Abstract 4361: The plasma proteome as a cardiovascular disease risk assessment tool in cancer survivors
Authors: Troth Emma V. , Ayala Matthew , Chadwick Jessica , Hales Erin , Hinterberg Michael , Kuzma Jessica N. , Paterson Clare , Ostroff Rachel , Walter Joan E. , Mueller Christian , Coresh Josef 
Published: April 2023

Abstract
Cardiovascular disease (CVD) is the most common non-cancer cause of death in cancer survivors and there is an unmet clinical need for easy, accurate, and safe CVD prognostic risk-stratification in adult cancer survivors. This study investigated whether a previously validated 27-plasma protein prognostic model for four-year cardiovascular (CV) events could have such a utility. We used the 27-plasma protein model to predict the four-year risk of a CV event (myocardial infarction, stroke, transient ischemic attack, heart failure hospitalization, death) in 906 participants with a prior history or active malignancy of any type of cancer and compared predictive results to follow-up CV outcome data. The participants were from the BASEL VIII or ARIC (visit 3) studies with a medically adjudicated prior diagnosis of cancer. BASEL VIII is an observational cohort study in patients with suspected coronary artery disease. ARIC is a multi-site cohort study funded by the NHLBI, NCI, and NPCR investigating risk factors for CV health. A subset analysis was conducted to assess model performance in participants with no prior history of CVD and those with stable CVD. The 27-plasma protein model accurately stratified participants into 4 distinct and non-overlapping (95% CI) risk bins. The median time to event for all cancer survivors who had an event in this study was 1.3 years. Observed 4-year event rates across the 4 risk bins (low, medium-low, medium-high, and high) were 11.0%, 17.3%, 31.2% and 60.2%, respectively, which were higher than stratified event rates from our previously published metacohort analyses (5.6%, 11.2%, 20.0% and 43.4%, respectively) in participants with elevated CVD risk factors (e.g., prior events, diabetes, kidney disease and suspected coronary artery disease). The plasma protein model accurately predicted 4-year CVD risk with a C-index of 0.71 (0.68, 0.74) and 4-year AUC of 0.74 (0.69, 0.79). Performance of the protein model was comparable between participants with no prior history of CVD (C-Index: 0.69; AUC: 0.71) and stable CVD (C-Index: 0.69; AUC: 0.72), demonstrating the model accurately predicts CV event risk in cancer survivors regardless of cardiovascular history. Cancer survivors in this cohort can be distinguished with 4-year CV event rates as high as 60.2%, underscoring the urgent need for an easy and accurate risk stratification tool for this population. Prognostic protein testing may provide a novel tool for CVD risk assessment in adult cancer survivors.
Citation Format: Emma V. Troth, Matthew Ayala, Jessica Chadwick, Erin Hales, Michael Hinterberg, Jessica N. Kuzma, Clare Paterson, Rachel Ostroff, Joan E. Walter, Christian Mueller, Josef Coresh. The plasma proteome as a cardiovascular disease risk assessment tool in cancer survivors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4361.