Abstract

Background: Lymphedema, abnormal lymphatic fluid accumulation in tissues, results in serious complications such as ulceration and reduces quality of life. Cancer treatment, through damage to lymph nodes and lymphatic vessels, is recognized as the main risk factor of lymphedema. However, understanding other risk factors is crucial for the prevention of lymphedema since there is no established curative treatment. Heart failure (HF) is considered an emerging risk factor for lymphedema through increased central and peripheral venous pressure, but the association of HF with incident lymphedema has not been systematically studied. Methods: In the Atherosclerosis Risk in Communities study, we included 9,895 individuals without prevalent lymphedema and cancer at visit 4 (1996-98) (n=9362 with no HF and n=533 with HF). Lymphedema was defined as two outpatient encounters (at least a week apart) or inpatient diagnoses through 2015 (ICD-9: 457.1 and ICD-10: I89.0). Participants without prevalent HF were categorized into two groups according to NT-proBNP, a marker of cardiac volume overload (>125 vs. ≤125 pg/mL [reference]), to acknowledge potential contribution of subclinical cardiac overload. Results: During a median follow-up of 17.7 (IQI 14.1-18.7) years, 149 participants developed lymphedema. 15-y cumulative incidence was higher in participants with HF and no HF with elevated NT-proBNP than those with no HF and non-elevated NT-proBNP (5.2% vs. 2.0% vs. 0.7%, respectively) ( Figure ). After accounting for potential confounders (e.g., body mass index, blood pressure, diabetes), the associations remained consistent (hazard ratios: 3.07 [95% CI 1.86, 5.08] for HF and 1.95 [1.33, 2.87] for no HF with elevated NT-proBNP). Results were consistent when using HF as a time-varying variable and censoring incident cancer. Conclusions: HF and subclinical elevation of NT-proBNP were associated with incident lymphedema, supporting the contribution of HF to the development of lymphedema.

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