Patients with renal cell carcinoma (RCC) often harbor risk factors for cardiovascular disease and may receive anti-VEGF agents, which are associated with cardiovascular toxicity. However, the risk for cardiovascular mortality in this patient population is currently unknown.
Utilizing the SEER database, we identified patients with RCC diagnosed between 2007 (approval of sunitinib) and 2015 and selected patients aged ≥45 years. We calculated standardized mortality ratios (SMRs) for cardiovascular mortality (ICD-10 codes I00-I99) by comparing the number of observed deaths in the database to the number of expected deaths in age-matched groups of the US general population drawn from the CDC WONDER database. Multivariable Cox regression was used to identify risk factors for cardiovascular mortality in patients with RCC.
We identified 36,576 patients with RCC, of which 33,748 (92.3%) were ≥45 years old and among these, 1650 (4.9%) died of cardiovascular diseases. The SMR for cardiovascular mortality was 2.85 (95% CI 2.72-2.99) for all patients, 2.78 (95% CI 2.62-2.95) for males and 2.86 (95% CI 2.64-3.10) for females. Among the various age groups, the SMR was 4.75 (95% CI 3.82-5.84) for patients aged 45-54 years, 3.35 (95% CI 2.93-3.83) for patients aged 55-64 years, 2.75 (95% CI 2.49-3.04) for patients aged 65-74 years, 2.25 (95% CI 2.07-2.45) for patients aged 75-84 years, and 1.47 (95% CI 1.33-1.61) for patients aged > 85 years. In multivariate analysis, advancing age (HR 1.06, 95% CI 1.06-1.07), male sex (HR 1.18, 95% CI 1.05-1.33), black race (HR 1.48, 95% CI 1.27-1.73), stage IV disease (HR 1.21, 95% CI 1.01-1.45), and performance of surgery directed to the primary tumor (HR 0.33, 95% CI 0.29-0.38) were independently associated with cardiovascular mortality.
Patients with RCC possess an almost 3-fold greater risk for cardiovascular mortality than the general population and this risk is even more pronounced in middle-aged patients. Aggressive management of modifiable cardiovascular risk factors in this patient population is thus warranted.