CC BY
15MEDICAL SCIENCES
IMPACT OF CONTINUOUS POSITIVE AIRWAY PRESSURE ON CARDIO VASCULAR OUTCOMES IN PATIENTS WITH CHRONIC HEART FAILURE AND OBSTRUCTIVE SLEEP
APNEA
Andreieva Ia.O.,
State Institution "Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of
Ukraine", Zaporizhzhia, Ukraine
PhD, Associate professor of department of internal medicine, family medicine, occupational medicine and
medical rehabilitation Mirnii D.P.,
State Institution "Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of
Ukraine", Zaporizhzhia, Ukraine PhD, Assistant ofprofessor of department of therapy, clinical pharmacology and endocrinology
Surmylo M.M.
State Institution "Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of
Ukraine", Zaporizhzhia, Ukraine
PhD, Associate professor of department of internal medicine, family medicine, occupational medicine and
medical rehabilitation
ABSTRACT
Aim. To determine whether CPAP therapy affects the prognosis and risk of cardiovascular events in HF patients with OSA.
Materials and methods. The 131 eligible patients were enrolled in this research. Each patient underwent a clinical evaluation during the consultation (with measurement of body mass and height), surveys with questionnaires, biological tests, echocardiography, cardiorespiratory monitoring, 6 minutes walking test.The average follow-up period was 3 years. We compared the cardiovascular outcomes of those patients who were intolerant of CPAP (untreated group, 74 patients) with those continuing CPAP therapy (57 patients).
Results. CPAP-treated patients had a higher median apnea-hypopnea index score than the untreated group (48.3 [interquartile range (iQr), 33,6 to 66,4] vs 36,7 [IQR, 27,4 to 55], respectively; p > 0,02), but age, body mass index, and time since diagnosis were similar. Deaths from cardiovascular disease were more common in the untreated group than in the CPAP-treated group during follow-up (14,8% vs 1,9%, respectively; p = 0,009), but no significant differences were found in the development of new cases of hypertension, cardiac disorder, or stroke. Total cardiovascular events (ie, death and new cardiovascular disease combined) were more common in the untreated group than in the CPAP-treated group (31% vs 18%, respectively; p < 0,05).
Conclusions. OSA is an independent risk factor for cardiovascular disease and that treatment with CPAP therapy reduces the risk of development of acute cardiovascular events and sudden cardiac death in patients with heart failure.
Keywords: heart failure, apnea, CPAP, cardiovascular outcomes.
Despite advances in pharmacologic therapy, morbidity, mortality, and rates of hospitalization for heart failure (HF) remain high [1, C. 4-5]. These data emphasize the importance of identifying all treatable conditions that could aggravate heart failure. One such condition may be obstructive sleep apnea (OSA) [2, C.922-926].
Sleep-related breathing disorders, including obstructive and central sleep apnea, often coexist with heart failure. The largest epidemiologic studies, which involved 450 and 81 patients with chronic heart failure, found rates of prevalence of obstructive sleep apnea of 37 percent and 11 percent, respectively [3, C.45].
Recurrent obstructive apnea disrupts sleep and subjects the heart to bouts of hypoxia, exaggerated negative intrathoracic pressure, and bursts of sympathetic activity provoking surges in blood pressure and heart rate. Such nocturnal stress can be relieved by therapy with continuous positive airway pressure. Randomized trials involving patients without heart failure also sug-
gest that treating obstructive sleep apnea with continuous positive airway pressure can lower daytime blood pressure [4, C. 1175-1178], but the results of randomized trials of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea are controversial.
Aim: to determine whether CPAP therapy affects the prognosis and risk of cardiovascular events in HF patients with OSA.
Materials and methods. The cross-section prospective study was conducted in the therapeutical, car-diological and pulmonological departments of the CU "Central hospital of Komunarskyi district" from May 2012 to June 2017. The 131 eligible patients with HF and OSAS were enrolled in this research. All patients had severe OSA. Patients were divided into 2 groups, as follows: 1st group - 57 patients with OSA and HF treated with CPAP and 2nd group - 74 untreated patients with OSA and HF.
Our present research was approved by the clinical research ethics committee of SI "Zaporizhzhia Medical
Academy of Post-Graduate Education Ministry of Health of Ukraine." Written informed consent was received from all patients. This research was provided in accordance with "the 1964 Helsinki Declaration."
Exclusion criteria from the study were the following: patients with congenital heart diseases, moderate or severe mitral and aortal stenosis, inflammatory heart diseases, patients with prostetic heart valves, with acute coronary events and stroke within previous 6 months, patients who had severe decompensated heart failure, patients with peripheral vascular diseases, acute and chronic respiratory pathologies (COPD, asthma, ets.), insulin dependent diabetes or thyroid dysfunction, severe renal insufficiency, acute infection diseases, rheu-matologic and oncological diseases, anemia, and any febrile condition or infectious disease, cognitive impairment, dementia, drug and alcohol abuse, skin diseases, rejection to sign the informed consents.
Each patient underwent a clinical evaluation during the consultation (with measurement of body mass and height), surveys with questionnaires, biological tests, laser doppler flowmetry (LDF), cardiorespiratory monitoring, 6 minutes walking test.
The cardiac function of all the patients in HF groups was graded on the basis of the New York Heart Association (NYHA) classification.
Body mass index (BMI) of the patients was calculated as weight divided by height squared (kgm2).
Laboratory evaluation included measurement of NT-proBNP along with other routine investigations as per clinical judgment. For NT-proBNP measurement, blood samples were drawn in nonfasting state. Determination of serum NT-proBNP was done by elec-trochemiluminescence immunoassay (Vector-best, Russia federation).
The 6MWT was performed according to international guidelines [1, C.11].
Cardio-respiratory monitoring was performed using cardiorespiratory monitor Somnocheck Effort (Weinmann, Germany). All participants were recorded for at least 8 hours. An apnea was defined as a complete cessation of airflow for >10 s, and a hypopnea as a >50% reduction in the nasal pressure signal or a 3050% decrease, associated with either oxygen desaturation of >3% or an arousal (defined according to the Chicago report or by autonomic activations on pulse transit time), both lasting for >10 s. The apnea-hypopnea index (AHI) was defined as the number of apneas and hy-popneas per hour of sleep. According to the American Association of Sleep medicine, the severity of OSAS was classified as mild (5<AHI<15 events/hour), moderate (15 <AHI<30events/hour) and severe (AHI>30 events/hour). Desaturation index (DI) was defined as the percentage of sleep time with oxygen satura-tion<90%. Also we estimated mean and minimal SaO2. All subjects didn't have previous treatment of OSAS.
All patients underwent transthoracic echocardiog-raphy. Transthoracic echocardiography was performed with Siemens ACUSON X300 ultrasound machines, with a 1,75 MHz probe. All echocardiography was performed by the same investigator. The echocardiography study was performed in the left lateral decubitus in the parasternal long-axis and 4-chamber views.
The LVEF was obtained using Simpson's biplane methods in 2-dimensional echocardiography Basic measurements of LV dimensions in diastole and systole, thicknesses of interventricular septum (IVSd) and left ventricular posterior wall (PWTd), and left ventricular mass (LVM) was measured by the M-mode technique according to European Association of Cardiovascular Imaging. The surface area of the body and left ventricular mass index (LVMI) was calculated. LVH was defined as LVMI > 125 g/m2. LV geometry was categorized into 4 groups: normal structure (LVMI<125 g/m2 and RWT<0,45), eccentric hypertrophy (EH, LVMI > 125 g/m2 and RWT<0,45), concentric remodeling (CR, LVMI<125 g/m2 and RWT > 0,45), and concentric hypertrophy (LVMI > 125 g/m2 and RWT > 0,45).LV diastolic function was evaluated by mitral inflow values. Mitral inflow velocities were measured from the apical 4-chamber view, with the sample volume placed at the mitral valve leaflet tips.12 The transmittal early diastolic (E-wave) and atrial (A-wave) velocities were measured, and the E/A ratio was calculated. Isovolumic relaxation time (IVRT) and deceleration time (DT) of the E velocity were obtained.
Participants were required to have a minimum level of adherence to CPAP therapy, which was defined as an average of 3 hours per night, during a 1 -week runin period in which sham CPAP was used (i.e., CPAP at subtherapeutic pressure). After that the patients were provided with an automated positive airway pressure machine (REMstar Auto, M or PR series, Philips Respi-ronics) that was initially set in automatic mode for 1 week and thereafter fixed to the 90th percentile of pressure that was calculated by the automated positive airway pressure device from the recorded data.
At randomization and at each follow-up visit, participants had resting blood pressure and heart rate measured at the clinic, and details of current medication use and health behaviors were documented through a structured interview.
The primary end point was a composite of death from any cardiovascular cause, myocardial infarction (including silent myocardial infarction), stroke, or hospitalization for heart failure, acute coronary syndrome (including unstable angina), or transient ischemic attack.
Statistical analysis. Results are expressed as the mean SD for quantitative variables if normally distributed and as the median (IQR) if otherwise distributed. Qualitative variables were expressed as the absolute number (percentage). The comparison of numerical data was achieved using the unpaired Student t test, and the comparison of categoric data was achieved using the x2 formula. The Kaplan-Meier method of survival analysis was applied for the calculation of survival rates, and log-rank analysis was used to detect differences between groups. The data were expressed as the odds ratio (confidence interval). A p value of > 0,05 was regarded as significant. Calculations were performed with SPSS-software (Version 23.0; SPSS, Chicago, IL).
Results. There were no significant differences between the CPAP group and the untreated group in terms of age, BMI, and cardiovascular risk factors at baseline,
but subjects in the untreated group had a significantly lower AHI, and more patients in the untreated group had undergone nasal surgery prior to the diagnosis of OSAS.
During the period of follow-up, there was a significant excess of cardiovascular deaths (ten deaths [17,5%] vs three deaths [2,9%], respectively; p > 0,009) and a nonsignificant increase in cardiovascular morbidity in the untreated group compared to those in the CPAP group. Furthermore, the total number of cardiovascular events (death and new cardiovascular disease combined) was significantly greater in the untreated group compared to that in the CPAP group (13 events [32%] vs 19 events [21%], respectively; p > 0,05). However, the difference in the total number of deaths between the two groups showed only a trend toward an increase in the untreated group (untreated group, 10 deaths [14,7%]; CPAP group, eight deaths [11 %]; p > 0,3 [log-rank test]).
Of those patients who died, there was no difference between the two groups in age at diagnosis, BMI, and AHI. Of the deaths in the CPAP group, only two were possibly cardiac in nature, and one of those occurred during surgery with the patient under general anesthesia. In the untreated group, six patients were known to have died from cardiovascular causes, and in the remaining three patients a presumptive cause of cardiovascular death was made by the family physician. In all cases, cardiovascular disease was the primary cause of death given on the death certificate. Most patients in the untreated group died during the night or early morning , and four of the nine deaths were sudden and unexpected.
Figure 1 illustrates the Kaplan-Meier survival analysis for cardiovascular death in CPAP users and nonusers.
Figure 1. Kaplan-Meier survival curve for cardiovascular death in CPAP-treated patients and untreated patients.
This study supports a beneficial effect of long-term CPAP therapy on cardiovascular mortality in patients with OSAS, which was independent of age, BMI, smoking and alcohol history, and severity of OSAS. The only significant difference between the CPAP group and the untreated group at baseline was a higher AHI in the CPAP group, which might have been expected to predispose those patients to a higher incidence of cardiovascular disease than those in the untreated group, as has been observed. Other relevant factors such as age, BMI, or the presence of other cardiovascular risk factors were similar at baseline in both groups.
The mechanisms by which OSAS predisposes a person to cardiovascular disease are not fully understood, but they likely include elevated sympathetic drive, secondary to recurrent hypoxias and arousals from sleep, with loss of the resetting of the baroreceptor control, and increased oxidative stress secondary to recurring oxygen desaturation and resaturation [5, C.
995]. The repetitive hypoxia and reoxygenation episodes that are characteristic of the OSAS result in the increased production of reactive oxygen species which is associated with a differential expression of specific genes through the activation/up-regulation of redox-ac-tivated transcription factors including hypoxia induci-ble factor-1 and nuclear factor B, among others. This up-regulation results in the increased production of an array of proteins including vascular endothelial growth factor [6, c. 337; 7, C. 735]. Circulating vascular endo-thelial growth factor levels are elevated in OSAS patients and fall with nasal CPAP therapy [8, C.26]. Furthermore, levels of nitric oxide, which is regarded as protective against vascular endothelial damage, are reduced in OSAS and increase with CPAP therapy [9, c. 25].
In conclusion, the present study supports the hypothesis that OSA is an independent risk factor for cardiovascular disease and that treatment with CPAP ther-
apy reduces the risk of development of acute cardiovascular events and sudden cardiac death in patients with heart failure.
References
1. White S. Evidence-based Strategies for Advanced Heart Failure. //Critical Care Nursing Clinics of North America. 2019, 31(1), C.1-13.
2. McEvoy R, Antic N, Heeley E, Luo Y, Ou Q, Zhang X et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. New England //Journal of Medicine. 2016, 375(10), C. 919-931.
3. Wang X, Zhang Y, Dong Z, Fan J, Nie S, Wei Y. Effect of continuous positive airway pressure on long-term cardiovascular outcomes in patients with coronary artery disease and obstructive sleep apnea: a systematic review and meta-analysis. //Respiratory Research. 2018, 19(1).
4. Kato T. Positive airway pressure therapy for heart failure. //World Journal of Cardiology. 2014, 6(11), C. 1175-1179.
5. Jean-Louis G, Brown C, Zizi F, Ogedegbe G, Boutin-Foster C, Gorga J et al. Cardiovascular disease
risk reduction with sleep apnea treatment. //Expert Review of Cardiovascular Therapy. 2010, 8(7), C. 9951005.
6. Xie W, Zheng F, Song X. Obstructive Sleep Apnea and Serious Adverse Outcomes in Patients with Cardiovascular or Cerebrovascular Disease. //Medicine. 2014, 93(29), C. 336-339.
7. Batool-Anwar S, Goodwin J, Kushida C, Walsh J, Simon R, Nichols D et al. Impact of continuous positive airway pressure (CPAP) on quality of life in patients with obstructive sleep apnea (OSA). //Journal of Sleep Research. 2016, 25(6), C. 731-738.
8. da Silva Paulitsch F, Zhang L. Continuous positive airway pressure for adults with obstructive sleep apnea and cardiovascular disease: a meta-analysis of randomized trials. Sleep Medicine. 2019, 54, C. 2834.
9. Martínez-García M, Capote F, Campos-Rodríguez F, Lloberes P, Díaz de Atauri M, Somoza M et al. Effect of CPAP on Blood Pressure in Patients With Obstructive Sleep Apnea and Resistant Hypertension. JAMA. 2013, 310(22), C. 24-27.
РОЛЬ ПСИХОЛОГИЧЕСКОГО ИССЛЕДОВАНИЯ СУИЦИДАЛЬНОГО ПОВЕДЕНИЯ У
ПОДРОСТКОВ
Бабарахимова С.Б.
соискатель степени PhD базовой докторантуры, ассистент кафедры психиатрии, наркологии,
детской психиатрии, медицинской психологии и психотерапии
Абдуллаева В.К.
доцент, д.м.н., заведующая кафедрой психиатрии, наркологии, детской психиатрии, медицинской психологии и психотерапии
Султонова К.Б. ассистент кафедры психиатрии, наркологии, детской психиатрии, медицинской психологии и психотерапии
Аббасова Д.С.
ассистент кафедры психиатрии, наркологии, детской психиатрии,
медицинской психологии и психотерапии Ташкентский Педиатрический Медицинский институт, Ташкент, Республика Узбекистан.
ROLE OF PSYCHOLOGICAL RESEARCH OF SUICIDAL BEHAVIOR IN ADOLESCENTS
Babarakhimova S.B.,
assistant of the Department of Psychiatry, Narcology, Child Psychiatry, Medical Psychology and Psychotherapy Abdullaeva V.K., doctor of science,
of the Department of Psychiatry, Narcology, Child Psychiatry, Medical Psychology and Psychotherapy Sultonova K.B.,
assistant of the Department of Psychiatry, Narcology, Child Psychiatry, Medical Psychology and Psychotherapy Abbasova D.S.
assistant of the Department of Psychiatry, Narcology, Child Psychiatry, Medical Psychology and Psychotherapy Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan
