Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy - PubMed (original) (raw)

Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy

Michael G Ziegler et al. Clin Hypertens. 2024.

Abstract

Background: Obstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.

Methods and results: Forty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.

Conclusions: OSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.

Trial registration: NCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125 .

Keywords: Ambulatory blood pressure; Baroreflex; Flow mediated dilation; Guanfacine; Heart rate variability; Hydrochlorothiazide; Norepinephrine.

© 2024. The Author(s).

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1

Fig. 1

24-h plasma norepinephrine (NE) and epinephrine (E) concentration in normal controls and OSA (mean ± sem). The concentration of NE and E in plasma was analyzed by sampling blood every two hours for 24-hours in the Clinical Research Center. All participants, 20 controls and 41 apneics, had all 12 NE and E data points. The shaded area indicates the sleep period. Both NE and E were higher in OSA than in normal controls (P < 0.001)

Fig. 2

Fig. 2

24-h systolic SBP and DBP adjusted to wake time for placebo, guanfacine and HCTZ. All data are centered at the end of sleep time (wake time = 0 h on the X-axis). Since arbitrary nighttime and daytime definitions can cause dipping status misclassification, we used a sleep diary to determine actual sleep and awake hours [38]. Guanfacine lowered SBP and DBP more than HCTZ during the wake period, sleep period and over 24-hours (P < 0.05)

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