Atherosclerotic Cardiovascular Diseases Are Associated With Incident Metastatic and Nonmetastatic Cancer

Background: Cardiovascular diseases are associated with higher cancer risk. However, their relationship with metastatic cancer, the primary determinant of cancer prognosis, has not been studied. Objectives: This study aimed to determine the association between atherosclerotic cardiovascular disease and the presence of metastasis at the time of cancer diagnosis. Methods: We analyzed data from 21,654 self-referred adults who were free of cancer and atherosclerotic cardiovascular disease at enrollment in a preventive health care program. To exclude silent cancers, a 1-year blanking period was implemented at the start of the follow-up. The relationship between atherosclerotic cardiovascular disease and metastatic cancer was assessed using cause-specific Cox regression, treating incident atherosclerotic cardiovascular disease as a time-dependent covariate. Interaction analysis further elucidated differences in metastasis risks between middle-aged adults (Q1-Q3 age ≤54 years) and older adults (Q4 age >54 years). Results: Over a median follow-up of 6 years (Q1-Q3: 3-12 years), we recorded 1,333 cases of atherosclerotic cardiovascular disease (6.2%) and 1,793 cases of cancer (8.3%), of which 1,036 (4.8 %) were nonmetastatic and 757 (3.5%) were metastatic at diagnosis. After adjusting for shared risk factors, atherosclerotic cardiovascular disease was independently associated with an increased risk of cancer metastasis at the time of cancer diagnosis (HR: 1.75; 95% CI: 1.33-2.29). This association was more pronounced among middle-aged adults (HR: 1.64; 95% CI: 1.03-2.61; P = 0.036) than in older adults (HR: 1.11; 95% CI: 0.78-1.60; P = 0.56), with a significant interaction (P_interaction = 0.039). Conclusions: Atherosclerotic cardiovascular disease is associated with a significantly increased risk of cancer, specifically metastasis at the time of cancer diagnosis, particularly in middle-aged adults. Recognizing this association could enhance the prevention and treatment of metastatic cancer in patients with atherosclerotic cardiovascular disease.