# Inflammation and Cardiovascular Disease in Rheumatoid Arthritis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $675,863

## Abstract

ABSTRACT
Individuals with rheumatoid arthritis (RA) are at 50% greater risk for developing heart failure (HF) and HF-
associated morbidity and mortality than non-RA controls. This risk persists even after adjustment for coronary
artery disease, implying that immunologic and inflammatory factors intrinsic to RA contribute to the increased
risk of HF. Our overall hypothesis is that myocardial inflammation and microvascular ischemia are prevalent in
RA patients, are mediated by antibodies to myocardial citrullinated proteins, promote impairment of left
ventricular (LV) structure/function, and are attenuated with RA therapies. Indeed, in 128 RA patients without
clinical CVD who underwent [18fluoro-deoxyglucose] positron emission-computed tomography (FDG PET-CT)
(the RHYTHM study), we observed FDG uptake (inflammation) in 35% and impaired myocardial blood flow
reserve (MFR) in 29%. Both myocardial inflammation and impaired MFR were strongly associated with clinical
and laboratory measures of RA disease activity; impaired MFR was also associated with higher LV mass, a
known precursor of HF. These data suggest that myocardial inflammation and impaired MFR mediate, in part,
early changes in LV structure/function that predate clinical HF; but it is critical to confirm these relationships in
longitudinal studies. Proximal events that mediate myocardial pathology in RA are unknown. We hypothesize
that antibodies against citrullinated myocardial proteins (APCAs) mediate, in part, this abnormal myocardial
phenotype (inflammation and impaired MFR), leading to myocardial remodeling and ultimately to functional
decline. Our preliminary data demonstrating seroreactivity in 30% of RHYTHM sera in a novel myocardial
protein array support this hypothesis. A related question is whether tumor necrosis inhibitors (TNFi’s) affect
myocardial inflammation. This is a far from insignificant question as TNFi’s were associated with increased HF
hospitalizations and death in non-RA HF patients and their risk for HF in RA is still unclear despite widespread
use. In the next funding period, we seek to extend the study period for the RHYTHM cohort for aims 1 and 3,
and to utilize an independently funded study (TARGET) for aim 2, in order to investigate the following aims:
1) To determine if imaging indicators of myocardial pathology at baseline (inflammation, impaired
MFR) are predictive of longitudinal (adverse) change in measures of LV structure and function over 4-6
years in RA patients without clinical cardiovascular disease (CVD) at baseline.
2) To determine, in a currently enrolling NIH-NIAMS funded randomized clinical trial (the TARGET
study), if RA therapies reduce myocardial inflammation.
3) To determine if seroreactivity to citrullinated myocardial antigens in RHYTHM participants is
associated with baseline myocardial inflammation and impaired MFR and/or with change over time in
parameters of LV structure/function. These investigations will advance understanding of mecha...

## Key facts

- **NIH application ID:** 10408660
- **Project number:** 5R01AR050026-16
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joan Marie Bathon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $675,863
- **Award type:** 5
- **Project period:** 2004-05-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408660

## Citation

> US National Institutes of Health, RePORTER application 10408660, Inflammation and Cardiovascular Disease in Rheumatoid Arthritis (5R01AR050026-16). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408660. Licensed CC0.

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