Abstract
Aim: Patients with obstructive sleep apnea (OSA) are likely to show increased arterial stiffness and progressive systemic atherosclerosis. Chest radiography reveals atherosclerotic changes in the aorta via measurement of aortic knob width. However, to our knowledge, aortic knob width in patients with OSA has never been evaluated.
Methods: We measured the aortic knob width in chest radiographs of 549 patients (age: 52.5 ± 13.2 years; 69 women) who underwent overnight polysomnography. Moreover, we evaluated the association between aortic knob width and other clinical characteristics, including cardio–ankle vascular index (CAVI) and apnea–hypopnea index (AHI). Multivariate linear regression analysis was conducted to identify factors associated with aortic knob width.
Results: A significant direct correlation between aortic knob width and CAVI and between aortic knob width and AHI was observed. In multivariate linear regression analysis, either CAVI or AHI was independently associated with aortic knob width (p = 0.004 and p < 0.001, respectively) in addition to age, male gender, body mass index, and systolic blood pressure.
Conclusion: A significant independent correlation between aortic knob width and OSA severity was observed. Our findings suggest that an increase in the aortic knob width suggests atherosclerotic changes in the aorta and may be associated with OSA and increased arterial stiffness.
Keywords: Obstructive sleep apnea, Aortic knob, Atherosclerosis, Arterial stiffness, Cardio–ankle vascular index
See editorial vol. 27: 499–500
Introduction
Obstructive sleep apnea (OSA) is a common disease and has been considered a critical issue due to its cardiovascular consequences. Patients with OSA experience repetitive episodes of blood pressure (BP) elevation in response to each apneic event, which prevents the physiological nighttime BP dip (i.e., non-dipping). In addition, OSA is associated with daytime hypertension1, 2). Daytime and nighttime BP elevation may stiffen the arteries in combination with increased oxidative stress3), which is caused by repetitive episodes of intermittent hypoxia and reoxygenation associated with apneas and hypopneas. Moreover, increased oxidative stress may facilitate atherosclerosis by impairing endothelial function and enhancing the inflammatory cascade, which further stiffens the arteries4). Indeed, arterial stiffness parameters, such as pulse wave velocity and cardio–ankle vascular index (CAVI), are elevated in patients with OSA5, 6). Additionally, repetitive respiratory efforts during obstructive apneas increase negative intrathoracic pressure7). This negative intrathoracic pressure in combination with increased arterial stiffness and atherosclerosis can lead to aortic dilatation and possibly aortic diseases, including aortic aneurysm and aortic dissection8, 9).
The aortic knob is composed of the descending thoracic aorta, as visualized in chest radiography. Dilatation and calcification of the aortic knob are considered to be atherosclerotic changes. Previous studies have revealed the correlation between aortic knob width and the severity of arterial stiffness or atherosclerotic diseases in patients with hypertension and coronary artery disease (CAD)10–12), as well as several markers of target organ damage13). However, to our knowledge, there have been no studies focusing on aortic knob width in patients with OSA or on the association between aortic knob width and OSA severity. Therefore, this study has been conducted to test our three hypotheses: (1) that aortic knob width increases as OSA severity increases; (2) that there is a dose–response relationship among apnea–hypopnea index (AHI), OSA severity, and aortic knob width; and (3) that this relationship is independent of arterial stiffness parameters and other factors associated with atherosclerosis.
Methods
Study Population
This study was a post hoc analysis of a prospectively collected dataset14). In this analysis, we collected data of participants who underwent overnight polysomnography and CAVI measurements the day after the procedure. Consecutive adults from July 2006 to December 2007 who underwent chest radiography on the same day as that of overnight polysomnography were included. The exclusion criteria were as follows: (1) chest radiograph not properly centered; (2) heart failure; (3) cerebrovascular disease with a neurologic deficit; (4) known aortic disease; (5) peripheral vascular disease or ankle–brachial index ≤ 0.9 at the time of CAVI measurement; (6) open chest surgery, and (7) receiving dialysis. The ethics committee of Toranomon Hospital approved this study (No. 787).
Data Collection
Medical history and anthropometric data were collected from patient records. After fasting overnight, all participants underwent blood tests, including glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and hemoglobin A1c. The presence of hypertension was defined based on the prescription of antihypertensive agents or when systolic/diastolic BP was ≥ 140/90 mmHg. The presence of diabetes mellitus was defined based on the prescription of anti-diabetic medication or when fasting glucose level was ≥ 126 mg/dL.
Aortic Knob Width
All patients underwent chest radiography in the posteroanterior view. An examiner who was blinded to the results of the patient's arterial stiffness measurements or OSA severity reviewed the chest radiographs. The widest point of the ascending aortic knob was measured along the horizontal line from the point of the lateral edge of the trachea to the left lateral wall of the aortic knob (Fig. 1). Intra-examiner reproducibility was determined by measuring the aortic knob width two times at least 1 month apart for ten randomly selected patients. Similarly, inter-examiner reproducibility was determined by measuring the same samples by another examiner.
Fig. 1.
Aortic knob width was measured along the horizontal line from the point of the lateral edge of the trachea to the left lateral wall of the descending aorta.
CAVI Measurement
CAVI was measured (VaSera VS-1000; Fukuda Denshi; Tokyo, Japan) using previously described methods15). Participants rested in the supine position for 5 min before measurement was performed. Electrocardiography, phonocardiography, and pressures and waveforms of the brachial and ankle arteries were obtained. CAVI was automatically calculated. Moreover, BP records used in the study were obtained through CAVI measurements.
Polysomnography
All participants underwent overnight polysomnography using a digital polygraph (SomnoStar Alpha Sleep System, SensorMedics Corp., Yorba Linda, CA, USA) equipped with electroencephalogram, electrooculogram, electromyogram, finger pulse oximeter, respiratory effort sensors, and airflow sensors. Accepted definitions and scoring methods were used to diagnose OSA16). OSA severity was classified according to AHI as follows: AHI < 5 events/h indicated no OSA; 5 ≤ AHI < 15 events/h indicated mild OSA; 15 ≤ AHI < 30 events/h indicated moderate OSA; and ≥ 30 events/h indicated severe OSA.
Statistical Analysis
Patients were assigned to four groups based on OSA severity. Continuous variables were expressed as mean and standard deviation or median and interquartile range, and categorical variables were expressed as numbers and percentages. Williams' test and Cochran–Armitage test were used to analyze the trend for continuous variables and percentages for categorical variables, respectively. Inter- and intra-examiner reproducibility were analyzed using the intraclass correlation coefficient (ICC). Univariate correlation analyses between aortic knob width and the following clinical variables were conducted: age, gender, body mass index (BMI), systolic BP, smoking history, presence of known CAD, CAVI measurement, AHI, total cholesterol triglycerides, high-density lipoprotein cholesterol, and hemoglobin A1c. Variables associated with aortic knob width in the univariate correlation analysis (p < 0.1) were used in the multivariate regression analysis. The final multivariate regression model used to identify the correlates of aortic knob width was determined by stepwise selection and forward/backward elimination with maximized Akaike information criterion. In addition, variance inflation factor (VIF) was calculated to identify possible multicollinearity between variables. Statistical analyses were performed using R software, version 3.4.3 (R Core Team, Austria). Two-sided p values < 0.05 were considered statistically significant.
Results
Patient characteristics are summarized in Table 1. A total of 549 patients were included in this study, with 45 (8.2%) showing no OSA; 68 (12.4%), mild OSA; 153 (27.9%), moderate OSA; and 283 (51.5%), severe OSA. The mean patient age was 52.5 ± 13.2 years, and 480 (87.4%) of the patients were men. An increasing trend in age and BMI was observed, which corresponded to an increase in OSA severity (p for trend < 0.001). The prevalence of hypertension and diabetes mellitus increased with an increase in OSA severity (p < 0.001 and p = 0.004, respectively).
Table 1. Baseline and clinical characteristics of patients.
| OSA severity | No (n = 45) |
Mild (n = 68) |
Moderate (n = 153) |
Severe (n = 283) |
p for trend |
|---|---|---|---|---|---|
| Age, years | 43.1 ± 15.1 | 52.5 ± 11.7 | 54.5 ± 12.4 | 52.9 ± 13.1 | < 0.001 |
| Male, n (%) | 29 (64) | 57 (84) | 131 (86) | 263 (96) | < 0.001 |
| BMI, kg/m2 | 23.5 ± 3.8 | 25.5 ± 4.0 | 25.9 ± 3.5 | 27.1 ± 4.2 | < 0.001 |
| Smoker, n (%) | 27 (60) | 33 (49) | 82 (54) | 141 (50) | 0.352 |
| Known CAD, n (%) | 0 (0) | 1 (1) | 5 (3) | 10 (4) | 0.155 |
| Hypertension, n (%) | 7 (16) | 31 (46) | 83 (54) | 149 (53) | < 0.001 |
| Diabetes mellitus, n (%) | 0 (0) | 3 (4) | 8 (5) | 29 (10) | 0.004 |
| Glucose, mg/dL | 96.8 ± 12.2 | 102.1 ± 22.3 | 107.7 ± 30.4 | 104.1 ± 21.0 | 0.069 |
| Hemoglobin A1c, % | 5.3 ± 1.3 | 5.3 ± 0.7 | 5.4 ± 0.6 | 5.5 ± 0.7 | 0.163 |
| Total cholesterol, mg/dL | 187.3 ± 35.4 | 201.0 ± 30.3 | 199.8 ± 33.4 | 198.8 ± 35.0 | 0.047 |
| Triglycerides, mg/dL | 132.4 ± 77.9 | 154.9 ± 83.0 | 151.8 ± 91.3 | 178.0 ± 153.7 | 0.032 |
| HDL cholesterol, mg/dL | 51.2 ± 11.3 | 49.6 ± 12.6 | 48.2 ± 12.5 | 46.4 ± 12.1 | 0.020 |
| Systolic BP, mmHg | 124.9 ± 15.1 | 130.8 ± 18.1 | 131.4 ± 17.0 | 133.2 ± 15.7 | 0.002 |
| Diastolic BP, mmHg | 78.0 ± 11.6 | 83.2 ± 10.5 | 84.0 ± 10.7 | 84.6 ± 10.7 | < 0.001 |
| CAVI | 7.0 ± 1.5 | 7.5 ± 1.2 | 7.7 ± 1.4 | 7.6 ± 1.4 | 0.011 |
| Antihypertensive drug | 1 (2) | 26 (38) | 68 (44) | 121 (43) | < 0.001 |
| Antidiabetic drug | 0 (0) | 1 (1) | 1 (1) | 2 (1) | 0.963 |
| Aortic knob width, mm | 32.9 ± 5.4 | 35.9 ± 5.0 | 37.5 ± 5.0 | 38.1 ± 4.9 | < 0.001 |
| AHI, /h | 2.2 ± 1.6 | 10.2 ± 3.0 | 23.1 ± 4.2 | 51.3 ± 15.8 | < 0.001 |
| Arousal index, /h | 18.2 ± 10.5 | 22.9 ± 9.4 | 28.9 ± 10.9 | 50.0 ± 18.6 | < 0.001 |
| ODI (3%), /h | 0.5 ± 1.0 | 4.7 ± 3.7 | 14.6 ± 6.6 | 42.2 ± 19.4 | < 0.001 |
| Lowest SpO2, % | 90.5 ± 3.9 | 80.8 ± 15.2 | 76.6 ± 14.9 | 73.3 ± 10.7 | < 0.001 |
AHI, apnea-hypopnea index; BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; CAVI, cardio–ankle vascular index; HDL, high-density lipoprotein; ODI, oxygen desaturation index; OSA, obstructive sleep apnea; SpO2, peripheral oxygen saturation.
ICC of intra- and inter-examiner reproducibility was 0.96 and 0.92, respectively, in ten randomly selected patients (age: 51.9 ± 14.0 years; 9 men; aortic knob width 37.9 ± 4.2 mm).
The mean aortic knob width was 37.2 ± 5.2 mm. An increase in aortic knob width and CAVI corresponded to an increase in OSA severity (p < 0.001 and p = 0.011, respectively) (Fig. 2, Table 1). In univariate analyses (Table 2), aortic knob width was positively and significantly correlated with CAVI (r = 0.37, p < 0.001, Supplemental Fig. 1). Similarly, aortic knob width was significantly correlated with AHI (r = 0.25, p < 0.001), arousal index (r = 0.26, p < 0.01), and 3% ODI (r = 0.24, p < 0.01), as well as several clinical variables. In multivariate linear regression analysis, the known CAD, hemoglobin A1c, antihypertensive drug, arousal index, and 3% oxygen desaturation index were omitted from the final model (Table 3) after stepwise selection. Model analysis revealed that age, BMI, systolic BP, CAVI, AHI, and male gender were independent correlates of aortic knob width. VIF of these variables were 1.9, 1.5, 1.2, 2.1, 1.2, and 1.1, respectively.
Fig. 2.
Box plots of aortic knob width according to the severity of obstructive sleep apnea (OSA).
Table 2. Correlations between aortic knob width and clinical variables.
| Variables | Correlation coefficient | p value |
|---|---|---|
| Age | 0.46 | < 0.001 |
| Male | 0.08 | 0.064 |
| BMI | 0.21 | < 0.001 |
| Systolic BP | 0.31 | < 0.001 |
| Smoker | 0.01 | 0.865 |
| Known CAD | 0.09 | 0.027 |
| Hemoglobin A1c | 0.21 | < 0.001 |
| Total cholesterol | −0.02 | 0.669 |
| Triglycerides | −0.01 | 0.906 |
| CAVI | 0.37 | < 0.001 |
| Antihypertensive drug | 0.20 | < 0.001 |
| Antidiabetic drug | 0.04 | 0.308 |
| AHI | 0.25 | < 0.001 |
| Arousal index | 0.26 | < 0.001 |
| ODI (3%) | 0.24 | < 0.001 |
| Lowest SpO2 | −0.14 | 0.001 |
AHI, apnea–hypopnea index; BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; CAVI, cardio–ankle vascular index; ODI, oxygen desaturation index; SpO2, peripheral oxygen saturation.
Supplemental Fig. 1.
The correlation between aortic knob width and cardio–ankle vascular index (CAVI).
Table 3. Multivariate linear regression analysis of aortic knob width.
| Partial correlation coefficient | p value | |
|---|---|---|
| Age | 0.37 | < 0.001 |
| BMI | 0.26 | < 0.001 |
| Systolic BP | 0.19 | < 0.001 |
| CAVI | 0.12 | 0.004 |
| AHI | 0.15 | < 0.001 |
| Male | 0.15 | < 0.001 |
AHI, apnea–hypopnea index; BMI, body mass index; BP, blood pressure; CAVI, cardio–ankle vascular index.
Discussion
To the best of our knowledge, this is the first study to examine the association between aortic knob width and OSA severity. The findings of this study provide several important insights that may help explain the associations between OSA and arterial stiffness/atherosclerosis or aortic diseases. First, aortic knob width increased as OSA severity increased. A significant dose–response relationship between aortic knob width and AHI was observed. Second, there was a significant correlation between aortic knob width and the arterial stiffness parameter, CAVI, which is consistent with the report of another study including 374 patients with hypertension10). Third, multivariate regression analysis revealed that in patients with OSA, AHI was associated with aortic knob width independent of CAVI. These findings suggest that OSA may increase aortic knob width through an increase in arterial stiffness and other mechanisms. One such mechanism could be apnea without respiratory effort leading to aortic dilatation due to negative intrathoracic pressure17).
Clinical implications of increased aortic knob width have been suggested in previous studies targeting several patient populations other than OSA. An independent direct correlation between aortic knob width and central systolic BP has been shown in patients with known or suspected CAD18). Erkan et al. have reported that in 126 patients with hypertension, there was a strong direct correlation between aortic knob width and one of the well-known atherosclerotic parameters, carotid intima-media thickness (IMT)11). Yun et al. have shown that in patients with CAD, aortic knob width was significantly and directly correlated with the extent of CAD12). These results suggested that aortic knob width could indicate the degree of early atherosclerosis, including arterial stiffness, as well as the progression and extent of systemic atherosclerotic diseases, including CAD. Presumably, in patients with OSA, increased arterial stiffness, IMT19, 20), and CAD progression21) can occur through pathophysiological mechanisms of OSA, such as increased oxidative stress and enhanced inflammatory response3). The dose–response relationship between aortic knob width and OSA severity in the present study suggests another means of stiffening or sclerotic process of the aorta in association with OSA.
The effect of negative intrathoracic pressure on the aorta in patients with OSA has been demonstrated based on high prevalence of OSA in patients with aortic dilatation, aneurysm, and dissection. Indeed, several studies have shown a close association between aortic disease and OSA. Sampol et al.9) have suggested that OSA is common in patients with aortic dissection. Another study has revealed that the prevalence of OSA in patients with abdominal aortic aneurysm was high and that OSA was a risk factor for the progression of the aneurysm8). In these studies, exaggerated negative intrathoracic pressure during obstructive respiratory events was speculated to play an important role in the possible link between OSA and aortic diseases in addition to the basal atherosclerotic change in the aorta. To further substantiate the adverse effects of exaggerated intrathoracic pressure on the aorta, an association between the OSA severity and increased aortic diameter has been reported in individuals without aortic disease22). These associations can be explained by accompanying hypertension. Hypertension is common in patients with OSA, and it is the most important cause of dilatation of the aorta in patients with aortic disease, such as thoracic aortic aneurysm. In addition, OSA promotes hypertension23). Therefore, hypertension due to OSA contributes to the dilatation of the aorta and development of aortic disease. Indeed, in our multivariate regression analysis, systolic BP was a significant correlate of aortic knob width independent of OSA severity and CAVI.
The association between aortic knob width and CAVI or AHI can emphasize the importance of aortic knob width in a real clinical setting. In patients with OSA, the degree of atherosclerosis may be estimated by measuring aortic knob width. This information can help stratify patients according to their underlying atherosclerotic risk. Furthermore, simple examinations, such as chest radiography, may provide novel information regarding OSA and may serve as a tool in its screening. Many patients with OSA remain undiagnosed24, 25), which represents an issue that needs to be resolved to prevent future cardiovascular diseases23). Although there are several parameters indicating the severity of atherosclerosis, most of them are evaluated to measure atherosclerosis alone. However, chest radiography is widely used in various clinical settings and during health checkups unrelated to OSA. Radiography can in fact provide information regarding OSA, which should be of interest to investigate in greater detail.
Several limitations of this study should be noted. First, because we excluded patients with aortic disease according to their medical history, some patients with dilated aortic knob width may have undiagnosed aortic disease, and this may have led to selection bias. In addition, although multivariate analysis was performed, there may be unknown confounding factors. Second, we cannot determine whether the association between aortic knob width and OSA severity includes a causal relationship due to the cross-sectional nature of this study. If aortic knob width changes following OSA treatment, it may confirm the causality between OSA and increased aortic knob width. Therefore, further longitudinal studies are warranted. Finally, we did not include any data on intrathoracic pressure or oxidative stress, which may act as mediating factors in the association between OSA severity and aortic knob width; moreover, there may be other unknown mechanisms. Collectively, this study is to some extent a proof-of-concept study, and results should be interpreted with caution.
Conclusion
In conclusion, the dilatation of aortic knob width detected using chest radiography was significantly correlated with OSA severity, independent of blood pressure and arterial stiffness. Therefore, dilated aortic knob width may be an indicator of severe OSA.
Acknowledgments
This study was partly supported by a Grant-in-Aid for Scientific Research (C) [Grant Number 26507010]; JSPS KAKENHI Grant Number JP17K09527; a grant to The Intractable Respiratory Diseases and Pulmonary Hypertension Research Group, from the Ministry of Health, Labor and Welfare (H29-027), and by MEXT*-Supported Program for the Strategic Research Foundation at Private Universities, 2014–2018 (*Ministry of Education, Culture, Sports, Science and Technology). These funding sources have no other roles in this study.
COI
Drs. Kasai, Tomita, and Ishiwata are affiliated to a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. Dr. Daida received manuscript fees, research funds, and scholarship funds from Kirin Co. Ltd.; Kaken Pharmaceutical Co., Ltd.; Abbott Japan Co., Ltd.; Astellas Pharma Inc.; Astrazeneca K.K.; Bayer Yakuhin, Ltd.; Boston Scientific Japan K.K.; Bristol-Myers Squibb; Daiichi Sankyo Company; MSD K.K.; Pfizer Inc.; Philips Respironics; Sanofi K.K.; and Takeda Pharmaceutical Co. Ltd. The other authors report no conflicts of interest.
References
- 1). Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, D'Agostino RB, Newman AB, Lebowitz MD, Pickering TG: Association of sleep-disordered breathing, sleep apnea, and hypertension in a large communitybased study. Sleep Heart Health Study. JAMA, 2000; 283: 1829-1836 [DOI] [PubMed] [Google Scholar]
- 2). Grote L, Ploch T, Heitmann J, Knaack L, Penzel T, Peter JH: Sleep-related breathing disorder is an independent risk factor for systemic hypertension. Am J Respir Crit Care Med, 1999; 160: 1875-1882 [DOI] [PubMed] [Google Scholar]
- 3). Lavie L: Obstructive sleep apnoea syndrome--an oxidative stress disorder. Sleep Med Rev, 2003; 7: 35-51 [DOI] [PubMed] [Google Scholar]
- 4). Masugata H, Senda S, Murao K, Inukai M, Himoto T, Hosomi N, Okada H, Goda F: Association between urinary 8-hydroxydeoxyguanosine, an indicator of oxidative stress, and the cardio-ankle vascular index in hypertensive patients. J Atheroscler Thromb, 2012; 19: 747-755 [PubMed] [Google Scholar]
- 5). Kotani K: Cardio-Ankle Vascular Index and Its Potential Clinical Implications for Sleep Apnea. Pulse (Basel), 2014; 1: 139-142 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6). Wang J, Yu W, Gao M, Zhang F, Gu C, Yu Y, Wei Y: Impact of Obstructive Sleep Apnea Syndrome on Endothelial Function, Arterial Stiffening, and Serum Inflammatory Markers: An Updated Meta-analysis and Metaregression of 18 Studies. J Am Heart Assoc, 2015; 4: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7). Shiomi T, Guilleminault C, Stoohs R, Schnittger I: Leftward shift of the interventricular septum and pulsus paradoxus in obstructive sleep apnea syndrome. Chest, 1991; 100: 894-902 [DOI] [PubMed] [Google Scholar]
- 8). Mason RH, Ruegg G, Perkins J, Hardinge M, Amann-Vesti B, Senn O, Stradling JR, Kohler M: Obstructive sleep apnea in patients with abdominal aortic aneurysms: highly prevalent and associated with aneurysm expansion. Am J Respir Crit Care Med, 2011; 183: 668-674 [DOI] [PubMed] [Google Scholar]
- 9). Sampol G, Romero O, Salas A, Tovar JL, Lloberes P, Sagales T, Evangelista A: Obstructive sleep apnea and thoracic aorta dissection. Am J Respir Crit Care Med, 2003; 168: 1528-1531 [DOI] [PubMed] [Google Scholar]
- 10). Korkmaz L, Erkan H, Korkmaz AA, Acar Z, Agac MT, Bektas H, Akyuz AR, Adar A, Celik S: Relationship of aortic knob width with cardio-ankle vascular stiffness index and its value in diagnosis of subclinical atherosclerosis in hypertensive patients: a study on diagnostic accuracy. Anadolu Kardiyol Derg, 2012; 12: 102-106 [DOI] [PubMed] [Google Scholar]
- 11). Erkan H, Korkmaz L, Agac MT, Acar Z, Kiris A, Erkan M, Korkmaz AA, Vatan B, Akyuz AR, Cnarka H: Relation between carotid intima-media thickness and aortic knob width in patients with essential hypertension. Blood Press Monit, 2011; 16: 282-284 [DOI] [PubMed] [Google Scholar]
- 12). Yun KH, Jeong MH, Oh SK, Park EM, Kim YK, Rhee SJ, Lee EM, Yoo NJ, Kim NH, Keun Y, Jeong JW: Clinical significance of aortic knob width and calcification in unstable angina. Circ J, 2006; 70: 1280-1283 [DOI] [PubMed] [Google Scholar]
- 13). Rayner BL, Goodman H, Opie LH: The chest radiograph. A useful investigation in the evaluation of hypertensive patients. Am J Hypertens, 2004; 17: 507-510 [DOI] [PubMed] [Google Scholar]
- 14). Kumagai T, Kasai T, Kato M, Naito R, Maeno KI, Kasagi S, Kawana F, Ishiwata S, Narui K: Establishment of the cardio-ankle vascular index in patients with obstructive sleep apnea. Chest, 2009; 136: 779-786 [DOI] [PubMed] [Google Scholar]
- 15). Shirai K, Utino J, Otsuka K, Takata M: A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb, 2006; 13: 101-107 [DOI] [PubMed] [Google Scholar]
- 16). Silber MH, Ancoli-Israel S, Bonnet MH, Chokroverty S, Grigg-Damberger MM, Hirshkowitz M, Kapen S, Keenan SA, Kryger MH, Penzel T, Pressman MR, Iber C: The visual scoring of sleep in adults. J Clin Sleep Med, 2007; 3: 121-131 [PubMed] [Google Scholar]
- 17). Gaisl T, Bratton DJ, Kohler M: The impact of obstructive sleep apnoea on the aorta. Eur Respir J, 2015; 46: 532-544 [DOI] [PubMed] [Google Scholar]
- 18). Higaki T, Kurisu S, Watanabe N, Ikenaga H, Shimonaga T, Iwasaki T, Ishibashi K, Dohi Y, Fukuda Y, Kihara Y: Usefulness of aortic knob width on chest radiography to predict central hemodynamics in patients with known or suspected coronary artery disease. Clin Exp Hypertens, 2015; 37: 440-444 [DOI] [PubMed] [Google Scholar]
- 19). Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF: Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med, 2007; 176: 706-712 [DOI] [PubMed] [Google Scholar]
- 20). Kasai T, Inoue K, Kumagai T, Kato M, Kawana F, Sagara M, Ishiwata S, Ohno M, Yamaguchi T, Momomura S, Narui K: Plasma pentraxin3 and arterial stiffness in men with obstructive sleep apnea. Am J Hypertens, 2011; 24: 401-407 [DOI] [PubMed] [Google Scholar]
- 21). Inami T, Seino Y, Otsuka T, Yamamoto M, Kimata N, Murakami D, Takano M, Ohba T, Ibuki C, Mizuno K: Links between sleep disordered breathing, coronary atherosclerotic burden, and cardiac biomarkers in patients with stable coronary artery disease. J Cardiol, 2012; 60: 180-186 [DOI] [PubMed] [Google Scholar]
- 22). Serizawa N, Yumino D, Takagi A, Gomita K, Kajimoto K, Tsurumi Y, Hagiwara N: Obstructive sleep apnea is associated with greater thoracic aortic size. J Am Coll Cardiol, 2008; 52: 885-886 [DOI] [PubMed] [Google Scholar]
- 23). Kasai T, Floras JS, Bradley TD: Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation, 2012; 126: 1495-1510 [DOI] [PubMed] [Google Scholar]
- 24). Young T, Evans L, Finn L, Palta M: Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep, 1997; 20: 705-706 [DOI] [PubMed] [Google Scholar]
- 25). Singh M, Liao P, Kobah S, Wijeysundera DN, Shapiro C, Chung F: Proportion of surgical patients with undiagnosed obstructive sleep apnoea. Br J Anaesth, 2013; 110: 629-636 [DOI] [PubMed] [Google Scholar]