Comparison of RANKL expression, inflammatory markers, and cardiovascular risk in patients with acute coronary syndrome with and without rheumatoid arthritis
The mechanisms responsible for increased cardiovascular risk in patients with rheumatoid arthritis (RA) involve local and systemic inflammatory processes. We aimed to compare inflammatory markers and mortality risk in patients with acute coronary syndrome (ACS) with and without RA. The study involved 95 ACS patients (46 with RA and 49 without RA) and 40 healthy controls. Serum levels of Receptor Activator of Nuclear Factor Kappa B Ligand (sRANKL), Osteoprotegerin (sOPG), high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity Tropinin I (hs-TnI) were tested in all participants. Additionally, ACS patients were assessed on RANKL expression (exRANKL) on coronary arteries and mortality risk on the Global Registry of Acute Coronary Events scale (GRACE). exRANKL was established in 35 (76%) ACS patients with RA, vs. 19 (39%) patients without RA, p < 0.001. RA patients had significantly higher levels of sRANKL and sOPG at 24 h and 48 h compared to ACS patients without RA and healthy controls (sRANKL 24 h: 121.33 vs. 51.67 vs. 36.94, p = 0.019; sRANKL 48 h: 89.21 vs. 36.95 vs. 36.94, p = 0.004; sOPG 24 h: 207.71 vs. 69.39 vs. 111.91, p < 0.001; sOPG 48 h: 143.36 vs. 69.38 vs. 111.91, p < 0.001). RA patients had significantly higher RANKL:OPG ratio at 48 h (0.062 vs. 0.53 vs. 0.33, p < 0.001), hs-CRP (28.82 vs. 23.67 vs. 2.60, p < 0.001) and hs-TnI (0.90 vs. 0.76 vs. 0.012). GRACE risk score was significantly higher in RA patients vs. those without RA (140.45 vs. 125.50, p = 0.030) and correlated with exRANKL, RANKL:OPG, hs-CRP, and hs-TnI. Our results indicate that exRANKL, inflammatory markers and mortality risk are amplified in ACS patients with RA compared to ACS patients without RA.
KeywordsAcute coronary syndrome Rheumatoid arthritis Inflammatory biomarkers Mortality RANKL GRACE
Compliance with ethical standards
All procedures were conducted in accordance with the WMA Declaration of Helsinki (1964) and approved by the local research ethics committee at the Medical University in Plovdiv.
Conflict of interest
All authors declare that they have no conflict of interest.
Informed consent was obtained from each participant involved in this research.
- 7.Wallberg-Jonsson S, Ohman M, Dahlqvist S (1997) Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. J Rheumatol 24(3):445–451Google Scholar
- 8.Wang J, Tan G-J, Han L-H, Bai Y-Y, He M, Liu H-B (2017) Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol 2:135–150Google Scholar
- 9.Patterson CC, Blankenberg S, Ben-Shlomo Y, Heslop L, Bayer A, Lowe G, Zeller T, Gallacher J, YoungI Yarnell J (2015) Which biomarkers are predictive specifically for cardiovascular or for non-cardiovascular mortality in men? Evidence from the Caerphilly Prospective Study (CaPS). Int J Cardiol 201:113–118CrossRefGoogle Scholar
- 20.Huang W, Fitzgerald G, Goldberg J, Gore J, McManus H, Awad H, Waring E, Allison J, Saczynski S, Kiefe I, Fox A, Anderson A, McManus D (2016) Performance of the GRACE risk score 2.0 simplified algorithm for predicting 1—year death after hospitalization for an acute coronary syndrome in a contemporary multiracial cohort. Am J Cardiol 118(8):1105–1110CrossRefGoogle Scholar
- 21.IBM Corp. Released (2016). IBM SPSS statistics for Windows, version 24.0. Armonk, IBMCorpGoogle Scholar
- 24.Gerber TC (2009) Diagnostic and prognostic implications of coronary artery calcification detected by computed tomography. Calcif Tissue Int 91:123–137Google Scholar