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

Eman M Ibrahem; Salwa S El-Gendi; Amal A Mahmoud; Sherif M Abdel-Aal; Fatma H El Nouby; Hanan Sharaf El-Deen Mohammed

doi:10.2174/1573397116666201113090145

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

Curr Rheumatol Rev. 2021;17(2):258-266. doi: 10.2174/1573397116666201113090145.

Authors

Eman M Ibrahem¹, Salwa S El-Gendi¹, Amal A Mahmoud², Sherif M Abdel-Aal³, Fatma H El Nouby⁴, Hanan Sharaf El-Deen Mohammed¹

Affiliations

¹ Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
² Clinical Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
³ Diagnostic Radiology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁴ Rehabilitation and Rheumatology Department, Faculty of Medicine, Aswan University, Aswan, Egypt.

PMID: 33185166
DOI: 10.2174/1573397116666201113090145

Abstract

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).

Keywords: CIMT.; Rheumatoid arthritis; atherosclerosis; combination therapy; matrix metalloproteinases; randomized clinical trial.

Publication types

Clinical Trial
Randomized Controlled Trial

MeSH terms

Adult
Arthritis, Rheumatoid / blood
Arthritis, Rheumatoid / complications
Arthritis, Rheumatoid / diagnostic imaging*
Cardiovascular Diseases / blood
Cardiovascular Diseases / etiology*
Carotid Intima-Media Thickness*
Cross-Sectional Studies
Female
Humans
Male
Matrix Metalloproteinases / blood
Middle Aged

Substances

Matrix Metalloproteinases

Associated data

ClinicalTrials.gov/NCT03194204