Effect Of Hyperthyroidism On The Hypercoagulable State And Thromboembolic Events In Patients With Atrial Fibrillation

Background and Objective:Previous studies have demonstrated patients with atrial fibrillation (AF) are at risk for thromboembolism. Hyperthyroidism(HT) is one of the most common reversible causes of atrial fibrillation. However, it remains unclear whether TH would increase thromboembolism events in AF.we aimed to clarify whether HT itself confers an additional influence on the thromboembolic event.Methods:We prospectively studied plasma D-dimer levels and thromboembolic event in patients with AF complicating hyperthyroidism (hyperthyroid AF, n=62). They were compared with sex-, age-, and risk factors-matched cohorts of patients with AF and normal thyroid function (nonthyroid AF, n=107) and hyperthyroid patients (Hyperthyroidism, n=100). Plasma D-dimer levels were used to evaluate the hypercoagulable state.Results:Baseline characteristics were comparable among the3groups. Among those patients with AF, there was no significant difference in gender (42%vs.36%,P=.42), mean CHADS-VASc score (1.6vs.1.6,P=0.64), left atrial diameter (43.7vs.42.6mm, P=0.28), and the number of patients with hypertension (35%vs.43%,P=0.42), diabetes (16%vs.13%, P=0.65), congestive heart failure (13%vs.8%,P=0.43), stroke (6%vs.6%,P=0.86), persistent AF (13%vs.9%,P=0.53) between patients with hyperthyroid AF and patients with nonthyroid AF. Although, patients with hyperthyroid AF were younger than patients with nonthyroid AF (55vs.59y, P=0.08), there was no significant difference in the number of patients older than65y (27%vs.29%,P=0.72). Before admission, there were no significant differences in the use of aspirin (19%vs.26%, P=0.35) or warfarin (6%vs.5%, P=0.73) for management of AF between patients with hyperthyroid AF and patients with nonthyroid AF. Among hyperthyroid patients, there was no significant difference in gender(42%vs.36%, P=0.50), age (55vs.52, P=0.19) and the number of patients with hypertension (35%vs.28%,P=0.38), diabetes (16%vs.14%,P=0.82), congestive heart failure (13%vs.11%,P=0.80), stroke (6%vs.3%,P=0.43), between patients with AF and without AF. Nevertheless, left atrial diameter was significantly larger in hyperthyroid patients with AF than without AF (42.9vs.36.6mm, P<0.001).D-dimer level was significantly higher in patients with hyperthyroid AF than with nonthyroid AF (0.66±0.06mg/1vs.0.34±0.02mg/1, P<0.001) and hyperthyroid patient (0.66±0.06mg/1vs.0.27±0.02mg/1, P<0.001). After nearly3years of follow-up, patients with hyperthyroid AF had a significantly higher incidence of ischemic stroke compared with patients with nonthyroid AF (HR:3.2,95%CI:1.01to5.59, P=0.04). Among those patients with AF, Logistic regression analysis revealed that both hyperthyroidism (OR:1.6,95%CI:1.2-2.6,P=0.02) and CHADS2-VAS score (OR:2.8,95%CI:1.6-5.0, P<0.01) were independent predictors for the occurrence of ischemic stroke. Meanwhile, Logistic regression analysis revealed that both D-dimer (OR:5.103,95%CI:1.03-4.54, P<0.05) and CHADS2-VAS score (OR:9.8,95%CI:2.3-7.6, P=0.007)were independent predictors for the occurrence of ischemic stroke in the hyperthyroid patient with AF. While, warfarin was independent protector for the occurrence of ischemic stroke in the hyperthyroid patient with AF (OR:0.85,95%CI:0.84-0.95, P=0.04), and patient with AF (OR:0.87,95%CI:0.82-0.90,P=0.03).Conclusions:The present study suggests that hyperthyroidism enhances the hypercoagulable state and increase thromboembolic events in patients with atrial fibrillation. Objective:Previous studies have demonstrated that D-dimer level is increased in patients with nonvalvular AF(NVAF). Meanwhile, D-dimer level can effectively predict subsequent embolic events in patients with the NVAF, even during oral anticoagulant therapy.We aimed to clarify whether hyperthyroidism itself confers an additional influence on the D-dimer level, and the relationship between D-dimer levels and thromboembolic risk in hyperthyroid patients with atrial fibrillation.Methods:We prospectively studied plasma D-dimer levels and thromboembolic event in patients with AF complicating hyperthyroidism (hyperthyroid AF, n=62). They were compared with sex-, age-, and risk factors-matched cohorts of patients with AF and normal thyroid function (nonthyroid AF, n=107) and hyperthyroid patients (Hyperthyroidism, n=100). Plasma D-dimer levels were used to evaluate the hypercoagulable state.Results:Baseline characteristics were comparable among the3groups. Among those patients with AF, there was no significant difference in gender (42%vs.36%,P=0.42), mean CHADS-VASc score (1.6vs.1.6,P=0.64), left atrial diameter (43.7vs.42.6mm,P=0.28), and the number of patients with hypertension (35%vs.43%, P=0.42), diabetes (16%vs.13%,P=0.65), congestive heart failure (13%vs.8%,P=0.43), stroke (6%vs.6%,P=0.86), persistent AF (13%vs.9%, P=0.53) between patients with hyperthyroid AF and patients with nonthyroid AF. Although, patients with hyperthyroid AF were younger than patients with nonthyroid AF (55vs.59y, P=0.08), there was no significant difference in the number of patients older than65y (27%vs.29%, P=0.72). Before admission, there were no significant differences in the use of aspirin (19%vs.26%, P=0.35) or warfarin (6%vs.5%, P=0.73) for management of AF between patients with hyperthyroid AF and patients with nonthyroid AF. Among hyperthyroid patients, there was no significant difference in gender(42%vs.36%, P=0.50), age (55vs.52,P=0.19) and the number of patients with hypertension (35%vs.28%,P=0.38), diabetes (16%vs.14%, P=0.82), congestive heart failure (13%vs.11%,P=0.80), stroke (6%vs.3%,P=0.43), between patients with AF and without AF. Nevertheless, left atrial diameter was significantly larger in hyperthyroid patients with AF than without AF(42.9vs.36.6mm, P<0.01).D-dimer level was significantly higher in patients with hyperthyroid AF than with nonthyroid AF (0.66±0.06mg/1vs.0.34±0.02mg/1, P<0.001) and hyperthyroid patient (0.66±0.06mg/1vs.0.27±0.02mg/1, P<0.001). After nearly3years of follow-up, patients with hyperthyroid AF had a significantly higher incidence of ischemic stroke compared with patients with nonthyroid AF (HR:3.2,95%CI:1.01to5.59,P=0.04). Patients with hyperthyroid AF of D-dimer level<0.6mg/L had a significantly lower incidence of ischemic stroke compared with patients of D-dimer level≥0.6mg/L (2VS.10,P=.04)Whatever among all atrial fibrillation patients or hyperthyroid patients with atrial fibrillation, the number of the D-dimer level<0.6mg/L of patients who occured stoke was significantly less than patients who did not occure stoke.Regardless of the clinical risk factors, among hyperthyroid patients whose D-dimer level was below0.6mg/L, the incidence of thromboembolic event levels was just3.5%per year, adversely, the incidence rose to11.1%per year during patients whose D-dimer level was above0.6mg/L. the trend of the incidence was also applied to all atrial fibrillation patients. If D-dimer level≥0.6mg/L was defined as positive and it was used to diagnosis stoke in thyperthyroid patients with atrial fibrillation, Positive predictive value33.3%, negative predictive value89.5%;while for all patients with atrial fibrillation, Positive predictive value23.7%negative predictive value90.3%. Among those patients with AF, Logistic regression analysis revealed that both hyperthyroidism (OR:1.6,95%CI:1.2-2.6, P=0.02) and CHADS2-VAS score(OR:2.8,95%CI:1.6-5.0, P<0.001) were independent predictors for the occurrence of ischemic stroke. Meanwhile, Logistic regression analysis revealed that both D-dimer (OR:5.103,95%CI:1.03-4.54, P<0.05) and CHADS2-VAS score (OR:9.8,95%CI:2.3-7.6, P<0.01)were independent predictors for the occurrence of ischemic stroke in the hyperthyroid patient with AF.Conclusions:The present study suggests that hyperthyroidism enhances the hypercoagulable state and increase thromboembolic events in patients with atrial fibrillation.