Abstract 4136285: Large-Scale Proteomics Identifies Novel Shared Biomarkers of Heart Failure and Cancer: the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: There is a bidirectional relationship between cancer and cardiovascular disease risk. Identifying proteins associated with both cancer and heart failure (HF) may provide insight into common biological pathways underlying both conditions. Methods: Among 10,136 participants in the community-based ARIC cohort study who were free of HF and cancer at study visit 2 (1990-92) and had aptamer-based proteomics (SomaScan v4), we assessed the association of 4,955 plasma proteins with incident HF and with incident site-specific cancer ascertained by cancer registry linkage supplemented with medical records (lung, post-menopausal breast, prostate, colorectal, and hematologic) using multivariable Cox models adjusted for demographics, clinical characteristics, and social determinants of health. Two-sample cis-Mendelian randomization ( cis- MR) was performed to evaluate potential causal effects of proteins on HF, left ventricular (LV) function, and site-specific cancer. Results: Mean age at baseline was 56±6; 54% were female; and 24% reported black race. Over a median follow-up of 10 [IQR 10, 10] years, there were 604 incident HF events and 1,207 incident cancers (169 lung, 85 hematologic, 105 colorectal, 206 breast, 288 prostate). Using a Bonferroni significance threshold (p < 1.0x10 -5 ), 23 proteins were associated with both HF and lung cancer, 2 with HF and hematologic malignancy, 1 with HF and colorectal cancer, and none with HF and breast or prostate cancer. Six proteins remained significantly associated with both HF and lung cancer after further adjustment for pack-years of smoking (Figure). In cis- MR of these six proteins, ICAM5 and MMP12 showed potential causal effect on LV volume and lung adenocarcinoma, and PLAUR showed potential causal effect on HF and lung adenocarcinoma. Conclusion: Among various types of cancer, proteins associated with lung cancer showed the greatest overlap with proteins associated with HF, which was largely accounted for by smoking exposure. We uncovered a set of 6 plasma proteins associated with both incident HF and lung cancer after accounting for smoking. MR identified proteins with potential causal effects on both lung adenocarcinoma and LV size (ICAM5, MMP12) and HF (PLAUR).