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      Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea

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          Abstract

          Background

          Obstructive sleep apnea (OSA) has been associated with cardiovascular disease (CVD), but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP).

          Results

          Of the 35 consecutive subjects with newly diagnosed moderate to severe OSA recruited from the Stanford Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP. Active nCPAP was titrated to pressures that would prevent sleep disordered breathing based on inpatient polysomnography. OSA patients had baseline vascular function abnormalities including decreased myocardial perfusion reserve (MPR), brachial flow mediated dilation (FMD) and nitroglycerin-induced coronary vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 ± 0.5 vs. 3.0 ± 1.3, p = 0.02) and brachial FMD (2.5% ± 5.7% vs. 9.0% ± 6.5%, p = 0.03) after treatment, but those randomized to sham nCPAP showed no significant improvement. There were no significant changes seen in chamber sizes, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin.

          Conclusions

          Patients with moderate to severe OSA had decreased MPR and brachial FMD that improved after 3 months of nCPAP. These findings suggest that relief of apnea in OSA may improve microvascular disease and endothelial dysfunction, which may prevent the development of overt cardiovascular disease. Further study in a larger patient population may be warranted.

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          Most cited references30

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          Prospective study of the association between sleep-disordered breathing and hypertension.

          Sleep-disordered breathing is prevalent in the general population and has been linked to chronically elevated blood pressure in cross-sectional epidemiologic studies. We performed a prospective, population-based study of the association between objectively measured sleep-disordered breathing and hypertension (defined as a laboratory-measured blood pressure of at least 140/90 mm Hg or the use of antihypertensive medications). We analyzed data on sleep-disordered breathing, blood pressure, habitus, and health history at base line and after four years of follow-up in 709 participants of the Wisconsin Sleep Cohort Study (and after eight years of follow-up in the case of 184 of these participants). Participants were assessed overnight by 18-channel polysomnography for sleep-disordered breathing, as defined by the apnea-hypopnea index (the number of episodes of apnea and hypopnea per hour of sleep). The odds ratios for the presence of hypertension at the four-year follow-up study according to the apnea-hypopnea index at base line were estimated after adjustment for base-line hypertension status, body-mass index, neck and waist circumference, age, sex, and weekly use of alcohol and cigarettes. Relative to the reference category of an apnea-hypopnea index of 0 events per hour at base line, the odds ratios for the presence of hypertension at follow-up were 1.42 (95 percent confidence interval, 1.13 to 1.78) with an apnea-hypopnea index of 0.1 to 4.9 events per hour at base line as compared with none, 2.03 (95 percent confidence interval, 1.29 to 3.17) with an apnea-hypopnea index of 5.0 to 14.9 events per hour, and 2.89 (95 percent confidence interval, 1.46 to 5.64) with an apnea-hypopnea index of 15.0 or more events per hour. We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors. The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population.
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            Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.

            Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both. To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons. Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998. A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female). Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication. Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category ( or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring. Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.
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              Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up.

              The incidence of a cardiovascular disease (CVD) was explored in a consecutive sleep clinic cohort of 182 middle-aged men (mean age, 46.8 +/- 9.3; range, 30-69 years in 1991) with or without obstructive sleep apnea (OSA). All subjects were free of hypertension or other CVD, pulmonary disease, diabetes mellitus, psychiatric disorder, alcohol dependency, as well as malignancy at baseline. Data were collected via the Swedish Hospital Discharge Register covering a 7-year period before December 31, 1998, as well as questionnaires. Effectiveness of OSA treatment initiated during the period as well as age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) at baseline, and smoking habits were controlled. The incidence of at least one CVD was observed in 22 of 60 (36.7%) cases with OSA (overnight oxygen desaturations of 30 or more) compared with in 8 of 122 (6.6%) subjects without OSA (p < 0.001). In a multiple logistic regression model, significant predictors of CVD incidence were OSA at baseline (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.8-13.6) and age (OR 23.4; 95% CI, 2.7-197.5) after adjustment for BMI, SBP, and DBP at baseline. In the OSA group, CVD incidence was observed in 21 of 37 (56.8%) incompletely treated cases compared with in 1 of 15 (6.7%) efficiently treated subjects (p < 0.001). In a multiple regression analysis, efficient treatment was associated with a significant risk reduction for CVD incidence (OR 0.1; 95% CI, 0.0-0.7) after adjustment for age and SBP at baseline in the OSA subjects. We conclude that the risk of developing CVD is increased in middle-aged OSA subjects independently of age, BMI, SBP, DBP, and smoking. Furthermore, efficient treatment of OSA reduces the excess CVD risk and may be considered also in relatively mild OSA without regard to daytime sleepiness.
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                Author and article information

                Journal
                J Cardiovasc Magn Reson
                Journal of Cardiovascular Magnetic Resonance
                BioMed Central
                1097-6647
                1532-429X
                2010
                3 September 2010
                : 12
                : 1
                : 50
                Affiliations
                [1 ]Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA
                [2 ]Department of Medicine, Division of Cardiovascular Medicine, New York University, New York, NY, USA
                [3 ]Department of Psychiatry, Stanford University Center of Excellence for Sleep Disorders, Stanford, CA, USA
                Article
                1532-429X-12-50
                10.1186/1532-429X-12-50
                2945335
                20815898
                f5c0a85a-9e67-46b8-bbf7-6167f4f2f775
                Copyright ©2010 Nguyen et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 March 2010
                : 3 September 2010
                Categories
                Research

                Cardiovascular Medicine
                Cardiovascular Medicine

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