Table 1.
Study Characteristics
Study | Description of Study Sample |
No. * | Age, Median (Range), y † |
Women, No. (%) |
Cardio- vascular Disease, No. (%) ‡ |
Endogenous Subclinical Hypo- thyroidism, No. (%) § |
Medication Users during Follow-up, No. (%)‖ |
Follow-up # | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||
Thyroxine | Anti- thyroid medication |
Start, y | Duration, Median (IQR), y |
Person- Years |
AF events, No. (%) |
|||||||
United States | ||||||||||||
Cardiovascular Health Study13 | Community-dwelling adults with Medicare eligibility in 4 US communities | 3,328 | 73 (64–98) | 1917 (57.6) | 845 (25.4) | 436 (13.1) | 308 (9.5) | NA | 1994–1995 | 11.7 (7.0–18.1) | 32,632 | 886 (26.6) |
Health ABC Study25 | Community-dwelling adults with Medicare eligibility in 2 US communities | 2,346 | 74 (69–81) | 1143 (48.7) | 625 (27.1) | 270 (11.5) | 114 (4.9) | 2 (0.1) | 1997 | 8.1 (7.4–8.3) | 16,155 | 201 (8.6) |
Osteoporotic Fractures in Men (MrOS) Study26 | Community-dwelling men aged 65 years or older in 6 US clinical centers | 678 | 72 (65–91) | 0 | 135 (19.9) | 45 (6.6) | 18 (2.7) | 0 | 2000–2002 | 12.6 (11.2–13.1) | 7,668 | 62 (9.1) |
Europe | ||||||||||||
Bari Study27 | Outpatients with heart failure followed up by Cardiology Department in Bari, Italy | 268 | 65 (21–92) | 55 (20.5) | 103 (38.4) | 23 (8.6) | 22 (8.2) | 8 (3.0) | 2006–2008 | 1.3 (0.6–1.9) | 339 | 14 (5.2) |
Leiden 85-plus Study28 | All adults aged 85 years living in Leiden, the Netherlands | 432 | 85 (85–85) | 281 (65.1%) | 166 (38.4) | 27 (6.3) | 5 (1.2) | 3 (0.7) | 1997–1999 | 5.5 (2.7–9.0) | 1,575 | 44 (10.2) |
SHIP29** | Adults living in Western Pomerania, Germany | 2,339 | 45 (20–85) | 1191 (50.9) | 100 (4.3) | 12 (0.5) | 172 (7.4) | 8 (0.3) | 1997–2001 | 11.5 (11.1–12.1) | 22,006 | 40 (1.7) |
InChianti Study30 | Community-dwelling adults aged 65 years or older living in Tuscany, Italy | 1,051 | 71 (21–103) | 581 (55.3) | 123 (11.7) | 26 (2.5) | 17 (1.6) | 2 (0.2) | 1998 | 9.0 (8.3–9.2) | 8,453 | 14 (1.3) |
Rotterdam Study16 | Inhabitants of Ommoord (The Netherlands) aged ≥ 55 years | 1,607 | 68 (55–93) | 975 (60.7) | 412 (25.6) | 91 (5.7) | NA | NA | 1990–1993 | 15.5 (11.4–16.9) | 20,892 | 226 (14.1) |
PROSPER Study31 | Community-dwelling elderly with high cardiovascular risk in The Netherlands, Scotland and Ireland | 5,334 | 74 (69–83) | 2,645 (49.6) | 2,356 (44.2) | 384 (7.2) | 57 (1.1) | 11 (0.2) | 1997–1999 | 3.3 (3.0–3.5) | 16,529 | 496 (9.3) |
EPIC-Norfolk Study32 | Adults aged 40 to 79 years living in Norfolk, England | 11,642 | 58 (39–78) | 6,181 (53.1) | 442 (3.8) | 607 (5.2) | NA | NA | 1995–1998 | 17.0 (16.1–18.0) | 137,861 | 575 (4.9) |
Australia | ||||||||||||
Busselton Health Study33 | Adults living in Busselton, Western Australia | 1,060 | 46 (18–81) | 539 (50.9) | 54 (5.1) | 37 (3.5) | 20 (1.9) | 1 (0.1) | 1981 | 14.0 (14.0–14.0) | 14,840 | 16 (1.5) |
| ||||||||||||
Overall | 11 Cohorts | 30,085 | 69 (18–103) | 15,508 (51.6) | 5,371 (17.9) | 1,958 (6.5) | 733 (2.4) | 35 (0.1) | 1981–2008 | 16.6 (10.7–18.7) | 278,955 | 2,574 (8.6) |
| ||||||||||||
Studies where IPD were not available | ||||||||||||
Framingham Heart Study9 | Adults aged ≥ 60 years from Framingham, USA | 1,759†† | ≥ 60 (NA) | 1037 (59.0) | NA | 183 (10.4) | NA | NA | 1978–1980 | 10.0 (NA) | NA | 156 (8.9) |
Rotterdam Study Cohorts I, II and III24‡‡ | Adults aged ≥ 55 years for Cohort II and ≥ 45 years for Cohort III from Ommoord, The Netherlands | 8,740 | 63 (45–105) | 5010 (57.3) | NA | 722 (8.3) | NA | NA | 2000–2001 Cohort II, 2006–2008 Cohort III | 6.8 (3.9–10.9) | 61,935 | 403 (4.6) |
Abbreviations: AF, atrial fibrillation; EPIC, European Prospective Investigation of Cancer; Health ABC Study, Health Aging and Body Composition Study; InChianti, Invecchiare in Chianti; IPD, individual participant data; IQR, Interquartile Range (25th–75th percentiles); NA, Data not Available; PROSPER, Prospective Study of Pravastatin in the Elderly at Risk; SHIP, Study of Health in Pomerania; TSH, thyroid stimulating hormone; y, Years
We excluded from our analyses participants with prevalent atrial fibrillation at baseline, missing outcomes for atrial fibrillation, subclinical hyperthyroidism and overt thyroid dysfunction, and intake of thyroxine or antithyroid medication at baseline.
We excluded participants younger than 18 years.
Cardiovascular disease at baseline was defined as known history of stroke, transient ischemic attack, myocardial infarction, angina pectoris, coronary angioplasty, or bypass surgery.
We used a common definition of subclinical hypothyroidism, TSH 4.5 mIU/L to 19.9mIU/L and normal free thyroxine level, but TSH cutoff values varied among the previous reports from each cohort, so numbers are different than in the original articles. To analyze only endogenous subclinical hypothyroidism, we excluded 253 participants in the Cardiovascular Health Study, 207 in the Health ABC Study, 43 in the Osteoporotic Fractures in Men Study, 15 in the Bari study, 12 in the Leiden 85+ study, 107 in the Study of Health in Pomerania, 21 in the Invecchiare in Chianti Study, 26 in the Rotterdam study, 188 in the PROSPER study, 301 in the EPIC-Norfolk study, and 4 in the Busselton Health study because they used thyroid medication at baseline.
We had no data on thyroid medication use during follow-up for 481 participants in the Study of Health in Pomerania, and all participants in the EPIC-Norfolk and the Rotterdam study. 91 participants in the Cardiovascular Health Study did not have information on thyroxin during follow-up, and information on antithyroid medication during follow-up was missing for all patients of the Cardiovascular Health Study. 5 persons took both thyroxine and anti-thyroid medication during the course of follow-up.
For all cohorts, we used the maximal follow-up data that were available, which may differ from previous reports of some cohorts. For the Cardiovascular Health Study, we set the baseline for our analysis to the year 5 visit of the original cohort because free thyroxine was measured at the year 5 visit.
SHIP includes participants from Pomerania, where an iodine supplementation program began in the mid-1990s. This shifted the distribution of TSH values towards the left in its first years, which lowered TSH values in the population of the SHIP Study during baseline examinations in 1997–2001.
Number of participants with euthyroidism and subclinical hypothyroidism. Participants with subclinical hyperthyroidism are not listed here, since they were not included in our sensitivity analysis or in the aggregate data from this cohort.
Data on characteristics of 8740 participants included in the longitudinal analysis by Chaker et al.24 was obtained through contact with the authors. Individual participant data of 1,602 participants was available for Rotterdam Study Cohort I (see above).