Accumulated data suggest that sleep apnea and milder forms of sleep- related breathing disorders (SRBD) may have an etiologic role in cardiovascular disease. The evidence, however, is far from conclusive, relying mostly on surrogate measures of SRBD and case-control designs. The broad goal of this project is to investigate, prospectively, the role of SRBD in cardiovascular disease, employing a multi-center cohort design. As part of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort study of atherosclerosis and cardiovascular disease, the applicants have recruited and examined 4,009 men and women from suburban Minneapolis in 1987-1989. Participants underwent a second exam in 1990-1992 and are currently being examined for the third time (1993-1995). A fourth exam in 1996-1998 has been funded. A wide range of lifestyle, biochemical, physiological, and clinical characteristics has been measured, including carotid artery intimal-medial thickness, a measure of early atherosclerosis. The cohort is followed for atherosclerosis progression and cardiovascular endpoints. All of these features make the ARIC Minneapolis cohort suitable for the multi-center Sleep Study. There are five specific aims for this project. First, the applicants will screen the 3,828 exam 2 returnees, by means of a mailed questionnaire, for SRBD-associated characteristics such as habitual snoring, observed apnea, and daytime somnolence. Second, a subset of 1,000 consenting individuals - 500 men and 500 women free of clinical cardiovascular disease - will be recruited for a home overnight Sleep Study to derive an apnea-hypopnea score. To increase the study's statistical power, the sample will be enriched with individuals having SRBD by over-sampling habitual snorers. Third, a total of 250 participants (an estimated 200 testing positive for SRBD and 50 testing negative) will undergo polysomnography in a Sleep Laboratory to: 1) validate the diagnosis, 2) better quantify SRBD, and 3) calculate the sensitivity and specificity of the home study. Fourth, in year 05, the applicants will test, cross-sectionally, specific hypotheses related to: 1) SRBD and asymptomatic carotid artery atherosclerosis; 2) SRBD and blood pressure; 3) SRBD and the use of hormone-replacement therapy; 4) SRBD and cognitive function; 5) habitual snoring and asymptomatic carotid atherosclerosis; 6) habitual snoring and prevalent cardiovascular disease. The fifth and long-term aim is to test, with adequate follow-up, whether SRBD is associated with atherosclerosis progression and with subsequent risk of cardiovascular disease. The proposed project has the advantages of 1) a multidisciplinary team of experienced cardiovascular epidemiologists, sleep researchers, and biostatisticians, and 2) an already established population-based cohort with high response rate and detailed measurements of cardiovascular risk factors, early atherosclerosis, and cardiovascular disease endpoints. It will, therefore, be an important and cost-efficient contribution to the multi-center Sleep Study.
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