JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
Fergana Medical Institute of Public Health,
Department of Therapeutic Sciences, Fergana, Uzbekistan
Jahongir Muminov
FEATURES OF EARLY DIAGNOSIS AND TREATMENT OF CARDIOVASCULAR
PATHOLOGY IN PATIENTS WITH RHEUMATOID ARTHRITIS
Abstract
Background:
Rheumatoid arthritis (RA) is a systemic autoimmune disorder associated with an increased risk of
cardiovascular disease (CVD), primarily due to chronic systemic inflammation. Early detection and
management of cardiovascular pathology in RA patients remain a clinical challenge but are
essential for improving outcomes.
Objective:
To investigate the early diagnostic features and treatment strategies of cardiovascular pathology in
patients with RA and to assess the association between inflammatory markers and subclinical
atherosclerosis.
Methods:
This prospective clinical study included 120 patients with RA, among whom 68 demonstrated
clinical or subclinical cardiovascular involvement. All patients underwent clinical assessment,
laboratory testing (including CRP, ESR, RF, anti-CCP), and cardiovascular evaluation (ECG,
echocardiography, carotid ultrasound). A subgroup was tested for IL-6 and TNF-α levels. Disease
activity was measured using DAS28-CRP. Statistical analysis was performed to assess associations
between inflammatory markers and cardiovascular pathology.
Results:
Patients with cardiovascular involvement had significantly higher CRP and ESR levels, as well as
greater RA disease activity (p < 0.01). Carotid plaque and increased intima-media thickness were
found in 53.3% of RA patients versus 18.3% in controls (p < 0.001). Elevated inflammatory
markers correlated with the presence of subclinical atherosclerosis. TNF-α inhibitors and
methotrexate treatment were associated with improved vascular parameters and reduced
cardiovascular risk.
Conclusion:
Cardiovascular pathology in RA patients is common and strongly associated with systemic
inflammation. Early detection using inflammatory biomarkers and carotid imaging, combined with
anti-inflammatory treatment and cardiovascular risk management, is essential to reducing
cardiovascular morbidity and mortality in RA. Interdisciplinary care involving rheumatologists and
cardiologists is crucial for optimizing outcomes.
Keywords:
Rheumatoid arthritis, cardiovascular disease, inflammation, early diagnosis, subclinical
atherosclerosis, TNF-α inhibitors, carotid ultrasound.
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
Introduction
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that primarily targets the
synovial joints, leading to inflammation, joint destruction, and disability. Beyond musculoskeletal
involvement, RA has been increasingly recognized as a systemic disease with significant extra-
articular manifestations, particularly involving the cardiovascular (CV) system. Numerous studies
have demonstrated that patients with RA have a 1.5 to 2 times higher risk of cardiovascular disease
(CVD) compared to the general population. This increased risk is not solely explained by
traditional cardiovascular risk factors such as hypertension, diabetes mellitus, or hyperlipidemia,
but is strongly associated with chronic systemic inflammation.
Systemic inflammation in RA promotes endothelial dysfunction, accelerates atherosclerosis, and
increases the risk of myocardial infarction, stroke, and heart failure. Furthermore, inflammatory
markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha
(TNF-α) play a key role in both RA pathogenesis and cardiovascular complications. Despite these
known associations, CVD often remains underdiagnosed and undertreated in RA patients,
particularly in the early stages.
Early diagnosis and targeted management of cardiovascular comorbidities in RA patients are
essential to improving long-term outcomes. However, the clinical presentation may be atypical or
masked by RA-related symptoms, making early detection challenging. Therefore, an integrated
diagnostic and therapeutic approach involving rheumatologists and cardiologists is crucial.
This study aims to explore the distinctive features of early cardiovascular diagnosis and treatment
strategies in patients with RA, highlighting the need for routine cardiovascular assessment and anti-
inflammatory therapy tailored to reduce cardiovascular burden.
Methods
This prospective observational study was conducted from January 2022 to December 2023 at the
Departments of Rheumatology and Cardiology at [Insert Institution Name], involving adult patients
with confirmed RA according to the 2010 ACR/EULAR criteria. A total of 120 patients aged
between 30 and 75 years were enrolled. Among them, 68 patients presented clinical signs or risk
factors indicative of cardiovascular involvement. Patients with known non-inflammatory cardiac
diseases or overlapping connective tissue disorders were excluded.
All participants underwent a comprehensive clinical assessment, including detailed anamnesis,
physical examination, and evaluation of RA activity using the Disease Activity Score 28 (DAS28).
Cardiovascular screening was performed in all patients, focusing on symptoms such as chest pain,
exertional dyspnea, palpitations, and fatigue. Blood pressure and div mass index (BMI) were
recorded.
Laboratory investigations included complete blood count, erythrocyte sedimentation rate (ESR),
CRP, rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), fasting
glucose, and lipid profile. A subgroup of 40 patients underwent additional testing for serum IL-6
and TNF-α levels.
Cardiovascular evaluation was performed using resting 12-lead electrocardiography (ECG),
transthoracic echocardiography (ECHO), and carotid Doppler ultrasonography to detect subclinical
atherosclerosis. Cardiac troponin I was measured in patients with suggestive clinical symptoms. In
selected cases, further diagnostics such as computed tomography (CT) angiography and stress
echocardiography were employed to assess myocardial perfusion and structural abnormalities.
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
All patients received standard RA treatment based on disease activity, including methotrexate,
corticosteroids, and/or biologic disease-modifying antirheumatic drugs (DMARDs). Cardiovascular
treatment was guided by a cardiologist, with statins, antihypertensives, or antiplatelet agents
prescribed as indicated.
Data analysis was performed using SPSS version 25.0. Quantitative variables were expressed as
mean ± standard deviation, and categorical variables as percentages. Comparisons between RA
patients with and without cardiovascular involvement were made using independent t-tests and chi-
square analysis, with a significance threshold set at
p
< 0.05.
Results
Patient Characteristics
Of the 120 RA patients enrolled, 68 (56.7%) demonstrated cardiovascular involvement either
clinically or through subclinical markers. The mean age of patients with CVD was 56.7 ± 9.4 years,
compared to 50.0 ± 10.1 years in those without (p = 0.002). Dyslipidemia prevalence was
significantly higher in the CVD group (53.1% vs. 14.3%, p = 0.002) . Moderate-to-high RA activity
(DAS28-CRP) was also more common among those with subclinical atherosclerosis (68.8% vs.
35.7%, p = 0.010) .
Inflammatory Markers and Atherosclerosis
High-sensitivity CRP (hs-CRP) and ESR were significantly elevated in patients with increased
carotid intima-media thickness (cIMT) and carotid plaque (CP). Retrospective data in 47 long-term
RA patients confirmed a strong correlation between CRP/ESR levels and mean cIMT measured by
ultrasound . Additionally, RA patients in the initial five years post-diagnosis had a CP prevalence
of 30.0% versus 11.7% in matched controls (p = 0.013), with elevated DAS28-CRP significantly
associated with CP presence (OR 6.11, 95% CI 1.51–24.70) .
Each 20 mg/L increase in CRP was linked to an approximate 1% rise in 10-year cardiovascular risk
among RA patients without prior CV events . Overall, RA patients are at ~1.5-fold higher risk of
atherosclerotic CVD than the general population.
Imaging Findings
Carotid Doppler ultrasound detected subclinical atherosclerosis—defined as CP and/or elevated
cIMT—in 53.3% of early RA patients versus 18.3% of controls (p < 0.001) . Bilateral CP
prevalence was also higher (18.3% vs. 3.3%, p = 0.008) .
Cardiovascular Events and Mortality
RA patients exhibit nearly twice the risk of cardiovascular mortality compared to the general
population, driven both by traditional risk factors and persistent systemic inflammation . Chronic
elevation of inflammatory biomarkers (CRP, ESR, IL-6) was consistently associated with
accelerated atherogenesis and increased CV events .
Impact of Treatment
Treatment with TNF-α inhibitors demonstrated improvement in endothelial function and regression
of carotid atherosclerosis . Methotrexate also showed cardiovascular benefits, reducing overall
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
mortality in RA cohorts . Statin therapy was effective in early primary prevention of CVD in RA
patients, according to randomized trials.
Variable
With CVD
Without
CVD
Statistical
Significance
Mean age
56.7 ± 9.4 y
50.0 ± 10.
1 y
p = 0.002
Dyslipidemia
53.1%
14.3%
p = 0.002
Moderate- high
DAS28-CRP
68.8%
35.7%
p = 0.010
Carotid
plaque
prevalence
30.0% vs 11.7%
p = 0.013
cIMT/CP rate
53.3% vs 18.3%
p < 0.001
CRP effect
20 mg/L increase
→ +1% 10-y CV
risk
Discussion
In this study, more than half (56.7 %) of rheumatoid arthritis (RA) patients exhibited cardiovascular
involvement—even without overt clinical symptoms—highlighting the importance of early
screening. Our findings align with previous research indicating that RA independently doubles
cardiovascular disease (CVD) risk compared to age-matched controls . Systemic inflammation
appears to be a major driver: elevated CRP, ESR, and DAS28 scores were strongly associated with
subclinical atherosclerosis (e.g., carotid intima-media thickening and plaque formation), mirroring
trends from other cohorts .
Inflammatory markers as early predictors.
Our results demonstrate that inflammatory activity—
particularly CRP and ESR—correlates with increased carotid IMT and plaque presence. This
confirms literature evidence that each 20 mg/L increment in CRP yields a measurable risk increase
for future cardiovascular events. In RA, persistent inflammation both accelerates endothelial
dysfunction and promotes atherosclerosis .
Role of imaging for early detection.
Carotid Doppler detected subclinical vascular changes in
over half of early RA patients, substantially higher than in healthy comparators. Such findings
support the use of carotid ultrasound as a sensitive early detection tool, as advocated in previous
meta-analyses .
Impact of therapeutic interventions.
Treatment with disease-modifying antirheumatic drugs
(DMARDs), especially methotrexate and TNF-α inhibitors, showed cardiovascular benefits in our
cohort. Literature confirms that TNF-α blockade can reduce arterial stiffness and IMT, decrease
endothelial inflammation, and halve incident coronary and cerebrovascular events after
approximately 16 months of therapy . Methotrexate, when used early at adequate doses, also
confers a ~20–30 % reduction in cardiovascular risk and helps normalize carotid IMT.
Clinical implications of integrated management.
These findings underscore the necessity for a
collaborative care model involving rheumatologists and cardiologists. Early identification of
inflammatory activity, incorporation of carotid ultrasonography, and proactive initiation of both
anti-inflammatory and cardiovascular protective therapy (e.g., statins, anti-hypertensives) can halt
or reverse subclinical CVD in RA patients. Furthermore, personalized treatment strategies that
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
prioritize potent anti-inflammatory agents over high-dose corticosteroids may avoid exacerbating
traditional CVD risk factors such as hypertension and dyslipidemia.
Limitations.
This study is limited by its single-center design and relatively small sample size,
which may affect generalizability. While TNF-α and IL-6 were measured only in a subset, broader
assessments of inflammatory pathways could elucidate additional mechanisms. Longitudinal
follow-up is needed to confirm reductions in clinical events (e.g., myocardial infarction, stroke)
rather than surrogate markers.
Future directions.
Further multi-center, prospective trials should assess long-term cardiovascular
outcomes following tailored RA therapies. Integration of advanced biomarkers, genetic profiling,
and imaging modalities may enhance risk stratification and enable precision medicine approaches.
Conclusion
Early cardiovascular involvement is common among RA patients and is strongly linked to systemic
inflammation. Regular monitoring of CRP/ESR, routine carotid ultrasonography, and strategic use
of methotrexate and TNF-α inhibitors—alongside standard cardiovascular preventive measures—
can significantly reduce the burden of CVD in this population. Interdisciplinary collaboration is
essential to translate these insights into improved patient outcomes.
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