| Part I:The Impact of Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnea and Hypertension on Home Blood Pressure and Target Organ DamageBackground and Objectives:Hypertension has been demonstrated as clearly correlated with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the first-line therapy for patients with more than moderate OSA. Home blood pressure telemonitoring can significantly reduce blood pressure. We conducted this randomized controlled trial to explore the impact of CPAP in patients with OSA and hypertension on home blood pressure and target organ damage.Methods:In this randomized, single center trial,120 patients with OSA (apnea hypopnea index>15 events/h) and hypertension were randomly assigned to CPAP group and non-CPAP group. All of the patients were given a home blood pressure equipment. The primary endpoint was change in home blood pressure between the two groups.Results:A total of 12 patients were lost to follow-up (CPAP:5, non-CPAP:7). At 12 months follow-up, the adjusted mean decrease of daytime home blood pressure was 21.5 mmHg [95% confidence index (CI):19.0,24.0] /6.2 mmHg (95%CI:3.7,8.8) in the CPAP group and 15.6 mmHg (95%CI:13.1,18.2)/5.1 mmHg (95%CI:2.5,7.7) in the non-CPAP group. The difference in the mean daytime home blood pressure between two groups was 5.9 mmHg (95%CI:2.3,9.5)/1.2 mmHg (95%CI:-2.6,4.9), P value: 0.002/0.543. The adjusted mean decrease of nighttime home blood pressure was 6.0 mmHg (95%CI:2.5,9.5)/3.7 mmHg (95%CI:0.9,6.5) in the CPAP group and-1.6 mmHg (95%CI:-5.1,2.0)/-3.5 mmHg (95%CI:-6.6,-0.6) in the non-CPAP group. The difference in the mean nighttime home blood pressure between two groups was 7.6 mmHg (95%CI:2.5,12.6)/7.2 mmHg (95%CI:3.1,11.3), P value:0.005/0.001. Compared to non-CPAP group, the decreases of brachial-ankle pulse wave velocity (4.9±2.8 VS 2.3±1.3 m/s, P<0.001), urine microalbumin creatinine ratio (38.1±55.2 VS 9.2±25.9 mg/g, P=0.003) and left ventricular mass index (22.5±7.6 VS 9.8±10.1 g/m2, P<0.001) were significantly higher in CPAP group.Conclusions:CPAP in combination with home blood pressure monitoring was effectively to improve home blood pressure and target organ damage.Part II:Effect of spironolactone on patients with resistant hypertension and obstructive sleep apneaBackground and Objectives:Obstructive sleep apnea hypopnea syndrome (OSAHS) and hyperaldosteronism are both prevalent in patients with resistant hypertension. The severity of OSAHS is positive correlated with plasma aldosterone (PAC). We conducted this randomized controlled trial to examine whether spironolactone could reduce the severity of OSAHS and lower blood pressure in patients with resistant hypertension.Methods:In this randomized, single center trial,30 patients with moderate to severe OSAHS (apnea hypopnea index> 15 events/h) and resistant hypertension were randomly assigned to therapy group. Patients in the therapy group were administered spironolactone 20 mg once daily (up to 40 mg once daily for 4 weeks, if required) in addition to original antihypertensive medication. Follow-up was 12 weeks. The primary endpoint was change in apnea hypopnea index (AHI) between the two groups.Results:At 12 weeks’follow-up, the adjusted mean of AHI decrease in the therapy group was 17.5 events/h [95% confidence index (CI):11.7,23.3] and 0.5 events/h (95%CI:-5.3,6.3) in the control group. The difference in the mean AHI decrease was 17.0 次/h(95%CI:8.6,25.5), P<0.001. The adjusted mean apnea index decrease and oxygen desaturation index decrease were significantly higher in the therapy group than that in the control group (P=0.016; P=0.001). The adjusted mean of lowest oxygen saturation and mean oxygen saturation increase were significantly higher in the therapy group than that in the control group (P=0.028; P<0.001). The decrease of clinic blood pressure was 22.2±9.5/11.3±8.6 mmHg and 10.0±6.9/3.3±6.3 mmHg in the control group (P:<0.001/0.007). Mean decrease of ambulatory blood pressure parameters in the therapy group was significantly higher than that in the control group (all P<0.05). None of the patients had spironolactone-associated side effects during follow-up.Conclusions:Spironolactone could reduce the severity of OSAHS and improve blood pressure in resistant hypertensive patients with moderate to severe OSAHS. These findings may assist in the treatment of OSAHS in patients with resistant hypertension.Part Ⅲ:The Presentation and Management of Hypertension in a Large Corhort of Takayasu ArteritisBackground and objectives:Takayasu arteritis is reported as one of the most common cause of secondary hypertension, especially in Asian countries. Hypertension is also one of the most important and common complications in Takayasu arteritis. Systemic investigation with large sample size of the presentation and management of hypertension secondary to Takayasu arteritis is rare around the world. We conducted the retrospective research to explore the presentation and management of hypertension secondary to Takayasu arteritis in a single center in Fuwai hospital.Methods:We retrospectively analyzed 381 Takayasu arteritis patients with hypertension hospitalized in Fuwai hospital between Jan.2004 to Feb.2014. Diagnosis of hypertension was according to clinic blood pressure or the central blood pressure measured during angiography.Results:Renal artery stenosis was the most common cause (264,69.3%), followed by the thoracic descending aorta stenosis (98,25.7%), abdominal aorta stenosis (78,20.5%) and severe aortic regurgitation (45,11.8%). More than two kinds of pathologies were found in 98 (25.7%) patients. The mean age of hypertension onset was 25.0±14.3 years of old, with 73 (19.2%) patients’age of hypertension onset<18 years of old. The mean blood pressure of upper extremity in patients without bilateral subclavian artery stenosis (321,84.3%) was 176.0±29.4 mmHg/97.2±23.0 mmHg, while in patients with bilateral subclavian artery stenosis (60,15.7%), the mean central blood pressure was 192.7±30.8 mmHg/102.4±121.1 mmHg. A total of 305 were followed for 38.4±36.7 months, and the rate of blood pressure control, improve and failure was 50.8%,41.0% and 8.2%, respectively. Immunosuppressive therapy (OR:2.402,95% Confidence interval: 1.253-4.603, P=0.008) and the pathogenesis of hypertension (P=0.010) were associated with prognosis of hypertension.Conclusions:The pathogenesis of hypertension due to Takayasu arteritis is very complex and multifactorial. Renal artery stenosis is the most frequently observed., followed by stenosis the thoracic descending aorta, abdominal aorta and severe aortic regurgitation. Immunosuppressive therapy and identifying the pathogenesis of hypertension is of great importance in patients with Takayasu arteritis.Part IV:Clinical Features and Prognosis in 247 Takayasu Arteritis Patients with Neurological ManifestationsBackground and objective:Neurological manifestations in Takayasu arteritis are variable and complex, which is associated with the specific arterial involvement. Stroke is the most serious symptom of TA and is an important contributor to patient mortality. Previous studies related to neurological manifestations in Takayasu arteritis is small sampled, so we conduct the present study to describe the clinical features and long-term outcomes of patients with Takayasu arteritis who experienced neurological symptoms in a singled center in china.Methods:A retrospective study was undertaken in patients with TA who attended Fuwai hospital from Jan.2002 to Nov.2013 (n=610). Patients who exhibited neurological symptoms (including dizziness, headache, syncope, visual disturbance, cerebrovascular events including transient ischemia attack and stroke) were analyzed (n=274). Clinical data and imaging features were analyzed, as well as the long-term outcomes.Results:The mean age at disease onset was 28.2±11.2 years with a female-to-male ratio of 1:4.3. The mean time between disease onset and diagnosis was 52.4±5.5 months. The most common neurological manifestation was dizziness (214,78.1%), followed by headache (70,25.5%) and syncope (60,21.9%). Visual disturbances and transient ischemia attack were all happened in 58 (21.2%) patients. Stroke was suffered in 30 (10.9%) patients (ischemic stroke 27, hemorrhagic stroke 2, ischemic+hemorrhagic stroke 1). Syncope, cerebrovascular events and visual disturbance were associated with disease activity (P<0.001; P=0.018; P<0.001). The most frequent type was type Ⅲ (112, 40.9%), and the most common affected supra-arch vessel was the left subclavian artery (147,53.6%). Dizziness was associated with subclavian artery involvement (x2=10.845, P=0.001) and vertebral artery involvement (x2=6.789, P=0.009). Transient ischemic attach was associated with subclavian artery involvement (x2=17.924, P<0.001). Ischemic stroke was related to common carotid artery involvement (x2=10.290, P=0.001), while hemorrhagic stroke was observed in patients with hypertension due to steno-occlusive lesions of renal artery and/or abdominal artery. A total of 175 (63.9%) patients were followed for a mean time of 3.7±0.3 years. Heart failure was the most common cardiovascular event in those who died (n=6) and in surviving cohorts.Conclusions:Neurological manifestations in patients with Takayasu arteritis were various and correlated with the site of artery involvement. Ischemic stroke was more common in patients with involvement of supra-arch vessels, while hypertension was one of the most important risk factors for hemorrhagic stroke in patients with TA.
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