Discussion
Based on the prospective definition of the HEIRS Study, we found serum ferritin concentration above 200 μg/L for women or 300 μg/L for men in 19.3% of more than 27,000 African Americans investigated in a multicenter primary care setting. Although the definition of what constitutes an elevated serum ferritin concentration in African Americans is open to discussion, participants with the combination of elevated serum ferritin concentration as defined by the HEIRS Study and transferrin saturations in the highest quartile to a significant extent more often had
HFE mutations and self-reported histories of iron overload or liver disease than those with nonelevated serum ferritin concentrations. Conversely, African American participants with the combination of elevated serum ferritin concentration and transferrin saturation in the lowest quartile gave histories of arthritis, diabetes mellitus and, for women only, heart failure significantly more often than those with nonelevated serum ferritin concentration. Although arthritis, diabetes mellitus, and heart failure are sometimes associated with certain iron overload conditions or increased indirect measures of iron status,
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considerable research points to strong associations of these conditions with inflammation.
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Increased levels of C-reactive protein in serum from blood donors before the onset of rheumatoid arthritis.
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The combination of elevated serum ferritin concentration and transferrin saturation in the highest quartile occurred in 6.7% of the participants, while the combination of elevated serum ferritin concentration and transferrin saturation in the lowest quartile occurred in 2.9%. This observation suggests that more participants with serum ferritin elevation had abnormalities related to increased iron stores or liver disease than to inflammation. Based on population risk estimates, approximately 11% of the cases of elevated serum ferritin concentration in combination with highest quartile transferrin saturation could be attributed to mutation of
HFE, self-reported iron overload, or self-reported liver disease. Because self-reporting may considerably underestimate true prevalence of disease,
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Agreement between patient reports of cardiovascular disease and patient medical records.
it seems likely that 11% is a conservative estimate. In addition to
HFE mutations, potential causes for increased body iron stores in African Americans include multiple blood transfusions in patients with sickle cell disease and other hematologic disorders
34Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease.
, 35Progression of iron overload in sickle cell disease.
and non-
HFE primary iron-loading conditions,
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Hemochromatosis and Iron Overload Screening (HEIRS) Study Research Investigators
Hemochromatosis and iron-overload screening in a racially diverse population.
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Ferroportin 1 (SCL40A1) variant associated with iron overload in African Americans.
some perhaps not yet identified. Potential causes of hepatic dysfunction in African Americans include hepatitis C infection,
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nonalcoholic steatosis and hepatitis (NASH),
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Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity.
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and heavy alcohol consumption.
39Changes in drinking patterns among whites, blacks, and Hispanics, 1984-1992.
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Limitations to our study include these considerations: The values for serum biochemical measures of iron status reported here represent single random determinations not confirmed by repeat testing. Other than testing for HFE mutations and concomitant transferrin saturation and interviewing patients for histories of certain diseases, possible explanations for an elevated serum ferritin concentration were not investigated in this screening cohort in the HEIRS Study.
We conclude that approximately 7% of African American primary care patients have the combination of serum ferritin concentration above 200 μg/L in women or 300 μg/L in men, and transferrin saturation above 29% in women or 35% in men, and that such individuals should be evaluated for increased body iron stores or liver disease.
Acknowledgments
Participating “HEIRS Study” Investigators and Institutions:
Field Centers
Birmingham, AL—University of Alabama at Birmingham:
Dr. Ronald T. Acton (Principal Investigator), Dr. James C. Barton (Co-Principal Investigator), Ms. Deborah Dixon, Dr. Susan Ferguson, Dr. Richard Jones, Dr. Jerry McKnight, Dr. Charles A. Rivers, Dr. Diane Tucker and Ms. Janice C. Ware.
Irvine, CA—University of California, Irvine:
Dr. Christine E. McLaren (Principal Investigator), Dr. Gordon D. McLaren (Co-Principal Investigator), Dr. Hoda Anton-Culver, Ms. Jo Ann A. Baca, Dr. Thomas C. Bent, Dr. Lance C. Brunner, Dr. Michael M. Dao, Dr. Korey S. Jorgensen, Dr. Julie Kuniyoshi, Dr. Huan D. Le, Dr. Miles K. Masatsugu, Dr. Frank L. Meyskens, Dr. David Morohashi, Dr. Huan P. Nguyen, Dr. Sophocles N. Panagon, Dr. Chi Phung, Dr. Virgil Raymundo, Dr. Thomas Ton, Professor Ann P. Walker, Dr. Lari B. Wenzel and Dr. Argyrios Ziogas.
London, Ontario, Canada—London Health Sciences Center:
Dr. Paul C. Adams (Principal Investigator), Ms. Erin Bloch, Dr. Subrata Chakrabarti, Ms. Arlene Fleischhauer, Ms. Helen Harrison, Ms. Kelly Jia, Ms. Sheila Larson, Dr. Edward Lin, Ms. Melissa Lopez, Ms. Lien Nguyen, Ms. Corry Pepper, Dr. Tara Power, Dr. Mark Speechley, Dr. Donald Sun and Ms. Diane Woelfle.
Portland, OR and Honolulu, HI—Kaiser Permanente Center for Health Research, Northwest and Hawaii, and Oregon Health and Science University:
Dr. Emily L. Harris (Principal Investigator), Dr. Mikel Aickin, Dr. Elaine Baker, Ms. Marjorie Erwin, Ms. Joan Holup, Ms. Carol Lloyd, Dr. Nancy Press, Dr. Richard D. Press, Dr. Jacob Reiss, Dr. Cheryl Ritenbaugh, Ms. Aileen Uchida, Dr. Thomas Vogt and Dr. Dwight Yim.
Washington, DC—Howard University:
Dr. Victor R. Gordeuk (Principal Investigator), Dr. Fitzroy W. Dawkins (Co-Principal Investigator), Ms. Margaret Fadojutimi-Akinsiku, Dr. Oswaldo Castro, Dr. Debra White-Coleman, Dr. Melvin Gerald, Ms. Barbara W. Harrison, Dr. Ometha Lewis-Jack, Dr. Robert F. Murray, Dr. Shelley McDonald-Pinkett, Ms. Angela Rock, Dr. Juan Romagoza and Dr. Robert Williams.
Central Laboratory
Minneapolis, MN—University of Minnesota Medical Center, Minneapolis, Minnesota:
Dr. John H. Eckfeldt (Principal Investigator and Steering Committee Chair), Ms. Catherine Leiendecker-Foster, Dr. Ronald C. McGlennen, Mr. Greg Rynders and Dr. Michael Y. Tsai.
Coordinating Center
Winston-Salem, NC—Wake Forest University:
Dr. David M. Reboussin (Principal Investigator), Dr. Beverly M. Snively (Co-Principal Investigator), Dr. Roger Anderson, Ms. Elease Bostic, Ms. Brenda L. Craven, Ms. Shellie Ellis, Dr. Curt Furberg, Mr. Jason Griffin, Dr. Mark Hall, Mr. Darrin Harris, Ms. Leora Henkin, Dr. Sharon Jackson, Dr. Tamison Jewett, Mr. Mark D. King, Mr. Kurt Lohman, Ms. Laura Lovato, Dr. Joe Michaleckyj, Ms. Shana Palla, Ms. Tina Parks, Ms. Leah Passmore, Dr. Pradyumna D. Phatak, Dr. Stephen Rich, Ms. Andrea Ruggiero, Dr. Mara Vitolins, Mr. Gary Wolgast and Mr. Daniel Zaccaro.
NHLBI Project Office
Bethesda, MD—Ms. Phyliss Sholinsky (Project Officer), Dr. Ebony Bookman, Dr. Henry Chang, Dr. Richard Fabsitz, Dr. Cashell Jaquish, Dr. Teri Manolio and Ms. Lisa O’Neill.
NHGRI Project Office
Bethesda, MD—Ms. Elizabeth Thomson.
Dr. Jean MacCluer, Southwest Foundation for Biomedical Research, also contributed to the design of this study.