IMPORTANCE More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) ...treatment on blood pressure in patients with resistant hypertension. OBJECTIVE To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS CPAP or no therapy while maintaining usual blood pressure control medication. MAIN OUTCOMES AND MEASURES The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg 95% CI, 0.6 to 5.6; P = .02) and 24-hour DBP (3.2 mm Hg 95% CI, 1.0 to 5.4; P = .005), but not in 24-hour SBP (3.1 mm Hg 95% CI, −0.6 to 6.7; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio OR, 2.4 95% CI, 1.2 to 5.1; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). CONCLUSIONS AND RELEVANCE Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00616265
Obstructive sleep apnea (OSA) is an independent cause of resistant hypertension (RH) but its association with refractory hypertension (RfH), a recently described form of severe hypertension, has not ...yet been investigated. This study seeks to analyze the association between the presence and severity of OSA/OSA syndrome with RfH and to compare it with a group of patients with OSA/OSA syndrome and RH. We conducted a multicenter, cross-sectional study of consecutive patients diagnosed with RH by means of 24-hour ambulatory blood pressure monitoring. Those patients with blood pressure levels ≥130/80 mm Hg, despite taking at least 5 antihypertensive drugs, were considered to have true RfH. All patients underwent a sleep study and completed a detailed clinical history related to OSA, current medication, and cardiovascular diseases. Overall, 229 patients were included (mean age, 58.3 years; 63% male), of whom 42 (18.3%) satisfied the criteria for RfH. Compared with those with RH, patients with RfH had a higher cardiovascular risk profile, higher blood pressure measurements, and a 2-fold greater risk of having both severe OSA (odds ratio, 2.1, with a prevalence of apnea-hypopnea index ≥15, 95.2% and apnea-hypopnea index ≥30, 64.3%) and OSA syndrome (apnea-hypopnea index ≥5+Epworth Sleepiness Scale >10; odds ratio, 1.9; 52.4% versus 37.3%; P=0.023), as well as higher OSA severity (apnea-hypopnea index, 41.8 versus 33.8 events/h; P=0.026). Patients with RfH had an even greater prevalence and severity of OSA and OSA syndrome than RH patients, highlighting the need to identify these patients to refer them to sleep units on a preferential basis.
RATIONALE:Continuous positive airway pressure (CPAP) can significantly reduce blood pressure (BP) levels in patients with resistant hypertension and sleep apnea (OSA); however, the effect on patients ...with refractory hypertension (RfH) is not known. This study seeks to evaluate the effect of CPAP treatment on BP levels in patients with OSA and RfH, compared with those with OSA and resistant hypertension.
METHODS:Post-hoc analysis of the HIPARCO randomized clinical trial on the effect of CPAP treatment on BP levels in patients with resistant hypertension. Those patients with uncontrolled 24-h ambulatory BP monitoring readings (>130 and/or >80 mmHg) in SBP or DBP were considered to have resistant hypertension (if they were taking three or four antihypertensive drugs) or RfH (if they were taking at least five drugs). OSA patients were randomized to receive CPAP or usual care for 3 months. They underwent a second 24-h ambulatory BP monitoring study to establish the effect of CPAP treatment on BP levels in both groups.
RESULTS:A total of 98 patients were randomized to CPAP (19 RfH/79 resistant hypertension) and 96 to usual care (21 RfH/75 resistant hypertension). BP readings dropped more marked in patients with RfH than resistant hypertension, in both 24-h SBP (−9 vs. −1.6 mmHg, P = 0.021) and 24-h DBP (−7.3 vs. −2.3 mmHg, P = 0.074), especially at night (−11.3 vs. −3.8, P = 0.121 and −8.8 vs. −2.2, P = 0.054) respectively. Adjusted difference between groups was statistically significant in 24-h SBP levels (−7.4 mmHg, P = 0.021).
CONCLUSION:CPAP lowers BP levels in both resistant hypertension and RfH patients although the degree of this reduction is higher in those with RfH especially during the night.
Refractory hypertension (RfH) is defined as a lack of blood pressure control despite the administration of at least 5 anti-hypertensive drugs. The factors associated with its natural history are ...unknown. This study aimed to evaluate both the incidence of RfH in an cohort of patients with resistant hypertension (RH) and the factors involved in that progression. This was an observational prospective multicenter study (24 centers) with 172 patients with confirmed RH (24-h ABPM) who underwent a further 24 h ABPM study at the end of the follow-up. Prospective information was obtained from all patients in their corresponding Hypertension Units via a standard clinical protocol, and they all underwent a sleep study. Thirty patients were diagnosed with RfH (17.4%) after a mean follow-up of 57 months, despite the prescription of a greater number of long-acting thiazide-like diuretics and mineralocorticoid receptor antagonists. The factors associated with progression to RfH were: a longer period since the diagnosis of RH (OR: 1.06, 95% CI: 1.01-1.1, p = 0.007); the HbA1c concentration (OR: 1.42, 95% CI: 1.42-1.8; p = 0.005); the initial heart rate (OR: 1.05, 95% CI: 1.01-1.09, p = 0.004); and poor adherence to continuous positive airway pressure (CPAP) in cases of obstructive sleep apnea (OR: 3.36, 95% CI: 1.47-7.7, p = 0.004). In conclusion, a considerable percentage of patients evolved from the RH to the RfH phenotype despite changes in their treatment. Some easily measurable variables, such as heart rate, the time since the diagnosis, the HbA1c level, and the presence of untreated obstructive sleep apnea (or poor adherence to CPAP) have been demonstrated to be prognostic factors in the progression to RfH.
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There is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients ...with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE.
Multi-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3–6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4h/day) were compared with those with not adherent or those who had not been prescribed CPAP.
Valid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96–2.7; p=0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07–15.1; p=0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2–11.6; p=0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05–1.02; p=0.053).
In patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events.
Existe cierta controversia sobre el efecto de la presión positiva continua en las vías respiratorias (CPAP) sobre la incidencia de eventos cardiovasculares (ECV). Sin embargo, no se ha evaluado la incidencia de ECV en los pacientes con apnea obstructiva del sueño (AOS) e hipertensión resistente (HR). Nuestro objetivo fue analizar el efecto a largo plazo del tratamiento con CPAP en pacientes con HR y AOS en la incidencia de ECV.
Estudio multicéntrico, observacional y prospectivo de pacientes con AOS y HR. Cada paciente acudió a revisión cada 3-6 meses y se midió la incidencia de ECV. Se compararon los pacientes con buena adherencia a la CPAP (al menos 4h/día) con aquellos con mala adherencia o aquellos a quienes no se les había indicado la CPAP.
Se obtuvieron datos válidos de 163 pacientes con 64 eventos de ECV. Se ofreció tratamiento con CPAP al 82%. Después de 58 meses de seguimiento, el 58,3% de los pacientes presentaron buena adherencia a la CPAP. Los pacientes con mala adherencia o sin prescripción de CPAP presentaron un aumento no significativo en la incidencia total de ECV (HR: 1,6; IC 95%: 0,96-2,7; p=0,07). Un análisis de sensibilidad mostró que los pacientes con mala adherencia a la CPAP tuvieron un aumento significativo en la incidencia de eventos cerebrovasculares (HR: 3,1; IC 95%: 1,07-15,1; p=0,041) y crisis hipertensivas (HR: 5,1; IC 95%: 2,2-11,6; p=0,006), pero la tendencia fue en la dirección opuesta con respecto a los eventos coronarios (HR: 0,22; IC 95%: 0,05-1,02; p=0,053).
En pacientes con HR y AOS moderada o grave, un tratamiento ineficaz con CPAP mostró una tendencia hacia un aumento en la incidencia de ECV (particularmente eventos neurovasculares y crisis hipertensivas), sin ningún cambio con respecto a los eventos coronarios.
Although adequate adherence is paramount in achieving the beneficial effects of continuous positive airway pressure therapy in patients with obstructive sleep apnea, long‐term adherence and the ...variables involved in continuous positive airway pressure compliance in patients with resistant hypertension and obstructive sleep apnea are yet unknown. We conducted a prospective, multicentre, observational study in 177 patients recruited from hypertensive units with resistant hypertension confirmed by means of 24‐hr blood pressure monitoring (blood pressure ≥ 130 and/or ≥ 80 mmHg, despite taking at least three antihypertensive drugs or < 130/80 mmHg with > 3 drugs) and obstructive sleep apnea (apnea–hypopnea index ≥ 5 in a respiratory polygraph) who were prescribed continuous positive airway pressure treatment. Good adherence was defined as an average cumulative continuous positive airway pressure use of ≥ 4 hr per night at the end of the follow‐up. A multivariate Cox regression analysis was performed to identify independent predictors of continuous positive airway pressure adherence. Patients were followed for a median of 57.6 (42–72) months after initiating continuous positive airway pressure therapy. At the end of the follow‐up, the median continuous positive airway pressure use was 5.7 (inter‐quartile range 3.9–6.6) hr per night, and 132 patients (74.5%) showed good continuous positive airway pressure adherence. The only baseline variable associated with poor adherence was the presence of previous stroke (hazard ratio 4.00, 95% confidence interval 1.92–8.31). Adequate adherence at 1 month also predicted good adherence at the end of the follow‐up (hazard ratio 14.4, 95% confidence interval 4.94–56). Both variables also predicted adherence at a threshold of 6 hr per night. Our results show that good continuous positive airway pressure adherence is an achievable and feasible goal in patients with resistant hypertension and obstructive sleep apnea. Previous stroke and short‐term adherence predicted long‐term adherence.
Obstructive sleep apnea (OSA) is an independent cause of resistant hypertension (RH) but its association with refractory hypertension (RfH), a recently described form of severe hypertension, has not ...yet been investigated. This study seeks to analyze the association between the presence and severity of OSA/OSA syndrome with RfH and to compare it with a group of patients with OSA/OSA syndrome and RH. We conducted a multicenter, cross-sectional study of consecutive patients diagnosed with RH by means of 24-hour ambulatory blood pressure monitoring. Those patients with blood pressure levels ≥130/80 mm Hg, despite taking at least 5 antihypertensive drugs, were considered to have true RfH. All patients underwent a sleep study and completed a detailed clinical history related to OSA, current medication, and cardiovascular diseases. Overall, 229 patients were included (mean age, 58.3 years; 63% male), of whom 42 (18.3%) satisfied the criteria for RfH. Compared with those with RH, patients with RfH had a higher cardiovascular risk profile, higher blood pressure measurements, and a 2-fold greater risk of having both severe OSA (odds ratio, 2.1, with a prevalence of apnea-hypopnea index ≥15, 95.2% and apnea-hypopnea index ≥30, 64.3%) and OSA syndrome (apnea-hypopnea index ≥5+Epworth Sleepiness Scale >10; odds ratio, 1.9; 52.4% versus 37.3%; P=0.023), as well as higher OSA severity (apnea-hypopnea index, 41.8 versus 33.8 events/h; P=0.026). Patients with RfH had an even greater prevalence and severity of OSA and OSA syndrome than RH patients, highlighting the need to identify these patients to refer them to sleep units on a preferential basis.
Introduction
Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. ...Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.
Methods
The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using
in vitro
models. In addition, PSGL-1 impact on T-cells function was evaluated by
ex vivo
models.
Results
Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.
Discussion
In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.
Abstract Study Objectives The STOP-Bang questionnaire is a validated screening tool for obstructive sleep apnea (OSA). We conducted this study to validate it among patients hospitalized with acute ...symptomatic pulmonary embolism (PE). Methods This prospective cohort study enrolled consecutive stable patients with acute PE who underwent an overnight sleep study within 7 days after diagnosis. Our outcomes were: (1) the STOP-Bang questionnaire’s utility for risk stratification, (2) the discrimination of the STOP-Bang questionnaire categories, (3) the false negative rate of STOP-Bang questionnaire prediction, and (4) the clinical utility of the STOP-Bang questionnaire to exclude OSA. We also calculated the test performance characteristics to predict OSA. Results During the study period, 268 patients completed a sleep study. OSA was found in 47% of patients. OSA incidence in low-, moderate-, and high-risk STOP-Bang groups was 22.4%, 48.2%, and 61.5%, respectively (p < .001). The area under the receiver operating characteristics curve of the STOP-Bang questionnaire for risk of OSA was 0.65. The false negative rate of a low-risk STOP-Bang questionnaire result to rule out OSA was 22.4% and the clinical utility was 21.6%. The sensitivity was 89.8% (97.2% for men and 80.4% for women). Conclusions The STOP-Bang questionnaire showed poor discrimination for the risk of OSA in hospitalized patients with acute symptomatic PE. It had a high false negative rate and a low clinical utility. The STOP-Bang questionnaire had a good sensitivity in men, and might be used to rule out OSA in this population.
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