Value of tumor necrosis factor-alpha and high-sensitive cardiac troponin-I as early predictors of subclinical atherosclerosis and their relation to disease activity in patients with rheumatoid arthritis: A case-control study.

Patients with rheumatoid arthritis (RA) have a higher risk of cardiovascular disease (CVD) compared to the general population, which leads to increased morbidity and mortality. Inflammation is the key in RA and CVD. Our study aimed to refine cardiovascular (CV) risk assessment in RA patients by using carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis. We also explored whether proinflammatory cytokines represented by tumor necrosis factor-alpha (TNF-α) and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, could be correlated in RA patients. The study included 80 RA patients and 80 control subjects. TNF-α and hs-cTnI levels were measured. Subclinical atherosclerosis was evaluated by cIMT by means of carotid ultrasound. Disease activity score 28 (DAS28) was used to evaluate disease activity. hs-cTnI and TNF-α serum levels were higher in RA patients compared to controls (p=0.001). There was a significant difference in the median of cIMT between cases and controls (median (IQR) 0.9 (0.2) for cases, 0.7 (0.1) for controls, (p=0.001). A significant correlation was found between the level of TNF-α and hs-cTnI (p=0.002). Also, there was a significant correlation between the cIMT level and TNF-α and hs-cTnI (p=0.003 and p=0.002, respectively). Significant correlation was found between cIMT, TNF-α, and hs-cTnI in relation to the DAS28 score (p < 0.001, p < 0.001, and p=0.001, respectively). In conclusion, patients with RA are more likely to develop subclinical atherosclerosis, as reflected in increased cIMT. Higher levels of hs-cTnI in RA patients may correlate with the presence of occult cardiovascular disease. TNF-α and hs-cTnI correlations can reveal the interplay between disease activity and CVD. Thus, inflammation must be the primary target of various therapeutic approaches.

Predictors of Cardiovascular Affection in Patients with Active Rheumatoid Arthritis: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: This is a secondary analysis of a randomized controlled trial that aimed to assess subclinical atherosclerosis in patients with rheumatoid arthritis (RA) by measuring carotid artery intima-media thickness (CIMT) and correlating it with disease activity and inflammatory markers (including levels of matrix metalloproteinase-3(MMP-3) and matrix metalloproteinase-9 (MMP-9)) and to detect the effectiveness of agents that inhibit matrix metalloproteinases (MMPs) as doxycycline in RA therapy. METHODS: One hundred and sixty RA patients were assigned in a randomized clinical trial (clinicaltrial. gov NCT03194204). Disease activity score 28(DAS28), laboratory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MMP-3, and MMP-9 were evaluated and mean CIMT was measured. Subjects were allocated randomly into one of two treatment arms, either methotrexate (MTX) alone or MTX with doxycycline 200mg per day orally. Follow up ESR, CRP, DAS28, MMP-3, and MMP-9 levels were re-evaluated after 3 months. RESULTS: There were positive significant correlations between CIMT and disease duration (r = 0.461, p = 0.001), age (r=0.459, p= 0.001), DAS28 score (r= 0.547, p = 0.001), ESR (r =0.413, p = 0.001), CRP (r = 0.281, p = 0.001), MMP-3 (r = 0.476, p = 0.001), and MMP-9 (r = 0.593, p =0.001). Patients treated with MTX and doxycycline showed lower levels of DAS28, ESR, CRP, MMP-3, and MMP-9 and this was statistically significant. CONCLUSION: CIMT seems to be the ultimate method to screen for subclinical atherosclerosis in RA patients. MMP-3 and 9 play a key role in both RA synovitis and cardiovascular changes, making them important therapeutic targets, especially with safe and cost-effective agents like doxycycline. This clinical trial was carried out in Assiut University Hospital (AUH), Assiut, Egypt (Clinical Trial Registration No. clinicaltrial.gov NCT03194204).