Cardio-kidney-metabolic syndrome and prostate cancer: Prognostic significance of higher stages for cardiovascular morbidity and mortality.

Abstract

358 Background: Patients with prostate cancer (PC) face a significant burden of cardiovascular disease (CVD). The newly established Cardio-kidney-metabolic syndrome (CKMS) integrates a multitude of comorbidities and risk factors that shape the pathophysiology of CVD. This study aims to evaluate the association between CKMS and cardiovascular (CV) outcomes and mortality in patients with PC. We hypothesized that higher stages of CKMS are associated with higher risk of CV events (CVE), CV mortality (CVm), PC specific mortality (PCsm) and all-cause mortality. Methods: In this retrospective study, we utilized the SEER-Medicare linkage to identify patients with localized or metastatic PC ≥ 65 years of age. The chronic conditions files were subsequently used to classify patients into three CKMS groups as follows: stages 0-1 (excess/dysfunctional adiposity and no CKMS risk factors), stages 2-3 (metabolic risk factors, chronic kidney disease (CKD), or subclinical CVD), and stage 4 (clinical CVD in CKMS). Multivariable Fine-Gray competing risk models were used to evaluate CVE, CVm, and PCsm. The CVE composite included myocardial infarction, heart failure, atrial fibrillation, ischemic stroke, and peripheral artery disease post cancer diagnosis. We assessed all-cause mortality using Cox proportional hazard models. All statistical models adjusted for age, race, marital status, education level, socioeconomic position, PC grade, PC stage, rurality, surgery, radiation, chemotherapy, and androgen deprivation therapy (ADT). Results: A total of 104,400 patients met our inclusion criteria, with CKMS stages 0-1 having 17,028, stages 2-3 having 35,353, and stage 4 having 52,019 patients. There was a significant increase in CVE incidence in patients with CKMS stages 2-3 when compared to stages 0-1 (sHR 1.38; 95%CI 1.32-1.43, p<0.001), with a decrease in PCsm (0.92; 95% CI 0.85-0.99, p=0.035). Compared to CKMS stages 0-1, stage 4 showed a greater increase in CVE incidence (sHR 2.94; 95%CI 2.83-3.05, p<0.001), with a significant increase in CVm (sHR 2.64; 95%CI 2.36-2.96, p<0.001), and all-cause mortality (sHR 1.69; 95%CI 1.62-1.78, p<0.001) (Table). Conclusions: Higher CKMS stages are associated with worse CV outcomes in patients with PC. These findings show the critical need for proper diagnosis and management of CKMS in PC patients. Fine-Gray competing risk and Cox proportional hazards regression for the various outcomes using the fully adjusted model. Stage CVE CVm PCsm All-cause mortality CKMS 0-1 Reference Reference Reference Reference CKMS 2-3 1.375 (1.322-1.430, p<0.001) 1.051 (0.92-1.18, p=0.43) 0.920 (0.851-0.99, p=0.035) 1.00 (0.95-1.06, p=0.801) CKS 4 2.939 (2.832-3.051, p<0.001) 2.64 (2.36-2.96, p<0.001) 1.0 (0.933-1.08, p=0.91) 1.69 (1.617-1.783, p<0.001) Overall Population, Competing Risk = (All-Cause Mortality), sHR (95% CI, p-value).