At study entry, 2,639 individuals (82%) were euthyroid. Subclinical hypothyroidism had the highest prevalence of any thyroid testing abnormality (n=496; 15%), with fewer participants displaying results consistent with overt hypothyroidism (n=51; 1.6%) or subclinical hyperthyroidism (n=47; 1.5%). Ages were similar across all thyroid status categories in these elderly subjects, with a mean age of 72.7 years (). Women were more likely to have subclinical thyroid dysfunction than men, achieving statistical significance for the comparison between the subclinical hypothyroid and euthyroid groups.
Baseline Characteristics By Thyroid Status in the Cardiovascular Health Study*
Examination of cardiovascular risk factors showed that study participants with subclinical hyperthyroidism had a higher BMI than euthyroid subjects, along with higher fasting insulin levels and a non-statistically significant higher prevalence of hypertension. Among those not using lipid-lowering medications, serum total LDL and cholesterol levels were lowest in the subclinical hyperthyroidism group and highest in the overt hypothyroidism group; furthermore, those with undetected overt hypothyroidism used lipid-lowering medication the most. However, lipid levels did not differ between the subclinical hypothyroid and euthyroid groups, and those with subclinical hypothyroidism had a slightly lower rate of lipid-lowering medication use.
Prevalent CVD by thyroid status
There was no difference in atrial fibrillation, coronary heart disease, cerebrovascular disease, or subclinical CVD at baseline between the euthyroid category and any of the three thyroid dysfunction categories ().
Prevalence of Cardiovascular Diseases According to Thyroid Status*
Thyroid medication use during the study
Thyroid medication use was available throughout follow-up. Seven participants in the subclinical hyperthyroidism group started thyroid hormone therapy during the follow-up period, 91 in the euthyroid group, 142 in the subclinical hypothyroid group, and 31 in the hypothyroid group. Due to the potential effect of thyroid hormone initiation on subsequent cardiovascular risk, thyroid hormone medication use was included in all adjusted analyses.
Incident atrial fibrillation by thyroid status
After excluding those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation over the 13-year follow-up than the euthyroid group, with 67 vs. 31 events per 1000 person-years; (p<.001) ( and ). This effect persisted after sequential adjustment for other risk factors for atrial fibrillation. As shown in , after adjustment for age, sex, clinical CVD at baseline, subsequent thyroid medication use, and other known risk factors for atrial fibrillation, participants with subclinical hyperthyroidism had nearly twice the risk of developing atrial fibrillation (hazard ratio 1.98; 95% CI, 1.29–3.03).
Figure Cumulative incidence of A. atrial fibrillation, B. coronary heart disease, C. cerebrovascular disease, and D. death from all causes over the 13 years of follow-up, according to thyroid status. Number at risk for atrial fibrillation plot: n=47 for subclinical (more ...)
Incidence of Atrial Fibrillation in Those Without Atrial Fibrillation at Baseline, According to Thyroid Status*
We subsequently repeated these analyses, limiting it to those with a TSH of 0.1 to 0.44 mU/L (n=40). The incidence rate in this subgroup was 59 per thousand person-years (p=.007 compared to euthyroid group). After adjustment for age, sex, baseline clinical cardiovascular disease, and thyroid hormone use during follow-up, the hazard ratio was 1.85 (95% CI 1.1–3.0).
Incident and recurrent cardiovascular events by thyroid status
There were no differences in the incidence of coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death between the euthyroid and subclinical or overt hypothyroid groups ( and ). There was a statistically significant increase in mortality in the subclinical hyperthyroid group (58.1 vs. 34.2 events per 1000 person-years; p=.02), which disappeared after adjustment for age and sex (p=.29). We subsequently evaluated the relationship between each thyroid group and each cardiovascular outcome using various modeling strategies in adjusted analyses. No thyroid category was statistically significantly different from the euthyroid category; thus, only our crude and final models are displayed in . After adjustment, those with subclinical hypothyroidism had a hazard ratio of 1.07 (95% CI, 0.90–1.28) for coronary heart disease. All-cause death was not increased in subclinical hyperthyroidism (HR 1.08; 95% CI, 0.72–1.62) or subclinical hypothyroidism (HR 1.14; 95% CI, 0.98–1.32). Estimates for each of the covariates included in the final model for coronary heart disease validate increased risk from age, male sex, diabetes, LDL cholesterol, hypertension, CRP, and baseline CVD in our study population, while showing no appreciable increase in risk from any of the thyroid categories.
Incidence of Cardiovascular Events and Mortality (per 1000 person-years) in Those Without Any CVD at Baseline, According to Thyroid Status*
Hazard Ratios for Events and Death, According to Thyroid Status*