Cohort Description

From a unique prospective cohort comprising rheumatoid arthritis (RA) patients who met the American College of Rheumatology classification criteria and were followed in our department, we selected 222 patients that were followed for at least one year. All patients provided informed consent and were willing and available to be reassessed regularly, every three to six months.

Clinical evaluation, anthropometric characteristics (age, gender, height, weight, BMI) and laboratory tests (cholesterol, low-density lipoprotein low-density lipoprotein (LDL)), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were performed at baseline and at every regular follow-up visit thereafter. Characteristics of RA, such as Rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) were measured at baseline. The Disease Activity Score in 28 joints using the previous week Visual Analogue Scale was calculated at every follow-up visit.

At every follow-up visit, three blood pressure (BP) measurements were taken (Omron 705CP; Omron Healthcare, Inc, Lake Forest, IL, USA) in the right upper limb after 5 minutes of rest with the subject seated and the arm supported at heart level, and the average BP was used. In the absence of antihypertensive treatment, “hypertension” was defined as the presence of systolic BP (SBP) ≥140mmHg and/or diastolic BP (DBP) ≥90mmHg. Similarly, in the absence of lipid-lowering treatment, dyslipidaemia was defined as LDL ≥160mg/dl. Family history of coronary artery disease (CAD) was defined as positive if a cardiac event (fatal or nonfatal myocardial infarction or coronary angioplasty and/or coronary artery bypass surgery) had occurred before the age of 55 years in male first-degree relatives and before the age of 65 years in female first-degree relatives.

At every follow-up visit the presence of a) cardiovascular disease (CVD), based on positive medical history, and/or clinical examination, and/or ECG abnormalities, b) diabetes mellitus (DM), on the basis of known declared pre-existing DM (e.g. drug treatment) or new fasting glucose>125mg/dl in 2 separate occasions or HbA1c>6,5% or abnormal OGTT, c) dyslipidaemia and d) hypertension were recorded, as defined above. Smoking status and any possible change (never smoked, ex-smoker, current smoker) was also recorded. Occurrence of any new cardiovascular event and death of any cause was also recorded. All treatment regiments were included for each patient at each visit and changes of drug treatment or dosage were also recorded. Patients were treated according to guidelines for optimal RA control (that is, disease remission) while avoiding administration of NSAIDs.

At baseline and yearly thereafter, the presence of atherosclerotic plaques in the carotid arteries was determined using a 14.0-MHz multifrequency linear array probe attached to a high-resolution ultrasound machine (Vivid 7 Pro; GE Healthcare, Little Chalfont, Buckinghamshire, UK) based on the international recommendations. All measurements were performed from the same experienced operator (George Kostantonis, Bs) In each subject, the following six sites (three paired left and right segments) were used for the investigation of atherosclerotic plaques: (1) at the common carotid artery, defined as the segment 1 cm proximal to carotid dilation; (2) at the carotid bulb, defined as the segment between the carotid dilation and carotid flow divider; and (3) at the internal carotid artery, defined as a 1-cm-long arterial segment distal to the flow divider. All segments were identified in the transverse and/or longitudinal planes and scanned from multiple angles to optimize the detection of non-obstructive plaques. Atherosclerotic plaques were defined at baseline or at follow-up end as focal structures at the far wall that encroached into the arterial lumen at least 0.5 mm or 50% of the surrounding IMT value or that demonstrated a thickness >1.5 mm measured on a digitally stored image.