Role of Cancer History in Cardiovascular Mortality Among Different Age-group Patients With Differentiated Thyroid Cancer.

Background: Cardiovascular disease (CVD) is the leading cause of noncancer-related mortality among differentiated thyroid cancer (DTC) survivors, which accounts for a large portion of subsequent primary malignancies in childhood cancer survivors. This study aims to assess the risk of cardiovascular mortality among DTC as a second primary malignancy (DTC-2) patients compared with DTC as a first primary malignancy (DTC-1) and the general population. Methods: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 159 395 DTC-1 and 20 010 DTC-2 patients diagnosed older than 30 between 1975 and 2020 and the corresponding US population (71 214 642 person-years; 41 420 893 cardiovascular deaths). Compared with general-population and DTC-1 patients, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among DTC-2 patients using Poisson regression. To adjust for unmeasured confounders, we performed a nested, case-crossover analysis among DTC-2 patients who died from CVD. Results: Although DTC-2 patients had a comparable risk compared with the population (IRR 1.01) and a mildly increased risk of cardiovascular mortality compared with DTC-1 patients (IRR 1.26), the association was pronounced among individuals aged 30 to 74 years, especially 30 to 44 years (DTC-2 vs population: IRR 8.89; DTC-2 vs DTC-1: IRR 3.00). The risk elevation was greatest within the first month after diagnosis, compared with the population. The case-crossover analysis confirmed these results. Conclusion: DTC-2 patients are at increased risk of cardiovascular mortality. Clinicians should carefully monitor CVD and manage other CVD-related factors, such as exogenous thyroxine and emotional distress, for DTC-2 patients, especially for those under 75 years. Novelty and Impact Statements: This study is the first comprehensive investigation into the cardiovascular mortality of DTC-2, revealing a higher risk compared to DTC-1 and the general population, especially for cases between 30 and 74 years old. The risk elevation was greatest within the first month after diagnosis. These findings emphasize the restriction of thyroid hormone suppression therapy and reinforce stress management to prevent premature DTC-2 patients from cardiovascular death.