Background/Purpose: Cardiovascular diseases are the leading cause of death in RA patients [Gravallese EM, Firestein GS. N Engl J Med. 2023;388:529-42]. However, risk calculation has many limitations because of the abnormal function of some lipoproteins and, although there are reliable image methods, they could be not accessible in some cases. Growth differentiation factor 15 (GDF15) is part of the TGFβ family; it has been recently associated with endothelial dysfunction and atherosclerosis and therefore could be a useful biomarker. [Wang D, Day EA. Nat Rev Endocrinol. 2021;17:592-607]. This study aimed to explore the correlation among GDF15, QRISK3, and coronary artery calcium score (CAC). 

Methods: Patients fulfilling the 2010 ACR/EULAR classification criteria for RA with positive RF and ACPA were included in this cross-sectional observational study.  The patients underwent medical evaluation by a rheumatologist who determined the degree of activity using DAS28 CRP. An expert radiologist analyzed the chest CT of RA patients and determined the CAC expressed in Agatston units (AU). GDF15 was measured in plasma, by an ELISA blind analysis, and expressed in picograms/milliliters. Laboratory variables were obtained by electronic record review. The instrument used to evaluate cardiovascular risk was QRISK3.  A control group of healthy patients was included, in which QRISK3 and GDF15 levels were analyzed. Data were described as percentages, mean ± standard deviation or median, and interquartile range (IQR) according to its distribution. The assessment of normality was done by the Kolmogorov-Smirnov test. Chi-square test, Fisher test, Student’s t-test, or Mann-Whitney U test were used for comparisons as required. The correlation among QRISK3, GDF15, and CAC was evaluated by Spearman’s method. A value of p< 0.05 was considered statistically significant.

Results: Fifty-six patients were invited, however, 2 were excluded because they had negative RF and ACPA. A total of 54 patients and 10 healthy controls were analyzed. Forty-eight (88.9%) female patients were included in the RA group and 8 (80%) in the control group. The mean age of RA patients was 58 + 11 years, and  45 + 12 years in the control group. BMI was similar between groups, 27.05 in RA patients vs 27.42 in the control group (p=0.956). The most common comorbidities were: hypertension (40.7%) and diabetes (24.1%). Mean CAC was 174.9 AU in RA patients. QRISK3 median score in RA patients was 7.9% (4.9-14.4) and 1.3% (0.5-7-9%) in the control group. GDF15 mean score was 1559.8 in RA patients vs 990 in the control group (p=0.044). Thirty-nine patients (72.2%) were in remission according to DAS28. A positive correlation between CAC and GDF15 levels was found (Rho=0.576, p< 0.01). In addition, a higher score in QRISK3 correlated positively with levels of GDF15 (Rho=0.577, p< 0.01). No association between DAS28 activity and GDF15 levels was found. 

Conclusion: The levels of GDF15 correlated positively with CAC and QRISK3. In addition, the levels of GDF15 were higher in patients with RA in comparison with the control group. GDF15 could become a novel cardiovascular biomarker useful for determining patients with high cardiovascular risk, however further studies are needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-coronary-artery-calcium-score-and-growth-differentiation-factor-15-in-rheumatoid-arthritis/