Comparison of RANKL expression, inflammatory markers, and cardiovascular risk in patients with acute coronary syndrome with and without rheumatoid arthritis

  • Velichka PopovaEmail author
  • Zaprin Vazhev
  • Mariela Geneva-Popova
  • Anastas Batalov


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.


Acute coronary syndrome Rheumatoid arthritis Inflammatory biomarkers Mortality RANKL GRACE 




Compliance with ethical standards

Ethical approval

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

Informed consent was obtained from each participant involved in this research.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of Rheumatology, Clinic of Rheumatology, UMHAT “Kaspela”Medical University of PlovdivPlovdivBulgaria
  2. 2.Faculty of Medicine, Department of Cardiosurgery, Clinic of Cardiac Surgery and Vessels Surgery, UMHAT “Sv.Georgy”Medical University of PlovdivPlovdivBulgaria
  3. 3.Faculty of Medicine, Department of Rheumatology, Clinic of Rheumatology, UMHAT “Sv. Georgy”Medical University of PlovdivPlovdivBulgaria

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