Abstract
Obstructive sleep apnea (OSA) is present in 60-83% of patients with resistant arterial hypertension (RAH). OBJECTIVES: The main objective of this work was to study the effect of continuous positive airway pressure (CPAP) on ambulatory blood pressure (BP) monitoring (ABPM) in patients with RAH and OSA. Secondary objectives were to assess the effects of CPAP on arterial stiffness, endothelial function, and the expression of several biomarkers probably involved in the relationship between RAH and OSA. PATIENTS AND METHODS: A single-center, open-label, prospective, controlled, parallel-group, randomized clinical trial was carried out in 68 patients with RAH and an apnea-hipopnea index (AHI) ≥15 hour-1 measured by conventional polysomnography. The patients were randomized to therapeutic CPAP or no CPAP for 12 weeks, keeping unchanged their antihypertensive treatment (Clinicaltrials.gov nº. NCT00863135). ABPM and blood and urine tests were performed, and central BP, augmentation index at heart rate 75 min-1 (AIx), and carotid-femoral pulse wave velocity (cfPWV) were measured using applanation tonometry (SphygmoCor®) at baseline and after 12 weeks of treatment. In a subgroup of 36 patients, we also measured serum adiponectin and leptin, and biomarkers of inflammation (serum high-sensitivity CRP, TNF-α and IL-6), oxidative stress (urinary F2-isoprostane), and endothelial dysfunction (plasma soluble ICAM-1, endothelin-1, and VEGF). The reactive hiperemia index was measured using digital plethysmography (EndoPAT 2000®) in another 33 patients. Statistical analysis was performed using the SPSS software, version 23. To compare the effect of CPAP between groups, logistic regression was used for binary dependant variables, and covariance analysis for continuous dependant variables, adjusting for their baseline value in both cases. RESULTS: Sixty-five patients completed the study (31 CPAP and 33 controls), 73% male, with a mean (SD) age of 60.5 (7.3) years, body mass index 35.6 (6.3) Kg/m2, 45.3% with diabetes, mean Epworth 11.1 (5.2) points, AHI 53.5 (25.2) [severe OSA, 78.1%], and baseline 24 h BP 139.9(13.9)/78.3(11.9) mmHg, treated with a median of 4 antihypertensive drugs. Mean CPAP use was 4.7 (2.5) h/night. Weight remained stable. When BP changes during the study were compared between both groups, CPAP improved sleepiness and some quality of life measures, and significantly decreased the frequency of non-dipping pattern for diastolic BP (32.2% vs 57.6%, odds ratio 0.27 [95% confidence interval, 0.09-0.81], P=0.02) but no significant differences were found in any BP change (-2,0/-2,1, -3,2/-2,8, and -1,8/-1,9 mmHg for 24 h, night-time and daytime BP changes, respectively) in the intention-to-treat analysis, or when we analyzed only the patients using CPAP ≥4 h/night. The main effect of CPAP was on night-time systolic BP in CPAP adherent patients with uncontrolled hypertension: -5.1 mmHg (95% confidence interval: -12.3 to +2.1; P=0.16). No statistically significant differences were observed between groups when we analyzed changes in central BP, AIx, cfPWV, albuminuria, insulin-resistance (HOMA-IR and QUICKI), adiponectin, leptin, hsCRP, IL-6, TNF-α, urine F2-isoprostane, soluble ICAM-1, endothelin-1, VEGF or RHI after 12 weeks of treatment. CONCLUSIONS: CPAP for 12 weeks decreased the frequency of non-dippers for diastolic BP although ambulatory BP, arterial stifness, endothelial function, and biomarkers of insulin-resistance, inflammation, oxydative stress, and endothelial dysfunction did not change significantly in patients with RAH and moderate to severe OSA.Palabras clave
Hipertensió resistent; Hipertensión resistente; Resistant hypertension; Síndrome d'apnees del son; Síndrome de apneas del sueño; Obstructive sleep apnea; Pressió positiva contínua a la via aèria; Presión positiva continua en la vía aérea; Continuous positive airway pressure
| Date of Award | 29 Nov 2016 |
|---|---|
| Original language | Spanish |
| Supervisor | Jaime Almirall Daly (Director) |