Treatment of OSA Associated Hypertension With Alpha 2 Agonist or Diuretic
Treatment of OSA Associated Hypertension With Alpha 2 Agonist or Diuretic
Patients who have obstructive sleep apnea (OSA) frequently stop breathing while they sleep.
 They often develop high blood pressure. We are not sure what drug is best to treat the high
 blood pressure. This study will give the patients guanfacine or hydrochlorothiazide (HCTZ)
 for 6 weeks after 2 weeks of placebo. The blood pressure response will be evaluated by 24
 hour monitoring.
This is a blinded crossover study measuring the antihypertensive efficacy of guanfacine vs
 HCTZ in up to 34 subjects. Subjects with an apnea-hypopnea index (AHI) > 10 and hypertension
 can enter the study. Hypertension is defined as a systolic blood pressure (SBP) > 140 or a
 diastolic blood pressure (DBP) > 90 on the average of three seated blood pressure
 measurements or a history of medical therapy for hypertension. Subjects who have tried and
 abandoned continuous positive airway pressure (CPAP) therapy for sleep apnea are eligible for
 this study. All others will be advised that CPAP is preferred treatment for sleep apnea and
 are eligible only if they decline CPAP or use it for too short a time at night to be
 effective.

 Then patients will have their antihypertensive drugs tapered off and receive single blind
 placebo for two weeks. After that, all subjects receive guanfacine or HCTZ for six weeks with
 a full evaluation at that time. Subjects are crossed over to HCTZ 12.5 mg for 2 weeks
 followed by HCTZ 25 mg for 4 more weeks Guanfacine 1mg will be taken daily at bedtime for 2
 weeks and then as a dose of 2 mg for the remaining 4 weeks. Subjects will receive a telephone
 call at the time of increased dosage as a reminder. Blood, urine and 24-hour blood pressure
 measurements, hemodynamic measurements, questionnaires and drug accountability are measured
 in the same manner toward at the the end of placebo and each drug treatment. The entire study
 will take 14 weeks, although each study period may be lengthened by one week if necessary for
 the convenience of the subject's personal schedule.

 Patients will provide blood pressure readings from their home monitor or in clinic and will
 not have the dose increased if they have systolic blood pressure below 105 mm Hg or side
 effects, such as excessive somnolence, drowsiness, or depression, suggesting that an
 increased dose might worsen side effects

 At the end of each treatment period, subjects will undergo noninvasive hemodynamic testing.
 Ultrasound will be used to measure aortic diameter and blood velocity in the ascending aorta
 in order to better estimate cardiac output. Then, finger plethysmography will be used to
 acquire beat-to-beat finger blood pressure and pulse rate. Beat-to-beat derived hemodynamic
 variables will be calculated by a model flow algorithm (e.g. brachial artery flow, stroke
 volume, cardiac output, ejection time, blood pressure rate of change, peripheral resistance).
 Applanation tonometry will be used to obtain pulse wave velocity and central arterial
 pressure. ECG will be recorded with standard ECG leads to determine heart rate variability in
 both time and frequency domains. Spontaneous baroreflex will be determined from beat-to-beat
 changes in blood pressure and pulse pressure interval. Forearm reactive hyperemia will be
 used to quantify endothelial dysfunction during 4 minutes of post-ischemic change. Subjects
 will then complete an Epworth Sleepiness Scale questionnaire (ESS) and a Functional Outcomes
 of Sleep Questionnaire (FOSQ) to find whether they are drowsy in the daytime and if they feel
 that they are compromised by not having adequate rest. Any adverse event will be recorded.
 They are asked about any concurrent medication over the prior period, including prescription
 medication, over the counter medication, and caffeine intake. Medication compliance is
 evaluated by pill count. Those who fail to return their pill bottle are requested to bring it
 in. Finally, a 24-hour ambulatory blood pressure monitor (ABPM) will be attached to
 automatically collect blood pressure and heart rate values every 15 minutes during the wake
 period and every 30 minutes during the sleep period.
Inclusion Criteria:

 1. Patients ranging from 20 - 80 years

 2. Body mass index (BMI) of 20-38 to include the typical obese OSA patients and avoid the
 practical difficulties in blood drawing from the massively obese

 3. Hypertension with blood pressures > 140/90 but less than 180/105 mmHg.

 4. Apnea-hypopnea index above 10

 Exclusion Criteria:

 1. Receiving medications other than anti-hypertensives known to influence the sympathetic
 nervous system, sleep medicines (including heavy alcohol use) or drugs with adverse
 interactions with study medication.

 2. Women who have premenstrual syndrome, or those who are pregnant or capable of
 pregnancy and unwilling to use effective non-hormonal contraception

 3. Shift workers or have symptoms of narcolepsy, restless legs syndrome or insomnia, in
 order to minimize confounding effects of other sleep disorders

 4. Have apneas which are primarily central

 5. Have sleep fragmentation caused by syndromes such as chronic pain or movement
 disorders

 6. Have diseases such as asthma or chronic obstructive pulmonary disease that compromises
 respiration.

 7. Have known coronary or cerebral vascular disease, history of arrhythmias,
 cardiomyopathy, history of psychosis, current alcohol or drug abuse.

 8. Have any contraindications to any study materials, such as heart block.

 9. Have secondary hypertension

 10. Have creatinine levels above 2.5 mg %, more than 1+ proteinuria by dipstick, hematuria
 or electrolyte disorders.