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 µg/24 h; 95% confidence interval (95% CI): -5.3 to +0.3 µg/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 µg/24 h; 95% CI: -6.1 to -0.4 µg/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.

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.

Cardiovascular and renal complications in patients with resistant hypertension.

With an increased prevalence, resistant hypertension is recognized as an entity with a high cardiovascular morbidity and mortality. In a large cohort of patients with resistant hypertension, the crude incidence rate of total cardiovascular events reached 4.32 per 100 patient-years of follow-up (19.6 %), with a cardiovascular mortality of 8.3 % (incidence rate of 1.72 per 100 patient-years). Cardiovascular event rates are significantly higher in resistant hypertensives compared with non-resistant (18.0 % versus 13.5 %). In the same way, the prevalence of established cardiovascular and renal disease, as the asymptomatic organ damage (represented by left ventricular hypertrophy, carotid wall thickening, arterial stiffness, and microalbuminuria) is higher in these patients. Many studies have demonstrated a strong association between damage to these organs with higher blood pressure levels, the diagnosis of true resistant hypertension, and refractory hypertension. All efforts should be employed in order to control blood pressure and also to regress and/or prevent subclinical cardiovascular and renal damage. The focus should be on prevention of cardiovascular and renal complications, improving the prognosis of resistant hypertension.

Diagnostic accuracy of the Berlin questionnaire in detecting obstructive sleep apnea in patients with resistant hypertension.

OBJECTIVES: Obstructive sleep apnea (OSA) is strongly associated with resistant hypertension. The Berlin questionnaire is the most widely used screening tool to identify patients at high risk of having OSA. The objective was to test the diagnostic accuracy of the Berlin questionnaire in detecting OSA in resistant hypertensive patients. METHODS: A cross-sectional analysis of 422 resistant hypertensive patients [31% men; mean (SD) age 62.4 (9.9) years] submitted to polysomnography (PSG), in whom the Berlin questionnaire was previously applied. OSA was defined by an apnea-hypopnea index of at least 5 per hour and moderate-to-severe OSA by an apnea-hypopnea index of at least 15. Statistical analysis included bivariate comparisons between patients at high and low risk by the Berlin questionnaire, and logistic regression to assess the predictors of agreement between the Berlin questionnaire and PSG. Sensitivity, specificity, positive and negative predictive values and likelihood ratios for the Berlin questionnaire in detecting OSA were calculated. RESULTS: OSA was diagnosed in 347 patients (82.2%) and moderate-to-severe OSA in 234 patients (55.5%). In patients at high risk, moderate-to-severe OSA was confirmed in 58.3%, whereas in those at low risk, it was excluded in 50.4%. The accuracy of the Berlin questionnaire in detecting OSA was 55.6%. The specificity, sensitivity, positive and negative predictive value of the Berlin questionnaire in detecting moderate-to-severe OSA was 40, 69, 58 and 50%, respectively. The positive and negative likelihood ratios were 1.15 and 0.78, with a very low agreement (kappa = 0.081). CONCLUSION: In a large cohort of resistant hypertensive patients, the Berlin questionnaire had a low accuracy of identifying patients with OSA and should not be used as a screening method for selecting patients to PSG.

Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension.

BACKGROUND: Obstructive sleep apnea (OSA) syndromes are strongly associated with resistant hypertension, although this has not been systematically examined. The aim of our study was to investigate the prevalence of OSA and its associated factors in a large cohort of resistant hypertensive patients. METHODS: A cross-sectional analysis with 422 resistant hypertensive patients (31.3% men; mean age = 62.4±9.9 years) submitted to a full-night polysomnography. The presence of OSA was defined by an apnea-hypopnea index (AHI) >5 per hour and moderate/severe OSA was defined by an AHI >15. Statistical analysis included bivariable comparisons between patients with and without moderate/severe OSA and logistic regressions to assess the independent correlates of OSA severity. RESULTS: Three-hundred forty-seven patients (82.2%) had OSA, and 234 patients (55.5%) had moderate/severe OSA. Patients with moderate/severe OSA were more frequently elderly and obese men with larger waist and neck circumferences, had higher prevalences of diabetes and left ventricular hypertrophy, and had higher proteinuria than patients with no/mild OSA. No difference was found in plasma aldosterone and renin activity. Nighttime systolic blood pressures and pulse pressures were higher in moderate/severe OSA, with lower nocturnal blood pressure fall. In multivariable logistic regression, male sex, older age, diabetes, obesity, increased waist and neck circumferences, and nighttime systolic blood pressure were the independent correlates of moderate/severe OSA. CONCLUSIONS: Resistant hypertensive patients had a very high prevalence of OSA, and patients with moderate/severe OSA had an adverse ambulatory BP profile, with higher nighttime systolic blood pressures and pulse pressures and higher prevalence of nondipping patterns. Other correlates of OSA severity were mainly demographic-anthropometric variables.

Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease: evidence of altered expression of FasL and perforin cytotoxic pathways.

BACKGROUND AND AIMS: Abnormal apoptosis may result in the persistence of activated intestinal T-cells in inflammatory bowel disease (IBD). We investigated apoptosis in distinct mucosal compartments, and the expression of Fas/Fas ligand and perforin in the inflamed and non-inflamed intestinal mucosa of patients with IBD. METHODS: Colon specimens from 15 patients with ulcerative colitis (UC) and inflamed and non-inflamed mucosa from 15 patients with Crohn's disease (CD) were analysed for densities and distribution of apoptotic cells determined by the terminal deoxynucleotidyltransferase-mediated dUDP-biotin nick-end labelling (TUNEL) method. Fas, FasL, and perforin-expressing cells were assessed by immunoperoxidase, and with anti-CD3, anti-CD20 and anti-CD68, by double immunofluorescence with confocal microscopy. Quantitative analysis was performed using a computer-assisted image analyser. RESULTS: Colonic lamina propria (LP) and epithelium from patients with UC showed higher rates of apoptosis than controls, but no difference was shown regarding patients with CD. In LP, co-expression of Fas was reduced with T-cells in inflamed CD mucosa, and with macrophages in all patients with IBD. No difference was found in the expression of Fas on B-cells. Rates of FasL-expressing cells in LP were higher in IBD than in controls, with no correlation with the rates of apoptosis. Rates of perforin-expressing cells in LP were greater in UC than in controls, and correlated to the rates of apoptosis. No difference was shown regarding the inflamed and non-inflamed CD mucosa. Rates of FasL and perforin-expressing intra-epithelial lymphocytes showed no difference among groups. CONCLUSIONS: Increased expression of FasL in IBD colonic LP not parallelled by Fas on T-cells and macrophages may indicate a reduced susceptibility to the Fas/FasL-mediated apoptosis of lymphoid cells. Expression of perforin is correlated to the tissue damage, and may represent the enhancement of a distinct cytotoxic pathway in UC.