Resistant hypertension and hyperaldosteronism.

Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of >or= 3 antihypertensive medications at effective doses, ideally including a diuretic. Although exact prevalence is unknown, clinical trials suggest that 20% to 30% of study participants are resistant. Hyperaldosteronism, obesity, refractory volume expansion, and obstructive sleep apnea are common findings in resistant hypertension patients. Multiple studies indicate that primary aldosteronism (PA) is common (approximately 20%) in patients with resistant hypertension. Screening for PA is recommended for most patients with resistant hypertension, ideally by measurement of 24-hour urinary aldosterone excretion, or by the plasma aldosterone/plasma renin activity ratio. Successful treatment of resistant hypertension is predicated on improvement of lifestyle factors; accurate diagnosis and treatment of secondary causes of hypertension; and use of effective multidrug regimens. A long-acting diuretic, specifically chlorthalidone, is recommended as part of the treatment regimen. Recent studies demonstrate that mineralocorticoid receptor antagonists provide substantial antihypertensive benefit when added to multidrug regimens, even in patients without demonstrable aldosterone excess.

Performance of NoSAS score versus Berlin questionnaire for screening obstructive sleep apnoea in patients with resistant hypertension.

Obstructive sleep apnoea (OSA) is the main secondary form associated with resistant hypertension (RH), but it is largely underdiagnosed and consequently undertreated in clinical practice. The Berlin questionnaire (BQ) is a useful tool among general population, but seems to not perform well among patients with RH. Recently, NoSAS score was validated in a large population, however, has not been tested in the cardiovascular scenario. Thus, we aimed to compare BQ versus the NoSAS score as screening tools for OSA in RH. In the present study, patients with confirmed diagnosis of RH were invited to perform polysomnography. OSA was diagnosed by an apnoea-hypopnoea index (AHI) ≥15 events/h. BQ and NoSAS were applied in a blinded way. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of the two sleep questionnaires to detect OSA in RH. The frequency of OSA was 64%. The BQ presented a better sensitivity (91 vs. 72%) and higher values of NPV (67 vs. 54%) than NoSAS score. In contrast, the NoSAS score had higher specificity for excluding OSA (58 vs. 33%) and higher PPV (75 vs. 70%). Compared to the BQ, NoSAS score had a better AUC (0.55 vs. 0.64) but these values are in the fail to poor accuracy range. In conclusion, both BQ and NoSAS score had low accuracy for detecting OSA in RH. Considering the high frequency of OSA, objective sleep study may be considered in these patients.

OSA and Prognosis After Acute Cardiogenic Pulmonary Edema: The OSA-CARE Study.

BACKGROUND: Acute cardiogenic pulmonary edema (ACPE) is a life-threatening condition. OSA may be a modifiable risk factor for ACPE recurrence. This study was designed to evaluate the impact of OSA on the incidence of cardiovascular events following ACPE recovery. METHODS: Consecutive patients with confirmed ACPE from 3 centers underwent a sleep study following clinical stabilization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. The mean follow-up was 1 year, and the primary outcome was ACPE recurrence. RESULTS: A total of 104 patients were included in the final analysis; 61% of the patients had OSA. A higher rate of ACPE recurrence (25 vs 6 episodes; P = .01) and a higher incidence of myocardial infarction (15 vs 0 episodes; P = .0004) were observed in patients with OSA than in those without OSA. All 17 deaths occurred in the OSA group (P = .0001). In a Cox proportional hazards regression analysis, OSA was independently associated with ACPE recurrence (hazard ratio [HR], 3.3 [95% CI, 1.2-8.8]; P = .01), incidence of myocardial infarction (HR, 2.3 [95% CI, 1.1-9.5]; P = .02), cardiovascular death (HR, 5.4 [95% CI, 1.4-48.4]; P = .004), and total death (HR, 6.5 [95% CI, 1.2-64.0]; P = .005). When the analysis was limited only to patients with OSA, levels of AHI and hypoxemic burden and rates of sleep-onset ACPE were significantly higher in those who presented with ACPE recurrence or who died than in those who did not experience these events. CONCLUSIONS: OSA is independently associated with higher rates of ACPE recurrence and both fatal and nonfatal cardiovascular events.

Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension.

Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension may help to control blood pressure and reduce cardiovascular risk. However, there are no studies systematically evaluating secondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients with resistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, including aortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renal parenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age: 52±1 years, 43% males, systolic and diastolic blood pressure: 176±31 and 107±19 mm Hg, respectively), obstructive sleep apnea (apnea-hypopnea index: >15 events per hour) was the most common condition associated with resistant hypertension (64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified (primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age >50 years (odds ratio: 5.2 [95% CI: 1.9-14.2]; P<0.01), neck circumference ≥41 cm for women and ≥43 cm for men (odds ratio: 4.7 [95% CI: 1.3-16.9]; P=0.02), and presence of snoring (odds ratio: 3.7 [95% CI: 1.3-11]; P=0.02) were predictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea appears to be the most common condition associated with resistant hypertension. Age >50 years, large neck circumference measurement, and snoring are good predictors of obstructive sleep apnea in this population.

Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension.

BACKGROUND: We previously described a significant correlation between plasma aldosterone concentration (PAC) and severity of obstructive sleep apnea (OSA) in patients with resistant hypertension. This investigation examines the relationship between aldosterone status and OSA in patients with resistant hypertensive-with and without hyperaldosteronism. METHODS AND RESULTS: One hundred and nine consecutive patients with resistant hypertension were prospectively evaluated with plasma renin activity (PRA), PAC, 24-hour urinary aldosterone excretion (UAldo), and polysomnography. Hyperaldosteronism (PRA < 1 ng x mL(-1) x h(-1) and UAldo > or = 12 microg/24-h) prevalence was 28% and OSA prevalence was 77%. In patients with hyperaldosteronism, OSA prevalence was 84%, compared with 74% in hypertensive patients with normal aldosterone levels. There were no significant differences in body mass index or neck circumference between aldosterone groups. PAC and UAldo were both significantly correlated with apnea-hypopnea index (AHI) in the high-aldosterone group (p = 0.568, p = 0.0009; p = 0.533, p = 0.002, respectively). UAldo correlated weakly with apnea-hypopnea index in the normal-aldosterone group, but there was no significant correlation between PAC and AHI in the normal-aldosterone group (p = 0.224, p = 0.049; p = 0.015, p = 0.898, respectively). CONCLUSIONS: Our analysis of patients with resistant hypertension confirms a markedly high prevalence of OSA in this group. Furthermore, severity of OSA was greater in those patients with hyperaldosteronism and related to the degree of aldosterone excess. The correlation between OSA severity and aldosterone supports the hypothesis that aldosterone excess contributes to greater severity of OSA.

Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension.

Obstructive sleep apnea (OSA) is a secondary cause of hypertension and independently associated with target-organ damage in hypertensive patients. However, OSA remains largely underdiagnosed and undertreated. The aim of the present study was to evaluate the characteristics and clinical predictors of OSA in a consecutive series of patients followed up in a hypertension unit. A total of 99 patients (age 46 + or - 11 years, body mass index 28.8 kg/m(2), range 25.1 to 32.9) underwent polysomnography. The clinical parameters included age, gender, obesity, daytime sleepiness, snoring, Berlin Questionnaire, resistant hypertension, and metabolic syndrome. Of the 99 patients, 55 (56%) had OSA (apnea-hypopnea index >5 events/hour). Patients with OSA were older and more obese, had greater levels of blood pressure, and presented with more diabetes, dyslipidemia, resistant hypertension, and metabolic syndrome than the patients without OSA. Of the patients with OSA, 51% had no excessive daytime sleepiness. The Berlin Questionnaire and patient age revealed a high sensitivity (0.93 and 0.91, respectively) but low specificity (0.59 and 0.48, respectively), and obesity and resistant hypertension revealed a low sensitivity (0.58 and 0.44, respectively) but high specificity (0.75 and 0.91, respectively) for OSA. Metabolic syndrome was associated with high sensitivity and specificity for OSA (0.86 and 0.85, respectively). Multiple regression analysis showed that age of 40 to 70 years (odds ratio 1.09, 95% confidence interval 1.03 to 1.16), a high risk of OSA on the Berlin Questionnaire (odds ratio 8.36, 95% confidence interval 1.67 to 41.85), and metabolic syndrome (odds ratio 19.04, 95% confidence interval 5.25 to 69.03) were independent variables associated with OSA. In conclusion, more important than the typical clinical features that characterize OSA, including snoring and excessive daytime sleepiness, the presence of the metabolic syndrome is as an important marker of OSA among patients with hypertension.

Interações medicamentosas: inibidores da enzima conversora da angiotensina, bloqueadores dos receptores da angiotensina II, inibidoresdiretos da renina. (AU) / Drugs interactions: angiotensin-converting enzyme inhibitors, angiotensinII-receptor antagonists, renin inhibitors

Os inibidores da enzima conversora da angiotensina (IECAs) são em geral bem tolerados, sendo a tosse seca e hipercalemia os principais efeitos colaterais relatados. Nessas situações, a substituição do IECA por um bloqueador do receptor da angiotensina (BRA) pode ser uma opção. Efeito clássico dos IECAs é a diminuição da taxa de filtração glomerular, que pode piorar a função renal, mais frequente em pacientes com desidratação, insuficiência cardíaca, em uso de anti-inflamatórios e com doença renal prévia. Em função da possibilidade de hipercalemia com o uso do IECA, BRA e/ou alisquireno, caso haja algum fator de risco, como idade avançada, desidratação, insuficiência renal, diabetes e administração concomitante de poupadores de potássio e/ou anti-inflamatórios, atenção especial deve ser dada à dieta, quando o consumo de potássio deve ser reduzido. A administração simultânea do IECA ou BRA, com diurético, ou com antagonista do canal de cálcio, promove efeito anti-hipertensivo sinérgico. A associação de BRA com IECA promove maior efeito antiproteinúrico do que com cada droga isoladamente. O uso de enemas em conjunto com diuréticos, IECAs, BRAs e anti-inflamatórios não hormonais pode aumentar o risco de insuficiência renal aguda causada pelo fosfato. A coadministração de amlodipina, valsartan, ramipril, hidroclorotiazida e atenolol demonstra sinergismo anti-hipertensivo, sem interação medicamentosa relevante. O alisquireno apresenta associação tolerável e segura quando administrado com IECA ou BRA, porém, quando em combinação com a furosemida, promove interação que pode requerer o aumento da dose do diurético. Por outro lado, em paciente que tenha depleção acentuada de volume ou de sódio, a associação de alisquireno com diuréticos pode provocar hipotensão sintomática.

Angiotensin-converting enzyme inhibitors (ACEi) are usually well tolerated; cough and hyperkalemia are the most frequently reported adverse reactions. In such cases, the replacement of the ACEi for an ARB are recommended ACEi may impair renal function, more frequently in patients with dehydration, congestive heart failure, renal dysfunction, and taking anti-inflammatory drugs. Prescription of ACEi, ARB, and/or aliskiren increases the risk of hypercalemia, and when there are risk factors associated as old age, dehydration, renal dysfunction, diabetes, and use of potassium sparing diuretics and/or anti-inflammatory drugs, the intakeof potassium must be decreased. Co-administration of ACEior ARB, with diuretics, or with calcium channel blockers, results in a synergic anti-hypertensive effect. The association between ARB and ACEi improves proteinuria. Enemas associated to diuretics, ACEi, ARB, and anti-inflammatory drugs may increase the risk of acute renal insufficiency dueto phosphate. Co-administration of amlodipine, valsartan, ramipril, hydrochlorothiazide, and atenolol demonstrates synergic anti-hypertensive effect, without relevant drug interaction. Aliskiren represents a safety association when used with ACEi or ARB, however, when prescribed with furosemide, may require increased dose of diuretic. On the other hand, if the patient has volume or sodium depletion, the association of aliskiren with diuretics may cause hypotension.

Fisiopatologia da hipertensão sistólica isolada / Physiopathology of isolated systolic hypertension

A hipertensão sistólica isolada (HSI) é definida como pressão arterial sistólica > 140 mmHg e pressão arterial diastólica < 90 mmHg, sendo a forma mais prevalente de elevação da pressão arterial em pacientes acima de 50 anos de idade. Vários fatores têm sido considerados possíveis moduladores do desenvolvimento progressivo da HSI. Estão associados ao seu desenvolvimento os hábitos nutricionais com maior ingestão de sal ao longo da vida, o remodelamento vascular,a rigidez arterial, a ativação do sistema renina-angiotensina aldosterona(SRAA), entre outros diversos fatores que ainda necessitam ser mais bem estudados.

Isolated systolic hypertension (ISH) is defined as systolic blood pressure > 140 mmHg and diastolic blood pressure < 90 mmHg. ISH is the most prevalent form of hypertension in individuals aged above 50 years. Several factors determine the development of ISH, as increased salt intake during life time, vascular remodeling, arterial stiffness, renin-angiotensin-aldosterone system activation, and other factors that should be better evaluated.