Incident cardiovascular events among middle-age men are associated with increased risk of subsequent prostate cancer diagnosis

Abstract

Abstract Introduction Prostate cancer is the second most common malignancy in men worldwide, but incidence is highly dependent on screening. Purpose We aimed to examine whether incident cardiovascular disease (CVD) events are associated with increased risk of future prostate cancer in middle-aged men. Methods We evaluated asymptomatic self-referred men who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention, or stroke. Study endpoint was the development of cancer during follow up. Cancer and mortality data were available for all subjects from national registries. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event. Results Final study population included 18,282 subjects. Median age was 47 years (Interquartile range [IQR] 41–54). During median follow up time of 12 years (IQR 4–17) 2,047 (11%) subjects developed CVD, 406 (2.2%) developed prostate cancer and 694 (4%) died. Compared with patients who were free of CVD or prostate cancer during follow up, risk of death was 4, 6 and 15 times higher for patients who developed CVD event, prostate cancer, or both during follow up, respectively (p <.001 for all). Time dependent survival analysis showed that subjects who developed CVD during follow up were 60% more likely to develop prostate cancer (95% Confidence Interval [CI] 1.2–2.1, p=.001). However, after multivariable adjustment, this association was no longer significant. Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in middle-aged men (age≤55 years; N=14,473) incident CVD was associated with a significant 70% increased risk of subsequent cancer diagnosis in multivariable model (95% CI 1.13–2.6, p=.011, p for interaction=.002). Exploratory analysis of men younger than 55 showed that independent association of incident CVD with subsequent cancer diagnosis was different among subjects with normal body mass index (BMI) (≤25 kg/m2) compared with those with increased BMI (HR 0.55; 95% CI [0.22–1.42]; p value=0.23 vs. 1.6; 95% CI [1.007–2.54]; p value=.047; p for interaction=.058, respectively). Conclusion Incident CVD is independently associated with increased risk of subsequent prostate cancer diagnosis among men ≤55 years. Routine prostate cancer surveillance should be considered after CVD event in this population. Funding Acknowledgement Type of funding sources: None.