Risk of Adverse Cardiovascular Outcomes in Differentiated Thyroid Cancer Survivors: A Systematic Review and Meta-Analysis

Introduction: Long-term cardiovascular (CV) risk is a concern for differentiated thyroid cancer (DTC) survivors.Methods: We performed a systematic review and meta-analysis evaluating the risks of CV mortality and morbidity in DTC survivors compared with the general population. Respective meta-analyses were conducted for data that were adjusted for relevant confounders and crude data. We searched five electronic databases from inception to October 2021, supplemented with a hand search. Two reviewers independently screened citations, reviewed full text articles, extracted data, and critically appraised the studies, with discrepancies resolved by a third reviewer. The primary outcome was CV mortality. Secondary outcomes included atrial fibrillation, ischemic heart disease, stroke, and heart failure. We estimated the relative risk (RR) and confidence intervals [CI] of outcomes using random-effects models (adjusted for age and gender), compared with the general population.Results: We reviewed 3409 unique citations, 65 full text articles, and included 7 studies. CV mortality risk was significantly increased in DTC survivors in one study adjusted for confounders-adjusted RR (aRR) 3.35 ([CI 1.66-6.67]; 524 DTC, 1572 controls). The risk of CV morbidity in DTC survivors, adjusted for risk factors, was estimated as follows: atrial fibrillation-aRR 1.66 [CI 1.22-2.27] (3 studies, 4428 DTC, I-2 = 75%), ischemic heart disease-aRR 0.97 [CI 0.84-1.13] (2 studies, 3910 DTC, I-2 = 0%), stroke-aRR 1.14 [CI 0.84-1.55] (2 studies, 3910 DTC, I-2 = 69%), and heart failure-aRR 0.98 [CI 0.60-1.59] (2 studies, 3910 DTC, I-2 = 79%). In meta-analyses of unadjusted data, the risks of CV mortality were not significantly increased but the CV morbidity risks were similar to adjusted data.Conclusions: There is limited evidence suggesting that DTC survivors may be at an increased risk of CV death and atrial fibrillation (after adjustment for confounders). We did not observe a significantly increased risk of ischemic heart disease, stroke, or heart failure. Most analyses were subject to significant heterogeneity and further research, with careful attention to CV risk factors, is needed to clarify CV risk in DTC survivors.Registration: PROSPERO CRD42021244743