Abstract MPTH75: Linking Pulmonary Function Decline and Cardiovascular Disease Risk via Plasma Proteomics

Background: Pulmonary function decline is associated with an increased risk of cardiovascular disease (CVD), yet the underlying molecular mechanisms remain unclear. We aimed to identify plasma proteins associated with forced expiratory volume in one second (FEV1) decline and subsequent CVD risk and to uncover their shared molecular mechanisms. Methods: Spirometric measurements of FEV1 were collected at visits 2 (1990–92) and 5 (2011–13) in the Atherosclerosis Risk in Communities (ARIC) Study for discovery, and at years 6 (1993–94) and 18 (2005–06) in the Cardiovascular Health Study (CHS) for replication ( Figure 1 ). Plasma proteomics (5K SomaScan) were assayed at baseline for each cohort. Annualized FEV1 decline was assessed using linear regression, adjusting for age, sex, race, smoking, BMI, kidney function, and baseline FEV1. Proteins associated with FEV1 decline were examined for incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality, adjusting for clinical risk factors. Colocalization analyses were performed to assess shared genetic architecture between replicated proteins, FEV1, and clinical outcomes. Results: Among 4,766 proteins, 24 were associated with FEV1 decline (FDR0.7). Conclusion: We identified and replicated plasma proteins, notably Apo F, linking pulmonary function decline to cardiovascular outcomes, offering insight into shared molecular mechanisms of cardiopulmonary disorders and providing potential intervention targets.