Assessment of Cardiovascular Risk by Coronary Calcium Score in Rheumatoid Arthritis Patients at Risk for Interstitial Lung Disease

BACKGROUND. Rheumatoid arthritis (RA) is an autoimmune disease, which primarily affects the synovial joints but also the cardiopulmonary systems. Interstitial lung disease (RA-ILD) and cardiovascular disease (CVD), are an area of growing interest in RA. Currently, no standardized guidelines exist for the screening of RA-ILD and CVD in patients with RA. Shared risk factors for the development of RA-ILD and CVD include male sex, cigarette smoking, positivity for anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF), disease onset after the age of 60, high disease activity and the presence of other extra-articular manifestations. Hence, the two conditions may be detected with a common diagnostic tool. CVD represents the main cause of death in patients affected by RA. Patients with RA show a higher prevalence of atherosclerosis and CVD compared to the general population, a finding not fully explained by traditional risk factors, with systemic inflammation playing a pivotal role. This limitation is reflected in conventional cardiovascular risk scores, which do not account for the contribution of inflammation in rheumatic diseases; for this reason, EULAR guidelines recommend multiplying the estimated risk by 1.5. Moreover, surrogate markers of atherosclerosis, such as the coronary artery calcium (CAC) score, have proven useful in identifying subclinical atherosclerosis in these patients. Although CAC scoring is conventionally performed using ECG-gated CT, studies have shown that the pooled agreement between the traditional method and CAC scoring on non-ECG-gated CT - such as high resolution chest CT (HRCT) - is excellent. OBJECTIVE. The primary objective was to investigate the prevalence of CAC score >0 among a cohort of RA patients at risk for having RA-ILD. The secondary objectives were to correlate measures of disease activity burden to CAC scores and to reclassify cardiovascular risk of RA patients with CAC scores. METHODS. Between July 2024 and February 2025 we recruited 65 patients at a single centre, the Rheumatology Unit, University and Hospital of Padua. All patients met the EULAR/ACR 2010 RA criteria and had at least two risk factors for ILD. All participants underwent HRCT, pulmonary function tests and lung ultrasound according to a screening protocol for the detection of RA-ILD, and for each patient a CAC score was calculated. RESULTS. The study population included 23 male and 42 female patients, with a median [IQR] age of 63 [56.5; 68], disease duration of 8 years [2;16] and DAS28 of 2.3 [1.34; 3.70]. The main result is that 64.7% patients had a CAC score>0, with a median score of 55.8 [0;483.8]. Male sex, arterial hypertension, dyslipidemia were significantly more represented among CAC>0 group. Subjects with CAC>0 showed a higher cumulative smoking exposure (pack-years, p=0.047). There were no significant differences in terms of disease duration, disease activity (DAS28, SDAI, CDAI) or serostatus (RF, ACPA) between the two groups. 9 patients out of 65 had RA-ILD and all of them had CAC>0, which was significantly higher than in patients without ILD. Including CAC score in the MESA calculation led to risk reclassification in 37.7% of patients, with 21 patients resulting in an upward shift to a higher risk category and only 2 in a downward shift. Finally, incorporation of the CAC score into the MESA model mainly reclassifies upward from the lower risk categories, even when LDL-C is at target. CONCLUSION. This study highlights HRCT as a tool for the simultaneous screening of RA-ILD and subclinical atherosclerosis in patients with RA. Incorporating CAC assessment into HRCT protocols routinely performed for ILD screening may offer a cost-effective approach to enhance cardiovascular risk stratification and optimize preventive management in this population.