Meta-analysis: Subclinical thyroid dysfunction and the risk for coronary heart disease and mortality

Background: Data on the association between subclinical thyroid dysfunction and coronary heart disease (CHD) and mortality are conflicting. Purpose: To summarize prospective evidence about the relationship between subclinical thyroid dysfunction and CHD and mortality. Data Sources: MEDLINE (1950 to January 2008) without language restrictions and reference lists of retrieved articles were searched. Study Selection: Two reviewers screened and selected cohort studies that measured thyroid function and then followed persons prospectively to assess CHD or mortality. Data Extraction: By using a standardized protocol and forms, 2 reviewers independently abstracted and assessed studies. Data Synthesis: 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; l(2) = 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; l(2) = 0% for all studies). Limitations: Individual studies adjusted for different potential con-founders, and 1 study provided only unadjusted data. Publication bias or selective reporting of outcomes could not be excluded. Conclusion: 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.