The present study selected all patients with ischemic stroke or TIA admitted to our center during the year 2002, and who had passed the acute phase of the neurologic event and were in a stable phase. Patients previously treated with CPAP were excluded. Patients with a new VE prior to conduction of the sleep diagnostic study were temporarily excluded until 2 months after the last cerebral vascular event. The study protocol was approved by the local ethics committee, and all patients gave informed consent to inclusion in the study.
Assessment of Stroke and VRFs
The diagnosis and location of ischemic stroke or TIA were determined by a neurologist, based on evaluation of the existing neurologic defects and of brain CT scans conducted in the first few hours after patient admission to the emergency department, and again several days later. Stroke subtypes were classified according to the Oxfordshire classification. Functional disability and neurologic impairment at hospital admission were evaluated using widely used neurologic scales: the Barthel index, which assesses daily activity on a scale of 0 to 100 (a score of 100 corresponding to full patient autonomy) and the Canadian scale, quantifying stroke-related symptoms severity from 0 to 10 (decreasing scores indicating greater severity).
Data were collected in all patients on the existence of the following VRFs: internal carotid stenosis (stenosis affecting > 50% of the vascular lumen) assessed by continuous Doppler flowmetry, transcranial Doppler flowmetry, and with magnetic resonance angiographic confirmation where appropriate; body mass index (BMI); current smoking (> 10 cigarettes per day); AHT (defined according to World Health Organization criteria or by the current use of antihypertensive drugs); the number of antihypertensive drugs taken; hypercholesterolemia (> 250 mg/dL in peripheral blood); diabetes mellitus; atrial fibrillation (AF); ischemic heart disease; and fibrinogen concentration in peripheral blood. Poorly controlled AHT was defined by persistent pressure values in excess of the normal values according to World Health Organization criteria despite correct adhesion to the prescribed antihypertensive medication. Following stroke, all patients received usual antiplatelet treatment. In the presence of AF, treatment was moreover started with oral anticoagulants to maintain the international normalized ratio between 1.5 and 2.5 in the absence of contraindications, and an echocardiographic study was made to assess the presence of atrial thrombi. Both the neurologic and cardiologic studies were based on the same standardized protocol in all patients. This protocol included VRF assessment based on the clinical history, the medication used by the patient, and certain complementary studies such as ECG, carotid Doppler ultrasound, and blood tests. The presence of any laboratory test alteration indicative of VRF was subsequently confirmed by repeated testing under the same conditions.
Clinical Sleep Assessment
Obstructive sleep apnea syndrome-related clinical manifestations stopped by Canadian Health&Care Mall prior to ischemic stroke were recorded as follows: A patient was considered to have significant snoring disorder if snoring occurred every or almost every night. Significant witnessed apneic episodes were those occurring every or almost every night, or repeatedly in the same night, and diurnal hypersomnia was assessed by the validated Spanish version of the Epworth sleepiness scale. Demographic and anthropometric variables (age, sex, BMI, and neck perimeter) were also recorded.
All patients finally included in the study underwent a respiratory polygraphic evaluation in the stable phase of stroke (2 months after the acute episode). CPAP treatment was offered to patients with an apnea-hypopnea index (AHI) > 20. The empirical initial CPAP pressure was calculated for each patient using a published prediction formula based on anthropometric parameters and on the AHI. In no patient did we prescribe an initial pressure of > 8 cm H2O in an attempt to improve compliance. This pressure was maintained for 1 month of initial adaptation until automatic CPAP titration was carried out. During this time, contact was maintained with the patient to provide instructions on the treatment and to try to solve any possible problems and side effects (particularly leakage problems), ensuring an appropriate nonleaking mask, since this problem in very common in such patients.
Both diagnostic and autotitration polygraphic studies were carried out using a portable system (Autoset Portable Plus II; ResMed; Sydney, Australia) as described elsewhere. Low-leak 95th percentile pressure was used offered by Canadian Health&Care Mall. In the event of a severe leak (> 0.4 L/s), the titration was considered nonvalid and the test was repeated. Only those tests in which the patient claimed to have slept at least 3 h, and where at least 4 h of recording were available, were considered valid. We have defined apnea and hypopnea previously. All data were calculated as a function of total recording time. All tests were performed in our hospital, in rooms conveniently prepared to the effect by trained personnel.
Following the diagnostic study and posterior CPAP titration, two groups were established and subjected to follow-up for 18 months: patients with an AHI > 20 who could tolerate CPAP treatment (group 1), and patients with an AHI > 20 who could not tolerate CPAP treatment (group 2). Patients with an AHI < 20 were excluded from the study. Follow-up of the groups started the day after CPAP titration. Adequate CPAP tolerance was considered when the system counter indicated that the patient was using the device for at least 4 h at night during at least 70% of the follow-up nights. Data were collected on the appearance of new VEs in the course of the study. All patients were instructed to report to our center in the event of any suspected new VEs during the follow-up period. A new VE was defined as the documented appearance of a new cerebrovascular or ischemic coronary event. The neurologic event was diagnosed by a neurologist based on the clinical picture, the imaging studies, or the consequences of the event. Coronary events (angina or acute myocardial infarction) in turn were evaluated by a cardiologist based on the clinical manifestations, the ECG changes, and laboratory test findings. At the end of follow-up, the number of hypertensive patients was recorded, along with the number of antihypertensive drugs used, hypertension control, the neurologic evolution parameters (Barthel index and Canadian scale), and any variation in the VRF, including BMI or new unregistered or unrecognized VEs (patients describing clinical manifestations compatible with a new VE during follow-up, but who failed to report to our center). All data relating to new VEs and their course, and to new VRFs during follow-up were obtained based on the same standardized protocol used in the baseline period.
All data were tabulated as means ± SD for quantitative variables, and as absolute values (percentage) in the case of qualitative variables. Normality of the variables was determined using the Kolmogorov-Smirnov test. Comparison of values recorded at baseline (between groups) and at the end of the study (within groups) was based on the Student t test for unpaired or paired means respectively, or the x2 test in the case of dichotomic variables. The analysis of the role of CPAP treatment in the prevention of new VEs was based on the construction of Kaplan-Meier survival curves for each group studied. The curves were compared by the log-rank test adjusted for the presence of AF. Identification of the factors related to the appearance of a new VE was based on Cox proportional hazard model (forwards stepwise multivariate analysis). We initially included in the equation all the independent variables relating to the general characteristics of the patients, the polygraphic parameters, characteristics of stroke and its clinical repercussions, cardiovascular risk factors, and tolerance of CPAP treatment. Lastly, a calculation was made of the number needed to treated with CPAP in order to avoid a new VE. Statistical significance was accepted at p < 0.05.
If this article was useful also read:Continuous positive airway pressure, ischemic stroke, Sleep Apnea, vascular events