Title : Cardiovascular Risk in Prostate Cancer Patients

Abstract:

Cardiovascular disease is a leading cause of mortality in prostate cancer patients¹. Prostate cancer patients receiving androgen deprivation therapy (ADT), a standard treatment course for this population, are at higher risk for cardiovascular disease than patients whose treatment plan does not include ADT^2,3. Moreover, prostate cancer patients often experience bone metastases, culminating in bone destruction through heightened osteoclast activity. In addition, ADT further contributes to bone mineral density loss. Given the related processes of decalcification in bone and calcification in the heart, elucidating the relationship between cardiovascular and spinal health in prostate cancer patients is of great interest. The bone-vascular axis, underlying the relationship between bone and heart, in prostate cancer patients is not well-understood. Prostate-cancer specific indicators of cardiovascular risk, as well as interrelated cardiovascular and osseous risk, are necessary in this population. Patients with prostate cancer routinely undergo 18-F Sodium Fluoride Positron Emission Tomography with Computed Tomography ([18F]-NaF PET/CT) scans to monitor metastatic bone disease. Metabolism in healthy and metastatic bone, as well as cardiovascular calcification, can be measured through [18F]-NaF PET/CT via Standard Uptake Values (SUV). The purpose of this study was to use [18F]-NaF PET/CT opportunistically to elucidate potential relationships between bone and heart in prostate cancer patients. The spine was chosen as a region of interest for bone metabolism as it is a common osteoporotic fracture site. Further, it tends to have uniform radiotracer uptake across patients due to its high blood perfusion, making it an ideal point of comparison. The study retrospectively identified 112 patients with a history of prostate cancer who had full-body [18F]NaF-PET/CT scans available. The standard uptake values (SUVmean and SUVmax) of each vertebra from C2 to S1, as well as the heart, were determined using a PET/CT image processor (Fiji PET/CT Viewer Plug-in, Beth Israel) (Image 1, 2). SUVmax and SUVmean measured bone and heart metabolism. Hounsfield Units (HU) served as a measure of bone mineral density. Linear correlations were used to assess  the relationships between spinal metabolism and heart metabolism, as well as spinal bone mineral density and heart metabolism. A multiple regression analysis was also used to determine the effect of radiotracer dose on the aforementioned relationships. Our study reports that spine SUVmax positively correlates with heart SUVmax. Elevated myocardial uptake has been associated with cardiovascular inflammation⁴. In addition, cancer is reported to be associated with the development of coronary artery calcification, even after accounting for atherosclerotic risk factors; such calcification can often manifest in heightened cardiovascular metabolism⁵. Furthermore, when patients have higher spinal metabolism, it is usually an indication of disease or poor health profile⁶. Our study further reports that spine HU negatively correlates with heart SUVmean. Vascular calcification is frequently accompanied by bone demineralization, which may explain this negative correlation⁷.

References:

1. Pinthus, J. H., et al., The prevalence of cardiovascular disease and its risk factors among prostate cancer patients treated with and without androgen deprivation. Journal of Clinical Oncology 2020 38:6_suppl, 364-364.
2. Shin DW, Han K, Park HS, Lee SP, Park SH, Park J. Risk of Ischemic Heart Disease and Stroke in Prostate Cancer Survivors: A Nationwide Study in South Korea. Sci Rep. 2020;10(1):10313. Published 2020 Jun 25.
3. Kintzel PE, Chase SL, Schultz LM, O'Rourke TJ. Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Pharmacotherapy. 2008;28(12):1511-1522.
4. Kaneta T, Hakamatsuka T, Takanami K, et al. Evaluation of the relationship between physiological FDG uptake in the heart and age, blood glucose level, fasting period, and hospitalization. Ann Nucl Med. 2006;20(3):203-208. doi:10.1007/BF03027431
5. Whitlock MC, Yeboah J, Burke GL, Chen H, Klepin HD, Hundley WG. Cancer and Its Association With the Development of Coronary Artery Calcification: An Assessment From the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc. 2015;4(11):e002533. Published 2015 Nov 9. doi:10.1161/JAHA.115.002533
6. Jadvar H. Is There Use for FDG-PET in Prostate Cancer?. Semin Nucl Med. 2016;46(6):502-506. doi:10.1053/j.semnuclmed.2016.07.004
7. Persy V, D'Haese P. Vascular calcification and bone disease: the calcification paradox. Trends Mol Med. 2009;15(9):405-416. doi:10.1016/j.molmed.2009.07.001

What will the audience learn from your presentation?

• The audience will learn how prostate cancer patients are at heightened cardiovascular and osseous risk and how these processes may be interrelated.
• Our audience will further understand how [18F]-NaF PET/CT can serve as a predictive tool for opportunistic risk screening in this population and can illuminate shared disease processes between heart and bone.
• Our findings will help physicians treat cardiovascular complications of metastatic prostate cancer and prostate cancer treatment, particularly ADT.
• Faculty can use this research to further investigate the mechanistic relationships between cancer and heart metabolism, between heart metabolism and osseous metabolism, and between heart metabolism and bone mineral density.

Biography:

Nikita Bastin studied Biology and English at the University of Pennsylvania and graduated with a BA in May, 2021. Her Biology Honors Thesis focused on cardiovascular risk assessment in prostate cancer patients. She then joined a research group at the University of California, San Francisco, studying breast cancer.