Prevalence and associated factors of obstructive sleep apnea in refractory hypertension.

BACKGROUND: Refractory hypertension (RfHT) and obstructive sleep apnea (OSA) share common pathophysiological mechanisms and probably are intrinsically associated, but their prevalence, clinical profile, and polysomnography (PSG) pattern remain misunderstood. OBJECTIVE: To describe OSA prevalence and PSG pattern of patients with RfHT in a large cohort of resistant hypertension (RHT). METHODS: This is a cross-sectional study involving 418 RHT patients (30.9% male; mean age of 62.5 ±â€Š9.9 years) who were submitted to full-night PSG. RfHT was defined as uncontrolled ambulatory blood pressure monitoring using five or more antihypertensive drugs, including spironolactone. Bivariate analysis compared RHT and RfHT and multivariate analysis was performed to assess the independent correlates of OSA. RESULTS: A total of 90 patients (21.5%) were diagnosed with RfHT (26.7% male; mean age of 58.5 ±â€Š8.3 years). In comparison with resistant ones, RfHT patients were younger, with higher smoking and previous cardiovascular diseases prevalence, especially stroke. There was no difference regarding anthropometric measures. OSA prevalence (80.0 vs. 82.9%) and moderate/severe OSA (51.1 vs. 57.0%) were similar in both groups as well as apnea-hypopnea index. In its turn, refractory hypertensive patients presented better sleep efficiency (78 vs. 71%), with higher total sleep time (315 vs. 281 min) and lower sleep latency (11 vs. 17 min). There was no difference regarding rapid eye movement sleep, oxygen saturation, microarousals index, and periodic limb movement. CONCLUSION: In this large RHT cohort, resistant and refractory hypertensive patients have similar OSA prevalence, although refractory ones, which by definition use spironolactone, are younger and apparently have a better sleep pattern.

Association between arterial stiffness and sleep apnoea in patients with resistant hypertension.

Resistant Hypertension (RHT) is associated with a higher risk of Obstructive Sleep Apnoea (OSA). OSA and aortic stiffness (AS) measured by Pulse Wave Velocity (PWV) are independent risk factors for cardiovascular events. We assessed, in a cross-sectional study, the association between AS measured by PWV and OSA severity in patients with RHT. All patients were submitted to polysomnography, PWV measure and 24 h ABPM. Bivariate analysis compared patients with and without moderate/severe OSA. Multivariate analysis was performed to assess the independent correlates of moderate/severe OSA. A total of 376 patients were included, 31% were men with a mean age of 63 ± 10 years. Moderate/severe OSA was diagnosed in 214 patients (57%), 63 patients (17%) presented AS. Uncontrolled ABPM (true RHT) was found in 215 patients (57.2%) and among them 113 were diagnosed with moderate/severe OSA. Evaluating AS in patients with mild, moderate and severe apnoea, we observed a progressive increase in PWV (8.19 ± 1.55, 8.51 ± 1.84, 8.67 ± 1.68, respectively). Classifying them in 2 groups: (1) without apnoea/mild apnoea and (2) moderate/severe apnoea, we found higher values in group 2 (8.21 ± 1.52 m/s vs. 8.60 ± 1.75 m/s, p = 0.02), especially among true RHT patients (8.28 ± 1.62 vs. 8.81 ± 1.86, p = 0.029), women (8.13 ± 1.49 vs. 8.55 ± 1.73, p = 0.036), and uncontrolled nocturnal systolic BP (8.49 ± 1.63 vs. 8.58 ± 1.78, p = 0.04). In conclusion, in this RHT cohort, although with borderline results, the more severe the apnoea, the greater the arterial stiffness, mainly among women, true RHT and patients with an adverse nocturnal BP profile.

Prevalence and clinical profile of refractory hypertension in a large cohort of patients with resistant hypertension.

Refractory hypertension (RfHT) is an extreme phenotype of resistant hypertension (RHT) and is considered uncontrolled blood pressure (BP) despite the use of five or more antihypertensives. The objective of this study was to characterize the prevalence and clinical profile of RfHT patients in a historical cohort of patients with RHT at two different times: before and after the introduction of spironolactone. First, this cross-sectional study evaluated 1048 RHT patients (72.3% females, mean [SD] age: 61.2 [11.3] years) referred to a hypertension clinic (prespironolactone period). All patients were submitted to a standard protocol including clinical and complementary exams. Second, the analysis evaluated patients after the introduction of spironolactone (postspironolactone period). Statistical analysis included bivariate comparisons between patients with RHT and patients with RfHT and logistic regressions to assess the independent correlations of RfHT. A total of 146 patients (13.9%) remained refractory despite the use of at least five antihypertensives (prespironolactone period). After the introduction of spironolactone, the prevalence increased to 17.6%. For any criterion, RfHT patients were younger and more obese. In the initial period, current smoking and left ventricular hypertrophy were independently correlated with RfHT. Furthermore, after spironolactone use, RfHT patients had lower aortic stiffness and peripheral artery disease (PAD), pointing to a lower cardiovascular risk despite the lack of BP control. Younger age and lower prevalence of PAD correlated independently with RfHT. In conclusion, there was a high prevalence of RfHT, especially in younger and obese patients, and spironolactone use seemed to reduce cardiovascular risk despite the lack of BP control.

Resistant and refractory hypertension: two sides of the same disease? / Hipertensão resistente e refratária: duas faces de uma mesma doença?

Abstract Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.

Resumo A Hipertensão Arterial Refratária (HARf) representa um fenótipo extremo da hipertensão arterial resistente (HAR), sendo considerada a falência ao tratamento apesar do uso de 5 ou mais classes de anti-hipertensivos, incluindo um diurético tiazídico de longa ação e um antagonista mineralocorticoide. A HAR é comum (10-20%) entre os hipertensos em geral, sendo decorrente de hiperatividade do Sistema Renina Angiotensina Aldosterona e retenção hidrossalina. Aqueles com HARf correspondem a 5-8% dos resistentes e parecem sofrer maior influência catecolaminérgica. Os resistentes tendem a ter maior idade, ao sobrepeso e à obesidade. Comorbidades incluem diabetes, apneia obstrutiva do sono e status de hiperaldosteronismo. Refratários são afro-americanos em maior proporção, mais jovens e, predominantemente, mulheres. Ambos são fortemente associados à elevada albuminúria, HVE, doenças cardio e cerebrovasculares, além da doença renal crônica. O fenômeno do jaleco branco parece ser mais evidente nos resistentes. Quanto ao tratamento, a intensificação da terapia diurética está indicada nos resistentes, enquanto na HARf, a falência à terapia impôs novas alternativas de tratamento ("simpaticolíticas"). Em conclusão, tanto a HAR quanto a HARf constituem-se desafios na prática clínica e devem ser abordadas como entidades clínicas distintas por profissionais especialistas que identifiquem comorbidades e venham a prover um tratamento específico, diversificado e individualizado.

Resistant and refractory hypertension: two sides of the same disease?

Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.