How does rheumatoid arthritis affect my heart?

Rheumatoid arthritis (RA) is an inflammatory arthritis that affects the joints and multiple organs, such as the eye, lungs, and heart.^1-5 Physician organizations such as the American College of Cardiology/American Heart Association and the European League Against Rheumatism agree that there is an increased cardiovascular (CV) morbidity and mortality in patients with RA.^6,7 While RA has been associated with this increased risk, other factors such as high levels of inflammatory markers have also been shown to increase the risk of incident myocardial infarction (MI) and stroke.^8-10 Inflammatory markers are defined as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody. Furthermore, evidence demonstrates that traditional CV risk factors such as high blood pressure, body mass index (BMI), and smoking affect patients with RA differently than those without RA.^11,12 Even after controlling for these traditional risk factors, patients with RA still have an increased risk of CV events.^13,14 These studies indicate that RA itself is associated with cardiovascular disease (CVD) events and CV mortality.

In a meta-analysis that included 111,758 patients, there were 22,927 CV events, including ischemic heart disease or cerebrovascular events.¹⁵ Compared to the general population, there was an observed overall increased mortality risk due to CVD in patients with RA (meta-standard mortality ratio 1.50, 95% confidence interval [CI] [1.39 – 1.61]). In another study, participants in the large prospective Nurses' Health Study (n=114,342) were observed for 20 years to examine the influence of incident RA on the risk of MI and stroke.⁹ Participants who developed RA during the course of the study (n=407) had an elevated risk of MI (adjusted relative risk [ARR] 2.0, 95% CI [1.23 – 3.29], p=0.005). The risk of having a nonfatal MI was significantly elevated (RR 2.17, 95% CI [1.22 – 3.87]). The risk of having a fatal MI or stroke was also elevated but was not statistically significant (RR 1.82, 95% CI [0.75 – 4.41] and RR 1.48, 95% CI [0.70 – 3.12], respectively). A number of other studies have also noted the increased risk of CV morbidity and mortality in patients with RA.^8,14,16

Patients with RA who had an MI or stroke had elevated inflammatory markers that are associated with increased CVD risk.^8,10 In a retrospective review of the Veterans Health Administration records, there were 37,568 patients with RA (mean age 63, 90% men) with a total of 896 incident hospitalized MI, 415 incident strokes, and 122 deaths from either MI or stroke.⁸ Researchers showed that there was an inverse association between levels of high-density lipoprotein cholesterol, CRP and increased risk for MI and stroke. For example, patients with higher CRP (>2.17 mg/dL) had an increased risk for MI (hazard ratio [HR] 2.43, 95% CI [1.77 – 3.33]) and stroke (HR 2.02, 95% CI [1.32 – 3.08]), compared to patients with lower CRP (<0.26 mg/dL). There was also a significant association between positive RF and anti-CCP antibody (HR 1.23, 95% CI [1.03 – 1.48]).

Review of current evidence show the different effect of traditional CV risk factors such as hypertension, type 2 diabetes mellitus, smoking, and hyperlipidemia on patients with RA. A large meta-analysis demonstrated a significantly greater risk for CV morbidity when patients with RA had an additional traditional CVD risk factor.¹² For instance, patients with RA and hypertension had an overall RR of 2.24 (95% CI [1.42 – 3.06]) for CV morbidity compared to patients with RA without hypertension. In another review, smoking was associated with positive RF, production of anti-CCP, increased disease severity, and poor response to treatment in patients with RA.¹¹ The combination of these associations may further increase CVD risk in patients with RA. Also, although high BMI is typically a risk factor for CVD, a low BMI (<18.5 kg/m²) in patients with RA is associated with a higher CVD risk.

RA itself has been shown to be an independent risk factor for CVD.^13,14 In a population-based study in the Netherlands, the prevalence odds ratio (OR) for CVD after controlling for traditional risk factors was 2.70 (95% CI [1.24 – 5.86]) for patients with RA. This was even greater than that of patients with type 2 diabetes (OR 2.01, 95% CI [0.90 – 4.51]), which has been widely established as associated with increased CVD risk.

This summary shows the breadth of literature available regarding the association of RA and increased CV outcomes. This association has been documented predominantly in longitudinal studies and systematic reviews. The longitudinal studies have included population and non-population-based studies. However, the data is extensive and remains robust for these associations.

^References

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