The authors have declared that no competing interests exist.
Obstructive sleep apnea (OSA) is an independent risk factor for the development of cardiovascular diseases. Aim of this present study was to evaluate and extend recent research on the influence of obstructive sleep apnea on vascular strain.
A total number of 98 patients were integrated in the study. Patients were grouped according to the Apnea-Hypopnea-Index (AHI) in patients with mild-to-moderate OSA (5/h ≤ AHI < 30/h), severe OSA (AHI ≥ 30/h) and controls (AHI < 5/h). Groups were matched in age, body-mass-index and cardiovascular risks. Vascular strain of common carotid arteries was assessed by ultrasound speckle-tracking. A minor group of 30 patients and controls further underwent assessment of vascular strain of brachial and femoral arteries. Additionally, all patients underwent blood testing to reveal potential influences of inflammatory markers on arterial stiffness. In additional analysis we examined the effect of statin therapy on vascular strain.
Patients with OSA showed significantly reduced values of vascular strain of common carotid arteries. Radial and circumferential strains were significantly lower in both patients with mild-to-moderate (p = .05) and patients with severe OSA (p = .001) compared to control. Vascular strain parameters of brachial and femoral arteries showed no consistent results. There were no significant correlations of inflammatory markers with vascular strain parameters. No significant differences in vascular strain were detected between statin and non-statin groups.
Patients with OSA show significantly reduced vascular strain assessed by ultrasound-based speckle-tracking. Vascular stiffness increases with the severity of the disease. Target vessels to assess vascular strain in patients with OSA are common carotid arteries, whereas other sites of the arterial tree are not reliable. No significant impact of current statin therapy on vascular strain was found. Further studies are needed to evaluate potential benefit of statins in secondary prevention of atherosclerosis in OSA.
Obstructive sleep apnea (OSA) is a widespread chronic disease which affects up to 17% of the population in industrialized countries [
This study was conducted according to the principles of the Declaration of Helsinki for Human Research and was approved by the local ethics committee of the University Hospital of Bonn. Written informed consent of all patients and controls was obtained prior to the examination. The Department of Pneumology and the Department of Angiology of the University Hospital of Bonn realized this study as a joint project.
From November 2016 till March 2017 126 consecutive patients with suspected OSA were examined. The diagnosis was confirmed via polysomnography. Thereby, apnea was defined as an air flow cessation for at least 10 seconds and hypopnea as an air flow reduction of minimum 50% for 10 seconds or more accompanied by an oxygen desaturation of > 3% or a cortical arousal which matches the definition of hypopnea of the American Academy of Sleep Medicine from 2012 [
All patients underwent cardiorespiratory polysomnography (Somnolab, Weinmann Medical Technology, Hamburg, Germany). Baseline examination included pulse oxymetry, electrophysiological surveillance (EEG, EOG, EMG) and ECG. Surveillance of sleep contained the recording of sleep phases and sleep stages, snoring [%/time of sleep], awakening reactions expressed as the total arousal index (TAI) [n/h], thoracic movement observation and the periodic limb movement during sleep (PLMS) [n/h]. AHI, which is described above, and Oxygen-Desaturation-Index (ODI) were of particular interest for this study. ODI expresses the oxygen desaturation phases (decrease of oxygen saturation > 3%) per hour.
Angiological diagnostics contained evaluation of Ankle-Brachial-Index (ABI) and color-coded duplex sonography of the arteries. ABI was defined as quotient of systolic blood pressure of tibial posterior artery and dorsalis pedis artery on both sides through mean systolic blood pressure of the upper limbs. An ABI value <0.9 was considered an indication for peripheral artery occlusive disease (pAOD), ABI >1.3 was interpreted as a lead to increased vascular stiffness. Color-coded duplex sonography was performed on carotid arteries, brachial arteries, aorta and the arteries of the lower limb down to popliteal artery using Philips® iE33® (Hamburg, Germany). Presence of one or more atherosclerotic lesions (plaques) in carotid arteries led to the diagnosis of cervical arterial occlusive disease (cAOD), one or more plaques in the arteries of the lower limb indicated peripheral artery occlusive disease (pAOD). Sonography was performed by skilled physicians who were blinded to the results of polysomnography.
Vascular strain analysis was performed on CCA one centimeter below the carotid bulb. Two-dimensional cross-sectional grey-scaled recordings of at least four consecutive heart beats were collected, triggered by electrocardiography (ECG). Assuming bilateral equal alterations of arteries as consequence of OSA the clip of the highest quality was chosen for further evaluation. Thereby, clips were transferred as DICOM file to an external workstation equipped with the speckle-tracking software package Image Arena®, Version 4.6 by TomTec Systems GmbH (Munich, Germany) for off-line analysis.
For measurement of circumferential and radial strain variables a region of interest (ROI) was marked manually in the intima-media complex of the vessel wall, adequate tracking was verified and adjusted, if necessary [
Within the main group of patients and controls without current statin therapy a total number of 30 consecutive patients underwent extended vascular strain analysis. Of those, 12 patients presented with mild-to-moderate OSA, 11 patients suffered from severe OSA, and 7 patients were diagnosed free of OSA. This analysis aimed to evaluate the value of brachial and femoral arteries in assessment of vascular strain in patients with OSA. For this purpose vascular strain was assessed not only in common carotid arteries, but additionally in the brachial arteries at the axial upper arm as well as in the femoral arteries one centimeter distal to the bifurcation of common femoral arteries.
Differential blood count, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), high sensitive C-reactive protein (hsCRP), lipoprotein a (Lip(a)), interleukin-6 (IL-6), fibrinogen and soluble interleukin-2-receptor (sIL-2r) were determined in blood. All parameters have previously been described in relation to increased arterial thickness respectively atherosclerosis in patients with OSA [
27 patients with current statin therapy were separated from the main group and integrated in the subgroup analysis. Of those, patients with an AHI < 5 were not included in further evaluation (n = 7). As control group served a sample of 20 patients gathered by chance with SPSS® out of all study participants (main group) with diagnosed OSA and without current statin therapy. The groups showed neither significant differences in BMI, packyears, age nor AHI and ODI. By comparing these groups we intended to glance at possible influences of statin therapy on vascular stiffness in patients with OSA and therefore generate new hypotheses for future investigations.
Statistical analysis was conducted with IBM® SPSS® Statistics®, Version 23. Intergroup differences of nominal scaled baseline characteristics were calculated by Chi-square-test and Cramer's V. Comparing the groups on behalf of Gaussian-distributed parameters was performed by ANOVA, non Gaussian-distributed parameters under went Mann-Whitney-U- and Kruskal-Wallis-tests. Correlation between vascular strain and blood parameters, respectively partial correlation related to PLMS, was performed by Spearman's rho. Two-tailed p-value was defined significant at the .05-level. Continuous variables were presented as mean ± standard deviation.
Dissenting from that, subgroup analysis between patients with or without current statin therapy was performed by t-test for uncombined samples instead of ANOVA on behalf of Gaussian distributed parameters.
Baseline characteristics are presented in
Mild-to-moderate OSA (n = 28) | Severe OSA (n = 25) | Control (n = 18) | |||
---|---|---|---|---|---|
Value | p |
Value | p |
Value | |
Sex: male [%] | 20 [71,4] | n. s. | 22 [88,0] | < .05 | 9 [50,0] |
Age [Years] | 58.2 ± 11.1 | n. s. | 54.5 ± 14.2 | n. s. | 51.7 ± 14.0 |
BMI [kg/m2] | 30.98 ± 5.72 | n. s. | 32.67 ± 5.55 | n. s. | 28.98 ± 4.77 |
AHI [n/h] | 14.1 ± 6.7 | < .001 | 55.9 ± 19.2 | < .001 | 2.1 ± 1.7 |
ODI [n/h] | 14.2 ± 7.4 | < .001 | 52.4 ± 22.3 | < .001 | 2.2 ± 2.2 |
PLMS [n/h] | 17.7 ± 27.6 | n. s. | 12.0 ± 17.5 | n. s. | 13.1 ± 30.9 |
TAI [n/h] | 23.4 ± 13.1 | n. s. | 38.6 ± 27.1 | < .001 | 12.4 ± 21.4 |
Snoring [%/time of sleep] | 34.1 ± 32.3 | < .01 | 28.7 ± 23.4 | < .05 | 8.7 ± 18.3 |
Nicotine abuse |
20 [71.4] | n. s. | 13 [52.0] | n. s. | 6 [33.3] |
Packyears [Years] | 18.8 ± 21.8 | < .01 | 11.6 ± 21.3 | n. s. | 4.9 ± 10.0 |
Diabetes [%] | 2 [7.1] | n. s. | 4 [16.0] | n. s. | 1 [5.6] |
Hypertension [%] | 21 [61.1] | n. s. | 17 [68.0] | n. s. | 11 [61.1] |
Hypercholesterolemia [%] | 8 [28.6] | n. s. | 3 [12.0] | n. s. | 3 [16.7] |
Renal dysfunction [%] | 0 | 0 | 0 | ||
CAD [%] | 2 [7.1] | n. s. | 2 [8.0] | n. s. | 0 |
Myocardial infarction [%] | 2 [7.1] | n. s. | 1 [4.0] | n. s. | 0 |
cAOD [%] | 15 [53.6] | n. s. | 12 [48.0] | n. s. | 5 [27.8] |
pAOD [%] | 16 [57.1] | n. s. | 10 [40.0] | n. s. | 7 [38.9] |
ABI < .90 [%] | 4 [14.3] | n. s. | 5 [20.0] | n. s. | 1 [5.6] |
ABI > 1.30 [%] | 6 [21.4] | n. s. | 4 [16.0] | n. s. | 5 [27.8] |
* vs. control
** current and former nicotine abuse
Results of vascular strain analysis of common carotid arteries are illustrated in
Mild-to-moderate OSA | Severe OSA | Control | |||
---|---|---|---|---|---|
Value | p |
Value | p |
Value | |
r.Vel |
.070 ± .049 | < .05 | .059 ± .054 | < .01 | .094 ± .054 |
r.Dis [mm] | .100 ± .065 | n. s. | .076 ± .060 | < .01 | .136 ± .061 |
r.Str [%] | 2.702 ± 1.457 | < .05 | 2.041 ± 1.414 | < .001 | 3.771 ± .952 |
c.Str |
2.175 ± 1.338 | < .01 | 1.825 ± 1.485 | < .001 | 3.390 ± 1.448 |
r.StrR [1/s] | .208 ± .107 | n. s. | .182 ± .131 | < .05 | .271 ± .098 |
c.StrR |
.150 ± .094 | < .01 | .136 ± .130 | < .001 | .231 ± .123 |
* vs. control
** non-Gaussian distributed
Results of vascular strain analysis at different sites of the arterial tree are presented in
Blood testing is shown in
AHI correlated positively with BMI (< .01), total cholesterol (p < .05) and monocytes (p < .001). AHI was related negatively to radial velocity (p < .05), radial displacement (p <. 01), radial strain (p < .001), circumferential strain (p < .01), radial strain rate (p < .05) and circumferential strain rate (p < .01). Similarly, ODI correlated positively with BMI (p < .01), CRP (p < .05) and monocytes (p < .001). Negative correlations occurred with r.Vel (p < .05), r.Dis (p < .01), r.Str (p < .001), c.Str (p < .01) as well as radial and circumferential strain rates (p < .05).
PLMS correlated with neither vascular strain nor blood parameters at any level of significance. Monocyte count correlated with TAI (p < .01) and snoring (p < .05). However, this was expected, since TAI and AHI correlated positively with the highest significance (p < .001). To clarify, if PLMS had an influence on correlation between vascular strain and blood parameters, partial correlation with PLMS as controlled variable was calculated. As a result, correlation between vascular strain and blood parameters remained still unchanged.
There were no significant correlations between derivates of vascular strain and blood parameters.
Additional analysis of patients with current statin therapy versus patients without current statin therapy is merged in
OSA affects arterial stiffness [
Vascular strain analysis at different sites of the arterial tree has been described before by Charvat-Resl et al. [
The role of inflammatory markers in OSA has been the subject of various other experimental and clinical studies [
In differential blood count only monocytes were significantly elevated in patients with severe OSA. This may connect to Alvarez-Martins et al. [
Drakatos et al. reported in 2016 that patients with OSA and increased periodic leg movement during sleep had significantly increased values of arterial stiffness assessed by photoplethysmography [
Comparing patients currently undergoing statin therapy with a matched sample of patients without statins stimulated further thought. All assessed vascular strain parameters were higher in the statin group compared to the non-statin one. However, no level of significance has been reached. Expectedly, it became evident that statins reduced the levels of total cholesterol and LDL. An effect on other blood parameters could not be observed. However, due to the small sample size, the informative value of this analysis can be seen as limited. Moreover, there was no discrimination between doses, duration of statin treatment and agent. Reports on the value of statins in secondary prevention of atherosclerosis in patients with OSA are rare and inconsistent [
Referring to Buratti et al. 2014 and 2016, who reported on an association between OSA and Alzheimer's disease [
This study has several limitations. The preeminent limitation, especially with regard to the subgroups, is the samples size. Also BMI increased with the severity of OSA. Although the differences did not reach a level of significance, this may have influenced the results, since BMI correlated with vascular strain parameters and represents an independent risk factor for arterial stiffening and atherosclerosis. This refers to smoking habits as well, for patients with mild-to-moderate OSA presented with significantly more packyears compared to controls. Another limitation is the definition of hypopnea being a matter of discussion up to now [
In conclusion, obstructive sleep apnea is a highly complicated disease for which the consequences are even more complex than the causes. To our knowledge this study is the largest clinical evaluation of vascular strain in patients with OSA up to now. The outstanding role of common carotid arteries in assessing of vascular strain has been highlighted. Other sites of the arterial tree have been shown to be unreliable and their value has been discussed critically. Further, this study was able to provide new information on the role of statin therapy in patients with OSA. Moreover, this study contributed to the implementing of vascular strain analysis into clinical routine.
Concluding, with regard to the high prevalence of pAOD and cAOD in this patient collective, it has to be underlined, how important a routine angiological screening of patients with OSA might be.
* vs. control; ** non-Gaussian distributed;
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* vs. control; ** non-Gaussian distributed;
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* non-Gaussian distributed;
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