Figure 1
Flowchart of the study.
Table 1
Real-world baseline characteristics and medications of the patients with atrial fibrillation with and without clinical hyperthyroidism before matching.
| Variables | The whole AF population | AF population without OAC | ||||
|---|---|---|---|---|---|---|
| HT AF (n = 3,880) | Non-HT AF (n = 178,711) | P-value | HT AF (n = 3,330) | Non-HT AF (n = 155,121) | P-value | |
| Age (years, mean, SD) | 60.1 ± 14.8 | 71.9 ± 13.6 | <0.001 | 59.9 ± 14.9 | 72.1 ± 13.7 | <0.001 |
| Sex | <0.001 | <0.001 | ||||
| Male | 1,355 (34.9) | 101,435 (56.8) | 1,139 (34.2) | 87,791 (56.6) | ||
| Comorbidities | ||||||
| Dyslipidemia | 202 (5.2) | 18,422 (10.3) | <0.001 | 165 (5.0) | 15,495 (10.0) | <0.001 |
| Chronic kidney disease | 232 (6.0) | 22,502 (12.6) | <0.001 | 198 (5.9) | 20,145 (13.0) | <0.001 |
| Obstructive pulmonary disease | 379 (9.8) | 35,923 (20.1) | <0.001 | 322 (9.7) | 32,618 (21.0) | <0.001 |
| Ischemic heart disease | 886 (22.8) | 63,793 (35.7) | <0.001 | 753 (22.6) | 55,482 (35.8) | <0.001 |
| Peripheral arterial disease | 57 (1.5) | 4,712 (2.6) | <0.001 | 47 (1.4) | 4,014 (2.6) | <0.001 |
| History of stroke | 223 (5.7) | 26,797 (15.0) | <0.001 | 185 (5.6) | 23,080 (14.9) | <0.001 |
| History of myocardial infarction | 57 (1.5) | 6,778 (3.8) | <0.001 | 48 (1.4) | 5,929 (3.8) | <0.001 |
| Malignancy | 135 (3.5) | 10,549 (5.9) | <0.001 | 120 (3.6) | 9,373 (6.0) | <0.001 |
| Components of CHA2DS 2-VASc | ||||||
| Congestive heart failure | 240 (6.2) | 21,632 (12.1) | <0.001 | 198 (5.9) | 18,741 (12.1) | <0.001 |
| Hypertension | 1,738 (44.8) | 100,341 (56.1) | <0.001 | 1,485 (44.6) | 85,996 (55.4) | <0.001 |
| Age (years) | <0.001 | <0.001 | ||||
| 65–74 | 765 (19.7) | 45,486 (25.5) | 645 (19.4) | 38,488 (24.8) | ||
| ≥75 | 724 (18.7) | 86,584 (48.4) | 610 (18.3) | 76,945 (49.6) | ||
| Diabetes mellitus | 548 (14.1) | 31,986 (17.9) | <0.001 | 466 (14.0) | 27,738 (17.9) | <0.001 |
| Prior stroke or systemic thromboembolism | 252 (6.5) | 29,643 (16.6) | <0.001 | 204 (6.1) | 25,053 (16.2) | <0.001 |
| Vascular disease | 927 (23.9) | 67,315 (37.7) | <0.001 | 787 (23.6) | 58,471 (37.7) | <0.001 |
| Sex: female | 2,525 (65.1) | 77,276 (43.2) | <0.001 | 2,191 (65.8) | 67,330 (43.4) | <0.001 |
| CHA2DS2-VASc score | <0.001 | <0.001 | ||||
| 0 | 532 (13.7) | 12,857 (7.2) | 465 (14.0) | 11,283 (7.3) | ||
| 1 | 1,134 (29.2) | 21,302 (11.9) | 986 (29.6) | 18,249 (11.8) | ||
| 2 | 751 (19.4) | 30,426 (17.0) | 644 (19.3) | 26,297 (17.0) | ||
| 3 | 552 (14.2) | 37,148 (20.8) | 464 (13.9) | 32,311 (20.8) | ||
| 4 | 445 (11.5) | 33,687 (18.8) | 377 (11.3) | 29,383 (18.9) | ||
| 5 | 276 (7.1) | 22,620 (12.7) | 226 (6.8) | 19,696 (12.7) | ||
| 6 | 114 (2.9) | 12,359 (6.9) | 104 (3.1) | 10,690 (6.9) | ||
| 7–9 | 76 (2.0) | 8,312 (4.6) | 64 (2.0) | 7,212 (4.6) | ||
| Total score | 2.2 ± 1.8 | 3.2 ± 1.9 | <0.001 | 2.2 ± 1.8 | 3.2 ± 1.9 | <0.001 |
| Medication | ||||||
| ACEI/ARB | 1,491 (38.4) | 75,769 (42.4) | <0.001 | 1,210 (36.3) | 62,690 (40.4) | <0.001 |
| CCB | 682 (17.6) | 48,664 (27.2) | <0.001 | 605 (18.2) | 42,425 (27.3) | <0.001 |
| β-blocker | 2,809 (72.4) | 61,562 (34.4) | <0.001 | 2,408 (72.3) | 51,644 (33.3) | <0.001 |
| Statin | 197 (5.1) | 19,519 (10.9) | <0.001 | 154 (4.6) | 15,674 (10.1) | <0.001 |
| Biguanides | 382 (9.8) | 18,936 (10.6) | 0.133 | 318 (9.5) | 16,090 (10.4) | 0.123 |
| Sulfonylurea | 392 (10.1) | 20,899 (11.7) | 0.002 | 339 (10.2) | 18,042 (11.6) | 0.010 |
| DPP4i | 76 (2.0) | 2,983 (1.7) | 0.164 | 60 (1.8) | 2,407 (1.6) | 0.249 |
| Insulin | 106 (2.7) | 6,125 (3.4) | 0.018 | 93 (2.8) | 5,384 (3.5) | 0.034 |
| Anticoagulants | 550 (14.2) | 23,590 (13.2) | 0.076 | NA | NA | NA |
| Anti-hyperthyroidism agents | ||||||
| Methimazole | 1,556 (40.1) | 0 (0.0) | NA | 922 (27.7) | 0 (0.0) | NA |
| Carbimazole | 455 (11.7) | 0 (0.0) | NA | 681 (20.5) | 0 (0.0) | NA |
| Propylthiouracil | 814 (21.0) | 0 (0.0) | NA | 374 (11.2) | 0 (0.0) | NA |
| Mixed (switch) | 1,055 (27.2) | 0 (0.0) | NA | 1,353 (40.6) | 0 (0.0) | NA |
[i] ACEI, angiotensin-converting enzyme inhibitors; AF, atrial fibrillation; ARB, angiotensin receptor blockers; CCB, calcium channel blockers; DPP4i, dipeptidyl peptidase 4 inhibitor; HT, hyperthyroidism; OAC, oral anticoagulants; NA, not applicable; SD, standard.
Figure 2
Cumulative event rates of ischemic stroke or systemic thromboembolism (A), ischemic stroke (B), and systemic thromboembolism (C) in AF patients with clinical hyperthyroidism and non-thyroid AF patients in a propensity score-matched cohort. AF: atrial fibrillation.
Figure 3
Cumulative event rates of ischemic stroke or systemic thromboembolism (A), ischemic stroke (B), and systemic thromboembolism (C) in AF patients with clinical hyperthyroidism and non-thyroid AF patients who were not prescribed with anticoagulants after propensity score matching. AF: atrial fibrillation.
Figure 4
Cumulative event rates of ischemic stroke or systemic thromboembolism (A), ischemic stroke (B), and systemic thromboembolism (C) in AF patients with clinical hyperthyroidism and non-hyperthyroidism AF patients who were prescribed with anticoagulants after propensity score matching. AF: atrial fibrillation.
Figure 5
Incidence densities of ischemic stroke or systemic thromboembolism (A), ischemic stroke (B), and systemic thromboembolism (C) in AF patients with clinical hyperthyroidism and non-thyroid AF patients in a real-world setting according to CHA2DS2-VASc score. AF: atrial fibrillation.
Table 2
Detailed information of Ischemic Stroke/Systemic Thromboembolism, Ischemic Stroke and Systemic Thromboembolism in AF patients with and without clinical hyperthyroidism who did not prescribe any anticoagulation therapy.
| Ischemic stroke/ Systemic thromboembolism | ||||||||
|---|---|---|---|---|---|---|---|---|
| CHA2DS2-VASc | HT AF | Non-HT AF | HT AF vs. Non-HT AF | |||||
| Numbers | Event (%) | ID (95% CI) § | Numbers | Event (%) | ID (95% CI) § | HR (95% CI) | P-value | |
| 0 | 465 | 21 (4.5) | 0.9 (0.5–1.3) | 11283 | 583 (5.2) | 1.0 (0.9–1.1) | 0.82 (0.53–1.27) | 0.376 |
| 1 | 986 | 32 (3.3) | 0.6 (0.4–0.8) | 18249 | 1462 (8.0) | 1.7 (1.6–1.8) | 0.36 (0.25–0.51) | <0.001 |
| 2 | 644 | 45 (7.0) | 1.5 (1.1–1.9) | 26297 | 3083 (11.7) | 3.1 (3.0–3.2) | 0.49 (0.36–0.65) | <0.001 |
| 3 | 464 | 43 (9.3) | 2.1 (1.5–2.7) | 32311 | 4512 (14.0) | 4.1 (4.0–4.2) | 0.52 (0.39–0.71) | <0.001 |
| 4 | 377 | 39 (10.3) | 2.7 (1.8–3.6) | 29383 | 4311 (14.7) | 4.7 (4.6–4.8) | 0.58 (0.42–0.80) | <0.001 |
| 5–9 | 394 | 67 (17.0) | 5.3 (4.0–6.6) | 37598 | 6800 (18.1) | 6.9 (6.7–7.1) | 0.80 (0.63–1.02) | 0.071 |
| Stratified | ||||||||
| 0–4 | 2936 | 180 (6.1) | 1.3 (1.1–1.5) | 117523 | 13951 (11.9) | 3.1 (3.0–3.2) | 0.41 (0.35–0.48) | <0.001 |
| 5–9 | 394 | 67 (17.0) | 5.3 (4.0–6.6) | 37598 | 6430 (17.1) | 6.9 (6.7–7.1) | 0.80 (0.63–1.02) | 0.071 |
| Total | 3330 | 247 (7.4) | 1.6 (1.4–1.8) | 155121 | 20381 (13.1) | 3.9 (3.8–4.0) | 0.44 (0.38–0.49) | <0.001 |
| Ischemic Stroke | ||||||||
| 0 | 465 | 21 (4.5) | 0.9 (0.5–1.3) | 11283 | 487 (4.3) | 0.9 (0.8–1.0) | 0.99 (0.64–1.53) | 0.954 |
| 1 | 986 | 28 (2.8) | 0.5 (0.3–0.7) | 18249 | 1226 (6.7) | 1.4 (1.3–1.5) | 0.37 (0.26–0.54) | <0.001 |
| 2 | 644 | 39 (6.1) | 1.3 (0.9–1.7) | 26297 | 2551 (9.7) | 2.5 (2.4–2.6) | 0.51 (0.37–0.70) | <0.001 |
| 3 | 464 | 35 (7.5) | 1.7 (1.1–2.3) | 32311 | 3627 (11.2) | 3.2 (3.1–3.3) | 0.53 (0.38–0.74) | <0.001 |
| 4 | 377 | 31 (8.2) | 2.1 (1.3–2.9) | 29383 | 3316 (11.3) | 3.6 (3.5–3.7) | 0.60 (0.42–0.86) | 0.005 |
| 5–9 | 394 | 57 (14.5) | 4.5 (3.3–5.7) | 37598 | 4747 (12.6) | 4.9 (4.8–5.0) | 0.93 (0.72–1.21) | 0.600 |
| Stratified | ||||||||
| 0–4 | 2936 | 154 (5.3) | 1.1 (0.9–1.3) | 117523 | 11207 (9.5) | 2.5 (2.5–2.5) | 0.44 (0.38–0.52) | <0.001 |
| 5–9 | 394 | 57 (14.5) | 4.5 (3.3–5.7) | 37598 | 4747 (12.6) | 4.9 (4.8–5.0) | 0.93 (0.72–1.21) | 0.600 |
| Total | 3330 | 211 (6.3) | 1.4 (1.2–1.6) | 155121 | 15954 (10.3) | 2.9 (2.9–2.9) | 0.48 (0.42–0.55) | <0.001 |
| Systemic Thromboembolism | ||||||||
| 0 | 465 | 1 (0.2) | 0.04 (–0.04–0.12) | 11283 | 123 (1.1) | 0.21 (0.17–0.25) | 0.19 (0.03–1.33) | 0.093 |
| 1 | 986 | 6 (0.6) | 0.11 (0.02–0.20) | 18249 | 313 (1.7) | 0.35 (0.31–0.39) | 0.32 (0.14–0.72) | 0.006 |
| 2 | 644 | 8 (1.2) | 0.25 (0.07–0.43) | 26297 | 721 (2.7) | 0.67 (0.62–0.72) | 0.38 (0.19–0.76) | 0.006 |
| 3 | 464 | 11 (2.4) | 0.51 (0.21–0.81) | 32311 | 1139 (3.5) | 0.96 (0.90–1.02) | 0.54 (0.30–0.98) | 0.042 |
| 4 | 377 | 11 (2.9) | 0.74 (0.30–1.18) | 29383 | 1254 (4.3) | 1.28 (1.21–1.35) | 0.58 (0.32–1.05) | 0.074 |
| 5–9 | 394 | 16 (4.1) | 1.15 (0.59–1.71) | 37598 | 2123 (5.7) | 2.05 (1.96–2.14) | 0.58 (0.36–0.95) | 0.030 |
| Stratified | ||||||||
| 0–4 | 2936 | 37 (1.3) | 0.25 (0.17–0.33) | 117523 | 3550 (3.0) | 0.75 (0.73–0.77) | 0.34 (0.25–0.47) | <0.001 |
| 5–9 | 394 | 16 (4.1) | 1.15 (0.59–1.71) | 37598 | 2123 (5.7) | 2.05 (1.96–2.14) | 0.58 (0.36–0.95) | 0.030 |
| Total | 3330 | 53 (1.6) | 0.33 (0.24–0.42) | 155121 | 5673 (3.7) | 0.99 (0.96–1.02) | 0.35 (0.26–0.45) | <0.001 |
[i] AF, atrial fibrillation; HT, hyperthyroidism; ID, incidence density; CI, confidence interval; HR, hazard ratio.
§ Incidence density: Number of events per 100 person-years.