Abstract

Convergent data suggest that advanced prostate cancer and coronary heart disease (CHD) share biological vulnerabilities that may be linked to adiposity. Here we explore whether leptin, as a marker and mediator of adiposity, could link prostate cancer to CHD. Patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a phase II trial (NCT02703623) studying androgen deprivation therapy, abiraterone, prednisone, and apalutamide were eligible if they had plasma and a chest CT scan available. Coronary artery calcium (CAC) scores and adipokine levels were measured upon enrollment. Of 164 patients, 87% were white. The mean age was 65.6 ± 7.5 years, 88% were either overweight or obese, 59% had hypertension, 48% had hyperlipidemia (HLD), 20% had type 2 diabetes mellitus, and 41% were former or current smokers. Coronary calcifications were found in 115 patients (70%). Among 47 patients with non-contrast chest CT scans, the median total CAC score was 133 AU (IQR 22.6-704.6). Four patients (9%) had a score of 0 AU (low risk) and 24 (51%) scores ≥100 AU, associated with high risk for major adverse cardiovascular events. Leptin levels correlated positively with the right coronary artery (RCA) CAC score [Pearson correlation coefficient (ρ) = 0.3715 (P = .0142)]. In a multivariate logistic regression analysis, older age, HLD, and higher leptin levels were independently associated with RCA calcification and a higher number of calcified coronary arteries. Among men with mCRPC, there was a high burden of CHD, and higher leptin levels were associated with coronary atherosclerosis independently of traditional cardiac risk factors.

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