Abstract Body (Do not enter title and authors here): Background: Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein that facilitates inflammation through leukocyte adhesion. Approximately 35% of African American individuals carry at least one copy of an ICAM1 missense variant (rs5491; p.K56M), which has been associated with increased risk of heart failure with preserved ejection fraction (HFpEF). Individuals with chronic kidney disease (CKD) are at high risk for HF, but whether the risk of HFpEF conferred by rs5491 extends to individuals with prevalent CKD is unknown.

Hypothesis: We hypothesized that in a CKD population, rs5491 is specifically associated with HFpEF, but not HF with reduced ejection fraction (HFrEF).

Methods: In the Chronic Renal Insufficiency Cohort (CRIC), participants were enrolled based upon an estimated glomerular filtration rate (eGFR) of 20 to 70 mL/min/1.73m². We estimated associations of rs5491 with incident HF and HF subtypes among African American individuals who were free from HF at baseline in CRIC. Models were adjusted for age, sex, systolic blood pressure, eGFR, body mass index, smoking, diabetes, C-reactive protein, the first 10 principal components of ancestry, and study site.

Results: Among 1267 African American participants without HF at baseline (mean age 57±11 years, 51% female, mean eGFR 45±15 mL/min/1.73m²), 464 (37%) had at least one copy of rs5491. During a median follow-up of 10.3 years (IQR: 4.7 – 15.0 years), there were 309 incident overall HF hospitalizations (160 HFpEF, 111 HFrEF, and 38 HF with unknown EF). Each additional rs5491 allele was significantly associated with incident HFpEF (HR 1.35 [95% CI: 1.03-1.76], P=0.029; Figure). The rs5491 variant was not associated with incident overall HF (HR 1.14, 95% CI: 0.93-1.39, P = 0.20) or incident HFrEF (HR 0.76, 95% CI: 0.53-1.10, P=0.15).

Conclusion: The ICAM1 p.K56M variant specifically confers increased risk of incident HFpEF among individuals with CKD.