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Area Under the Curve and Other Summary Indicators of Repeated Waking Cortisol Measurements

From the Biostatistics and Epidemiology Branch (D.B.F., M.E.A., C.M.B., T.A.H., L.E.C.), Toxicology and Molecular Biology Branch (D.B.M.), Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia; Department of Social and Preventive Medicine (J.M.V.), School of Public Health and Health Professions, State University of New York at Buffalo, Buffalo, New York.

Address correspondence and reprint requests to Desta B. Fekedulegn, Biostatistics and Epidemiology Branch, National Institute for Occupational Safety and Health, HELD/BEB, MS 4050, 1095 Willowdale Rd., Morgantown, WV 26505. E-mail: djf7{at}cdc.gov

Objective: To derive the area under the curve and related summary measures of stress from saliva samples collected over time and to provide insight into the interpretation of the derived parameters. In research designed to assess the health consequences of stress these samples are often used as a physiologic indicator of the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis. To make these repeated measurements of salivary cortisol more useful in defining the relationships between stress and health there is a need to derive two forms of area under the curve that summarize the measurements: area under the curve with respect to ground (AUC_G) and area under the curve with respect to increase (AUC_I). The latter parameters, AUC_I, however, is seldom used by research scientists.

Methods: In this study, interpretation and generic definition of the area under the curve was provided through graphical analyses and examination of its association with other summary measures using data from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Pilot Study. In generic form, AUC_I is derived as the area under the curve above the baseline value minus the area above the curve below the baseline value.

Results: The sign and magnitude of AUC_I are related to the profile and the rate of change of the measurements over time. The parameter showed significant associations with other summary indicators that measure pattern or rate of change of the measurements over time.

Conclusion: Principal components analyses revealed that summary parameters derived from repeated cortisol measurements can be grouped into two meaningful general categories: measures of the magnitude of response and measures of the pattern of response over time.

Key Words: repeated cortisol measurements • area under the curve • principal component analysis • total hormonal secretion • time course of salivary cortisol

Abbreviations: AUC_G = area under the curve with respect to ground; AUC_I = area under the curve with respect to increase; AUC_B = area under the curve with respect to baseline; HPA = hypothalamic-pituitary-adrenal; PCA = principal component analyses.

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