Association between Cardiovascular Risk Factors and Long-Term All-Cause Mortality in Thyroid Cancer Survivors: An Israeli Population-Based Study

Background: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed long-term all-cause mortality and its association with cardiovascular risk factors in Israeli TC survivors compared to the general population.   Methods: The computerized database of Clalit Health Services, the largest healthcare fund in Israel, was used to identify individuals who were diagnosed with TC during 2001-2014 (exposed group) and age- and sex-matched individuals from the same healthcare system without thyroid disease or a cancer history (non-exposed group). Cox regression hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality were calculated by exposure status. Findings: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5,677 (10·2%) exposed patients and 1,235 individuals out of 23,962 (5·2%) non-exposed patients died. The TC survivors had an increased risk of all-cause mortality (HR=1·89, 95% CI 1·71-2·10), after adjusting for cardiovascular risk factors already present at the beginning of the follow-up. This increased risk was most pronounced in the 55- to 64-year old age group (HR=1·49, 95% CI 1·33-1·67). At the end of the follow-up, the TC survivors who died had a higher prevalence of hypertension (14·6% vs. 10·3%, P=0·002), more dyslipidemia (11·4% vs. 7·2%, P<0·001), and more cardiovascular disease (33·6% vs. 22·3%, P=0·05) compared to those who died in the non-TC group. In addition, there was no association between the presence of a second primary malignancy in the former group and the presence of a primary malignancy in the latter group.   Interpretation: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among Israeli TC survivors compared to matched non-TC individuals. Follow-up, primary and secondary prevention of cardiovascular risk factors in TC survivors are mandatory.    Funding Statement: The authors declare: "none." Declaration of Interests: The authors declare: "none." Ethics Approval Statement: The Medical Ethics Committee of the CHS provided approval to conduct this study. Signed informed consent from the participants was waived since the study was based on existing databases.