Risk of Incident Circulatory Disease in Patients Treated for Differentiated Thyroid Carcinoma With No History of Cardiovascular Disease

Konstantinos A. Toulis; David Viola; George Gkoutos; Deepiksana Keerthy; Kristien Boelaert; Krishnarajah Nirantharakumar

Disclosures

Clin Endocrinol. 2019;91(2):323-330. 

In This Article

Results

The study population included 14 312 individuals consisting of 3009 patients with DTC matched for age, BMI, sex and smoking status to 11 303 controls, all of whom had no circulatory disease at baseline. The study population was followed up to a median of 5 years (range of follow-up 1.8-10.2 and 2.2-10.5 for the DTC and the control cohort, respectively). The mean age of the participants was 50.5 years, and, at baseline, patients treated for DTC were less likely to have diabetes (3.4% vs. 5.4% in controls) or receive treatment for dyslipidemia (8.4% vs. 10.4% in controls). On the other hand, the prevalence of hypertension was similar (16.1% vs. 17.3%) in both groups. During the observation period, a total of 1172 (8.2%) deaths from any cause were recorded. Death from any cause was more frequent in patients treated for DTC compared to controls (12.4% vs. 7.1% in controls). Approximately 50% had a documented TSH measurement during the first 3 years after the initial diagnosis, and among them, approximately 45% had TSH <0.1 mIU/L (Appendix S1, Table S2). Baseline characteristics by exposure group are presented in detailed in Table 1.

Risk of Incident Cardiovascular Event

A total of 1259 incident circulatory events (ischaemic heart disease, stroke or transient ischaemic attack, heart failure and atrial fibrillation) were recorded in the study population during the observation period. In the DTC cohort, ischaemic heart disease, stroke or transient ischaemic attack, heart failure and atrial fibrillation were recorded in 67 (2.23%), 83 (2.76%), 40 (1.33%) and 102 (3.39%) patients, respectively. In the control cohort, the observed events were 284 (2.51%), 280 (2.48%), 141 (1.25%) and 262 (2.32%), respectively.

No significant difference in the risk of incident ischaemic heart disease was detected between the DTC and control cohort (Crude HR: 0.94, 95% CI: 0.72-1.23, P-value = 0.657). This finding remained unchanged after adjustment for age, gender, BMI, smoking, social deprivation index, presence of hypertension, diabetes mellitus or use of lipid-lowering medications (Adjusted HR: 1.04, 95% CI: 0.80-1.36, P-value = 0769, Table 2). Similarly, no significant difference in the risk of incident heart failure between the DTC and control cohort was noted (Crude HR: 1.13, 95% CI: 0.80-1.61, P-value = 0.485 and aHR: 1.27, 95% CI: 0.89-1.81, P-value = 0.189, Table 2). On the other hand, the risk of incident atrial fibrillation was significantly higher in patients with DTC compared to controls (Crude HR: 1.57, 95% CI: 1.25-1.98, P-value < 0.001) and this finding remained robust after covariates adjustment (aHR: 1.71, 95% CI: 1.36-2.15, P-value < 0.001). The risk of stroke/TIA was found to be significantly elevated in patients treated for DTC only in the adjusted analysis (Crude HR: 1.19, 95% CI: 0.93-1.52, P-value = 0.170 and aHR: 1.34, 95% CI: 1.05-1.72, P-value = 0.020). A visual representation of the outcome-specific risk of suffering a circulatory event is presented in Figure 1.

Figure 1.

Incidence of circulatory disease in patients with differentiated thyroid carcinoma and controls over the observation period. The y-axis represents the outcome-specific cumulate e incidence (%) and the x-axis represents the analysis time in years [Colour figure can be viewed at wileyonlinelibrary.com]

Mortality was twice high in the DTC cohort (Crude HR: 1.86, 95% CI: 1.65-2.11, P-value < 0.001 and aHR: 2.07, 95% CI: 1.83-2.35, P-value < 0.001).

Sensitivity Analyses

A sensitivity analysis limited to patients with incident DTC and their respective controls involved a study sample of 1637 patients with DTC and 6162 matched controls. In this subgroup, the adjusted risk of death from any cause was significantly higher in patients with DTC compared to controls (aHR: 2.91, 95% CI: 2.46-3.45, P-value < 0.001).

The risk of incident atrial fibrillation remained significantly higher in patients with DTC compared to controls (Crude HR: 1.52, 95% CI: 1.09-2.11, P-value = 0.0014 and aHR: 1.86, 95% CI: 1.33-2.60, P-value < 0.001). No difference in the risk of incident ischaemic heart disease (Crude HR: 0.73, 95% CI: 0.48-1.12, P-value = 0.145 and aHR: 0.86, 95% CI: 0.56-1.32, P-value = 0.491) and heart failure (Crude HR: 0.79, 95% CI: 0.41-1.50, P-value = 0.467 and aHR: 0.95, 95% CI: 0.50-1.82, P-value = 0.881) was revealed. With regard to the risk of stroke/TIA, no significant difference was found between patients and controls (Crude HR: 0.84, 95% CI: 0.56-1.25, P-value = 0.389 and aHR: 0.99, 95% CI: 0.66-1.49, P-value = 0.974). Results of the sensitivity analyses by exposure status on an outcome-specific basis are detailed in Table 3. An additional sensitivity analysis on the basis of age bands (<55, ≥55, <65, ≥65) was also performed and provided no evidence of a differential outcome on the basis of age band.

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