What Is the Most Common Cause of Death in Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that primarily affects the joints but also has widespread systemic effects. While joint damage and disability are well-recognized concerns, RA significantly increases the risk of life-threatening complications beyond the musculoskeletal system.

Understanding the most common causes of death in RA patients highlights the importance of early detection and proactive management.

Cardiovascular Complications

Individuals with RA face a heightened risk of cardiovascular disease, the leading cause of mortality in this population. Chronic systemic inflammation accelerates atherosclerosis and increases the likelihood of adverse cardiac events. The following cardiovascular conditions significantly impact survival rates.

Coronary Artery Disease

RA is associated with a nearly 50% increased risk of coronary artery disease (CAD) compared to the general population, according to a 2021 study in Arthritis & Rheumatology. Persistent inflammation promotes endothelial dysfunction, oxidative stress, and atherosclerotic plaque formation. Traditional risk factors such as hypertension, dyslipidemia, and obesity are often worsened by prolonged corticosteroid use. A meta-analysis in Annals of the Rheumatic Diseases (2022) found that RA patients experience myocardial infarctions at a younger age and with greater severity than non-RA individuals. Delayed diagnosis due to atypical symptoms further worsens outcomes. Aggressive lipid management, regular cardiovascular screening, and anti-inflammatory therapies—such as TNF inhibitors and IL-6 blockers—help mitigate CAD risk.

Heart Failure

Heart failure is another major contributor to mortality in RA, with patients exhibiting a 1.5- to 2-fold increased risk compared to the general population, according to a 2020 study in JAMA Cardiology. Chronic inflammation leads to myocardial fibrosis and impaired ventricular function, even in the absence of traditional risk factors. Heart failure with preserved ejection fraction (HFpEF) is more common in RA, characterized by stiffened ventricles that impair diastolic filling. The European Heart Journal (2023) reported that RA-related heart failure has worse outcomes due to delayed recognition and suboptimal treatment. NSAIDs, frequently used for symptom relief, may exacerbate fluid retention and increase heart failure risk, requiring careful prescribing. Disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, have demonstrated cardioprotective effects by reducing systemic inflammation, underscoring the importance of comprehensive RA management.

Arrhythmias

RA patients have an elevated risk of arrhythmias, particularly atrial fibrillation (AF), which increases the likelihood of stroke and heart failure. A large cohort study in Circulation (2021) found that RA patients have a 40% higher incidence of AF compared to non-RA individuals, independent of conventional risk factors. Systemic inflammation contributes to electrical remodeling of the atria, promoting fibrosis and conduction abnormalities. Autonomic dysfunction, a known RA complication, may further predispose individuals to arrhythmic events. QT prolongation, linked to increased mortality, raises the risk of ventricular arrhythmias and sudden cardiac death. Beta-blockers and anticoagulation therapy are often necessary, but careful monitoring is required as certain RA treatments, including JAK inhibitors, have been associated with thromboembolic events. Regular electrocardiographic screening in high-risk RA patients can aid early detection and improve outcomes.

Respiratory Involvement

Lung complications are a significant yet often underrecognized cause of mortality in RA. Chronic inflammation affects pulmonary structures, leading to both obstructive and restrictive lung diseases.

Interstitial lung disease (ILD) is one of the most severe manifestations, with fibrosis progressively impairing gas exchange and leading to respiratory failure. A 2022 study in The Lancet Rheumatology reported that ILD occurs in up to 10% of RA patients, though subclinical forms are detected in nearly 30% using high-resolution computed tomography (HRCT). The risk is particularly elevated in those with longstanding RA, seropositivity for anti-citrullinated protein antibodies (ACPAs), and a history of smoking. Once fibrosis becomes extensive, treatment options are limited, with antifibrotic agents such as nintedanib showing modest efficacy in slowing disease progression.

Beyond ILD, RA increases the prevalence of airway diseases, including bronchiectasis and small airway dysfunction. Bronchiectasis, marked by permanent bronchial dilation, predisposes patients to recurrent infections and progressive lung damage. A meta-analysis in Chest (2023) found that RA patients with bronchiectasis have a significantly higher risk of hospitalization due to respiratory infections. Small airway impairment, detected through pulmonary function testing, often precedes clinically apparent pulmonary decline, highlighting the need for early screening in patients with persistent respiratory symptoms.

Pleural involvement, though often asymptomatic, can present as pleural effusions. A retrospective analysis in Respiratory Medicine (2021) noted that while RA-related pleural disease is typically self-limiting, recurrent or large effusions may require drainage. Pulmonary nodules, another manifestation, can be mistaken for malignancies, leading to unnecessary biopsies. Though typically benign, these nodules can cavitate and predispose to infections, particularly in immunosuppressed patients receiving biologic therapies.

Infection Susceptibility

Severe infections remain a leading cause of hospitalization and mortality in RA patients. The combination of chronic inflammation, immunosuppressive treatments, and preexisting comorbidities makes common infections more severe.

Respiratory tract infections, including bacterial pneumonia, account for a substantial proportion of infectious complications. A BMJ Open cohort study (2022) reported that RA patients are nearly twice as likely to require hospitalization for pneumonia compared to those without RA. Opportunistic infections, such as Pneumocystis jirovecii pneumonia (PJP), pose a significant threat, particularly in those receiving prolonged corticosteroid therapy or biologic agents.

RA treatment significantly influences infection risk. Biologic DMARDs, including TNF inhibitors, IL-6 receptor antagonists, and JAK inhibitors, have been linked to a higher likelihood of bacterial, viral, and fungal infections. A systematic review in Clinical Infectious Diseases (2023) found that patients on JAK inhibitors had a 1.7-fold increased risk of herpes zoster reactivation, emphasizing the importance of vaccination before starting therapy. Long-term corticosteroid use also suppresses immune responses, increasing susceptibility to tuberculosis reactivation. Screening for latent tuberculosis before starting biologic therapy is a standard precaution, with the American College of Rheumatology (ACR) recommending annual reassessments for high-risk individuals.

Lifestyle and environmental factors further shape infection risk. Malnutrition, common in RA due to chronic inflammation and reduced appetite, weakens host defenses, making even mild infections severe. Poor oral health has been associated with a higher prevalence of bloodstream infections, as periodontal bacteria can translocate into circulation and exacerbate systemic inflammation. Preventive measures, including routine dental care and pneumococcal and influenza vaccinations, reduce infection-related complications. Despite these interventions, RA patients are less likely to receive recommended vaccines, highlighting a gap in preventive care that impacts long-term outcomes.

Malignancy Associations

RA is linked to an elevated risk of certain cancers, with both disease-related factors and treatment exposures contributing to malignancy development. Chronic inflammation plays a role in oncogenesis, particularly in lymphoid tissue, where persistent immune activation fosters an environment conducive to malignant transformation.

Lymphomas, especially diffuse large B-cell lymphoma, occur at a higher rate in RA patients. Epidemiological data from the Journal of Clinical Oncology (2023) indicate a nearly twofold increased risk compared to the general population. This association is most pronounced in individuals with severe disease activity, suggesting that prolonged inflammatory burden contributes to lymphomagenesis.

Beyond hematologic malignancies, lung cancer incidence is notably higher in RA, even among never-smokers. Fibrotic lung changes, which can arise independently of treatment, may create a microenvironment that facilitates carcinogenesis. A retrospective analysis in Thorax (2022) found that RA patients with interstitial lung abnormalities had a 1.8-fold increased likelihood of developing lung cancer. Skin cancers, particularly non-melanoma types, are also more common in individuals undergoing long-term immunosuppressive therapy. Certain RA treatments, such as JAK inhibitors, carry FDA warnings regarding heightened malignancy risks.