RESUMO
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 24âh 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: -2.5âµg/24âh; 95% confidence interval (95% CI): -5.3 to +0.3âµg/24âh; Pâ=â0.07] 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: -3.3âµg/24âh; 95% CI: -6.1 to -0.4âµg/24âh; Pâ=â0.027). 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.
Assuntos
Aldosterona/urina , Pressão Positiva Contínua nas Vias Aéreas , Vasoespasmo Coronário/urina , Hipertensão/urina , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/urina , Idoso , Vasoespasmo Coronário/complicações , Diuréticos/uso terapêutico , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Oxigênio/sangue , Apneia Obstrutiva do Sono/complicações , Espironolactona/uso terapêuticoRESUMO
Confirmation of medication adherence is a challenge in clinical practice and essential for the accurate diagnosis of resistant hypertension. Although it is well established that drug adherence is critical for controlling blood pressure, there are still difficulties applying a simple, inexpensive, and reliable assessment of adherence in the clinical setting. We aimed to test a simple method to assess adherence in resistant hypertensive (RH) patients. A pilot study with normotensives or mild/moderate hypertensive subjects was performed to provide a fluorescence cutoff point for adherence. After that, 21 patients referred to the Resistant Hypertension Clinic had triamterene prescribed and were monitored for a 30-day period. We conducted two unannounced randomly selected home visits for urine collection to test drug intake that day. Office, home and 24-hour ambulatory blood pressure, biochemical data, and the 8-item Morisky Medication Adherence Scale (MMAS-8) were systematically acquired. According to adherence indicated by urine fluorescence, subjects were divided into adherent and nonadherent groups. We found 57% of nonadherence. No differences were found between groups regarding baseline characteristics or prescribed medications; Kappa's test showed concordance between adherence through MMAS-8 items and fluorescence (kappa = 0.61; 95% confidence interval: 0.28-0.94; P = .005). Nonadherent patients had higher office (81 ± 11 vs. 73 ± 6 mm Hg, P = .03), 24-hour ambulatory blood pressure monitoring (75 ± 9 vs. 66 ± 7 mm Hg, P = .01), and home blood pressure measurement (77 ± 9 vs. 67 ± 8 mm Hg, P = .01) diastolic blood pressure than their counterparts. Nonadherence to antihypertensive therapy is high in patients with RH, even when assessed in clinics specialized in this condition. Fluorometry to detect a drug in the urine of RH patients is safe, easy, and reliable method to assess adherence.
Assuntos
Anti-Hipertensivos/uso terapêutico , Vasoespasmo Coronário/tratamento farmacológico , Vasoespasmo Coronário/psicologia , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Adesão à Medicação , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/urina , Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Vasoespasmo Coronário/urina , Diuréticos/administração & dosagem , Diuréticos/urina , Estudos de Viabilidade , Feminino , Fluorometria , Humanos , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e Especificidade , Triantereno/administração & dosagem , Triantereno/uso terapêutico , Triantereno/urinaRESUMO
Patients with resistant hypertension belong to a very high cardiovascular risk group and have a high prevalence of target organ damage. Microalbuminuria and low estimated glomerular filtration rate are associated with resistant hypertension, and could be a cause and/or complication of hypertension. In this review, we explore the relationship between these 2 markers of kidney disease and the prevalence of resistant hypertension. We identified different phenotypes of resistant hypertension that associate with microalbuminuria and/or low estimated glomerular filtration rate. These phenotypes suggest that high sympathetic activity associated with fluid overload and endothelial dysfunction may contribute differently to the development of resistant hypertension.