Heart Failure Risk Linked To Rheumatoid Arthritis

Introduction: 

Heart failure is a serious condition that currently affects nearly 7 million people in the United States. It occurs when the heart's muscles weaken to the point where they are no longer able to pump sufficient blood through the body. This deprives the body of the oxygen that is necessary for organ and tissue functions to be carried out, leading to serious complications. Many of the existing treatment options for Heart failure have proven to be ineffective in reducing the number of hospitalizations and fatalities the condition causes. This is especially the case for Heart Failure with preserved ejection fraction (HFpEF), which is a type of heart failure where the left ventricle is not able to properly fill up with blood between heartbeats, and accounts for the majority of hospitalizations caused by heart failure. This insufficiency has pointed to a general lack of understanding of the underlying mechanisms of the condition. Previous research has proposed inflammation as a common risk associated with the development of HF, more specifically HFpEF, therefore making it increasingly necessary for medical professionals to understand how inflammation, in particular, has influenced the functions of the cardiovascular system. Rheumatoid Arthritis (RA) is a chronic inflammatory condition that has been linked to Heart Failure, excluding other cardiovascular conditions like Coronary Artery Disease. Thus, with this suspected association, a clinical trial has been organized to study patients with RA and determine how inflammation affects the presentation of heart failure. 

Methods: 

A clinical trial was conducted using patients with Rheumatoid Arthritis to study how chronic inflammation affects the onset of Heart Failure, especially HFpEF. 3 groups were used in this examination– the first of which was a control group consisting of patients without RA. Their associated risk for heart failure was assessed throughout the study. Two experimental groups were used with patients who had RA, with one group demonstrating signs of greater inflammation and another group that was using antirheumatic medications. This was done to analyze how the risk of Heart failure fluctuated based on various conditions. A second cohort was used with cMRI imaging to determine directly how cardiac structure and function changed in response to markers of inflammation in RA patients. 

The study used electronic health records for Vanderbilt University Medical Center to find 9,889 RA patients who had at least two RA diagnosis codes and were then prescribed medications to treat the chronic illness. They then paired up each RA patient with one that demonstrated no signs of RA or any other interfering disease, yet was the same age, sex, and race. The measure of heart failure was standardized by analyzing whether a patient had a heart failure diagnosis code before, or if they had received IV diuretics within 90 days, as that was a common treatment for heart failure. The second cohort consisted of a smaller group of 115 people, of which 59 had RA while 56 did not. Everyone who was selected showed no signs of heart failure. Each member underwent Cardiac MRI imaging to evaluate their cardiovascular function and had blood testing done for proteins. 

Results: 

By the end of the study, the patients with RA ended up being more prone to comorbidities like Coronary Artery disease, atrial fibrillation, and traditional cardiovascular risk factors. Antihypertensive medications were also more commonly used among patients with RA, strengthening the link between the two. Additionally, Heart failure incidence was noticeably greater among patients with RA when compared to the control group, with 766 incidences in total. Among the 766 patients in total, 138 had died, with the majority being RA patients. This pointed towards a higher morbidity with chronic inflammation. Many of the RA patients who had heart failure were also at a later stage in the RA diagnosis. Looking specifically at HFpEF, traditional cardiovascular risk factors were strongly associated with its development, while atrial fibrillation presented as the most prevalent comorbidity. 

The second cohort aimed to determine how the cardiac function of patients with RA differed from that of healthy people. It was also designed to evaluate whether inflammation-related proteins in the blood, measured via the blood test, affected heart structure and function. The results demonstrated that in most cases, the measures of heart size, LVEF (pumping strength), and Blood Pressure were similar across both groups. However, patients with RA had worse ventricular-vascular coupling, suggesting that their heart and blood vessels were not working together as well. In patients with RA, 24 inflammation-related proteins were more abundant than in patients without it, proving they experienced additional inflammation. Of those 24, 4 were linked directly to higher LVEF measures and better ventricular-vascular coupling. Meanwhile, one of the proteins (Artemin) led to worsened heart function through weaker heart contractions and poorer heart-vessel interactions. Altogether, the results suggested that the inflammation in RA likely affected the heart before obvious symptoms of heart disease appeared.  

Discussion: 

Overall, RA patients were at a higher risk of experiencing heart failure than non-RA patients. The presence of markers of inflammation was linked to a higher heart failure risk in RA patients, with about two-thirds of the cases of heart failure being HFpEF in both groups. Medications that were meant to reduce inflammation in RA patients also managed to reduce the risk of HFpEF. Artemin, which was the protein that had been linked to worsened heart function, was then proposed as a novel biomarker for the risk of HF in inflammatory conditions since it was present the most in RA patients. 

Conclusion: 

While this study was conducted using EHR data from a single medical care center-- limiting its generalizability--, the results were validated by similar findings from the Mayo Clinic and

registries from Denmark and Sweden. Furthermore, there were potentially external variables not measured in this study that affected the onset of HF, thus limiting the validity of these conclusions. Nevertheless, this study demonstrated that RA is associated with a higher risk of HF due to the inflammation it is associated with. 

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