¹Suad Hannawi, ²Maria Al-Salmi, ¹Haifa Hannawi

¹Emirates Health Services, ²Sharjah University

Background(s): Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease. Cardiovascular disease (CVD) is the most common cause of mortality and morbidity in RA patients. Moreover, RA patients are at an increased risk for subclinical hypothyroidism. Subclinical hypothyroidism (SH), which is characterized by elevated thyroid stimulating hormone (TSH) levels and normal circulating free thyroid hormones has been identified as an independent risk factor for atherosclerosis and CVD, through its adverse effect on endothelial function. Previously we reported that SH is associated with an increase in the carotid intima-media thickness (cIMT) among RA patients. cIMT is a marker for atherosclerosis.  In this study, we extended our investigations to examine the effect of thyroid function test (TFT) at RA onset on atherosclerosis progression over a year of RA diagnosis. This is the first study to investigate the effect of TFT parameters among clinically euthyroid early RA on the cIMT progression after one year of RA onset.

Method(s): Early RA patients (total of 31), more than 18 years old,  met the classification criteria of ACR-EULAR for RA had been recruited. Early RA was defined as 6 months of RA symptoms onset. All the patients with other concomitant autoimmune diseases or with chronic comorbidities (diabetes Mellitus, hypertension, thyroid disorder, liver disease, renal diseases, dyslipidemia, CVD, and stroke/TIA), pregnant women, patients with current/past smoking, and with alcohol consumption were excluded.

Thyroid function tests and cIMT were obtained at RA diagnosis; week 0 (wk0),  before commencement of antirheumatic therapy for all the patients who met the inclusion criteria.  cIMT repeated by the same sonographer after one year of RA diagnosis and treatment (wk 52). A High-resolution B-mode US scanner with a 7.5 MHz linear probe was used to measure the cIMT. The cIMT measurement was obtained bilaterally at 10 mm proximal to the bifurcation of the common carotid artery, as the distance between the leading edge of the intima-luminal and the media-adventitial interface at the wall. Three image readings were obtained for each carotid artery. The mean average of 6 measurements of the cIMT thickness at wk0 and at wk52. The cIMT progression was calculated by subtracting the average of the cIMT at wk 0 from the average of the cIMT at wk 52.

Both extracranial carotid arterial systems were widely scanned to detect plaque, which was defined as a focal widening relative to adjacent arterial segments, with a lump into the arterial lumen. Atheroma was considered present if both the proximal and distal parts of it were attached to the typical double-lined intima-media structure.

Fasting TFT (T4; Free thyroxine parameters, T3; Free triiodothyronine, and TSH; thyroid stimulating hormone (TSH)), Antithyroglobulin antibody (ATG), and Thyroid peroxidase (TPO) blood tests, and the cIMT ultrasound measurements were obtained within a week of RA diagnosis.

Univariate linear regression analysis was performed to investigate the correlation between the TFT parameters and the cIMT progression over a year. Continuous variables were reported as standard deviations ± standard deviation (µ±SD), and the categorical variables as percentages.

Result(s): A total of 31 female RA patients were included. The mean age of the participants was 50±14 (min 24, max 87) years. ATG was positive in 14 (45%) of the patients.  The mean TSH level was 2.35± 1.41 mlU/L (min 0.02, max 5.35. normal range; NR:0.27-4.2), mean T4 was 15.49± 2.68 pmol/L (min 8.92, max 21.89. NR: 12-22), mean T3 was 4.25± 0.76 pmol/L (min 2.6, max 5.55. NR: 4-6.8), mean ATG level was 251±351 IU/mL (min 12, max 1089. NR <116), and the mean TPO was  29±51 IU/ml.  (min 0.2, max 171. NR <30).

The mean cIMT at wk0 was 0.58± 0.10 mm (min 0.38, max 0.81), mean cIMT at wk52 was  0.61± 0.13 mm (min 0.43, max 0.93). cIMT progression over one year occurred in 18 (58%) of RA patients, despite the start of RA treatment with a target of achieving remission as per the EULAR treat-to-target (T2T) remission criteria. The mean cIMT progression was 0.05± 0.08 mm (min  0, max 0 .4). Also, 2 (6%) of the RA patients developed a new atheroma.

Linear regression analysis revealed a positive linear relationship between cIMT and TSH (p=0.03, CI 0.00, 0.05), and the thyroglobulin level (p=0.000, CI 0.00, 0.00). There was no significant correlation between the cIMT progression and the level of T3, T4, and TPO.

Conclusion(s): Subclinical hypothyroidism at RA onset is a risk factor for atherosclerosis progression. Early detection and management of thyroid dysfunction might be important to hinder subclinical atherosclerosis progression in RA patients.