Patients
This cross-sectional study was performed nested of a RA patients’ cohort from an outpatient Cardio-Rheumatology clinic of a tertiary-care hospital in Monterrey, Mexico. We recruited Mexican mestizo RA patients aged 40–75 years, who fulfilled the 2010 American College of Rheumatology/EULAR (ACR/EULAR) criteria for RA. Mexican mestizo was defined as individuals born in Mexico with a Spanish-derived last name and Mexican ancestry belonging to a third-generation family [10]. Patients with previous CV events (myocardial infarction, stroke, or peripheral artery disease), cancer, overlap syndrome, or pregnancy were excluded.
The Research and Ethics committee of our institution approved this study with registration number MI14-006. The study was conducted following the ethical standards outlined in the Declaration of Helsinki and its subsequent amendments. All study subjects provided verbal informed consent before their inclusion.
A medical history and physical examination were performed during the first visit. Demographic and clinical characteristics were collected, and anthropometric measures, such as weight, height, and body mass index (BMI), were obtained. Blood pressure was measured after a 15-min rest on the left arm of all patients. Disease characteristics included disease duration, current medication with glucocorticoids, and/or disease-modifying antirheumatic drugs (DMARD) (synthetic and/or biological). Disease activity was evaluated by the Disease Activity Score 28‐joints C‐reactive protein (DAS28‐CRP), considering remission < 2.5; low disease activity 2.5–3.19; moderate disease activity 3.2–5.09; and high disease activity > 5.1 [11].
A blood sample was drawn for lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C]), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies (considering a value > 20.0 U/mL and > 5 U/mL as seropositive by ELISA, respectively).
Carotid ultrasound
A high-resolution B-mode carotid ultrasound was performed with a linear 10-MHz transductor and a Logiq E9 ultrasound system (GE Healthcare, Milwaukee, WI, USA) by a certified radiologist. The subject was placed in a supine position according to the American Society of Echocardiography guidelines. CP was defined as a focal narrowing ≥ 0.5 mm of the surrounding lumen or a carotid intima-media thickness ≥ 1.2 mm [12].
2019 WHO CVD risk charts
The CV risk evaluation was performed by a certified cardiologist, blinded to the carotid ultrasound results, using the 2019 WHO CVD risk charts for the Central Latin America region, which considers Mexico. Charts are available to estimate CV risk using two modalities: a laboratory-based model including age (40–75 years), gender, smoking status, systolic blood pressure (90–200 mmHg), history of diabetes, and TC (140–300 mg/dL), and a non-laboratory-based model in which BMI replaces TC. The laboratory-based model was used because it has the greatest discrimination, according to the recommendation [7]. The score was multiplied by 1.5 as stated in the EULAR recommendations of 2015 [6]. Patients were classified into five categories: low risk < 5%; moderate risk 5–10%; high risk 10–20%; very high risk 20–30%; and critical risk > 30%. Indications to start statin therapy by these charts were patients with high, very high or critical CV risk, patients with moderate CV risk older than 40 years with TC > 200 mg/dl or LDL-C > 120 mg/dl, and patients with low CV risk older than 40 years with TC > 300 mg/dl [7]. Subsequently, patients who did not meet these conditions but had CP were reclassified to a high-risk category with the indication of starting statin therapy.
Patients’ selection
At the time this study was performed, our cohort had a total of 490 RA patients recruited. Patients without previous or current statins’ treatment, with a carotid ultrasound performed and necessary data to calculate the CV risk with the 2019 WHO CVD risk charts (age, gender, smoking status, systolic blood pressure, history of diabetes and TC) collected or measured at the time of recruitment, were consecutively included for this study.
Statistical analysis
For quantitative variables the distribution of normality was evaluated using visual (histograms and probability plots) and analytical (Kolmogorov–Smirnov test) methods. A descriptive analysis was done using frequencies (%), mean ± SD, or median (p25–p75), accordingly. Cohen’s kappa (k) coefficient was used to evaluate the concordance between statin therapy initiation according to the 2019 WHO CVD risk charts and the presence of CP. k values were calculated and stratified qualitatively by score (0.00–0.20 slight agreement, 0.21–0.40 fair agreement, 0.41–0.60 moderate agreement, 0.61–0.80 substantial agreement, and 0.81–1.0 almost perfect agreement). The Chi-square test was used for comparisons of qualitative variables. A p value < 0.05 was considered statistically significant. The statistical analysis was performed using SPSS v.25.0 (IBM Corp., Armonk, NY, USA).