Inflammatory cytokines differ between patients with high versus low CHA2DS2-VASc scores in sinus rhythm-a possible mechanism for adverse cardiovascular events

Avishag Laish-Farkash; Ziv Sevilya; Olga Perelshtein Brezinov; Lior Fortis; Eli Lev

doi:10.1016/j.ijcrp.2022.200155

Inflammatory cytokines differ between patients with high versus low CHA2DS2-VASc scores in sinus rhythm-a possible mechanism for adverse cardiovascular events

Int J Cardiol Cardiovasc Risk Prev. 2022 Oct 25:15:200155. doi: 10.1016/j.ijcrp.2022.200155. eCollection 2022 Dec.

Authors

Avishag Laish-Farkash¹, Ziv Sevilya¹, Olga Perelshtein Brezinov¹, Lior Fortis¹, Eli Lev¹

Affiliation

¹ Cardiology Department, Samson Assuta Ashdod University Medical Center, Ashdod, and Ben Gurion University of the Negev, Israel.

Abstract

Background: The CHA₂DS₂-VASc score was shown to predict systemic thromboembolism and mortality in certain groups of patients in sinus rhythm (SR). Previous data showed that patients in SR with high CHA₂DS₂-VASc score have higher plasma levels of inflammatory markers such as sP-selectin and C-reactive protein. We further investigated this group.

Methods: Blood samples were collected from consecutive patients in SR. Plasma was extracted and stored at -80 °C. Concentrations of a panel of soluble markers IL-1β, IL-6, IL-8, IL-10, TNF-α and VEGF were measured by Magnetic Luminex Performance Assay. The PLF4 cytokine blood level was measured by ELISA.

Results: 66 patients were enrolled (age 53 ± 18 years, 60% women). Patients with high CHA₂DS₂-VASc scores (n = 23) had significantly higher median IQR concentrations of TNF-α [10.34 (8.55,14.92) vs. 7.69 (6.06, 9.85) pg/ml, p = 0.009] and a trend towards higher levels of IL-1β [0.59 (0.4,0.8) vs. 0.44 (0.31, 0.62) pg/ml, p = 0.07] and IL-8 [5.92 (4.5,9.4) vs. 5.04 (3.63, 6.04) pg/ml, p = 0.07], compared to the group with low scores (n = 43). Median IQR concentrations of VEGF, IL-6, IL-10 and PF4 did not significantly differ between the CHA₂DS₂-VASc score groups.

Conclusion: Patients in SR with high versus low CHA₂DS₂-VASc scores have high plasma concentrations of systemic inflammation cytokines. The already proven high levels of sP-selectin, that promotes release of inflammatory cytokines from leukocytes, is in line with these results. This pro-inflammatory state in patients with high CHA₂DS₂-VASc scores, may explain the higher rate of adverse cardiovascular events associated with elevated CHA₂DS₂-VASc score even without atrial fibrillation.

Keywords: CHA2DS2-VASc score; Inflammation; Inflammatory cytokines; Sinus rhythm; TNF-α.