Abstract Body (Do not enter title and authors here): Background: Chronic kidney disease (CKD) and heart failure (HF) are interrelated but the bidirectional associations between the two conditions are not completely understood.

Hypothesis: Bidirectional associations between CKD and HF are common in ambulatory populations and have implications for survival.

Methods: We conducted a prospective cohort study of 11595 participants who attended ARIC Visit 4 (1996-98) with data on prevalent CKD and HF status, with follow-up for incident events through 2021. We assessed the prospective association of prevalent CKD (defined as eGFR<60 ml/min per 1.73 m² or urine albumin-creatinine ratio of ≥30 mg/g) at Visit 4 with incident HF. We also assessed the association of prevalent HF at Visit 4 with incident CKD through 2019. Analyses accounted for mortality as a competing risk. We cross-categorized CKD and HF at Visit 4 and assessed prospective associations with mortality relative to those with neither condition.

Results: The mean age in the study population was 63 years, with 56% women; and 23% Black adults. Among 1222 with prevalent CKD, 529 (43%) developed HF; among 433 with prevalent HF, 137 (31%) developed CKD. After multivariable adjustment, prevalent CKD (vs no CKD) was associated with incident HF (HR 1.87; 95% CI, 1.65–2.12; Figure). Prevalent HF (vs no HF) was also associated with incident CKD (HR 1.33; 95% CI, 1.09–1.62). The co-occurrence of prevalent CKD and HF was associated with greater mortality risk (HR, 2.07; 95% CI, 1.78–2.42) than prevalent CKD alone (HR, 1.47; 95% CI, 1.37–1.59) or prevalent HF alone (HR, 1.33; 95% CI, 1.18–1.50), when compared with neither condition (p_interaction<0.001).

Conclusions: Bidirectional associations between CKD and HF are common in ambulatory populations. The co-existence of both CKD and HF is associated with higher mortality compared to either alone. There is a need to refine strategies to mitigate risk associated with bidirectional CKD and HF associations.