Hypertension, Metabolic Disorder
Conditions
Keywords
continuous positive airway pressure, hypertension, coronary heart disease, metabolic disorder, obstructive sleep apnea
Brief summary
Obstructive sleep apnea(OSA) is an important identifiable cause of hypertension. Previous study has suggested that OSA significantly increases cardiovascular morbidity and mortality, especially in patients with pre-existing cardiovascular disease.The standardized treatment of moderate/severe OSA is continuous positive airway pressure (CPAP). Most of short-term trials indicated that CPAP treatment reduced BP in patients with OSA. But relevant studies have a relative short duration with only but few more than one year. In our opinion, they are not sufficient to detect the real effect of CPAP on reduction in BP. Besides, the impact of OSA on metabolic disorder is still unclear.We hypothesized that long-term CPAP treatment could reduce blood pressure and improve metabolic disorder in patients with coronary heart disease (CHD)and OSA.
Detailed description
Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive partial (hypopnea) or complete (apnea) occlusion of the upper airway during sleep caused by collapse of the pharyngeal airway, resulting in sleep fragmentation and oxyhemoglobin desaturation. Kiely and colleague's study showed that over 20% of hypertensive patients exhibit OSA, whereas prevalence of hypertension in the setting of OSA exceeds 50%. One study confirmed that OSA is an important identifiable cause of hypertension. OSA is considered as one of the most common risk factors of resistant hypertension. Previous study has suggested that OSA significantly increases cardiovascular morbidity and mortality, especially in patients with pre-existing cardiovascular disease. Several studies confirmed that CPAP reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with OSA. Additionally, some papers reported that there was a protective effect of CPAP therapy against death from cardiovascular disease in patients with severe OSA. Other researches regarding the antihypertensive effect of CPAP therapy, however, showed that CPAP had no antihypertensive effect. But relevant studies have a relative short duration with only but few more than one year. In our opinion, they are not sufficient to detect the real effect of CPAP on reduction in BP. According to our knowledge, there is no report about long-term effect of CPAP on BP in hypertensive patients with coronary revascularization (CRV) and OSA under conventional antihypertensive medications. Therefore, we conducted a long-term, prospective controlled study to investigate the effects of CPAP on BP, metabolic disorder, clinical symptoms, cardiovascular and cerebrovascular events in patients with CHD and OSA on conventional treatment.
Interventions
DEVICEcontinuous positive airway pressure
mean continuous positive airway pressure use was at least 4 hours per night;continuous positive airway pressure group received fixed-level continuous positive airway pressure titration using an automated pressure
Sponsors
Chinese Pulmonary Vascular Disease Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* men and women, aged 45 to 75 years old * verified diagnosis of hypertension by medical history or receiving antihypertensive drugs * established diagnosis of CHD * at least 3-month optimal treatment for hypertension * moderate or severe OSA
Exclusion criteria
* if they had secondary hypertension * central sleep apneas * history of significant chronic renal, or hepatic failure or severe pulmonary disease * diagnosed with malignant cancer with a life expectancy of less than 2years * regular use of medications that can affect BP(including corticosteroids or sedative drugs) * severe psychiatric disease * sustained excessive alcohol use * current use of CPAP treatment for OSA or pharyngeal surgery for OSA * New York Heart Association Class III-IV degree * declined to participate or were unable to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change of Daytime Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Pre-treatment and Post-treatment | baseline and follow-up at 36 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Epworth Sleepiness Scale (ESS) | baseline，end of study ( up to 54 months) | The epworth sleepiness scale（ESS） measures a person's general level of daytime sleepiness, or their average sleep propensity in daily life (ASP). It is a simple questionnaire based on retrospective reports of the likelihood of dozing off or falling asleep in a variety of different situations. The ESS is the most commonly used method for measuring a person's ASP.The ESS ranges from 0-24, higher scores indicate more severe daytime sleepiness. |
Other
| Measure | Time frame |
|---|---|
| Cardiovascular and Cerebrovascular Events | Baseline, 1 month, 3 month, 6 month, 12 month, 18 month, 24 month, 30 month, 36 month |
Participant flow
Recruitment details
We recruited consecutive patients from outpatient and inpatient departments of Fuwai Hospital from January 2009 to June 2012. Patients were randomly assigned to either continuous positive airway pressure (CPAP) group or no CPAP therapy (control).
Pre-assignment details
A total of 243 patients were screened between January 2009 and June 2012. Out of 97 (39.9%) patients diagnosed with obstructive sleep apnea (OSA), 5 subjects declined to participate in the study, and 9 subjects were excluded because of the following: apnea-hypopnea index (AHI) \<15 (n = 8 patients) and severe heart failure (n = 1 patient).
Participants by arm
| Arm | Count |
|---|---|
| Continuous Positive Airway Pressure(CPAP) Group The CPAP group received fixed-level CPAP titration using an automated pressure setting device for one night. The optimal CPAP pressure for each patient in the CPAP group was set at the minimum pressure required to abolish snoring, obstructive respiratory events, and airflow limitation for 95% of the night. | 42 |
| Control The control group received the standardized antihypertensive medications but without receiving CPAP machine. | 41 |
| Total | 83 |
Baseline characteristics
| Characteristic | Continuous Positive Airway Pressure(CPAP) Group | Control | Total |
|---|---|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 6.8 | 62.7 years STANDARD_DEVIATION 6.7 | 62.4 years STANDARD_DEVIATION 6.6 |
| morning systolic and diastolic BP (mmHg) diastolic BP | 83 mm Hg STANDARD_DEVIATION 7 | 83 mm Hg STANDARD_DEVIATION 8 | 83 mm Hg STANDARD_DEVIATION 7 |
| morning systolic and diastolic BP (mmHg) systolic BP | 146 mm Hg STANDARD_DEVIATION 8 | 148 mm Hg STANDARD_DEVIATION 11 | 147 mm Hg STANDARD_DEVIATION 9 |
| Region of Enrollment China | 42 participants | 41 participants | 83 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 30 Participants | 31 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 42 | 0 / 41 |
| serious Total, serious adverse events | 1 / 42 | 5 / 41 |
Outcome results
Primary
Change of Daytime Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Pre-treatment and Post-treatment
Time frame: baseline and follow-up at 36 months
Population: 4 participants withdrew before the end of study. Two subjects were lost to follow-up in the control group, and 4 patients (all of them had no SCCE) with very poor CPAP compliance were also excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Continuous Positive Airway Pressure(CPAP) Group | Change of Daytime Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Pre-treatment and Post-treatment | Change of SBP | -8 mm Hg | Standard Deviation 11 |
| Continuous Positive Airway Pressure(CPAP) Group | Change of Daytime Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Pre-treatment and Post-treatment | Change of DBP | -4 mm Hg | Standard Deviation 11 |
| Control | Change of Daytime Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Pre-treatment and Post-treatment | Change of SBP | -3 mm Hg | Standard Deviation 6 |
| Control | Change of Daytime Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Pre-treatment and Post-treatment | Change of DBP | -3 mm Hg | Standard Deviation 11 |
Comparison: The sample size was calculated to assess a minimum reduction of 5 ± 5 mm Hg in systolic BPafter CPAP treatment, assuming an alpha error of 5% and a statistical power of 80%.p-value: <0.05t-test, 2 sided
Secondary
Change in Epworth Sleepiness Scale (ESS)
The epworth sleepiness scale（ESS） measures a person's general level of daytime sleepiness, or their average sleep propensity in daily life (ASP). It is a simple questionnaire based on retrospective reports of the likelihood of dozing off or falling asleep in a variety of different situations. The ESS is the most commonly used method for measuring a person's ASP.The ESS ranges from 0-24, higher scores indicate more severe daytime sleepiness.
Time frame: baseline，end of study ( up to 54 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous Positive Airway Pressure(CPAP) Group | Change in Epworth Sleepiness Scale (ESS) | 7.0 score on a scale | Standard Deviation 3.4 |
| Control | Change in Epworth Sleepiness Scale (ESS) | 3.7 score on a scale | Standard Deviation 2.3 |
p-value: 0.001t-test, 2 sided
Other Pre-specified
Cardiovascular and Cerebrovascular Events
Time frame: Baseline, 1 month, 3 month, 6 month, 12 month, 18 month, 24 month, 30 month, 36 month