The pK56M ICAM1 HFpEF risk variant and inflammatory biomarkers

Introduction: The ICAM1 variant rs5491 (p.K56M) is common among Black individuals and has been associated with risk of heart failure with preserved ejection fraction (HFpEF). The pathways by which rs5491 leads to HFpEF are not known. Methods: Among Black individuals within the Multi-Ethnic Study of Atherosclerosis, we evaluated associations of rs5491 with 3 inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-alpha receptor 1 [TNFR-1]).Results: Among 1558 Black participants (mean age 62 +/- 10 y, 47 % female), each additional rs5491 allele was associated with higher hsCRP after covariate adjustment (beta: 0.15, SE: 0.07, P = 0.02). Each additional rs5491 allele was associated with higher TNFR-1 (beta: 0.06, SE: 0.02, P = 0.02), but not IL-6 (beta: 0.04, SE: 0.04, P = 0.29). The association between rs5491 and HFpEF remained significant after adjustment for hsCRP.Conclusion: In Black individuals, rs5491 (p.K56M) is associated with higher hsCRP and higher TNFR-1, but not IL-6.