Additive Effects of Obstructive Sleep Apnea and Hypertension on Early Markers of Carotid Atherosclerosis
ABSTRACT Obstructive sleep apnea (OSA) has emerged as an independent risk factor for atherosclerosis. However, OSA is frequently associated with several risk factors for atherosclerosis, including hypertension (HTN). The impact of OSA and HTN alone compared with the association of both conditions on carotid atherosclerosis is not understood. We studied 94 middle-aged participants free of smoking and diabetes mellitus who were divided into 4 groups: controls (n=22), OSA (n=25), HTN (n=20), and OSA+HTN (n=27). All of the participants underwent polysomnography and carotid measurements of intima-media thickness, diameter, and distensibility with an echo-tracking device. Compared with controls, intima-media thickness and carotid diameter were similarly higher in OSA (713+/-117 and 7117+/-805 microm), and HTN groups (713+/-182 and 7191+/-818 microm), with a further significant increase in OSA+HTN patients (837+/-181 and 7927+/-821 microm, respectively; P<0.01). Carotid distensibility was significantly lower in HTN (P<0.05) and OSA+HTN subjects (P<0.001) compared with controls. In the OSA+HTN group, carotid distensibility was significantly lower than in the OSA group and controls (P<0.05 for each comparison). Multivariate analysis showed that intima-media thickness was positively related to systolic blood pressure and apnea-hypopnea index. Apnea-hypopnea index was the only factor related to carotid diameter. Age and systolic blood pressure were independently related to carotid distensibility. In conclusion, the association of OSA and HTN has additive effects on markers of carotid atherosclerosis. Because early markers of carotid atherosclerosis predict future cardiovascular events, including not only stroke but also myocardial infarction, these findings may help to explain the increased risk of cardiovascular disease in patients with OSA.
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ABSTRACT: Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnoea, is associated with impaired vascular function despite unaltered response to nitric oxide donors. This study addressed whether arginase contributes to the endothelial dysfunction in CIH rats. Adult male Sprague-Dawley rats were exposed for 21 days to CIH (5% oxygen, 12 times/h, 8 h/day). The internal carotid arteries were isolated to study endothelial nitric oxide synthase (eNOS) and arginase-1 levels by western blot and immunohistochemistry, and their vasoactive responses using wire myography. Relaxation to sodium nitroprusside (SNP; nitric oxide donor) in the presence or absence of soluble guanylyl cyclase inhibitor, and acetylcholine with and without a NOS inhibitor [N-nitro-L-arginine (L-NA)] and the arginase inhibitor BEC were determined. Arteries from the CIH rats presented higher active contraction induced by KCl (3.5 ± 0.4 vs. 2.3 ± 0.2 N/m), augmented media-to-lumen ratio (∼40%), decreased relaxation to acetylcholine (12.8 ± 1.5 vs. 30.5 ± 4.6%) and increased sensitivity to SNP (pD2 7.3 ± 0.1 vs. 6.7 ± 0.1). Arginase inhibition reversed the impaired acetylcholine-induced relaxation in CIH arteries (49.5 ± 7.4%), an effect completely blocked by L-NA. In the carotid arteries, arginase-1 protein level was increased, whereas eNOS levels decreased in the CIH arteries. The current results suggest that endothelial dysfunction in CIH-induced hypertension may result from imbalanced arginase-1 to eNOS expression, vascular remodelling and increased contractile capacity, rather than decreased vascular response to nitric oxide.Journal of Hypertension 03/2015; 33(3):515-24. DOI:10.1097/HJH.0000000000000453 · 4.22 Impact Factor
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ABSTRACT: The role of obstructive sleep apnea (OSA) in the mortality and further cardiovascular risk in subjects with ischemic stroke remains a contentious issue. Oxidative stress and inflammatory reaction due to OSA have seldom been studied in stable ischemic stroke patients.Patients/Methods This cross-sectional, prospective study involved 92 consecutive ischemic stroke patients who were admitted to the Rehabilitation ward. All subjects received polysomnography and laboratory tests for oxidative stress and inflammatory biomarkers, including: C-reactive protein (CRP), interleukin 6 (IL-6), total antioxidant capacity (TAC) and urinary 8-hydroxy-2-deoxyguanosine. Differences in study variables between patients with or without severe OSA were compared, and multivariate linear regression analyses were used to assess the relationship between OSA severity and target biomarkers.ResultsParticipants in the severe OSA group were significantly older (p=0.002), had a significantly higher risk of hypertension (p=0.021) and a lower level of CRP (p=0.006). Among the subjects with ischemic stroke and severe OSA, the levels of CRP, IL-6 and TAC were positively correlated with the desaturation index (DI) and the TAC levels were negatively correlated with mean arterial oxygen saturation (SaO2). Regression analysis results indicated that the TAC levels remained significantly and negatively correlated with mean SaO2 levels. Moreover, the CRP levels remained significantly correlated with the apnea-hypopnea index and DI after controlling for covariates.Conclusions The present study demonstrated that a preferentially adaptive antioxidative response to hypoxia emerges, and the role of OSA with respect to inflammatory reaction is attenuated, in ischemic stroke patients with OSA.Sleep Medicine 11/2014; 16(1). DOI:10.1016/j.sleep.2014.07.027 · 3.10 Impact Factor