Chronic inflammation is associated with impaired cardiac structure and function in patients with inflammatory arthritis: the ARTCADIA Study
Authors: Sengelov M , Maria Dons M D , Trine Charlotte Bistrup Petersen T C B P , Niklas Dyrby Johansen N D J , Filip Soeskov Davidovski F S D , Nino Emanuel Landler N E L , Kristoffer Grundtvig Skaarup K G S , Katja Vu Bartholdy K V B , Gunnar Gislason G G , Mette Bjoerndal Axelsen M B A , Jens Joergen Lykkegaard J J L , Merete Lund Hetland M L H , Annette Hansen A H , Dorte Vendelbo Jensen D V J , Tor Biering-Soerensen T B S 
Published: October 2024

Abstract

Background
Inflammation as an underlying cause of cardiac dysfunction has been underscored in recent years. Patients with inflammatory arthritis (IA) are at risk of being exposed to a high degree of chronic and systemic inflammation. It is therefore important to investigate whether high inflammatory burden impacts cardiac structure and function in patients with IA.

Purpose
To examine the impact of long-term inflammation on measures of cardiac structure and function in individuals with rheumatoid arthritis (RA) and axial Spondyloarthritis (axSpA), collectively referred to as IA, in a large cohort.

Methods
In a prospective cohort study, outpatients with a diagnosis of IA were included over two years during their biannual rheumatological routine appointment. In total, 1,285 participants were included. Participants were evaluated at a cardiology research center where echocardiography was performed following a pre-defined protocol. To evaluate chronic inflammation, C-reactive protein (CRP) was averaged from clinical outpatient visits registered in a rheumatological database. Uni- and multivariable linear regressions were used to examine the relationship between echocardiographic measures and log-transformed CRP.

Results
Among the 1,285 participants, 903 (70%) were diagnosed with RA, 358 (28%) with axSpA, and 24 (2%) with other forms of IA. Mean age was 60 ± 13 years, 64% were female. The median number of outpatient visits was 30 (Interquartile range (IQR): 18 - 48), median disease duration was 12 (IQR: 6 - 20) years, and the median outpatient CRP was 5.7 (IQR: 3.7 – 9.8) mg/L. 519 (40%) patients had hypertension (HT), 113 (9%) diabetes mellitus (DM), 76 (5.9%) ischemic heart disease (IHD) and 35 (2.5%) heart failure (HF). Mean left ventricular (LV) ejection fraction was 54.6 ± 5.7%, mean numerical global longitudinal strain (GLS) was 17.8 ± 2.4%, mean LV mass index (LVMi) was 73 ± 18 g/m2 and mean tricuspid annular plane systolic excursion (TAPSE) was 2.5 ± 0.4 cm.
In univariable analyses, higher levels of CRP were significantly associated with lower GLS, p &lt; 0.001; higher E/e’, p = 0.001; higher LVMi, p &lt; 0.001 and lower TAPSE, p = 0.005 (Figure). The associations remained significant after adjusting for clinical characteristics including disease duration, age, sex, blood pressure, body mass index, physical activity, pack-years of smoking, cholesterol, HT, DM, heart rate, atrial fibrillation, IHD and HF (p &lt; 0.05 for all associations). We observed no significant interactions between the IA diagnosis and inflammation across the significant echocardiographic measures.

Conclusion
In a large cohort of patients with IA, increasing levels of chronic inflammation determined by outpatient CRP was associated with impaired measures of cardiac structure and function and remained significant after adjusting for clinical characteristics. The prognostic and clinical implication of these findings needs to be explored in future studies.Linear regression splines