Heart Failure Risk Among African-American Women With an ICAM1 Missense Variant

Prarthana J. Dalal, Division of Hematology and Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Pedro Giro, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Laura J. Rasmussen-Torvik, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Clyde W. Yancy, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Sanjiv J. Shah, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Alex P. Reiner, Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Bernhard Haring, Department of Medicine III, Saarland University Hospital, Homburg, Saarland, Germany; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Lisa Warsinger Martin, Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Gretchen L. Wells, Division of Cardiology, University of Alabama Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.
JoAnn E. Manson, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Charles Kooperberg, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Charles B. Eaton, Center for Primary Care and Prevention, Department of Family Medicine, Department of Epidemiology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island, USA.
Ravi B. Patel, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address: ravi.patel@northwestern.edu.

Document Type

Journal Article

Publication Date

3-11-2024

Journal

JACC. Heart failure

DOI

10.1016/j.jchf.2024.02.002

Keywords

genetics; heart failure with preserved ejection fraction; intercellular adhesion molecule-1; rs5491; women

Abstract

BACKGROUND: A common genetic variant of ICAM1 among African-American individuals (rs5491; p.K56M) is associated with heart failure (HF) hospitalization, but whether this risk is specific to heart failure with preserved ejection fraction (HFpEF) remains unclear. Older women are at high risk for HFpEF, and the relationship between rs5491 and HFpEF across the age spectrum is unknown. OBJECTIVES: This study assessed risk of HF and its subtypes conferred by ICAM1 p.K56M (rs5491). METHODS: Associations of rs5491 with risk of HF and its subtypes were estimated among African American individuals in WHI (Women's Health Initiative). The study evaluated whether the association between rs5491 and HF hospitalizations was modified by baseline age. Subsequently, African-American women in WHI and MESA (Multi-Ethnic Study of Atherosclerosis) were pooled and analyses were repeated. RESULTS: Among 8,401 women in WHI, the minor allele frequency of rs5491 was 20.7%, and 731 HF hospitalizations occurred over 19.2 years. The rs5491 variant was not associated with HF or its subtypes across WHI. Interaction analyses suggested that age as a continuous variable modified the association of rs5491 with HFpEF hospitalization (interaction P = 0.04). Upon categorizing women into age decades, rs5491 conferred increased risk of HFpEF among women ≥70 years (HR per additional rs5491 allele: 1.82 [95% CI: 1.25-2.65]; P = 0.002) but was not associated with HFpEF risk among women <70 years. Pooling African-American women in WHI (n = 8,401) and MESA (n = 856) demonstrated that the effect modification by age on the association of rs5491 with HFpEF became more significant (interaction P = 0.009), with consistent HFpEF risk effect estimates among women ≥70 years. CONCLUSIONS: ICAM1 p.K56M (rs5491) is associated with HFpEF among African-American women ≥70 years.

Department

Medicine

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