Nicolas Ochs, MD; Reto Auer, MD; Douglas C. Bauer, MD; David Nanchen, MD; Jacobijn Gussekloo, MD, MPH; Jacques Cornuz, MD, MPH; Nicolas Rodondi, MD, MAS
Acknowledgment: The authors thank Professor Jayne A. Franklyn (University of Birmingham, Birmingham, United Kingdom), Professor Anne R. Cappola (University of Pennsylvania, Philadelphia, Pennsylvania), Dr. Alice M. Arnold (University of Washington, Seattle, Washington), Dr. Patrick Maisonneuve (European Institute of Oncology, Milan, Italy), Dr. Mark Vanderpump (Royal Free Hampstead NHS Trust, Hampstead, United Kingdom), Professor Mike Tunbridge (Oxford Radcliffe Hospitals, Oxford, United Kingdom), Dr. Iervasi (Clinical Physiology Institute, Pisa, Italy) and Dr. Hak (Erasmus MC University Medical Center, Rotterdam, the Netherlands) for their assistance and for supplying additional data from their studies.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Nicolas Rodondi, MD, MAS, Department of Ambulatory Care and Community Medicine, University of Lausanne, Bugnon 44, 1011 Lausanne, Switzerland; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Ochs, Nanchen, Cornuz, and Rodondi: Department of Ambulatory Care and Community Medicine, University of Lausanne, Bugnon 44, 1011 Lausanne, Switzerland.
Dr. Auer: Department of Medicine, University of Lausanne, Bugnon 46, 1011 Lausanne, Switzerland.
Dr. Bauer: University of California, San Francisco, 185 Berry Street,
Suite 5700, San Francisco, CA 94107.
Dr. Gussekloo: Department of Public Health and Primary Care, Leiden University Medical Center, V06-P, Postbus 9600, 2300 RC Leiden, the Netherlands.
Data on the association between subclinical thyroid dysfunction and coronary heart disease (CHD) and mortality are conflicting.
To summarize prospective evidence about the relationship between subclinical thyroid dysfunction and CHD and mortality.
MEDLINE (1950 to January 2008) without language restrictions and reference lists of retrieved articles were searched.
Two reviewers screened and selected cohort studies that measured thyroid function and then followed persons prospectively to assess CHD or mortality.
By using a standardized protocol and forms, 2 reviewers independently abstracted and assessed studies.
Ten of 12 identified studies involved population-based cohorts that included 14 449 participants. All 10 population-based cohort studies examined risks associated with subclinical hypothyroidism (2134 CHD events and 2822 deaths), whereas only 5 examined risks associated with subclinical hyperthyroidism (1392 CHD events and 1993 deaths). In a random-effects model, the relative risk (RR) for subclinical hypothyroidism for CHD was 1.20 (95% CI, 0.97 to 1.49; P for heterogeneity = 0.14; I2 = 33.4%). Risk estimates were lower when higher-quality studies were pooled (RR, 1.02 to 1.08) and were higher among participants younger than 65 years (RR, 1.51 [CI, 1.09 to 2.09] for studies with mean participant age <65 years and 1.05 [CI, 0.90 to 1.22] for studies with mean participant age ≥65 years). The RR was 1.18 (CI, 0.98 to 1.42) for cardiovascular mortality and 1.12 (CI, 0.99 to 1.26) for total mortality. For subclinical hyperthyroidism, the RR was 1.21 (CI, 0.88 to 1.68) for CHD, 1.19 (CI, 0.81 to 1.76) for cardiovascular mortality, and 1.12 (CI, 0.89 to 1.42) for total mortality (P for heterogeneity >0.50; I2 = 0% for all studies).
Individual studies adjusted for different potential confounders, and 1 study provided only unadjusted data. Publication bias or selective reporting of outcomes could not be excluded.
Subclinical hypothyroidism and hyperthyroidism may be associated with a modest increased risk for CHD and mortality, with lower risk estimates when pooling higher-quality studies and larger CIs for subclinical hyperthyroidism.
Is subclinical thyroid dysfunction associated with increased risk for coronary heart disease and mortality?
This systematic review of 12 prospective cohort studies found that both subclinical hypothyroidism and hyperthyroidism were possibly associated with a small increased risk for coronary heart disease and mortality.
Data were uncertain. Confidence intervals around risk estimates were wide, particularly for those related to subclinical hyperthyroidism. Higher-quality studies showed lower estimates of risk than lower-quality studies.
Randomized trials testing the efficacy of thyroxine replacement and antithyroid medications for subclinical hypothyroidism and subclinical hyperthyroidism are needed.
Study flow diagram.
TSH = thyroid-stimulating hormone.
Table 1. Population-Based Studies of Subclinical Thyroid Dysfunction and Risk for CHD and Mortality*
Appendix Table 1. Quality Assessment of Included Studies
Forest plots for subclinical hypothyroidism.
The diamonds represent relative risks and the horizontal lines represent 95% CIs of the effect of subclinical hypothyroidism. CHD = coronary heart disease; CV = cardiovascular.
Table 2. Stratified Analysis of the Association of Subclinical Hypothyroidism with Risk for CHD
Appendix Table 2. Stratified Analysis of the Association of Subclinical Hypothyroidism with Risk for Total Mortality
Appendix Table 3. Stratified Analysis of the Association of Subclinical Hypothyroidism with Risk for Cardiovascular Mortality
Forest plots for subclinical hyperthyroidism.
The diamonds represent relative risks and the horizontal lines represent 95% CIs of the effect of subclinical hyperthyroidism. CHD = coronary heart disease; CV = cardiovascular.
Table 3. Stratified Analysis of the Association of Subclinical Hyperthyroidism with Risk for CHD
Appendix Table 4. Stratified Analysis of the Association of Subclinical Hyperthyroidism with Risk for Total Mortality
Appendix Table 5. Stratified Analysis of the Association of Subclinical Hyperthyroidism with Risk for Cardiovascular Mortality
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Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, et al. Meta-analysis: Subclinical Thyroid Dysfunction and the Risk for Coronary Heart Disease and Mortality. Ann Intern Med. 2008;148:832-845. doi: 10.7326/0003-4819-148-11-200806030-00225
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Published: Ann Intern Med. 2008;148(11):832-845.
Cardiology, Coronary Heart Disease, Endocrine and Metabolism, Thyroid Disorders.
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