Harris - Clinical Science Project

Due to the many shared risk factors, there is a bi-directional link between cardiovascular disease (CVD) and cancer, the two leading causes of death in the world. Although new treatments for cancer have improved survival, cancer survivors have a greater prevalence of CVD. While disparities associated with African American (AA) race and greater adiposity are shared risk factors between CVD and cancer, how they contribute to the prognosis and prevalence of cardiovascular outcomes in newly-diagnosed patients with cancer is unknown. Perhaps most disturbing is the fact that African Americans have a 42-134% greater rate of cancer mortality compared with Caucasians. Accordingly, there is a critical need to understand the impact of these health disparities and provide insight into novel therapeutic targets that can reduce the overall risk of CVD in patients diagnosed with cancer. The central hypothesis of this clinical project is in newly-diagnosed patients with cancer, health disparities associated with race and adiposity combine to accelerate the rate of vascular aging, via a reduction in cardiovascular function, a decrease in leukocyte telomere length (LTL), and an increase in the senescent associated secretory phenotype (SASP), thus contributing to a greater risk of CVD. In support, compelling preliminary data demonstrate that cardiovascular function is impaired and circulating markers of cellular senescence are increased in both obese and AA patients compared with lean and Caucasian patients with early-stage breast and prostate cancer. For the current proposal we will conduct a comprehensive assessment of cardiovascular function that will include evaluation of conduit- and micro- vascular endothelial function, arterial stiffness, carotid artery intima-media thickness, skeletal muscle mitochondrial function, and exercise tolerance over time in newly diagnosed patients with breast and prostate cancer. In addition, biological aging and cellular senescence will be assessed over time by LTL and a comprehensive panel of the SASP (IL-1?, IL-6, IL-8, IL-15, IL-18, TNF-a, MMP-1, IFN?, GDF15, and OPN), respectively. Further understanding of how newly onset cancer and cancer therapies affect functional, physiological, psychosocial, biological, and cellular outcomes of cardiovascular aging in patients with cancer will ultimately lead to primary and secondary prevention efforts aimed at reducing the overall disease burden.