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Biomarker-calibrated Energy and Protein Consumption and Cardiovascular Disease Risk Among Postmenopausal Women

Prentice, Ross L.a; Huang, Yinga,b; Kuller, Lewis H.c; Tinker, Lesley F.a; Horn, Linda Vand; Stefanick, Marcia L.e; Sarto, Gloriaf; Ockene, Judithg; Johnson, Karen C.h

doi: 10.1097/EDE.0b013e31820839bc
Cardiovascular Disease: Original Article

Background: Nutritional epidemiology cohort studies primarily use food frequency questionnaires (FFQs). In part because FFQs are more reliable for nutrient densities than for absolute nutrient consumption, reports from association studies typically present only nutrient density measures in relation to disease risk.

Methods: We used objective biomarkers to correct FFQ assessments for measurement error, and examined absolute energy and protein consumption in relation to cardiovascular disease incidence. FFQs and subsequent physician-adjudicated cardiovascular disease incidence were assessed for 80,370 postmenopausal women in the age range 50–79 years at enrollment in the comparison group of the Dietary Modification Trial or the prospective Observational Study in the Women's Health Initiative. Urinary recovery biomarkers of energy and protein were obtained from a subsample of 544 women, with concurrent FFQ information.

Results: After biomarker correction, energy consumption was positively associated with coronary heart disease incidence (hazard ratio = 1.18; 95% confidence interval = 1.04–1.33, for 20% consumption increment) and protein density was inversely associated (0.85 [0.75–0.97]). The positive energy association appeared to be mediated by body fat accumulation. Ischemic stroke incidence was inversely associated with energy and protein consumption, but not with protein density.

Conclusions: A positive association between energy and coronary heart disease risk can be attributed to body mass accumulation. Ischemic stroke risk is inversely associated with energy and protein consumption, possibly due to correlations between consumption and physical activity.


From the aDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; bDepartment of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY; cDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA; dDepartment of Medicine, Northwestern University, Chicago, IL; eStanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA; fDepartment of Obstetrics and Gynecology, University of Wisconsin, Madison, WI; gDivision of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA; and hDepartment of Preventive Medicine, University of Tennessee, Memphis, TN.

Submitted 23 July 2010; accepted 18 October 2010; posted 5 January 2011.

Supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health, U. S. Department of Health and Human Services (contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, and 44221); and partially supported by grant P01 CA53996 from the National Cancer Institute at the National Institutes of Health (to R.L.P.).

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Correspondence: Ross L. Prentice, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave North, PO Box 19024, Seattle, WA 98109. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.