Subclinical hypothyroidism and the risk of coronary heart disease and mortality.
BACKGROUND
Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease.


OBJECTIVE
To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism.


METHODS
The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched.


METHODS
Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations.


RESULTS
Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease.


CONCLUSIONS
Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.
Rodondi
Nicolas
N
Department of Ambulatory Care and Community Medicine, University of Lausanne, Bugnon 44, 1011 Lausanne, Switzerland. Nicolas.Rodondi@hospvd.ch
den Elzen
Wendy P J
WP
Bauer
Douglas C
DC
Cappola
Anne R
AR
Razvi
Salman
S
Walsh
John P
JP
Asvold
Bjørn O
BO
Iervasi
Giorgio
G
Imaizumi
Misa
M
Collet
Tinh-Hai
TH
Bremner
Alexandra
A
Maisonneuve
Patrick
P
Sgarbi
José A
JA
Khaw
Kay-Tee
KT
Vanderpump
Mark P J
MP
Newman
Anne B
AB
Cornuz
Jacques
J
Franklyn
Jayne A
JA
Westendorp
Rudi G J
RG
Vittinghoff
Eric
E
Gussekloo
Jacobijn
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003327:Coronary Disease / Q000150:complications / Q000401:mortality*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011446:Prospective Studies; D012306:Risk; D013972:Thyrotropin / Q000097:blood*; D055815:Young Adult
D013972:Thyrotropin