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Effect of intensified diuretic therapy on overnight rostral fluid shift and obstructive sleep apnoea in patients with uncontrolled hypertension

Kasai, Takatoshia,b; Bradley, T. Douglasa,b,e; Friedman, Odedc,d; Logan, Alexander G.c,d,e

doi: 10.1097/HJH.0000000000000047
ORIGINAL PAPERS: Hypertension management

Objectives: Fluid displacement from the lower extremities to the upper body during sleep is strongly associated with obstructive sleep apnoea in hypertensive patients. The present pathophysiological study tests the hypothesis that intensified diuretic therapy will reduce the apnoea-hypopnoea index and blood pressure of uncontrolled hypertensive patients with obstructive sleep apnoea in proportion to the reduction in overnight change in leg fluid volume.

Methods: Uncontrolled treated hypertensive patients underwent overnight polysomnography and measurement of overnight changes in leg fluid volume and neck circumference. Those with an apnoea-hypopnoea index at least 20 events per hour (n = 16) received metolazone 2.5 mg and spironolactone 25 mg daily for 7 days after which the daily dose was doubled for 7 additional days. Baseline testing was again repeated.

Results: Intensified diuretic therapy reduced the apnoea-hypopnoea index from 57.7 ± 33.0 to 48.5 ± 28.2 events per hour (P = 0.005), overnight change in leg fluid volume from –418.1 ± 177.5 to –307.5 ± 161.9 ml (P < 0.001) and overnight change in neck circumference from 1.2 ± 0.6 to 0.7 ± 0.4 cm (P < 0.001). There was an inverse correlation between the reduction in overnight change in leg fluid volume and decrease in apnoea-hypopnoea index (r = –0.734, P = 0.001). The reduction in overnight change in leg fluid volume was also significantly correlated with the change in morning blood pressure (r = 0.708, P = 0.002 for SBP; r = 0.512, P = 0.043 for DBP).

Conclusion: The findings provide further evidence that fluid redistribution from the legs to the neck during sleep contributes to the severity of obstructive sleep apnoea in hypertension and may be an important link between these two conditions.

aSleep Research Laboratories of the University Health Network Toronto Rehabilitation Institute and Toronto General Hospital

bCentre for Sleep Medicine and Circadian Biology, University of Toronto

cDepartment of Medicine, Mount Sinai Hospital, New York, New York, USA

dProsserman Centre for Health Research, Samuel Lunenfeld Research Institute of the Mount Sinai Hospital

eDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada

Correspondence to Alexander G. Logan, MD, Suite 435, Mount Sinai Hospital, 600 University Ave, Toronto, ON M5G1X5, Canada. Tel: +1 416 586 5187; fax: +1 416 586 8434; e-mail:

Abbreviations: ΔBW, overnight change in body weight; ΔCC, calf circumference; ΔLFV, leg fluid volume; ΔNC, neck circumference; ΔTBF, overnight change in total body fluid; ACE, angiotensin-converting enzyme; AHI, apnoea-hypopnoea index; BP, blood pressure; eGFR, estimated glomerular filtration rate; OSA, obstructive sleep apnoea; REM, rapid eye movement; SaO2, oxyhaemoglobin saturation; SD, standard deviation; TST, total sleep time

Received 25 June, 2013

Accepted 4 October, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins