Abstract
Introduction:
It has been shown that there is a correlation between Obstructive Sleep Apnea Syndrome (OSAS) and pulmonary thromboembolism (PTE); OSAS is a risk factor for PTE. We aimed to evaluate the frequency of OSAS in PTE patients, the correlation of OSAS with the severity of PTE, and its effect on 1-month mortality in PTE patients.
Methods:
This single-center, prospective, comparative case control study contains 198 patients diagnosed with non-massive PTE in our hospital between the dates of 01/07/2018–04/01/2020 who were confirmed by imaging methods. Daytime sleepiness was assessed with Epworth questionnaires, and OSAS risk was assessed with Berlin, STOP, STOP-BANG sleep questionnaires. Alongside demographic and clinical data, comorbidities, Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI), WELLS scores, troponin, D-dimer values, echocardiyography (ECHO) findings were also examined. Epworth, Berlin, STOP, STOP-BANG sleep groups were compared in terms of PTE parameters.
Results:
A hundred and thirty-eight patients (69.6%) was assesed as high risk group according to Berlin, meanwhile STOP-BANG defined 174 patients (87.8%), furthermore STOP has considered 152 patients in the high risk group (76.7%) and Epworth questionnaire determined this number as 127 (64.1%). As a result of the logistic regression analysis, statistically significant correlation was found between Berlin score and heart failure, PESI, sPESI and troponin values; between Epworth score and WELLS score; between STOP-BANG score and PESI score (p<0.05). During the 1-month follow-up period, 9 of the patients were exitus and mortality was 4.5%.
Conclusion:
OSAS risk is more common in patients with PTE and it may be a risk factor for PTE. It has been shown that the risk of OSAS may aggravate PTE severity and prognosis.
Keywords: Obstructive sleep apnea syndrome, pulmonary thromboembolism, excessive daytime sleepiness
INTRODUCTION
Pulmonary thromboembolism (PTE) is an acute clinical disease caused by the occlusion of the pulmonary arteries and / or branches of thrombi that can occur in all veins, especially in the lower extremity deep veins (1). Factors leading to intravascular coagulation have been defined as vascular endothelial injury, hypercoagulability, and venous stasis (2). The annual average incidence of PTE is 39–115/100000 (3). Pulmonary thromboembolism is a major cardiovascular disease that can cause 300 000 deaths per year (3).
Obstructive sleep apnea syndrome (OSAS) is a syndrome characterized by recurrent or partial upper respiratory tract obstruction episodes during sleep, often accompanied by blood oxygen desaturation and arousals (4). Although the gold standard method in the diagnosis of OSAS is polysomnography (PSG), standard questionnaires based on clinical findings; Epworth sleepiness scale, Berlin questionnaire, STOP, STOP-BANG questionnaires can guide the evaluation of the disease (5–7)
Cardiovascular diseases are one of the most important complications of OSAS (8). Studies have shown that there is a correlation between OSAS and coronary heart disease, cardiac arrhythmia, heart failure, and pulmonary hypertension (8). Obstructive sleep apnea syndrome is thought to be associated with PTE due to persistent hypercoagulability, endothelial dysfunction, and venous stasis (9). The prevalence of OSAS has increased in PTE patients compared to the normal population (10). Finally, the correlation between OSAS with Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI) scores, which shows the severity and prognosis of PTE, has been shown in previous studies (11,12).
Highlights
The prevalence of OSAS is increased in PTE patients.
The risk of OSAS can aggravate the risk and severity of PTE.
Excessive daytime sleepiness can increase the risk of PTE.
In this study, we aimed to evaluate the prevalence of OSAS in non-massive PTE patients, the correlation between the risk of OSAS with the severity of PTE, and its effect on early mortality in PTE patients.
METHOD
The study was planned as a single center, prospective, comparative case-control study. 198 patients hospitalized in our hospital between 01/07/2018 and 04/01/2020, whose diagnosis of non-massive PTE was confirmed by pulmonary CT angiography or pulmonary ventilation perfusion scintigraphy, were included in the study. The approval of the Yedikule Chest Diseases and Chest Surgery Training and Research Hospital Ethics Committee was obtained for the study (Decision number: 22.06.2018/1324).
Different questionnaires are used in risk assessment of OSAS. Epworth sleepiness scale consists of eight questions about daily life of the patient. Degree of sleepiness and risk of falling asleep while engaged in different activities are rated on a scale of 0 to 3. Berlin questionnaire includes questions about snoring, daytime somnolence, body mass index, and hypertension It is a brief and validated screening tool that identifies persons in the community who are at high risk for OSAS. STOP questionnaire, developed and validated in surgical patients at preoperative clinics. Combined with body mass index, age, neck size, and gender, (STOP-BANG questionnaire) it had a high sensitivity, especially for patients with moderate to severe OSAS.
In the study, PESI and sPESI scores were examined in order to determine the severity of PTE in patients hospitalized with a diagnosis of acute non-massive PTE. Excessive daytime sleepiness was analyzed with the Epworth sleepiness scale; OSAS risk was analyzed with the questionnaires of Berlin, STOP, and STOP-BANG.
Patients older than 18 years of age with a confirmed PTE diagnosis were included in the study. Patients with below mentioned diagnoses and conditions were excluded from this study; (i) patients diagnosed with deep vein thrombosis (DVT) with bilateral lower extremity Doppler ultrasonography without confirmed PTE, (ii) patients diagnosed with massive PTE, (iii) patients undergoing thrombolytic therapy, (iv) patients treated with vena cava filter, (v) patients with hemodynamically instable, (vi) patients under 18 years of age with a history of PTE, (vii) patients who previously used anticoagulants for any reason, (iix) patients developed recurrent PTE under anticoagulant.
Comorbidities and PTE risk factors were questioned. Body mass index (BMI) of the patients were calculated and neck circumference was measured. Patients were divided into two groups according to geriatric (65 years old) and obesity (BMI 30 kg / m2) criteria. Berlin, Epworth, STOP, STOP-BANG questionnaires were performed (5–7). PhilipS Ingenuty Elite device with 128 detectors was used for Pulmonary CT Angiography and Toschita Aplio 300 device was used for lower extremity ultrasonography. Pulmonary embolism severity index, sPESI and WELLS scoring were calculated (13). D-dimer level was measured using Siemens BCS VP coagulometry device, b-type natriuretic peptide (proBNP) and Troponin-I levels were measured through immunoassay device (Access 2, Beckman Coulter Inc. 2014). Complete blood count, biochemical parameters and procalcitonin results of the patients were examined. Complete blood count parameters were measured with the Sysmex XT4000i device. Biochemical parameters and procalcitonin results were measured with Beckman Coulter AU 2700 device.
Echocardiography (ECHO) findings were evaluated with Philips Matrix echocardiography device, Ejection fraction, pulmonary artery pressure were measured and ECHO findings were recorded. Pulmonary hypertension has been defined as the pulmonary artery mean systolic pressure higher than 25 mm Hg (14). Patients were divided into two groups according to the presence of pulmonary hypertension. The presence of right ventricular dysfunction was evaluated by the criteria of right ventricular dilatation (end-diastolic right ventricle / left ventricle diameter ratio >1), tricuspid insufficiency, and pulmonary artery pressure >25 mm Hg by the cardiologist (15).
A hundred and ninety-eight patients were followed up through the patient registry system. After excluding the 4 patients whose data cannot be followed-up, 30-day mortality of 194 patients was evaluated.
Statistical Analysis
In a study, conducted with sleep questionnaires, the frequency of OSAS in the community was reported to be 4–27% (5,16). In the studies, the frequency of OSAS in patients with PTE was reported to be more than 29% (17). The sample size was calculated as 198 considering 95% power and 5% margin of error.
The study was carried out in consideration of the data belonging to the 198 patients. The data was completed by transferring to the IBM SPSS Statistics 23 program. While evaluating the study data, central tendency measures (mean, standard deviation) for numerical variables and frequency distributions (number, percentage) for categorical variables were given. The independent sample t test was used to determine whether there was a difference between the two groups and the chi-square test to examine the correlation between the two categorical variables. Logistic regression was used to analyze the effects on risk parameters.
RESULTS
Between the mentioned dates when the study has been executed, 198 patients who met the inclusion criteria among 606 patients who were hospitalized in our chest diseases clinics with the pre-diagnosis of PTE were included in the study and OSAS questionnaires were filled out.
The mean age of the patients was 58.2±16.3 (25–88). Eighty-four of them (42%) were over 65 years old. Their average weight was 81.0±15.8 (40–131) kg; mean neck circumference 42.4±4.4 (25–56.5) cm; average BMI 28.7±5.9 (15.5–57) kg/m2; 71 of them (35.8%) had a BMI over 30 kg/m2. 121 of them (61.1%) were male (Table 1).
Table 1.
Demographic information, clinical findings and comorbidities of the patients (n=198)
| Demographic informations | n (%)/ort ± ss |
|---|---|
| Age | 58.2±16.3 |
| Age >65 | 84 (42.4%) |
| Weight (kg) | 81.0±15.8 |
| Neck circumference | 42.4±4.4 |
| BMI | 28.7±5.9 |
| BMI >30 | 71 (35.8%) |
| Sex (male patients) | 121 (61.1%) |
| Smoking History | 124 (62.6%) |
| Clinical Findings | |
| Risk Factors | 164 (82.8%) |
| Immobilization | 154 (77.7%) |
| Malignancy | 32 (16.1%) |
| Surgery | 30 (15.1%) |
| Use of oral contraceptives | 3 (1.5%) |
| Trauma | 9 (4.5%) |
| History of DVT | 15 (7.5%) |
| Comorbidities | |
| Hypotyroidism | 13 (6.5%) |
| DM | 33 (16.6%) |
| HT | 82 (41.4%) |
| CVD | 8 (4%) |
| Malignancy | 32 (16.1%) |
| Hyperlipidemia | 3 (1.5%) |
| Chronic kidney disease | 1 (0.5%) |
| IHD | 31 (15.6%) |
| CHF | 19 (9.5%) |
| COPD | 31 (15.6%) |
| Asthma | 7 (3.5%) |
BMI: Body Mass Index; DVT: Deep Vein Thrombosis; DM: Diabetes Mellitus; Ht: Hypertension; CVD:Cerebrovascular Disease; IHD: Ischemic Heart Dişsease; CHF: Congestive Heart Failure; COPD: Chronic Obstructive Lung Disease
According to the PESI score, 64 of the patients were (32.3%) class 1, 50 (25.2%) were class 2, 42 (21.2%) were class 3, 26 (13.1%) were class 4, 16 (8%) were class 5. The sPESI score further revealed that, 118 (59.5%) of the patient were sPESI ≥1, 80 (40.4%) of the patients were sPESI <1. According to the WELLS score 27 (13.6%) were grouped as low risk, 113 (57%) as medium risk, 58 (29.2%) as high risk. D-dimer level of 169 (85.3%) of the patients and Troponin level of 44 (22.2%) of them were found to be high.
The average blood pressure range of the patients is 70.7±10.0 mmHg for diastolic and 117.0±17.2 mmHg for systolic. Oxygen saturation and pulse rate were within the normal range (94.8±4.1 and 87.6±15.6 respectively). Systolic pulmonary artery pressure was found to be higher than 25 mmHg in 148 of the patients (74.7%). The mean ejection fraction was 57.77±7.1 (25–75). Thirty-two of the patients (16.1%) were found to have right ventricular dysfunction. Other findings found with ECHO in 99 (50%) patients are as follows; tricuspid insufficiency, aortic insufficiency, left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial dilatation, biatrial dilatation, pericardial effusion, mitral stenosis, and left ventricular systolic dysfunction.
As a result of the completed questionnaires, high risk was found in 138 (69.6%) of the patients with Berlin questionnaire, in 174 (87.8%) with STOP-BANG questionnaire, in 152 (76.7%) with STOP questionnaire, and in 127 (64.1%) with Epworth sleepiness scale.
The mean age, weight and BMI, percentage of patients over 65 years of age, percentage of obesity, and percentage of female patients were significantly higher in the Berlin high-risk group compared to those in the Berlin low-risk group (p<0.05). In the Berlin high risk group, patients with sPESI and PESI scores are higher than in the Berlin low risk group (p<0.05). Patients in the Berlin high-risk group have a higher troponin levels and lower mean ejection fraction than patients in the Berlin low-risk group (p<0.05). The statistical comparison is shown in Table 2. The mean age and BMI of patients in the high risk group according to Epworth were significantly higher than those of patients over 65 years of age, patients with a diagnosis of malignancy and patients in the Epworth low risk group. In the Epworth high risk group, the number of patients with a diagnosis of HT, the number of patients with high risk PESI-sPESI score, and the number of patients with moderate-high risk WELLS score are higher than Epworth low risk group. The troponin levels were higher than the Epworth low-risk group in the Epworth high-risk group. The statistical comparison is shown in Table 3.
Table 2.
Comparison of PTE parameters between high risk and low risk patient groups with the Berlin score
| Demographic information | Berlin high risk | Berlin low risk | p value |
|---|---|---|---|
| Age | 62.39±14.98 | 48.55±15.34 | 0.001* |
| Age >65 | 74 (53.6%) | 10 (16.7%) | 0.001* |
| Weight | 82.9±15.95 | 76.56±14.63 | 0.009* |
| Neck Circumference | 42.71±4.41 | 41.59±4.18 | 0.098 |
| BMI | 29.94±6.29 | 25.7±3.39 | 0.001* |
| BMI >30 | 65 (47.1%) | 6 (10%) | 0.001* |
| Sex: Male | 74 (53.6%) | 47 (78.3%) | 0.001* |
| Female | 64 (46.4%) | 13 (21.7%) | |
| PESI low score | 66 (47.8%) | 48 (80.0%) | 0.001* |
| PESI high score | 72 (52.2%) | 12 (20.0%) | |
| sPESI score <1 | 41 (29.7%) | 39 (65%) | 0.001* |
| sPESI score ≥1 | 97 (70.3%) | 21 (35%) | |
| WELLS low score | 17 (12.3%) | 10 (16.7%) | 0.413 |
| WELLS score moderate-high | 121 (87.7%) | 50 (83.3%) | |
| Thrombus and ECHO findings | |||
| Main branch | 48 (34.8%) | 17 (28.3%) | 0.374 |
| Segmental branch | 90 (65.2%) | 43 (71.7%) | |
| Pulmonary hypertension | 97 (93.3%) | 51 (94.4%) | 1.000 |
| EF | 57.11±7.79 | 59.1±4.81 | 0.032* |
| Another ECHO finding | 70 (52.6%) | 29 (50%) | 0.738 |
| Dilatation | 26 (19.5%) | 6 (10.3%) | 0.117 |
| D-dimer level | 119 (98.3%) | 50 (94.3%) | 0.166 |
| Troponin level | 40 (33.6%) | 4 (7.8%) | 0.001* |
| proBNP | 150.19±591.49 | 49.43±323.24 | 0.126 |
BMI: Body Mass Index; ECHO: Echocardiography; EF: Ejection fraction; PESI: Pulmonary Embolism Severity Index; proBNP: b-type natriuretic peptide; sPESI: simplified PESI.
Table 3.
Comparison of PTE parameters between patient groups with Epworth score high risk and low risk
| Demographic Findings | Epworth high risk | Epworth low risk | p value |
|---|---|---|---|
| Age | 60.5±15.94 | 54.08±16.36 | 0.008* |
| Age >65 | 61 (48%) | 23 (32.4%) | 0.033* |
| Weight | 82.51±16.1 | 78.24±14.96 | 0.068 |
| Neck Circumference | 42.75±4.11 | 41.68±4.74 | 0.099 |
| BMI | 29.42±5.93 | 27.29±5.62 | 0.0105* |
| BMI >30 | 51 (40.2%) | 20 (28.2%) | 0.092 |
| Sex: Male | 72 (56.7%) | 49 (69%) | 0.088 |
| Female | 55 (43.3%) | 22 (31%) | |
| PESI Low Score | 65 (51.2%) | 49 (69.0%) | 0.015* |
| PESI High Score | 62 (68.8%) | 22 (31.0%) | |
| sPESI Score <1 | 41 (32.3%) | 39 (54.9%) | 0.002* |
| sPESI Score ≥1 | 86 (67.7%) | 32 (45.1%) | |
| WELLS Low Score | 12 (9.4%) | 15 (21.1%) | 0.022* |
| WELLS Score Moderate –High | 115 (90.6%) | 56 (78.9%) | |
| Thrombus and ECHO finding | |||
| Main branch | 44 (34.6%) | 21 (29.6%) | 0.466 |
| Segmental branch | 83 (65.4%) | 50 (70.4%) | |
| Pulmonary hypertension | 92 (93.9%) | 56 (93.3%) | 1.000 |
| EF | 57.81±7.18 | 57.54±6.91 | 0.802 |
| Another ECHO Findings | 63 (52.1%) | 36 (51.4%) | 0.932 |
| Dilatation | 23 (19%) | 9 (12.9%) | 0.273 |
| D-dimer level | 110 (96.5%) | 59 (98.3%) | 0.661 |
| Troponin level | 35 (31.3%) | 9 (15.5%) | 0.026* |
| proBNP | 158.31±612.85 | 49.09±302.36 | 0.096 |
BMI: Body Mass Index; ECHO: Echocardiography; EF: Ejection fraction; PESI: Pulmonary Embolism Severity Index; proBNP: b-type natriuretic peptide; sPESI: simplified PESI.
The mean age, weight, neck circumference, BMI, percentage of patients over 65 years of age, percentage of obese patients, percentage of patients with a diagnosis of HT and patients with a high PESI risk score are significantly higher than the STOP-BANG and STOP low risk groups compared with the STOP-BANG and STOP high risk groups. In the STOP-BANG high risk group female gender and WELLS moderate-high risk score are higher than the STOP-BANG low risk group. In the STOP high-risk group mean proBNP levels and percentage of patients with other ECHO findings were significantly higher than the STOP low-risk group. The statistical comparison is shown in Table 4.
Table 4.
Comparison of PTE parameters among patient groups with STOP and STOP-BANG scores at high risk and low risk
| Demographic findings | STOP-BANG high score | STOP-BANG low score | P value | STOP high score | STOP low score | P value |
|---|---|---|---|---|---|---|
| Age | 59.65±15.92 | 47.67±15.8 | 0.001* | 60.44±15.5 | 50.78±17.04 | 0.001* |
| Age >65 | 79 (45.4%) | 5 (20.8%) | 0.022* | 73 (48%) | 11 (23.9%) | 0.004* |
| Weight | 83.05±14.98 | 65.92±13.45 | 0.000* | 83.25±15.12 | 73.48±15.84 | 0.001* |
| Neck circumference | 42.97±4.08 | 37.98±3.82 | 0.000* | 42.95±4.27 | 40.45±4.13 | 0.001* |
| BMI | 29.21±5.89 | 24.59±4.16 | 0.000* | 29.54±6.02 | 25.71±4.4 | 0.001* |
| BMI >30 | 68 (39.1%) | 3 (12.5%) | 0.011* | 63 (41.4%) | 8 (17.4%) | 0.003* |
| Sex | ||||||
| Female | 113 (64.9%) | 8 (33.3%) | 0.003* | 91 (59.9%) | 30 (65.2%) | 0.514 |
| Male | 61 (35.1%) | 16 (66.7%) | 61 (40.1%) | 16 (34.8%) | ||
| PESI low score | 91 (52.3%) | 23 (95.8%) | 0.000* | 78 (51.3%) | 36 (78.3%) | 0.001* |
| PESI high score | 83 (47.7%) | 1 (4.2%) | 74 (47.7%) | 10 (21.7%) | ||
| sPESI score <1 | 66 (37.9%) | 14 (58.3%) | 0.056 | 58 (38.2%) | 22 (47.8%) | 0.242 |
| sPESI score ≥1 | 108 (62.1%) | 10 (41.7%) | 94 (61.8%) | 24 (52.2%) | ||
| WELLS low score | 20 (11.5%) | 7 (29.2%) | 0.018* | 18 (11.8%) | 9 (19.6%) | 0.181 |
| WELLS score moderate-high | 154 (88.5%) | 17 (70.8%) | 134 (88.2%) | 37 (80.4%) | ||
| Main branch | 55 (31.6%) | 10 (41.7%) | 0.325 | 48 (31.6%) | 17 (37%) | 0.496 |
| Segmental branch | 119 (68.4%) | 14 (58.3%) | 104 (68.4%) | 29 (63%) | ||
| Pulmonary hypertension | 131 (94.2%) | 17 (89.5%) | 0.344 | 110 (93.2%) | 38 (95%) | 1.000 |
| EF | 57.74±7.07 | 57.52±7.22 | 0.891 | 57.43±7.46 | 58.62±5.6 | 0.324 |
| Another ECHO findings | 89 (53%) | 10 (43.5%) | 0.393 | 82 (56.2%) | 17 (37.8%) | 0.031* |
| Dilatation | 30 (17.9%) | 2 (8.7%) | 0.378 | 25 (17.1%) | 7 (15.6%) | 0.806 |
| D-dimer level | 147 (97.4%) | 22 (95.7%) | 0.512 | 128 (97.7%) | 41 (95.3%) | 0.598 |
| Troponin level | 41 (27.3%) | 3 (15%) | 0.237 | 37 (28.2%) | 7 (17.9%) | 0.198 |
| proBNP | 133.18±559.08 | 20.92±78.59 | 0.328 | 150.87±596.24 | 16.54±67.83 | 0.007* |
BMI: Body Mass Index; ECHO: Echocardiography; EF: Ejection fraction; PESI: Pulmonary Embolism Severity Index; proBNP: b-type natriuretic peptide; sPESI: simplified PESI.
Comparison of the PTE severity and risk scores of the patients’ high risk group and low risk group, according to the OSAS survey scores, is summarized in Table 5.
Table 5.
Comparison of the PTE risk scores of patients groups with high risk and low risk according to the OSAS survey scores
| Berlin | Epworth | STOP-BANG | STOP | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| High | Low | P | High | Low | P | High | Low | P | High | Low | P | |||
| N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | |||||||
| Pulmonary embolism risk score | ||||||||||||||
| PESI | 1 | <65 | 31 (22.4) | 33 (55) | 0.000 | 32 (25.2) | 32 (45.1) | 0.046 | 49 (28,2) | 15 (62,5) | 0.001 | 42 (27,6) | 22 (47,8) | 0.021 |
| 2 | 66–85 | 35 (25.4) | 15 (25) | 33 (26) | 17 (23.9) | 42 (24.1) | 8 (33.3) | 36 (23.7) | 14 (30.4) | |||||
| 3 | 86–105 | 36 (26.1) | 6 (10) | 31 (24.4) | 11 (15.5) | 42 (24.1) | 0 (0) | 36 (23.7) | 6 (13) | |||||
| 4 | 106–125 | 23 (16.7) | 3 (5) | 18 (14.2) | 8 (11.3) | 26 (14.9) | 0 (0) | 24 (15.8) | 2 (4.3) | |||||
| 5 | ≥125 | 13 (9.4) | 3 (5) | 13 (10.2) | 3 (4.2) | 15 (8.6) | 1 (4.2) | 14 (9.2) | 2 (4.3) | |||||
| PESI | Low risk | <85 | 66 (47.8) | 48 (80.0) | 0.000 | 65 (51.2) | 49 (69.0) | 0.015 | 91 (52.3) | 23 (95.8) | 0.000 | 78 (51.3) | 36 (78.3) | 0.001 |
| High risk | ≥86 | 72 (52.2) | 12 (20.0) | 62 (68.8) | 22 (31.0) | 83 (47.7) | 1 (4.2) | 74 (47.7) | 10 (21.7) | |||||
| SPESI | Low risk | <1 | 41 (29.7) | 39 (65) | 0.000 | 41 (32.3) | 39 (54.9) | 0.002 | 66 (37.9) | 14 (58.3) | 0.056 | 58 (38.2) | 22 (47.8) | 0.242 |
| High risk | ≥1 | 97 (70.3) | 21 (35) | 86 (67.7) | 32 (45.1) | 108 (62.1) | 10 (41.7) | 94 (61.8) | 24 (52.2) | |||||
| WELLS | Low risk | <2 | 17 (12.3) | 10 (16.7) | 0.675 | 12 (9.4) | 15 (21.1) | 0.043 | 20 (11.5) | 7 (29.2) | 0.042 | 18 (11.8) | 9 (19.6) | 0.254 |
| Moderate risk | 2–6 | 79 (57.2) | 34 (56.7) | 73 (57.5) | 40 (56.3) | 100 (57.5) | 13 (54.2) | 86 (56.6) | 27 (58.7) | |||||
| High risk | ≥6 | 42 (30.4) | 16 (26.7) | 42 (33.1) | 16 (22.5) | 54 (31) | 4 (16.7) | 48 (31.6) | 10 (21.7) | |||||
| WELLS | Low | <2 | 17 (12.3) | 10 (16.7) | 0.413 | 12 (9.4) | 15 (21.1) | 0.022 | 20 (11.5) | 7 (29.2) | 0.018 | 18 (11.8) | 9 (19.6) | 0.181 |
| Moderate-high risk | 2–6 | 121 (87.7) | 50 (83.3) | 115 (90.6) | 56 (78.9) | 154 (88.5) | 17 (70.8) | 134 (88.2) | 37 (80.4) | |||||
PESI: Pulmonary Embolism Severity Index; sPESI: simplified PESI.
As a result of the logistic regression analysis applied to the parameters that are significant in the correlation between PTE severity and risk with OSAS survey scores; the PESI high risk score is 3.136 times higher and the sPESI high risk score is 4.394 times higher in the Berlin high risk group compared to the Berlin low risk group (p<0.05). In the Berlin high risk group, the diagnosis of DM is 8.402 times higher, the diagnosis of HT is 7.825 times, and the diagnosis of heart failure is 8.850 times higher than the Berlin low risk group (p<0.05). In the STOP-BANG high risk group, the PESI high risk score is 13.099 times higher than the STOP-BANG low risk group (p<0.05). The diagnosis of HT is 6.903 times higher in the STOP high risk group compared to the STOP low risk group (p<0.05). The Troponin level of those in the Berlin high-risk group is 5.949 times higher than the Berlin low-risk group (p<0.05). The other ECHO findings of those in the STOP high-risk group are 2.110 times higher than those in the STOP low-risk group (p<0.05). The correlation between the parameters showing the severity and risk of PTE and OSAS survey scores are shown in Table 6.
Table 6.
Correlation between parameters showing severity and risk of PTE and OSAS survey scores
| Cox & Snell R Square | Nagelkerke R Square | Exp (B) OR | P | 95% lower | 95% upper | ||
|---|---|---|---|---|---|---|---|
| PESI skoru | Berlin | 0.143 | 0.192 | 3.136 | 0.003* | 1.486 | 6.617 |
| STOP-BANG | 0.143 | 0.192 | 13.099 | 0.014* | 1.681 | 102.050 | |
| Omnibus p=0.000 | |||||||
| sPESI score | Berlin | 0.103 | 0.139 | 4.394 | 0.000* | 2.308 | 8.366 |
| Omnibus p=0.000 | |||||||
| WELLS score | Epworth | 0.025 | 0.046 | 2.567 | 0.025* | 1.127 | 5.849 |
| Omnibus p=0.025 | |||||||
| Troponin | Berlin | 0.081 | 0.119 | 5.949 | 0.001* | 2.002 | 17.684 |
| Omnibus p=0.000 | |||||||
| ECHO Findings | Stop | 0.024 | 0.032 | 2.110 | 0.033* | 1.063 | 4.189 |
| Omnibus p=0.030 | |||||||
| DM | Berlin | 0.068 | 0.114 | 8.402 | 0.004* | 1.941 | 36.366 |
| Omnibus p=0.000 | |||||||
| Hypertension | Berlin | 0.248 | 0.334 | 7.825 | 0.000* | 2.818 | 21.727 |
| Stop | 6.903 | 0.003* | 1.916 | 24.872 | |||
| Omnibus p=0.000 | |||||||
| CHF | Berlin | 0.040 | 0.086 | 8.850 | 0.036* | 1.153 | 67.902 |
| Omnibus p=0.004 | |||||||
CHF: Congestive Heart Failure; ECHO: Echocardiography; OSAS: Obstructive sleep apnea syndrome; PESI: Pulmonary Embolism Severity Index; PTE: Pulmonary thromboembolism; sPESI: simplified PESI.
In the study, the average hospitalization day of the patients was found to be 9.1±4.1 (3–34) days. During the first month follow-up period, 9 of the patients died and the 1-month mortality rate was found to be 4.5%. As a result of the Kaplan Maier analysis applied, a statistically significant difference was found between the Epworth groups in terms of life expectancy (p<0.05). Accordingly, those in the Epworth high group had a significantly higher mean life expectancy than those in the Epworth low group.
DISCUSSION
In our study, it is found that the prevalence of OSAS and the frequency of excessive daytime sleepiness have increased in patients with PTE compared to the normal population. It has been shown that the risk of OSAS is associated with Wells score indicating the risk of PTE; PESI, sPESI score, troponin and proBNP levels indicating PTE severity and prognosis. It was further revealed that excessive daytime sleepiness may be associated with the WELLS score.
There are also studies backing the correlation between PTE and OSAS in the literature (9–12). It is thought that OSAS affects vascular endothelial damage, venous stasis, hypercoagulability mechanisms and is associated with PTE (9). Hemodynamic changes associated with OSAS cause venous stasis and predispose patients to thrombosis (8). When patients diagnosed with OSAS were compared with patients without OSAS, it was found that D-dimer, thrombocyte, and fibrinogen levels increased and fibrinolytic activity decreased in patients diagnosed with OSAS (18). Intermittent hypoxia resulting from sleep fragmentations, intrathoracic pressure changes, recurrent hypercapnia, and recurrent desaturation reoxygenation periods play a role in the development of the procoagulant state (18). In addition, sedentary life and obesity, which play a role in the development of OSAS, induce procoagulant formation (19). This procoagulant activity contributes to an increased risk of PTE (18).
Although polysomnography is the gold standard method in the diagnosis of OSAS, standard questionnaires based on clinical findings, Epworth sleepiness scale, Berlin questionnaire, STOP, STOP-BANG questionnaires could also be guiding in practical use (5–7). In the literature, the sensitivity of the STOP-BANG questionnaire has been determined as 83.6% for AHI >5, 92.9% for AHI >15, and 100% for AHI >30 (20). The sensitivity of the Berlin questionnaire was 100% and the specificity was 91% (21). The sensitivity of the STOP-BANG questionnaire and the specificity of the Epworth questionnaire were found to be higher than other sleep questionnaires (22). It was found that the STOP-BANG questionnaire is a more accurate tool in determining the OSAS risk compared to other sleep questionnaires (22). The Berlin questionnaire for the detection of mild OSAS, the STOP-BANG and Berlin Questionnaire for the detection of moderate and severe OSAS have the highest specificity and sensitivity among sleep questionnaires (7). STOP-BANG has high sensitivity in detecting mild, moderate, and severe OSAS (7). STOP and STOP-BANG questionnaires were found to be applicable in determining mild, moderate and severe OSAS, with reasonable accuracy and high methodological validity (7). In our study, STOP-BANG, STOP, Berlin questionnaires were used to determine the risk of OSAS; while Epworth questionnaire was used to determine daytime sleepiness.
In the study in which the OSAS risk was determined by the Berlin questionnaire, 65% of the patient group with a diagnosis of PTE had a high OSAS risk, and 36% of the control group without PTE had a high OSAS risk (21). Similarly, OSAS risk in PTE patients was determined by the STOP –BANG questionnaire, and 69.3% of PTE patients were found to have a high OSAS risk (20). In the study in which sleep questionnaires were used in general, the prevalence of OSAS in the normal population was found to be 4.98–27.3% (5,16). In our study, using STOP-BANG questionnaire, which has the highest accuracy in determining the risk of OSAS, the group with high risk of OSAS was found to be 87.8%. The group with high risk of OSAS determined by other questionnaires were found to be 69.6% with the Berlin questionnaire and 76.7% with the STOP questionnaire. Epworth questionnaire evaluating excessive daytime sleepiness, which is a symptom with high sensitivity, although not specific for OSAS, was found to be positive in 64.1% of the patients (>10 points). It was found that the risk of OSAS and excessive daytime sleepiness increased in PTE patients compared to the normal population.
Obesity, older age, and male gender increase the prevalence of OSAS (23). In the study of Bostanci et al., it was found that patients with sleep-disordered breathing developed more severe intermittent hypoxia over the age of 65 than those below the age of 65 (24). In our study, excessive daytime sleepiness detected by Epworth questionnaire in patients with PTE; and OSAS risk determined by the Berlin, STOP, STOP-BANG questionnaire was associated with age. At the same time, the risk of OSAS detected by Berlin, STOP, STOP-BANG questionnaire and excessive daytime sleepiness determined by Epworth questionnaire were found to be higher over 65 years of age than under 65 years of age.
Obesity is one of the most important known risk factors for OSAS and cardiovascular diseases (23). Obesity is thought to induce procoagulant activity and increase the risk of PTE (9). It has been found that the risk of OSAS in PTE patients is associated with BMI (20). In the literature, it has been found that the prevalence of OSAS in obese patients is higher than in non-obese patients (23). In our study, it was found that the OSAS risk determined by the Berlin, STOP, and STOP-BANG questionnaire was associated with the BMI. At the same time, it was found that the risk of OSAS, which was determined by the Berlin, STOP, and STOP-BANG questionnaire, increased in obese patients compared to non-obese patients.
It has been stated in the literature that OSAS may cause thrombus formation and coagulation disorders due to sleep fragmentations and nocturnal hypoxia (25). It has also been shown that OSAS is associated with sPESI score and may affect the prognosis of PTE (12). According to an other study in the literature, PESI score was found to be higher in PTE patients in the presence of moderate and severe OSAS compared to the presence of mild OSAS, as a result, OSAS was found to be a risk factor for the risk and severity of PTE (26). Similarly, in these patients, the sPESI score was found to be higher in the presence of moderate and severe OSAS compared to the presence of mild OSAS, and it was determined that OSAS aggravated the severity of PTE (11). In our study, it was found as a result of the logistic regression test that the OSAS risk determined by the Berlin questionnaire was associated with the PESI and sPESI score, and it was found in accordance with the literature. Daytime sleepiness determined by the Epworth questionnaire was found to be associated with the WELLS score as a result of the logistic regression test and was found to be consistent with the literature. Finally, in line with the literature it was found that the OSAS risk determined by the STOP-BANG questionnaire was associated with the PESI score.
Obstructive sleep apnea syndrome is a procoagulant disease and increases pulmonary artery obstruction due to hypoxia (9,19). It is thought that OSAS leads to heart failure by increasing sympathetic activity and decreasing intrathoracic pressure (9). It has been shown that intrathoracic pressure changes increase venous return in the right ventricle, intraventricular septum shifts to the left, prevents left ventricular filling, decreasing heart rate and cardiac output during each apnea and HT causes arrhythmias because it increases sympathetic activity (9). It has been found that OSAS also plays a role in the development of ventricular remodeling and heart failure by increasing cardiac stress with oxidative stress and inflammatory mechanisms (9). In PTE, an increase in pulmonary vascular resistance is observed as a result of anatomical obstruction and vasoconstriction (9). Right ventricular volume and pressure increase, wall tension increases (9). As the tension of cardiomyocytes increases, proBNP is released from cardiomyocytes (27). Troponin release occurs as a result of the increase in the oxygen demand of the right ventricle (28). Heart failure associated with PTE contributes to the development of OSAS by increasing pharyngeal collapse and decreasing pharyngeal calibration (26). In the literature, cardiovascular results of OSAS in patients diagnosed with PTE have been investigated and it has been stated that OSAS may be associated with right ventricular dysfunction in patients diagnosed with PTE (29). Similarly, it has been reported that OSAS is associated with ejection fraction, troponin level, and the severity of current cardiopulmonary disease in patients with a diagnosis of PTE (11). It has been found that the severity of OSAS in PTE patients is associated with N-terminal B-type natriuretic peptide (NT-proBNP) (12). In our study, it was found as a result of the logistic regression test that the OSAS risk determined by the Berlin questionnaire was associated with the troponin levels and the presence of heart failure, and it was found to be compatible with the literature. Also in our study the correlation between troponin and Epworth questionnaire and proBNP levels and STOP score was shown.
A hundred and eighteen (59.5%) of the patients included in our study were found as sPESI ≥1. With a follow-up of 1 month it was observed that the mortality rate was 4.5%. When we compared our study with the studies done by Geissenberger et al. percentage of patients with a sPESI score ≥1 were less (12). In the study done by Ghiasi et al., no correlation was found between 30-day mortality and OSAS risk in PTE patients who were followed up for 1 month (20). In the study done by Geissenberger et al., the effect of OSAS on prognosis was investigated in PTE patients, and the patients were followed up for an average of 53 months, and the mortality rate was found to be significantly higher in the group with AHI ≥15 (12). The mortality rates in the studies done by Ghiasi et al. and Geissenberger et al. were 24% and 10.9% respectively, and the mortality rates were higher than our study because unlike these studies, patients who were given thrombolytic therapy were not included in our study (12,20). In the literature, the 1-month mortality rate of PTE patients was reported as 4%, while the mortality rate of our study was 4.5% thus it was observed that the mortality rate in our study population was compatible with the literature (30). Studies involving massive and hemodynamically unstable patients with longer follow-up are required to show the effect of OSAS on mortality in PTE patients.
The most important limitation of our study is that PSG which is the gold standard method in the diagnosis of OSAS was not used. Polysomnography is a costly and hardly available method. In our study, we used sleep questionnaire studies, although it was known that their usage is not recommended to diagnose OSAS in adults. They are applicable, inexpensive and validated methods in daily patient practice, to determine the risk of OSAS (31). Patients with massive PTE and hemodynamic instability were not included in the study. If this group of patients were also included, the correlation between OSAS and PTE could be even more obvious and probably its effect on mortality could have been different. Furthermore our study lacked a control group to compare the prevalence of OSAS but instead we used reported prevelance in literature. Although the sample size of this study was not very large, comparison of different tests at the same group of patients contributes to the literature.
In conclusion, it was thought that OSAS risk is more common in patients with PTE than in the general population, so it may be a risk factor for PTE. The risk of OSAS was found to be associated with the WELLS score, which indicates the risk of PTE, and the PESI and sPESI scores indicating its severity. It has been shown that the risk of OSAS can increase the risk of PTE and may aggravate its severity. Obstructive sleep apnea syndrome risk was found to be associated with troponin and proBNP levels indicating right ventricular dysfunction and prognosis in these patients. Although it was shown in our study that the risk of OSAS can aggravate the prognosis of PTE, it is thought that larger studies showing the effect of OSAS, diagnosed by polysomnography, on the severity and prognosis of PTE are needed.
Footnotes
Ethics Committee Approval: The approval of the Yedikule Chest Diseases and Chest Surgery Training and Research Hospital Ethical Committee was obtained for the study (Decision number: 22.06.2018/1324).
Informed Consent: Informed consent was obtained from all individual participants included in the study.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept- ÖK; Design- CÖ, SNS; Supervision- CÖ, ŞA; Resource- SNS, CÖ; Materials- STO, MS; Data Collection and/or Processing- STO, ÖK; Analysis and/or Interpretation- ÖK, SNS; Literature Search- MS, STO; Writing- ÖK, CÖ, ŞA; Critical Reviews- CÖ, ŞA.
Conflict of Interest: The authors declared that there is no conflict of interest.
Financial Disclosure: This study received no funding.
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