Introduction: Prostate cancer is the most common malignancy among men in the United States. Few studies have evaluated cardiovascular disease (CVD) risk comprehensively among prostate cancer patients with treatment dose-response relations. The primary aim of our study is to assess the incidence of cardiovascular diseases among prostate cancer patients compared to a general population cohort. A secondary aim is to investigate socioeconomic status (SES) and clinical risk factors for cardiovascular disorders among prostate cancer patients. Methods: Cohorts of 18,134 cancer patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73,470 men without cancer matched on age, birth state and follow-up time were identified. CVD diagnoses were identified from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios (HRs), adjusted for race/ethnicity, education, baseline Body Mass Index (BMI), baseline Charlson Comorbidity Index (CCI), risk group, age at diagnosis, hyperlipidemia, smoking status, therapy type, and diagnosis year based on a comprehensive evaluation of confounding variables. Results: The risks of CVDs, including hypertension, arterial diseases, and venous diseases, among prostate cancer survivors compared to general population were increased for all follow-up periods after cancer diagnosis (1-5 years: HR=1.17, 95% CI=1.13-1.20; 5-10 years: HR=1.11, 95% CI=1.07-1.16; 10-16 years: HR=1.13, 95% CI=1.06-1.21). The risk of CVD was increased with obesity, baseline comorbidities, lower SES, and advanced-stage cancer, and differed by first-course cancer treatment, with CVDs higher for androgen deprivation therapy (ADT) and conservative treatment. Compared to intermittent ADT, continuous ADT was associated with increased risks of all-cause mortality among prostate cancer patients (HR=1.78, 95% CI=1.04-3.05). We also observed that an increasing duration of ADT was associated with an increased risk of arterial diseases (dose-response p=0.022) and an increased risk of all-cause mortality (dose-response p value=0.0439). Conclusions: We found an increased risk of CVDs that lasted through 10-16 years post-prostate cancer diagnosis. Lifestyle interventions to decrease the risk of CVDs in prostate cancer survivors may be potentially beneficial to increasing life expectancy. SOURCE OF Funding: This work was supported by grants from the NIH (R01 CA244326, R21 CA185811, R03 CA159357, M.Hashibe, PI), the Huntsman Cancer Institute, and the Cancer Control and Population Sciences Program (HCI Cancer Center Support Grant P30CA042014). This research was supported by the Utah Cancer Registry, which is funded by the National Cancer Institute's SEER Program, Contract No. HHSN261201800016I, the US Center for Disease Control and Prevention's National Program of Cancer Registries, Cooperative Agreement No. NU58DP0063200-01, with additional support from the University of Utah and Huntsman Cancer Foundation. Partial support for all datasets within the Utah Population Database is provided by the University of Utah, Huntsman Cancer Institute and the Huntsman Cancer Institute Cancer Center Support grant, P30 CA42014 from the National Cancer Institute.
