The prevalence of Obstructive Sleep Apnea (OSA) in middle-aged adults is at least 4% in males and 2% in females and will probably increase with the obesity epidemic in this country. Individuals with OSA are at increased risk for fatal and non-fatal cardiovascular disease (CVD) events. Treatment with continuous positive airway pressure (CPAP) may reduce CVD risk;however, the mechanisms, time course, and durability of its benefit are not known. These are especially important issues since patients with OSA often are not compliant or are intermittently compliant with CPAP therapy. This research proposal describes our plans to evaluate the time course and magnitude of the effects of CPAP therapy on two measures of arterial function, namely arterial stiffness and endothelium-dependent vasodilation. This study has four specific aims that address four inter- related hypotheses: To determine if (i) CPAP therapy reduces carotid-to-femoral pulse wave velocity, a marker of aortic stiffness, (ii) CPAP therapy improves flow-mediated vasodilation of the brachial artery, a marker of endothelial function, (iii) the time course of changes in arterial function observed with CPAP therapy and their duration after cessation of therapy, and (iv) if coronary artery flow regulation observed in patients with OSA improves after CPAP therapy. Multimodality non-invasive cardiac and vascular imaging will be used to prospectively investigate these aims in 130 CPAP-naive adults (21-45 years old) with moderate to severe OSA, before starting CPAP therapy, after 4 and 12 weeks, and then 712 days after withdrawal. This study will have adequate power to adjust for possible confounders such as degree of obesity, sleepiness, sex, race, and CPAP compliance. This training grant and research study will provide the applicant with training and research experiences to permit her to become an independent investigator that designs and conducts rigorous patient- oriented research projects related to sleep disorders and CVD. Dr. Korcarz's long-term career goal is to be an independent investigator that performs cutting edge physiological research related to sleep disorders and cardiovascular disease risk.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (O1))
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Scott, Jane
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University of Wisconsin Madison
Internal Medicine/Medicine
Schools of Medicine
United States
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Korcarz, Claudia E; Peppard, Paul E; Young, Terry B et al. (2016) Effects of Obstructive Sleep Apnea and Obesity on Cardiac Remodeling: The Wisconsin Sleep Cohort Study. Sleep 39:1187-95
Korcarz, Claudia E; Benca, Ruth; Barnet, Jodi H et al. (2016) Treatment of Obstructive Sleep Apnea in Young and Middle-Aged Adults: Effects of Positive Airway Pressure and Compliance on Arterial Stiffness, Endothelial Function, and Cardiac Hemodynamics. J Am Heart Assoc 5:e002930
Tattersall, Matthew C; Barnet, Jodi H; Korcarz, Claudia E et al. (2016) Late-Onset Asthma Predicts Cardiovascular Disease Events: The Wisconsin Sleep Cohort. J Am Heart Assoc 5:
Stein, James H; Stern, Rebecca; Barnet, Jodi H et al. (2016) Relationships between sleep apnea, cardiovascular disease risk factors, and aortic pulse wave velocity over 18 years: the Wisconsin Sleep Cohort. Sleep Breath 20:813-7
Fujishiro, Kaori; Diez Roux, Ana V; Landsbergis, Paul et al. (2015) Occupational characteristics and the progression of carotid artery intima-media thickness and plaque over 9?years: the Multi-Ethnic Study of Atherosclerosis (MESA). Occup Environ Med 72:690-8
Gunnarsson, Sverrir I; Peppard, Paul E; Korcarz, Claudia E et al. (2015) Minimal nocturnal oxygen saturation predicts future subclinical carotid atherosclerosis: the Wisconsin sleep cohort. J Sleep Res 24:680-6
Stern, Rebecca; Tattersall, Matthew C; Gepner, Adam D et al. (2015) Sex differences in predictors of longitudinal changes in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 35:478-84
Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D et al. (2015) Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis. Atherosclerosis 239:412-8
Gepner, Adam D; Korcarz, Claudia E; Colangelo, Laura A et al. (2014) Longitudinal effects of a decade of aging on carotid artery stiffness: the multiethnic study of atherosclerosis. Stroke 45:48-53
Gunnarsson, Sverrir I; Peppard, Paul E; Korcarz, Claudia E et al. (2014) Obstructive sleep apnea is associated with future subclinical carotid artery disease: thirteen-year follow-up from the Wisconsin sleep cohort. Arterioscler Thromb Vasc Biol 34:2338-42

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