Patients with differentiated thyroid cancerhad a greater risk of dying from cardiovascular disease compared with their peers who did not have cancer, even after accounting for traditional cardiovascular risk factors, a Dutch study showed.
The risk of cardiovascular mortality during follow-up was more than three times as high (hazard ratio 3.35, 95% CI 1.66-6.74) and the risk of all-cause mortality was more than four times as high (HR 4.40, 95% CI 3.15-6.14), according to Joop Lefrandt, MD, PhD, of the University Medical Center Groningen in the Netherlands, and colleagues.
"To the best of our knowledge, this is the first study reporting an increased risk of cardiovascular mortality in patients with differentiated thyroid carcinoma," they reported online in the Journal of Clinical Oncology, adding that the results "stress the importance of a close follow-up and could encourage assessment and treatment of cardiovascular risk factors during follow-up for [the cancer]."
The researchers also found that each 10-fold drop in the level thyroid stimulating hormone (TSH) was associated with a greater risk of cardiovascular mortality (HR 3.08, 95% CI 1.32-7.21), "supporting the current European Thyroid Association and the American Thyroid Association guidelines of tempering TSH suppression in patients with low risk of cancer recurrence."
Differentiated thyroid carcinoma is associated with a relatively good prognosis, with reported 10-year survival rates of 80% to 95%.
"Since the survival rate ... is high, there is increasing interest in possible harmful long-term effects of treatment," the authors noted. "Particularly, the use and the extent of thyroid hormone suppression therapy have become controversial in recent years, since thyroid hormone suppression therapy may increase cardiovascular morbidity."
To explore the issue, Lefrandt and colleagues examined data from 524 patients treated for differentiated thyroid carcinoma at their center. All were diagnosed from January 1980 to June 2010 and were treated with total thyroidectomy and radioiodine ablation. The patients were then matched by age and sex to 1,572 cancer-free participants in a population-based study performed in the same geographic region.
Additional therapies administered in the carcinoma group included adjuvant neck radiotherapy for local uncontrolled disease in 35 patients and systemic sorafenib (Nexavar) for progressive distant metastatic disease in five patients. No other systemic cancer therapies were used.
In both groups, the average age was 49 and about a quarter of the patients were men. Median follow-up was 8.5 years in the carcinoma group and 10.5 years in the control group.
During follow-up, 19.1% of the patients in the carcinoma group died, including 4.2% from cardiovascular disease (myocardial infarction, stroke, abdominal aortic aneurysm, or pulmonary embolism), 7.4% from progression of the cancer, and 7.4% from other or unknown causes.
In the control group, 5.4% died from any cause, including 1.5% from cardiovascular disease and 3.9% from other or unknown causes.
Risks of both all-cause and cardiovascular mortality were higher in the carcinoma group after adjustment for age, sex, and established cardiovascular risk factors, including body mass index, diabetes, smoking, hypertension, hypercholesterolemia, and history of cardiovascular disease at baseline.
And lower levels of TSH were associated with an increase in cardiovascular -- but not all-cause -- mortality after adjustment for those same factors plus differentiated thyroid carcinoma risk classification, histology, cumulative radioiodine dose, and neck radiotherapy.
Although the mechanism behind the elevated risk of cardiovascular death is unknown, "an increased risk for atrial fibrillation, impaired diastolic function, and an increased left ventricular mass have been found in patients with differentiated thyroid carcinoma receiving thyroid hormone suppression therapy," according to the authors. "Induction of these adverse cardiovascular effects ... may lead to an increased risk for stroke, heart failure, and myocardial infarction, respectively, and possibly contribute to the increased cardiovascular mortality."
The study was limited, they acknowledged, by the observational design, which precludes a definitive conclusion about causality, by differences in how causes of death were determined in the cases and the controls, by changes in the TSH assays used over time, and by possible bias stemming from trends in the treatment of cardiovascular disease.
The authors reported no conflicts of interest.
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