Role of Sleep Apnea and Sympathetic Activity in Resistant Hypertensive Patients.

The study will be double blind and consist of two parallel groups. Patients with type 2 diabetes with a creatinine clearance above 20 ml/min and with microalbuminuria or proteinuria who have both resistant hypertension and sleep apnea will be studied. Creatinine clearance and proteinuria will be assessed from a 24 hour urine collection not older than 6 months. Microalbuminuria will be assessed from at least 2 out of 3 positive random urine samples with the last one not older than 6 months. Blood pressure will be considered as resistive to treatment if the patient is on 3 or more antihypertensive medications with blood pressure readings of greater than 140/90 mmHg on the last 2 out of 3 office visits. Sleep apnea syndrome will be defined by the presence of at least 5 apneic or hypopneic episodes per hour during an overnight sleep study.

Screening will be done in the following manner: Patients seen in the Hypertension Unit at the University of Ottawa Heart Institute, General Nephrology Clinic and Progressive Renal Insufficiency Clinic at the Ottawa Hospital, will be screened by the study coordinator. For the patients who meet the study criteria, the attending physician is asked for permission to contact each patient. If patients agree to participate, they will undergo a sleep study. Screening of patients and subsequent sleep studies will continue until 54 consecutive patients with moderate to severe sleep apnea (15 apneic or hypopneic episodes per hr) are found and enrolled into the study. The prevalence of sleep apnea in the specialty clinic population will be calculated as the number of patients with sleep apnea diagnosed based on a sleep study divided by the total number of clinic patients screened who underwent a sleep study.

After the baseline visit and completion of all preliminary procedures, specific studies for microneurography, plasma renin and aldosterone will be performed. Consequently, a 24 hour blood pressure monitor and a 24 hour urine collection for creatinine clearance, microalbuminuria and proteinuria will be done. Once all the testing has been completed, the patient will be randomized to therapeutic or sub-therapeutic treatment with nasal continuous positive airway pressure for 6 weeks. After 6 weeks of treatment the specific studies, 24 hour blood pressure monitoring and 24 hour urine collection will be repeated.

Inclusion criteria

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• Males and females 18 years or older
• On 3 or more antihypertensive medications with resistant hypertension of >140/90 mmHg (resting) despite treatment
• Diagnosis of sleep apnea (15 apneic/hypopneic episodes per hour and a score of 10 on Epworth sleepiness scale).
• Creatinine clearance > 20 ml/min with microalbuminuria or proteinuria, (results within past 6 months)

Exclusion criteria

• Acute coronary syndrome within 6 months
• Patients with clinically documented congestive heart failure
• Patients with relevant cardiac arrhythmias (second and third-degree heart block or premature ventricular complexes in Lown classes IV or V)
• Pregnant or lactating women
• Patients with leg injury involving nerve damage
• Patients with symptomatic peripheral neuropathy
• Patients with predominant central sleep apnea
• Patients mentally unable to give informed consent
• Professional drivers
• Patients with a resting blood pressure >180/110 mmHg
• Patients taking clonidine
• Patients with sleep apnea causing daily drowsiness
• Patients with severe hyperkalemia (>5.5 mmol/L) or hypokalemia (<3.3 mmol/L)
• Patients with a BMI of >35