Cassianne Robinson-Cohen1, Leila R Zelnick1, Andrew N Hoofnagle2, Pamela L Lutsey3, Gregory Burke4, Erin D Michos5,6, Steven J C Shea7,8, Russell Tracy9,10, David S Siscovick11, Bruce Psaty12,13,14, Bryan Kestenbaum1, Ian H de Boer1. 1. Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington 98195. 2. Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195. 3. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455. 4. School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27109. 5. Division of Cardiology, Johns Hopkins University, Baltimore, Maryland 21218. 6. Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205. 7. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032. 8. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York 10027. 9. Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405. 10. Department of Biochemistry, University of Vermont, Burlington, Vermont 05405. 11. New York Academy of Medicine, New York, New York 10029. 12. Cardiovascular Health Research Unit, Departments of Epidemiology and Medicine, University of Washington, Seattle, Washington 98101. 13. Department of Health Services, University of Washington, Seattle, Washington 98195. 14. Group Health Research Institute, Seattle, Washington 98101.
Abstract
Context: Low 25-hydroxyvitamin D [25(OH)D] is associated with coronary heart disease (CHD) in people who are white and Chinese but not black or Hispanic. Vitamin D binding globulin (VDBG) avidly binds 25(OH)D, reducing its bioavailability, and differs in isoform and concentration by race. Objective: Evaluate associations of VDBG with CHD and whether accounting for VDBG or estimating bioavailable 25(OH)D explains the heterogeneity of the association of 25(OH)D with CHD. Design and Setting: We conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis. Participants with an incident CHD event over 12 years of follow-up (n = 538) and a randomly assigned subcohort (n = 999) were included. We measured baseline 25(OH)D, VDBG, and isoforms using mass spectrometry and estimated bioavailable 25(OH)D from published equations. Results: VDBG was associated with an increased risk of CHD [hazard ratio, 1.77 (95% confidence interval, 1.46 to 2.14) per standard deviation increment, P < 0.0001], without evidence of heterogeneity by race or isoform (each P for interaction > 0.1). Low total 25(OH)D was differentially associated with CHD events, by race, with or without adjustment for VDBG (P for interaction = 0.04 or 0.05, respectively). Associations of 25(OH)D with CHD were strengthened with adjustment for VDBG among participants who were white or Chinese, and bioavailable 25(OH)D was associated with CHD events only among white participants. Conclusions: High VDBG concentration was associated with CHD events in all racial and ethnic groups. Incorporation of VDBG strengthened existing associations of 25(OH)D with CHD but did not explain racial heterogeneity in associations of 25(OH)D with CHD.
Context: Low 25-hydroxyvitamin D [25(OH)D] is associated with coronary heart disease (CHD) in people who are white and Chinese but not black or Hispanic. Vitamin D binding globulin (VDBG) avidly binds 25(OH)D, reducing its bioavailability, and differs in isoform and concentration by race. Objective: Evaluate associations of VDBG with CHD and whether accounting for VDBG or estimating bioavailable 25(OH)D explains the heterogeneity of the association of 25(OH)D with CHD. Design and Setting: We conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis. Participants with an incident CHD event over 12 years of follow-up (n = 538) and a randomly assigned subcohort (n = 999) were included. We measured baseline 25(OH)D, VDBG, and isoforms using mass spectrometry and estimated bioavailable 25(OH)D from published equations. Results:VDBG was associated with an increased risk of CHD [hazard ratio, 1.77 (95% confidence interval, 1.46 to 2.14) per standard deviation increment, P < 0.0001], without evidence of heterogeneity by race or isoform (each P for interaction > 0.1). Low total 25(OH)D was differentially associated with CHD events, by race, with or without adjustment for VDBG (P for interaction = 0.04 or 0.05, respectively). Associations of 25(OH)D with CHD were strengthened with adjustment for VDBG among participants who were white or Chinese, and bioavailable 25(OH)D was associated with CHD events only among white participants. Conclusions: High VDBG concentration was associated with CHD events in all racial and ethnic groups. Incorporation of VDBG strengthened existing associations of 25(OH)D with CHD but did not explain racial heterogeneity in associations of 25(OH)D with CHD.
Authors: Jason P Linefsky; Kevin D O'Brien; Ronit Katz; Ian H de Boer; Eddy Barasch; Nancy S Jenny; David S Siscovick; Bryan Kestenbaum Journal: J Am Coll Cardiol Date: 2011-07-12 Impact factor: 24.094
Authors: Pamela L Lutsey; Erin D Michos; Jeffrey R Misialek; James S Pankow; Laura Loehr; Elizabeth Selvin; Jared P Reis; Myron Gross; John H Eckfeldt; Aaron R Folsom Journal: JACC Heart Fail Date: 2015-04-08 Impact factor: 12.035
Authors: Ian H de Boer; Gregory Levin; Cassianne Robinson-Cohen; Mary L Biggs; Andy N Hoofnagle; David S Siscovick; Bryan Kestenbaum Journal: Ann Intern Med Date: 2012-05-01 Impact factor: 25.391
Authors: Lesley A Inker; Christopher H Schmid; Hocine Tighiouart; John H Eckfeldt; Harold I Feldman; Tom Greene; John W Kusek; Jane Manzi; Frederick Van Lente; Yaping Lucy Zhang; Josef Coresh; Andrew S Levey Journal: N Engl J Med Date: 2012-07-05 Impact factor: 91.245
Authors: Longjian Liu; Ming Chen; Shelley R Hankins; Ana E Nùñez; Robert A Watson; Perry J Weinstock; Craig J Newschaffer; Howard J Eisen Journal: Am J Cardiol Date: 2012-06-02 Impact factor: 2.778
Authors: Andrew B Petrone; Natalie L Weir; Brian T Steffen; Michael Y Tsai; John Michael Gaziano; Luc Djoussé Journal: Am J Cardiol Date: 2013-06-01 Impact factor: 2.778
Authors: Camille E Powe; Catherine Ricciardi; Anders H Berg; Delger Erdenesanaa; Gina Collerone; Elizabeth Ankers; Julia Wenger; S Ananth Karumanchi; Ravi Thadhani; Ishir Bhan Journal: J Bone Miner Res Date: 2011-07 Impact factor: 6.741
Authors: Ishir Bhan; Camille E Powe; Anders H Berg; Elizabeth Ankers; Julia B Wenger; S Ananth Karumanchi; Ravi I Thadhani Journal: Kidney Int Date: 2012-03-07 Impact factor: 10.612
Authors: Clark M Henderson; Susan L Fink; Hanan Bassyouni; Bob Argiropoulos; Lindsay Brown; Thomas J Laha; Konner J Jackson; Raymond Lewkonia; Patrick Ferreira; Andrew N Hoofnagle; Julien L Marcadier Journal: N Engl J Med Date: 2019-03-21 Impact factor: 91.245
Authors: Amy J Kogon; Lance S Ballester; Jarcy Zee; Natalie Walker; Joshua J Zaritsky; Meredith A Atkinson; Christine B Sethna; Andrew N Hoofnagle; Mary B Leonard; Michelle R Denburg Journal: Pediatr Nephrol Date: 2022-07-19 Impact factor: 3.651
Authors: Scott M Gordon; Jonathan H Chung; Martin P Playford; Amit K Dey; Denis Sviridov; Fayaz Seifuddin; Yun-Ching Chen; Mehdi Pirooznia; Marcus Y Chen; Nehal N Mehta; Alan T Remaley Journal: Atherosclerosis Date: 2018-09-25 Impact factor: 5.162
Authors: JoAnn E Manson; Shari S Bassuk; Nancy R Cook; I-Min Lee; Samia Mora; Christine M Albert; Julie E Buring Journal: Circ Res Date: 2020-01-02 Impact factor: 17.367
Authors: Shejuti Paul; Suzanne E Judd; Virginia J Howard; Monika S Safford; Orlando M Gutiérrez Journal: Am Heart J Date: 2019-08-19 Impact factor: 4.749
Authors: Simon Hsu; Andrew N Hoofnagle; Deepak K Gupta; Orlando M Gutierrez; Carmen A Peralta; Steven Shea; Norrina B Allen; Gregory Burke; Erin D Michos; Joachim H Ix; David Siscovick; Bruce M Psaty; Karol E Watson; Bryan Kestenbaum; Ian H de Boer; Cassianne Robinson-Cohen Journal: J Clin Endocrinol Metab Date: 2020-12-01 Impact factor: 5.958