enalapril and Sleep-Apnea--Obstructive

Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA), is sympathetically mediated. We compared the effect of Doxazosin (DO, a peripheral alpha-receptor inhibitor) and Enalapril (EN, an ACE inhibitor) on digital vasoconstriction and nocturnal blood pressure (BP) in hypertensive OSA patients.. A double-blind, crossover study comparing equipotent dosages of DO (4 mg/day for 2 weeks with 8 mg/day for an additional 2 weeks) and EN (10mg/day and 20mg/day, respectively) was undertaken in 16 male OSA patients (age 55+/-7 years, body mass index 30.1+/-3.8 kg/m(2)) with hypertension. Assessments including ambulatory 24-h BP, full-night polysomnography with simultaneous peripheral arterial tone (PAT) and beat-to-beat finger BP monitoring (Finapres) were made at the end of each treatment period. Nighttime BP and digital vasoconstrictions associated with apneic events (measured as the ratio of PAT amplitudes during and after apneas) were analyzed.. There were no differences between the two treatments in the 24-h BP profile and OSA severity. But the nighttime average beat-to-beat finger BP was significantly higher under DO treatment (systolic BP 129+/-13 vs. 119+/-23 mm Hg, P=0.02; diastolic BP 81+/-12 vs. 74+/-14 mm Hg, P=0.04, DO and EN respectively). In a linear mixed effects regression model, the PAT ratio during apnea increased 5.3% under DO compared with EN (P<0.0001). Each percentage decrease of apneic related oxygen desaturation was associated with 0.9% decrease in the PAT ratio (P<0.0001). REM sleep was associated with 2.2% decrease of PAT ratio compared to NREM sleep (P=0.002).. Digital vasoconstrictions associated with apneic events are alpha-receptor mediated. DO compared to EN has a proportionally poor effect on nocturnal BP control in OSA patients, which may be due to the enhanced sympathetic nervous system activity characteristic of this condition.

Topics: Adrenergic alpha-Antagonists; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Double-Blind Method; Doxazosin; Enalapril; Heart Rate; Humans; Hypertension; Male; Middle Aged; Polysomnography; Sleep; Sleep Apnea, Obstructive; Vasoconstriction

Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid-femoral pulse wave velocity, 24-hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30-day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non-OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non-OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (β=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08-8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Brazil; Cardiovascular Diseases; Diuretics; Echocardiography; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Polysomnography; Pulse Wave Analysis; Risk Factors; Sleep Apnea, Obstructive; Vascular Stiffness

Angiotensin-converting enzyme (ACE) inhibitors may induce cough and rhinopharyngeal inflammation. Obstructive sleep apnea (OSA) is characterized by upper airway inflammation. We describe a patient who, during enalapril treatment, developed cough, upper airway symptoms, and diurnal sleepiness, with an increased number of obstructive apnea-hypopnea episodes (apnea-hypopnea index [AHI], 25) during sleep. Her symptoms and AHI improved 1 month after enalapril was discontinued and diuretic therapy (hydrochlorothiazide-spironolactone) was initiated. Similar findings were observed in 4 other patients with OSA who had ACE inhibitor-induced cough. The mean +/- SD AHI was 33.8+/-21.0 during enalapril treatment and 20.0+/-17.0 after withdrawal of this drug (P = .04). Exhaled nitric oxide, a marker of airway inflammation, was increased during enalapril treatment (15.0 +/- 4.3 parts per billion) and decreased after discontinuation of this drug (9.0 +/- 2.6; P = .03). No significant difference in the AHI and exhaled nitric oxide was observed in 4 patients with OSA who did not experience cough, before or after withdrawal of ACE inhibitor treatment. These findings suggest that ACE inhibitor treatment may contribute to OSA by inducing upper airway inflammation.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Breath Tests; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Polysomnography; Risk Factors; Sleep; Sleep Apnea, Obstructive