Resistant Hypertension, Sleep Apnea and Hyperaldosteronism. Faculty Disclosure

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1 Resistant Hypertension, Sleep Apnea and Hyperaldosteronism David A. Calhoun, M.D. Professor of Medicine Vascular Biology and Hypertension Program Center for Sleep/Wake Disorders University of Alabama at Birmingham Faculty Disclosure Medtronic: Grant Support 1

2 Resistant Hypertension Blood pressure that remains uncontrolled with use of 3 antihypertensive agents. Ideally one of the agents should be a diuretic and all agents should be prescribed at doses to provide optimal benefit. Prevalence of Resistant Hypertension in US NHANES % 14.5% 8.8% Roberie and Elliot, Curr Opinion Cardiol, in press 2

3 Prevalence of Primary Aldosteronism in Subjects With Resistant Hypertension % 2% 22% 19% Seattle Birmingham Oslo Prague 1. Gallay BJ, et al. Am J Kidney Dis. 21;37: Calhoun DA, et al. Hypertension. 22;4: Eide IK, et al. J Hypertens. 24;22: Strauch B, et al. J Hum Hypertens. 23;17: High Prevalence of Unrecgonized Sleep Apnoea* in Drug-Resistant Hypertension Prevalence AHI 1 96% 5 OSA Prevalence % % AHI (events/hr) All Men Women Logan et al. J Hypertens 21;19:2271 * >1 events/hr 3

4 % OSA M F Prevalence of OSA M Middle-Aged Adults 1 Hypertension 2 Resistant Hypertension 3 1 Young et al. NEJM AHI 5 events/hr. 2 Worsnop et al. Am J respir Crit Care Med AHI 5 events/hr. 3 Logan et al. J Hypertens 21. AHI 1 events/hr. M F Sleep Apnea Syndrome: A Possible Contributing Factor to Resistant Hypertension BP Uncontrolle d BP Controlled BMI (kg/m 2 ) Neck (cm) Waist/hip ratio AHI (events/hr) 44 32* HI (%) Lavie and Hoffstein. Sleep 21;24:721 4

5 CPAP in Patients with Resistant Hypertension Logan et al, Euro Respir Care 23 Aldosterone Levels and Risk of OSA in Subjects with Resistant Hypertension % * PAC (ng/dl) Urine Aldo (µg/24-hr) PA (%) * 1 19% OSA Positive OSA Negative Calhoun et al. CHEST 23 5

6 Study Protocol Subjects with Resistant Hypertension and Control Subjects without Resistant Hypertension Plasma aldosterone, renin level, 24-hour urine for aldosterone and creatinine Full-night diagnostic polysomnogram Biochemical and polysomnography results of evaluated subjects with resistant hypertension (n=71)* and without resistant hypertension (n=29)* Resistant Hypertension Control Characteristic mean±sd median mean±sd median PAC, ng/dl 12.4± ± PDR, µunits/ml 21.4 ± ± Serum Cr, mg/dl 1.1 ± ±.1 1. Serum K, meq/l 3.8 ± ± AHI, events/hr 24.1± ± HI, % 7.4± ± OSA Prevalence 85% 83% Data are presented as mean±sd. Different from resistant hypertension subjects (p <.5). 6

7 Figure 1 Apnea-hypopnea index and hypoxic index correlates with plasma aldosterone in resistant hypertension subjects 8 8 Ranked PAC (ng/dl) Ranked PAC (ng/dl) Ranked AHI (events/hr) Ranked HI (%) Rho =.44, p =.2 Rho =.38, p =.1 Figure 2 Apnea-hypopnea index and hypoxic index does not correlate 3 with plasma aldosterone in control subjects 3 Ranked PAC (ng/dl) Ranked PAC (ng/dl) Ranked AHI (events/hr) Ranked HI (%) Rho =.12, p =.52 Rho =.2, p =.99 7

8 Serum and 24-hr Urinary Aldosterone Related to Severity of OSA in Patients with Resistant Hypertension and Hyperaldosteronism Gonzaga et al., J Clin Sleep Med 29 PATIENTS WITH RESISTANT HYPERENSION AND OSA NORMAL ALDOSTERONE HIGH ALDOSTERONE Apnea-hypopnea index (events/hour) r =.17 p =NS Apnea-hypopnea index (events/hour) r =.59 p = Urinary aldosterone (mcg/day) Urinary aldosterone (mcg/day) Gonzaga et al., J Clin Sleep Med 29 8

9 Sim J et al, J Hypertens, 211 Results * 59 * Baseline Post SPL Events/Hour * AHI HI Supine Index REM Index AHI, Apnea-Hypopnea Index; HI, Hypoxic Index; REM, Rapid eye movement sleep; * p<.5. Gaddam et al, J Human Hypertens 29 9

10 BNP and ANP Levels in Patients with Resistant Hypertension vs. Control Subjects pg/ml P=.8 BNP P=.1 ANP Resistant Controls Gaddam et al., Arch Intern Med 28 BNP and ANP Levels in Patients with High and Normal Aldosterone and Resistant Hypertension vs. Control Subjects pg/ml P=.2 P=.1 BNP P=.2 P<.1 ANP HIGH ALDOSTERONE NORMAL ALDOSTERONE CONTROLS Gaddam et al., Arch Intern Med 28 1

11 Neck Circumference and Upper Airway Resistance After Lower Body Positive Pressure Lower body positive pressure (filled squares) Controls (open squares) Chiu et al, Am J Respir Crit Care Med 26 Change in AHI in Patients with CHF Exacerbation after Diuresis Bucca et al, CHEST 27 11

12 Effect of 8-12 Weeks of CPAP Use in Hypertensive Patients with OSA All Subjects (n=24) Mean CPAP Use 2.2 hr/night CPAP Compliant (n=12) Mean CPAP Use 5.4 hr/night Acelajado et al, submitted Resistant Hypertension High/Low Dietary Salt Cross-Over Evaluation 6 patients low-salt diet 1 week 6 patients low-salt diet 1 week 12 patients wash-out 2 weeks 6 patients high-salt diet 1 week 6 patients high-salt diet 1 week Pimenta et al. Hypertension 29 12

13 Results: High-Low Salt Cross-Over High-salt (n=12) Low-salt (n=12) Weight (kg) 94.3± ±17.6* BNP (pg/ml) 35.1± ±1.8* Serum K (meq/l) 3.8±.3 4.1±.5 PAC (ng/dl) 11.1± ±9.3* PRA (ng/ml/h).9± ±32.6 Ualdo (mcg/24-hr) 11.7± ±11.2* UK (meq/24-hr) 56.9± ±27.7* UNa (meq/24-hr) 261.5± ±27.2* TFC (kohms -1 ) 29.3± ±3.5 * Different from high-salt, p<.5 Pimenta et al. Hypertension 29 Reduction in Blood Pressure High to Low Salt Ingestion Blood pressure reduction (mmhg) Office Daytime Nighttime Systolic Diastolic Pimenta, HYPERTENSION, 29 13

14 Pimenta, HYPERTENSION, 28 Du Cailar, HYPERTENSION 21 Dietary Salt Related to Severity of Sleep Apnea in Patients with Resistant Hypertension Pimenta et al, 211, submitted. 14

15 Kasai et al, JACC, 211 Krum H et al. Circulation 211;123:

16 RENAL DENERVATION SIMPLICITY HTN-2 TRIAL Baseline BP=178/97 mm Hg on 5.2 medications n=16 Simplicity HTN-2 Investigators. Lancet 21;376: METABOLIC EFFECTS OF RENAL DENERVATION Mahfoud et al. Circulation 211;123:

17 Witkovski et al. Hypertension 211;58:559. Maria C Acelajado Tanja Dudenbostel Eric Judd Roberto Pisoni Bin Zhang Eduardo Pimenta Suzanne Oparil Acknowledgements \ 17

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