Author Contributions: Drs Jamison and Guarino had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Jamison, Hartigan, Kaufman, Goldfarb, Gaziano.
Acquisition of data: Jamison, Hartigan, Kaufman, Warren, Guarino, Gaziano.
Analysis and interpretation of data: Jamison, Hartigan, Kaufman, Goldfarb, Warren, Guarino, Gaziano.
Drafting of the manuscript: Jamison, Kaufman, Goldfarb, Warren, Guarino.
Critical revision of the manuscript for important intellectual content: Jamison, Hartigan, Kaufman, Goldfarb, Warren, Guarino, Gaziano.
Statistical analysis: Hartigan, Guarino.
Obtained funding: Jamison, Gaziano.
Administrative, technical, or material support: Jamison, Hartigan, Kaufman, Goldfarb, Warren, Guarino, Gaziano.
Study supervision: Jamison, Hartigan, Kaufman, Goldfarb, Warren, Gaziano.
Financial Disclosures: Dr Gaziano reported that in the past 5 years he has received investigator-initiated federal funding from the National Institutes of Health and the Department of Veterans Affairs, as well as nonfederal investigator-initiated funding from McNeil Consumer Products, Amgen, and VeroScience. He also reported receiving research support and supplies from BASF, DMS Pharmaceuticals, and Wyeth Pharmaceuticals; receiving honoraria from Bayer and Pfizer for speaking engagements; serving as a consultant for McNeil Consumer Products, Wyeth Pharmaceuticals, and Bayer; and serving as an expert witness for Merck, Nutraquest, and GlaxoSmithKline. No other authors reported financial disclosures.
HOST Study Participants: Writing Group: R. Jamison, J. M. Gaziano, D. S. Goldfarb, P. Guarino, P. Hartigan, J. Kaufman, S. Warren.
Executive Committee: R. Jamison (chair), J. M. Gaziano (cochair), R. Cxypoliski, S. Fortmann, D. S. Goldfarb, P. Guarino, P. Hartigan, M. Helmuth, J. Kaufman, K. McCully, K. Robinson, S. Warren, and P. Peduzzi (ex officio).
Events Adjudication Committee: D. Forman, T. Gaziano, T. Kurth, D. Mesler.
Data and Safety Monitoring Board: N. Levinsky (chair) [deceased], J. Kopple (chair), B. Brown Jr [deceased], A. Cheung, K. Detre [deceased], T. Greene, M. Klag, A. Motulsky, T. Hostetter, P. Ridker.
VA Cooperative Studies Human Rights Committee, West Haven, Connecticut: R. Marottoli (chair), H. Allore, D. Beckwith, W. Farrell, R. Feldman, R. Mehta, J. Neiderman, E. Perry, S. Kasl, M. Zeman.
VA Principal Investigators, Coinvestigators, and Coordinators: Ann Arbor: E. Young, K. Belanger; Bay Pines: R. Lopez, N. Grunsten; Birmingham: P. Sanders, MD, D. Killian, N. Shanklin; Boston: J. Kaufman, E. Dibbs; Bronx: E. Langhoff, D. Tyrrell; West Haven: S. Crowley, A. Piexoto, A. DeLorenzo, C. Joncas; Cleveland: R. T. Miller, K. Kaelin, M. Markulin; Dallas: D. Dev, D. Coussirat, A. Sajgure; Dayton: M. Saklayen, H. Neff, S. Shook; Denver: M. Chonchol, M. Levi, L. Clegg, A. Singleton; Detroit: D. Abu-Hamdan, L. Bey-Knight, K. King, E. Jones, Washington, DC: C. Palant, H. Sheriff, C. Simmons, J. Sinks; Gainesville: C. Wingo, B. McAllister, J. Sallustio, N. Smith; Hines: S. Popli, P. Linnerud, A. Zuluaga; Houston: G. Dolson, G. Tasby; Indianapolis: R. Agarwal, R. Lewis, D. Jasinski, N. Sachs, D. Veneck; Jackson: S. Ur Rehman, A. Basu, K. Ingram; Charleston: R. Paul, J. Raymond, K. Holmes; Kansas City: T. Wiegmann, J. Abdallah, A. Nagaria, D. Smith, A. Renft, T. Finnigan; Richmond: G. Feldman, S. Schmid; Memphis: C. Cooke, B. Wall, R. Patterson; Miami: G. Contreras, E. Jaimes, G. O'Brien; Minneapolis: K. Ma, J. Rust, S. Otterness; New Orleans: V. Batuman, C. Kulivan; New York: D. S. Goldfarb, M. Shea, F. Modersitzki; Northport: T. Dixon, E. Pastoriza, L. Titus; Palo Alto: R. Jamison, I. Cook, M. Anderson; Pittsburgh: P. Palevsky, P. Salai; Portland: S. Anderson, J. Walczyk; Seattle: A. Lindner, C. Stehman-Breen, E. Pascual, J. Nugent-Carney; San Diego: S. Thomson, S. Mullaney, J. Dingsdale; San Juan: C. Rosado, C. Azcona-Vilchez; Syracuse: S. Betcher, C. Rewakowski; West Palm Beach: D. Cohen, G. Flanagin, J. Steffe; Buffalo: J. Lohr, N. Fucile, L. Yohe; Milwaukee: S. Blumenthal, D. Schmidt.
Study Chair's Office, VA Palo Alto Healthcare System, Palo Alto, California: R. Jamison (study chair), M. Helmuth, G. Georgette, T. Shannon, H. Johnson, M. Martin.
VA Medical Center, Boston, Massachusetts: J. Gaziano (study cochair), R. Cxypoliski, N. Best, N. Pastore, D. Jones, A. Rayne, Z. Castrillon.
VA Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven: P. Peduzzi (director), M. Antonelli (associate director of operations), L. Durant, E. Jobes, S. Joyner, M. Perry, E. Petrokaitis, S. Zellner.
VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico: M. Sather (director), M. Chavez, J. Day, D. Garnand, S. Jenkins, M. Nicholson, D. Raisch, T. Sutton.
Massachusetts Veterans Epidemiology Research and Information Center, West Roxbury: M. Brophy, D. Humphries, D. Govan, L. Carlton, J. Wang.
VA Office of Research and Development, Clinical Science R&D, Washington, DC: T. J. O’Leary (director), G. D. Huang (deputy director, Cooperative Studies Program).
Funding/Support:This work was supported by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development. The VA Palo Alto Health Care System received payment from PamLab for performing chemical analyses, including the salary of a research technician and for supplies. Abbott Laboratories donated the homocysteine analytic kits.
Role of the Sponsors: The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, approved the manuscript for submission but was not involved in the design of the study or the collection, management, analysis, or interpretation of the data. Neither PamLab nor Abbott Laboratories was involved in the design or conduct of the study; the collection, management, analysis, and interpretation of the data; or review or approval of the manuscript.
Additional Contributions: We thank Ron Van Groningen, BS, VA Palo Alto HCS Chemistry Laboratory, for supervising the chemical analyses; and Philip Lavori, PhD, VA Palo Alto Cooperative Studies Program Coordinating Center, and Department of Health Research and Policy, Stanford University; David Tong, MD, California Pacific Medical Center Stroke Center, San Francisco; Paul Jungers, MD, Department of Nephrology, Necker Hospital, Paris, France; and Gere Sunder-Plassmann, MD, Klinische Abteilung fur Nephrologie und Dialyse, Universitatsklinik fur Innere Medizin III, University of Vienna, Vienna, Austria, for helpful advice and information. None of these individuals received compensation for their contributions.