated with resistant hypertension (RHT) and obstructive sleep apnoea (OSA). We conducted a randomized controlled study to assess the effect of continuous positive airway pressure (CPAP) treatment on 24-h urinary aldosterone excretion in patients with RHT and moderate/severe OSA. Methods: A total of 117 patients were randomized (57 CPAP and 60 control groups). Aldosterone excretion was determined by 24 h urine (24h-UAldo) collected at randomization and after 6 months of follow-up. Twenty-four hour UAldo differences were assessed by general linear model with the allocation group (CPAP or control) as a fixed factor adjusted for their respective baseline values. Both intention-to-treat and per-protocol (45 patients with optimal adherence to CPAP) analyses were performed. Results: Baseline 24h-UAldo was higher in severe OSA than in moderate OSA patients. After CPAP treatment, there was a borderline significant reduction in 24h-UAldo [mean difference: −2.5 &mgr;g/24 h; 95% confidence interval (95% CI): −5.3 to +0.3 &mgr;g/24 h; P = 0.07] in intention-to-treat analysis, whereas in the per-protocol analysis, the CPAP group had a greater reduction in 24h-UAldo than the control group (mean difference: −3.3 &mgr;g/24 h; 95% CI: −6.1 to −0.4 &mgr;g/24 h; P = 0.027). This effect occurred solely in patients with uncontrolled ambulatory BPs, and was more pronounced in those with the nondipping pattern, not using spironolactone, less obese, and with lowest sleep SaO2 levels. Conclusion: Only optimal CPAP treatment reduced aldosterone excretion in patients with uncontrolled RHT, while on intention-to-treat the effect was borderline. Although nondefinitive, our results suggest that CPAP treatment might improve cardiovascular outcomes by reducing aldosterone excess in resistant hypertensive individuals with OSA. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01508754.

Prognostic impact of baseline urinary albumin excretion rate in patients with resistant hypertension: a prospective cohort study

Moderately increased albuminuria, defined as urinary albumin excretion rate (UAER) between 30 and 300–mg/24–h is a well-known cardiovascular risk factor, especially in diabetic and hypertensive patients. This study aim to analyze the prognostic value of baseline UAER in a still understudied group, patients with resistant hypertension (RHT). This is a prospective observational study, which had enrolled 1048 outpatients with RHT, who were submitted to a clinical-laboratory assessment and ambulatory blood pressure monitoring (ABPM) during the follow-up. Primary endpoints were a composite of fatal and non-fatal cardiovascular events, all-cause mortality and cardiovascular mortality. Survival analysis by multiple Cox regression assessed the associations among endpoints, baseline UAER, glomerular filtration rate (GFR), and ABPM control. After a mean 7.5 years follow-up, 233 patients died, 120 from cardiac death; 215 cardiovascular events occurred, 90 strokes and 116 coronary diseases. UAER above 30–mg/24–h increased above 40% the risk of fatal and non-fatal cardiovascular events, and of all-cause mortality. At these UAER levels, secondary outcomes were associated to increased risk of stroke and risk of end-stage renal disease, but did not affect coronary events. Both the GFR below 60–mL/min and uncontrolled ABPM were related to nearly two-fold raised risk of fatal and non-fatal cardiovascular events, when coupled with UAER above 30–mg/24–h. In conclusion, moderately increased albuminuria predicts cardiovascular events and all-cause mortality in RHT, and its prognostic impact is enhanced in association with a GFR under 60–mL/min and uncontrolled baseline ABPM.

Effects of Continuous Positive Airway Pressure Treatment on Clinic and Ambulatory Blood Pressures in Patients With Obstructive Sleep Apnea and Resistant HypertensionNovelty and Significance

The effect of continuous positive airway pressure (CPAP) on blood pressures (BPs) in patients with resistant hypertension and obstructive sleep apnea is not established. We aimed to evaluate it in a randomized controlled clinical trial, with blinded assessment of outcomes. Four hundred thirty-four resistant hypertensive patients were screened and 117 patients with moderate/severe obstructive sleep apnea, defined by an apnea–hypopnea index ≥15 per hour, were randomized to 6-month CPAP treatment (57 patients) or no therapy (60 patients), while maintaining antihypertensive treatment. Clinic and 24-hour ambulatory BPs were obtained before and after 6-month treatment. Primary outcomes were changes in clinic and ambulatory BPs and in nocturnal BP fall patterns. Intention-to-treat and per-protocol (limited to those with uncontrolled ambulatory BPs) analyses were performed. Patients had mean (SD) 24-hour BP of 129(16)/75(12) mm Hg, and 59% had uncontrolled ambulatory BPs. Mean apnea–hypopnea index was 41 per hour and 58.5% had severe obstructive sleep apnea. On intention-to-treat analysis, there was no significant difference in any BP change, neither in nocturnal BP fall, between CPAP and control groups. The best effect of CPAP was on night-time systolic blood pressure in per-protocol analysis, with greater reduction of 4.7 mm Hg (95% confidence interval, −11.3 to +3.1 mm Hg; P=0.24) and an increase in nocturnal BP fall of 2.2% (95% confidence interval, −1.6% to +5.8%; P=0.25), in comparison with control group. In conclusion, CPAP treatment had no significant effect on clinic and ambulatory BPs in patients with resistant hypertension and moderate/severe obstructive sleep apnea, although a beneficial effect on night-time systolic blood pressure and on nocturnal BP fall might exist in patients with uncontrolled ambulatory BP levels.

Effects of Continuous Positive Airway Pressure Treatment on Clinic and Ambulatory Blood Pressures in Patients With Obstructive Sleep Apnea and Resistant HypertensionNovelty and Significance: A Randomized Controlled Trial

The effect of continuous positive airway pressure (CPAP) on blood pressures (BPs) in patients with resistant hypertension and obstructive sleep apnea is not established. We aimed to evaluate it in a randomized controlled clinical trial, with blinded assessment of outcomes. Four hundred thirty-four resistant hypertensive patients were screened and 117 patients with moderate/severe obstructive sleep apnea, defined by an apnea–hypopnea index ≥15 per hour, were randomized to 6-month CPAP treatment (57 patients) or no therapy (60 patients), while maintaining antihypertensive treatment. Clinic and 24-hour ambulatory BPs were obtained before and after 6-month treatment. Primary outcomes were changes in clinic and ambulatory BPs and in nocturnal BP fall patterns. Intention-to-treat and per-protocol (limited to those with uncontrolled ambulatory BPs) analyses were performed. Patients had mean (SD) 24-hour BP of 129(16)/75(12) mm Hg, and 59% had uncontrolled ambulatory BPs. Mean apnea–hypopnea index was 41 per hour and 58.5% had severe obstructive sleep apnea. On intention-to-treat analysis, there was no significant difference in any BP change, neither in nocturnal BP fall, between CPAP and control groups. The best effect of CPAP was on night-time systolic blood pressure in per-protocol analysis, with greater reduction of 4.7 mm Hg (95% confidence interval, −11.3 to +3.1 mm Hg; P=0.24) and an increase in nocturnal BP fall of 2.2% (95% confidence interval, −1.6% to +5.8%; P=0.25), in comparison with control group. In conclusion, CPAP treatment had no significant effect on clinic and ambulatory BPs in patients with resistant hypertension and moderate/severe obstructive sleep apnea, although a beneficial effect on night-time systolic blood pressure and on nocturnal BP fall might exist in patients with uncontrolled ambulatory BP levels.