Atherothrombotic Risk Factors in Patients With Rheumatoid Arthritis

Abstract

Background: The onset of cardiovascular complications has increased the mortality rate in rheumatoid arthritis (RA) patients. Presently, there is a need to diagnose cardiovascular co-morbidity in rheumatic disease. While biomarkers such as P-selectin glycoprotein ligand-1 (PSGL-1), fibrinogen, anti-thrombin III (AT-III), hsCRP, lipoprotein (a) (lp(a)), leptin, adiponectin, and asymmetric dimethyl arginine (ADMA) are already established as independent risk factors for the development of atherosclerosis, the association of these biomarkers with disease activity in RA patients is unclear.

Methods: The case-control study comprised 40 cases along with age- and gender-matched controls recruited from a tertiary care hospital in southern India. Platelet activation in plasma was analyzed by flow cytometry using CD41 per CPCY 5.5 (platelet marker) and human CD62P FITC monoclonal antibody (P-selectin marker). Other parameters were quantified through nephelometry and ELISA. The association between the risk factors and RA disease severity, as per the disease activity score (DAS/DAS28), was analyzed. Furthermore, an ROC analysis was done to assess the utility of these biomarkers in the diagnosis of RA.

Results: With the exception of leptin, adiponectin, and ADMA, there was a significant increase in the levels of PSGL-1, fibrinogen, AT-III, hsCRP, and lp(a) when compared to healthy controls. Conventional risk factors contributing to dyslipidemia were also assessed, in which the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was found to be significantly higher in RA patients compared to controls. Moreover, a significant positive correlation was identified between DAS score and activated platelets, fibrinogen, and hsCRP. ROC analysis identified that fibrinogen could predict the RA disease status with 95% accuracy, followed by activated platelets and hsCRP.

Conclusion: Several of the studied atherothrombotic risk factors were significantly altered in patients with RA. Activated platelets, fibrinogen, and hsCRP were associated with disease activity and also served as good diagnostic predictors for RA. Based on our findings, further studies could explore the potential of introducing anti-thrombotic agents in the treatment regimen of patients with RA.

Keywords: atherothrombotic risk factors; biomarkers; diagnostic predictors; disease activity; rheumatoid arthritis.

Figure 1. a: Dot plots by SSC (Y-axis) and FSC (X-axis). b: Dot plots by SSC (Y-axis) and FSC x (X-axis). c: Cells stained positive for CD41 and CD62

FSC, forward scatter; SSC, side scatter

Figure 2. ROC curve analysis for the differential diagnosis of RA based on atherothrombotic risk factors

RA, rheumatoid arthritis

Figure 3. Scatter plot analysis between DAS28 score vs activated platelets among rheumatoid patients

DAS, disease activity score

Figure 4. Scatter plot analysis between DAS28 score vs fibrinogen among rheumatoid patients

DAS, disease activity score

Figure 5. Scatter plot analysis between DAS28 score vs hsCRP among rheumatoid patients

DAS, disease activity score