Increased Risk of Long-Term Cardiovascular Mortality and All-Cause Mortality in Patients With Differentiated Thyroid Carcinoma
In a study reported in the Journal of Clinical Oncology, Esther N. Klein Hesselink, of University Medical Center Groningen in the Netherlands, and colleagues evaluated long-term cardiovascular mortality in patients with differentiated thyroid cancer. They found that risk of cardiovascular and all-cause mortality is increased in these patients, independent of age, sex, and cardiovascular risk factors.
Study Details
Subjects from two cohorts consisting of 524 Dutch patients with differentiated thyroid cancer and 1,572 sex- and age-matched controls from a large population-based study in the same geographic region were retrospectively compared for cardiovascular mortality (primary endpoint), all-cause mortality, and the relationship between thyroid-stimulating hormone (TSH) and outcomes. Multivariate analysis included age, sex, body mass index (BMI), diabetes, smoking, hypertension, hypercholesterolemia, and history of cardiovascular disease at baseline.
Differentiated thyroid cancer patients and controls had a mean age of 49 ± 14 years, 74% vs 74% were female, 23% vs 30% were smokers, median BMI was 25.2 vs 25.5 kg/m2, 17.7% vs 11.5% had hypertension, 5.0% vs 3.4% had hypercholesterolemia, 4.2% vs 2.5% had diabetes, and 2.5% vs 2.9% had a history of cardiovascular disease.
The median cumulative radioiodine dose for differentiated thyroid cancer patients was 200 mCi (range, 55–426 mCi). A total of 35 patients (6.7%) received adjuvant neck radiotherapy for uncontrolled local disease, usually with a dose of 50 to 70 Gy. None of the 5 patients (1.0%) with progressive distant metastatic disease treated with sorafenib (Nexavar) died from a cardiovascular cause. Differentiated thyroid cancer patients received no other systemic therapies (including doxorubicin).
Cardiovascular and All-Cause Mortality
Median follow-up was 8.5 years (interquartile range, 4.1–15.9 years) in patients with differentiated thyroid cancer and 10.5 years (interquartile range, 9.9–10.9 years) in controls. Overall, 100 patients with differentiated thyroid cancer died (19.1%), 22 (4.2%) as a result of cardiovascular disease, 39 (7.4%) as a result of differentiated thyroid cancer, and 39 (7.4%) as a result of other/unknown causes. Death occurred in 85 controls (5.4%), 24 (1.5%) as a result of cardiovascular disease, and 61 (3.9%) as a result of other/unknown causes.
Patients with differentiated thyroid cancer had significantly increased risk for cardiovascular mortality on an unadjusted model (hazard ratio [HR] = 2.33, P = .015) and after adjustment for age, sex, and cardiovascular risk factors (HR = 3.35, P = .001). Differentiated thyroid cancer patients also had significantly increased risk of all-cause mortality on an unadjusted model (HR = 3.15, P < .001) and after adjustment for age, sex, and cardiovascular risk factors (HR = 4.40, P < .001).
Effect of TSH Level
TSH level was significantly predictive of cardiovascular mortality in differentiated thyroid cancer patients after adjustment for age, sex, cardiovascular risk factors, differentiated thyroid cancer risk classification, histology, cumulative radioiodine dose, and neck radiotherapy (HR = 3.08, 95% confidence interval [CI] = 1.32–7.21, for each 10-fold decrease in geometric mean TSH level). TSH level was not significantly associated with all-cause mortality (adjusted HR = 1.43, 95% CI = 0.97–2.12).
The investigators concluded: “The risk of cardiovascular and all-cause mortality is increased in patients with [differentiated thyroid cancer], independent of age, sex, and cardiovascular risk factors. A lower TSH level is associated with increased cardiovascular mortality, supporting the current European Thyroid Association and the American Thyroid Association guidelines of tempering TSH suppression in patients with low risk of cancer recurrence. Furthermore, patients with [differentiated thyroid cancer] may benefit from assessment and treatment of cardiovascular risk factors.”
Joop D. Lefrandt, MD, PhD, of University Medical Center Groningen, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
