Background/Purpose: Autoimmune thyroid disease often coexists with RA and has been associated with an elevated cardiovascular (CV) risk, especially in hypothyroid patients. However, the existing studies show conflicting results and long term follow up studies are scarce. Therefore, we have investigated whether RA patients with thyroid dysfunction have an increased incidence of CV disease (CVD) compared to euthyroid RA patients.

Methods: Thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) were assessed in 348 RA patients participating in an ongoing prospective cohort study designed to assess CV risk factors, morbidity and mortality. Cox proportional hazard models were used to calculate hazard rates (HR) for incident CVD.

Results: The participants were predominantly females (66.1%) with a mean age of 63 ± 8 years and a mean disease duration of 7 ± 4 years. At baseline 4.6% was hypothyroid (n=16, TSH >4.0 mU/L, FT4 <10 pmol/L), 4.0% was hyperthyroid (n=14, TSH <0.3, FT4 >24 pmol/L), 2.6% had subclinical hyperthyroidism (n=9, TSH<0.3 and normal FT4), 2.9% had subclinical hypothyroidism (n=10, TSH>4.0 and normal FT4) and 85.9% (n=299) was euthyroid. 99 patients (28%) developed CVD during 15 years of follow up. 50% of the subclinical hypothyroid, 25% of the hypothyroid, 44.4% of the subclinical hyperthyroid, 21.4% of the hyperthyroid and 27.4% of the euthyroid RA patients developed CVD. Compared to the euthyroid persons, age and gender adjusted HR were 0.77 (95%CI 0.24 – 2.47; P=0.65) for hyperthyroid patients, 0.75 (95% CI 0.27 – 2.09; P=0.58) for hypothyroid patients, 1.26 (95%CI 0.46 – 3.44; P=0.67) for subclinical hyperthyroidism and 2.54 (95%CI 1.03-6.30; P=0.04) for subclinical hypothyroidism. Only subclinical hypothyroidism was associated with incident CVD compared to euthyroid patients in all models, with a HR of 2.94 (95% CI 1.05 – 8.19; P=0.04) in the final model after adjustment for prevalent CV disease, metabolic syndrome, RA duration, disease activity and creatinine.

Conclusion: Coexistence of subclinical hypothyroidism with RA is associated with an increased incidence of CVD. If external validation can confirm this amplified CV risk, thyroxine supplementation and CV risk management may be warranted in this subgroup of patients.