Division of Hematology and Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
JACC Heart Fail. 2024 Sep;12(9):1614-1624. doi: 10.1016/j.jchf.2024.02.002. Epub 2024 Mar 25.
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.
This study assessed risk of HF and its subtypes conferred by ICAM1 p.K56M (rs5491).
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.
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.
ICAM1 p.K56M (rs5491) is associated with HFpEF among African-American women ≥70 years.
非洲裔美国人个体中一种常见的细胞间黏附分子 1（ICAM1）基因变异（rs5491；p.K56M）与心力衰竭（HF）住院相关，但该风险是否特定于射血分数保留的心力衰竭（HFpEF）尚不清楚。老年女性是 HFpEF 的高危人群，而 rs5491 与整个年龄段 HFpEF 的关系尚不清楚。
本研究评估了细胞间黏附分子 1 p.K56M（rs5491）对 HF 及其亚型的风险。
在 WHI（妇女健康倡议）中评估了 rs5491 与 HF 及其亚型风险的关系。研究评估了 rs5491 与 HF 住院之间的关联是否受基线年龄的影响。随后，将 WHI 和 MESA（多民族动脉粥样硬化研究）中的非裔美国女性进行合并，并重复了分析。
在 WHI 中的 8401 名女性中，rs5491 的次要等位基因频率为 20.7%，19.2 年内共发生 731 例 HF 住院。rs5491 变异与 HF 或其各亚型均无相关性。交互分析表明，年龄作为连续变量改变了 rs5491 与 HFpEF 住院的关联（交互 P = 0.04）。将女性分为年龄十年组后，rs5491 增加了≥70 岁女性 HFpEF 的发病风险（每增加一个 rs5491 等位基因的 HR：1.82[95%CI：1.25-2.65]；P = 0.002），但与<70 岁女性 HFpEF 风险无关。合并 WHI 中的非裔美国女性（n = 8401）和 MESA（n = 856）的结果表明，年龄对 rs5491 与 HFpEF 关联的影响修饰作用变得更加显著（交互 P = 0.009），≥70 岁女性的 HFpEF 风险效应估计一致。
ICAM1 p.K56M（rs5491）与≥70 岁非裔美国女性 HFpEF 相关。
