Effect of obstructive sleep apnea on the response to hypertension therapy

ABSTRACT

Obstructive sleep apnea (OSA) often precedes cardiovascular disease, partly due to treatment resistant hypertension. The nocturnal apneas of OSA trigger increased sympathetic nervous discharge during both sleep and wakefulness. Apneas also trigger cardiac release of the endogenous diuretic atrial natriuretic peptide. We hypothesized that treatment of the excess sympathetic nervous activity of OSA with a β₁ blocker would lower 24 h blood pressure (BP) more than diuretic therapy. Subjects with OSA associated hypertension received 2 weeks of placebo followed by the β₁ blocker nebivolol or hydrochlorothiazide (HCTZ) for 6 weeks in a blinded crossover study. BP, baroreflex sensitivity (BRS), heart rate variability (HRV), arterial reactivity, and stiffness were measured after placebo and each treatment. The β₁ blocker lowered clinic BP by −11/−8 mmHg, more than the −3/−1 effect of HCTZ (P < 0.01). The β₁ blocker lowered 24 h diastolic blood pressure (DBP) more than HCTZ. Although given at bedtime, neither drug increased BP dipping. Nebivolol increased HRV in the high-frequency band. Nebivolol did not alter BRS while HCTZ significantly diminished BRS compared to nebivolol (P < 0.01). Nebivolol increased flow-mediated brachial artery dilation when compared to HCTZ and slowed pulse wave velocity, indicating a decrease in arterial stiffness.

Diuretic therapy failed to lower BP in OSA subjects and this might account for the frequent association of OSA with treatment resistant hypertension. However, blockade of the excess sympathetic nervous activity of OSA with a β₁ blocker lowered both clinic and 24 h DBP.

KEYWORDS:

• ABPM
• baroreflex
• endothelium
• FMD
• HCTZ
• HRV
• nebivolol
• OSA
• PWV
• PWA

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

Financial support for this research came from the Forest Research Institute and NIH (grant number M01RR00827).

Additional information

Funding

Financial support for this research came from the Forest Research Institute and NIH (grant number M01RR00827).