Association of Non-HDL cholesterol with cardiovascular risk and subclinical atherosclerosis in patients with rheumatoid arthritis
O A Garza Flores, V Cervantes-Ramirez, A Leal Valdez, F M Garcia-Garcia, E C Garza-Gonzalez, I C Reynosa-Silva, I J Colunga-Pedraza, R I Arvizu-Rivera, J A Cardenas-de la Garza, H H Garza-Sepulveda, R Flores-Ramirez, E F Carrizales-Sepulveda, D A Galarza-Delgado, J R Azpiri-LopezAbstract
Introduction
Rheumatoid arthritis (RA) is associated with increased cardiovascular risk (CVR), driven by chronic inflammation and a higher burden of traditional risk factors. Non-HDL cholesterol, which encompasses all atherogenic lipoproteins, has been proposed as a useful marker in this population, with ≥130 mg/dL considered a threshold indicating moderate risk. Carotid ultrasound is a sensitive and non-invasive tool widely used in clinical practice to detect subclinical atherosclerosis. Traditional CVR calculators, while useful, tend to underestimate the actual risk in patients with RA.
Objective
To determine whether non-HDL cholesterol ≥130 mg/dL is associated with higher cardiovascular risk, assessed through lipid profile, CV risk calculators, and carotid ultrasound, in patients with rheumatoid arthritis.
Methods
We conducted a cross-sectional, comparative study that included RA patients aged 45 to 80 years who met the 2010 ACR/EULAR classification criteria. Patients with prior cardiovascular disease, pregnancy, or overlap syndromes were excluded. Participants were divided into two groups: those with non-HDL cholesterol ≥130 mg/dL and those with non-HDL cholesterol <130 mg/dL. Disease activity and impact were assessed using the DAS28-CRP, DAS28-ESR, and HAQ scales. Carotid ultrasound evaluations were performed in B-mode by a single experienced operator, following a standardized protocol. A carotid plaque (CP) was defined as diffuse intima-media thickening (CIMT) ≥1.2 mm or focal thickening ≥0.5 mm. Carotid hyperplasia was defined as CIMT ≥0.8 mm.Normality was assessed using the Kolmogorov–Smirnov test. Comparisons were made using the Student’s t-test, Chi-square test, or Mann–Whitney U test, as appropriate. A p-value ≤0.05 was considered statistically significant.
Results
Patients with non-HDL cholesterol < 130 mg/dL exhibited a more elevated lipid profile, with higher levels of total cholesterol (205.01 vs. 154.57 mg/dL), LDL (117.62 vs. 75.55 mg/dL), triglycerides (142.00 vs. 109.60 mg/dL), and VLDL [28.70 vs. 21.90 mg/dL] (p<0.001 for all), as well as a higher prevalence of dyslipidemia (49.5% vs. 33.1%, p=0.010). Despite this, the group showed lower disease activity (DAS28-CRP: 3.39 vs. 3.92, p=0.029; DAS28-ESR: 4.33 vs. 4.54, p=0.042) and greater use of bDMARDs (24.7% vs. 10.8%, p=0.003).They also had higher scores on major cardiovascular risk calculators such as Framingham (7.4 vs. 5.1, p<0.001), ACC/AHA (2.85 vs. 2.20, p=0.027), SCORE and Reynolds (p=0.023 and 0.034, respectively), with no significant differences in QRISK3 or carotid plaque presence.
Conclusion
Unexpectedly, RA patients with non-HDL cholesterol <130 mg/dL demonstrated a more adverse lipid profile and higher calculated CV risk, but lower inflammatory activity, likely related to increased bDMARD use. These findings support the presence of the lipid paradox in RA and highlight limitationsof traditional CVR assessment tools in this population.