Cardiovascular disease in Rheumatoid Arthritis

doi:10.15406/mojor.2025.17.00690

MOJ

eISSN: 2374-6939

Orthopedics & Rheumatology

Mini Review Volume 17 Issue 1

Cardiovascular disease in Rheumatoid Arthritis

Amarilis J Perez De-Jesus,

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Andrea C Vincenti Perez

Clinical and Research Department, Caguas Rheumatology Center Clinic, Puerto Rico

Correspondence: Amarilis J Perez De-Jesus, MD, Rheumatology Service, Clinical and Research Department, Caguas Rheumatology Center Clinic, Caguas, Puerto Rico

Received: February 19, 2025 | Published: March 6, 2025

Citation: De-Jesus AJP, Perez ACV. Cardiovascular disease in Rheumatoid Arthritis. MOJ Orthop Rheumatol. 2025;17(1):11-12. DOI: 10.15406/mojor.2025.17.00690

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Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects multiple organs. In this condition, an inflammatory process affects the joints, cartilage, and other organs, including the heart. Heart disease is a consequence of this inflammatory process and is one of the leading causes of increased mortality in patients diagnosed with rheumatoid arthritis. The increase in cardiac morbidity and cardiovascular diseases is not necessarily explained by the presence of traditional cardiovascular risk factors seen in the general population. Undoubtedly, these risks for cardiovascular disease can be present, but other factors are inherent to the presence of rheumatoid arthritis.

The inflammatory process in RA, with the consequent elevation of inflammatory markers and endothelial dysfunction, creates the ideal environment for the development of atherosclerosis and myocardial dysfunction. Clinically, these patients often present with silent heart disease. The literature already establishes that these patients have increased morbidity and mortality associated with cardiovascular disease, congestive heart failure, cerebrovascular events, and myocardial infarctions. Thus, we are dealing with a patient who experiences joint pain and inflammation that we can observe and document, but at the same time, they may have an inflammatory process at the cardiovascular level that we cannot see or detect unless we actively look for it.

Pathophysiology

The pathology of cardiovascular disease in rheumatoid arthritis involves several components: immune system dysregulation and chronic inflammation resulting from the interaction of genetic and environmental factors. Evidence supports the claim that the inflammatory process is the major factor leading to the increase in cardiovascular disease in RA patients.

Levels of cytokines (tumor necrosis factor-alpha, interleukin-17, interleukin-6, interleukin-1 beta) are elevated in both rheumatoid arthritis and cardiovascular disease. The elevation of these cytokines is associated with endothelial cell activation, a crucial factor for pannus formation in synovial tissue and the pathogenesis of cardiovascular disease. Endothelial activation promotes the expression of adhesion molecules and other chemokines that facilitate the migration of leukocytes into the joint space or vascular endothelium, further recruiting neutrophils and propagating the inflammatory process. Helper T cells release interferon-gamma, which, together with tumor necrosis factor-alpha and interleukin-17, causes endothelial apoptosis, destroying the antithrombotic properties of endothelial cells. RA patients have unstable atherosclerotic plaques that are vulnerable to rupture. These patients are in a hypercoagulable state.

Targeted cytokine therapies have confirmed the role of these cytokines in these processes. For example, patients treated with tumor necrosis factor blockers show improved endothelial vascular function. Cardiovascular patients also benefit from anti-interleukin-1 beta therapies.

The use of interleukin-6 blockers reduces the inflammatory response and troponin T release following a heart attack. There is no doubt that these pro-inflammatory substances play a decisive role in the development of cardiovascular disease in RA patients.¹

Lipid abnormalities

RA patients have a unique type of dyslipidemia characterized by elevated triglycerides and low levels of low-density lipoproteins (LDL) and high-density lipoproteins (HDL). These low LDL levels are associated with inflammation, and high levels of inflammation are crucial in the development of cardiovascular disease in RA. Low LDL levels are linked to increased erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP) levels, both markers of active inflammatory processes. When the inflammatory process is controlled, LDL and HDL levels increase.

Additionally, disease-modifying anti-rheumatic drugs (DMARDs) such as anti-TNF, anti-IL-6, and JAK inhibitors can increase lipid levels. Lipid level alterations in RA patients increase the risk of cardiovascular disease as they cause instability in atherosclerotic plaques. RA patients have more atherosclerotic plaques than those without RA.

Hypercoagulable state

As previously mentioned, one of the effects of pro-inflammatory substances is endothelial apoptosis, leading to the loss of antithrombotic properties. Consequently, RA patients are in a hypercoagulable state, which further increases their cardiovascular disease risk. Endothelial damage allows thrombogenic particles to come into contact with the blood, triggering coagulation cascades and arterial occlusion.

Risk factors

Although efforts have been made to establish algorithms to predict cardiovascular disease risk in RA patients, they have not been very effective. Current algorithms, such as the Coronary Risk Evaluation Score and the Framingham Score, generally overestimate or underestimate the risk in RA patients.

Attempts have been made to develop new algorithms by incorporating RA-specific factors alongside traditional risk factors, but these have not been useful. Therefore, when evaluating RA patients, we must consider risk factors such as age, sex, diabetes, lipid status, hypertension, and smoking history. We must also take into account RA disease activity, functional capacity, corticosteroid use, presence of subcutaneous nodules, use of DMARDs, nonsteroidal anti-inflammatory drugs, rheumatoid factor positivity, anti-citrullinated protein antibody presence, methotrexate and anti-TNF use, race, and family history of myocardial infarctions. A comprehensive assessment, including medical history, physical examination, and medication use, is essential to identify patients at higher cardiovascular risk.

RA patients exhibit a phenomenon known as "paradoxical obesity," which appears to be associated with catabolic weight loss linked to high levels of inflammation. There is an increase in fat mass, particularly abdominal and visceral fat, with a loss of lean body mass. This process, called rheumatoid cachexia, occurs in 10-67% of RA patients. Due to this cachexia, their body mass index is lower. Cachexia is associated with active disease, meaning that inflammation levels are high. Thus, a lower BMI correlates with a higher risk of cardiovascular disease. This cardiovascular disease is not associated with obesity but rather with active inflammation and increased body fat with decreased muscle mass. In RA patients, obesity is not a significant predictor of cardiovascular disease.^2,3

RA patients also exhibit increased insulin resistance at a rate of 54%, compared to 40-45% in the general population.

Corticosteroid use is associated with an increased risk of cardiovascular disease, but it should be considered that patients on corticosteroids usually have more severe disease. This increased risk may be due to more severe inflammatory processes.

The inflammatory process ultimately determines cardiovascular disease risk in these patients. The presence of certain inflammatory markers suggests a higher cardiovascular risk. Patients with positive anti-CCP, positive rheumatoid factor, elevated sedimentation rate, elevated. C-reactive protein, and increased white blood cells are at higher cardiovascular risk. As noted earlier, specific cytokines and pro-inflammatory substances play a crucial role in the development of cardiovascular disease in RA patients. We emphasize the importance of considering both traditional cardiovascular risk factors and RA-specific risks when assessing these patients.

Conclusion

It is crucial to identify cardiovascular diseases early in RA patients as they contribute to increased mortality. Evaluation includes history-taking, physical examination, ECG, echocardiography, laboratory tests, and cardiology consultation.

Other conditions such as congestive heart failure, pulmonary hypertension, myocarditis, and microvascular disease, which are more prevalent in RA patients, should also be ruled out.

Management should focus on reducing inflammatory activity by targeting pro-inflammatory and hypercoagulable substances. These patients require meticulous care involving rheumatologists, cardiologists, and a multidisciplinary team to achieve disease balance and control factors contributing to disease progression.