A 60-year-old Caucasian male patient with a long-standing history of hypertension comes to the office for a follow-up. His current medications include furosemide, losartan, hydrochlorothiazide, aspirin, and a multivitamin. He is adherent with his medications and has been taking them at optimal doses for more than a year. He is complaining of excessive daytime sleepiness and fatigue. On exam, he is morbidly obese (body mass index of 43), his blood pressure is 158/90, his pulse is 72, his respiration rate is 18, and he has a right atrial oxygen saturation of 93%. The rest of his physical examination is unremarkable. His blood pressure (BP) has been consistently elevated above 150/90 during every office visit since the last year. His Epworth Sleepiness Scale score is 17. His current electrocardiogram shows evidence of left ventricular hypertrophy. His laboratory exam reveals normal hematology, chemistry, glycated hemoglobin, and thyroid levels. He undergoes an overnight polysomnography. His Apnea Hypopnea Index (AHI) number is 34 episodes per hour, which is consistent with severe obstructive sleep apnea (OSA).
Which of the following statements is incorrect?
The correct answer is: C. Continuous positive airway pressure (CPAP) management does not affect antihypertensive dosing in patients with severe OSA and resistant hypertension.
This patient has resistant hypertension, which is defined as elevated blood pressure above target goal with concurrent use of three antihypertensive agents, one of which is a diuretic. Causes of resistant hypertension are multifactorial and include obesity, dietary non-compliance, alcohol, and drugs. Secondary causes include OSA, renal parenchymal disease, renal artery stenosis, and primary aldosteronism.1 Because of its high prevalence, OSA is the most common secondary cause of resistant hypertension (64 %).2 There is increased aldosterone secretion in patients with OSA, which contributes to the development of resistant hypertension.3 Other mechanisms include increased sympathetic activity, endothelial dysfunction, and oxidative stress due to intermittent hypoxia.4,5
CPAP has been shown to reduce the sympathetic activity, decrease inflammatory markers, and reverse the endothelial dysfunction. Some, but not all, short-term controlled trials have shown CPAP to be effective in reducing nocturnal BP as well as daytime BP in patients with OSA. The role of OSA and therefore the role of CPAP therapy may be greater in those with resistant hypertension.6 Effects on blood pressure may not be seen for several weeks after starting CPAP. De-escalation of therapy has been seen in patients with resistant hypertension who are treated with CPAP, though that effect may not be universal.7 It should be noted that in trials of CPAP combined with drug therapy, effects on BP are greater with the medication than with CPAP.8
Primary aldosteronism has been associated with resistant hypertension and has been independently incriminated in the development of OSA.9 Resistant hypertension is accompanied by significant fluid retention, which can worsen OSA by increasing peripharyngeal fluid accumulation.10 A small study investigated the use of spironolactone in patients with resistant hypertension and OSA. Eight-week treatment with spironolactone led to reduction of OSA severity (the AHI number decreased from 39 to 22) with a concomitant reduction in hypertension. This study was not randomized, and causality cannot be established. However, it offers spironolactone as a promising option for control of hypertension in this population.11
Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation 2008;117:e510-26.
Pedrosa RP, Drager LF, Gonzaga CC, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension 2011;58:811-7.
Calhoun DA, Nishizaka MK, Zaman MA, Harding SM. Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea. Chest 2004;125:112-7.
Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000;283:1829-36.
Oza N, Baveja S, Khayat R, Houmsse M. Obstructive sleep apnea and atrial fibrillation: understanding the connection. Expert Rev Cardiovasc Ther 2014;12:613-21.
Martínez-García MA, Capote F, Campos-Rodríguez F, et al. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA 2013;310:2407-15.
Dernaika TA, Kinasewitz GT, Tawk MM. Effects of nocturnal continuous positive airway pressure therapy in patients with resistant hypertension and obstructive sleep apnea. J Clin Sleep Med 2009;5:103-7.
Pépin JL, Tamisier R, Barone-Rochette G, et al. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med 2010;182:954-60.
Dudenbostel T, Calhoun DA. Resistant hypertension, obstructive sleep apnoea and aldosterone. J Hum Hypertens 2012;26:281-7.
White LH, Bradley TD, Logan AG. Pathogenesis of obstructive sleep apnoea in hypertensive patients: role of fluid retention and nocturnal rostral fluid shift. J Hum Hypertens 2015;29:342-50.
Gaddam K, Pimenta E, Thomas SJ, et al. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J Hum Hypertens 2010;24:532-7.