Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role?

BACKGROUND: The increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls. OBJECTIVE: To study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity. METHODS: Eighty RA patients and 44 healthy controls were included. All subjects were younger than 45years for females and 55years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress-echocardiography, diseases activity assessed by DAS-28, X-ray hands for Larsen score and function assessment by HAQ. RESULTS: RA patients had significantly higher serum IL 1, 6 and 18 than controls (p=0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine-stress-echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p=0.00), 10 had DAS-28>5.1, 20 had DAS-28 from 3.2 to5.1 and 4 were in remission (p=0.001). CRP was higher in patients with hypertensive reaction (p=0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS-28 (p<0.001 in all). Only IL18 showed significant positive correlation with X-ray score in all patients. CONCLUSION: Disease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA.

Erythroferrone Expression in Anemic Rheumatoid Arthritis Patients: Is It Disordered Iron Trafficking or Disease Activity?

PURPOSE: Erythroferrone (ERFE) is well acknowledged for its inhibitory function on hepcidin synthesis in the liver during stress erythropoiesis, thereby ensuring sufficient iron supply to bone marrow erythroblasts. Hepcidin plays an indispensable role in the pathogenesis of anemia of chronic disease (ACD). Thus, ERFE was suggested to protect against ACD in various diseases. Rheumatoid arthritis (RA) is commonly involved with ACD and high hepcidin levels, with a further increase of the latter in active states. The present study is a case-control study that aimed to determine the pattern of ERFE expression in RA patients with concomitant ACD and study its relationship with hepcidin, erythropoietin (EPO) and disease activity. PATIENTS AND METHODS: Fifty-five RA patients with ACD were categorized into active and inactive RA using the disease activity score (DAS28); 15 healthy subjects were included as control subjects. ERFE was measured for patients and control subjects using quantitative real-time polymerase chain reaction, in addition to testing for CBC, ESR, CRP, iron profile parameters and hepcidin. EPO was assessed for patients of both active and inactive RA groups. RESULTS: ERFE and hepcidin showed the highest levels in active RA; ERFE values were similar in control subjects and inactive RA patients, while hepcidin was significantly higher in inactive RA than control subjects. Patients with high ERFE levels had higher RBC, Hct, MCV, hepcidin and EPO levels. Stepwise regression analysis has identified DAS28 and disease duration as the best predictors of ERFE values, whereas ERFE and hepcidin were independent predictors of disease activity. CONCLUSION: We introduce ERFE as a novel marker of RA activity. Although the inhibitory effect of ERFE on hepcidin is not evident, our results still indicate that ERFE may have a beneficial erythropoietic effect in the context of ACD in RA disease activity.

Plasma Soluble Urokinase Plasminogen Activator Receptor Levels in Systemic Lupus Erythematosus Patients.

This study aimed to determine whether plasma soluble urokinase plasminogen activator receptor (suPAR) could serve as an activity biomarker in systemic lupus erythematosus (SLE) patients. suPAR levels were assessed in SLE patients, compared to healthy controls and correlated with disease activity. Sixty SLE patients were enrolled with assessment of disease activity using SLE Disease Activity Index (SLEDAI), C3, soluble urokinase plasminogen activator receptor level. Patients were divided according to disease activity into three groups: Patients in remission, mild to moderate activity, and high disease activity. Twenty apparently healthy individuals, age and sex matched, were included as a control group and subjected to routine laboratory tests and soluble urokinase plasminogen activator receptor level. The age range of the patients was 19 - 45 years with a mean of 29.07±6.84. suPAR, ESR and C3, but not CRP showed significant differences (P < 0.001), among SLE patients' subgroups. Plasma suPAR demonstrated higher levels among highly active than mild to moderately active or patients in remission, having higher discriminating ability regarding disease activity in comparison to ESR and C3 levels. It was higher in cases of nephritis. The optimum cut-off level of suPAR was >3.5 ng/ml, diagnostic validity tests for suPAR have shown to be 100% for sensitivity, specificity, positive predictive value and 74.1% for negative predictive value. These findings indicate that suPAR may be one of the valuable indicators of disease activity in SLE.