Introduction: Inflammation plays a crucial role in cardiovascular disease (CVD). Tumour Necrosis Factor Alpha Converting Enzyme (TACE) is a membrane bound protein responsible for cleaving Tumour Necrosis Factor Alpha (TNFα) and its associated receptors releasing soluble Tumour Necrosis Factor Alpha Receptor I and II (sTNFRI and sTNFRII). sTNFRI has unfavourable effects increasing inflammation and causing endothelial cell dysfunction whereas sTNFRII has favourable effects by activating angiogenic and survival pathways. However, clinical studies exploring the potential role of such biomarkers to predict major adverse cardiovascular events in very high risk patients is lacking.
Purpose: To evaluate whether gene expression of TACE and protein levels of sTNFRI and sTNFRII correlates with increasing cardiovascular risk.
Methods: Consecutive patients were recruited from the cardiac catheterisation laboratory and outpatient clinics. Group 1 were defined as Very high risk patients (VHR) with a 10 year risk SCORE ≥10% risk of fatal CVD. VHR patients were subdivided in Acute Coronary Syndrome patients (ACS-VHR) and elective percutaneous coronary intervention patients (ELEC-VHR). Group 2 were low, moderate and high risk patients (non-VHR) with a 10 year risk SCORE <10% risk of fatal CVD. TACE gene expression levels were measured in the peripheral blood using real time PCR. Plasma levels of, sTNFRI and sTNFRII levels were measured using enzyme-linked immunosorbent assay (ELISA).
Results: A total of 318 patients were recruited. The VHR (n=208) patients consisted of ACS-VHR (n=117) and ELEC-VHR (n=91). The non-VHR (n=110) patients consisted of low risk (LR) (n=77), moderate risk (MR) (n=31) and high risk (HR) (n=2) patients. TACE gene expression was higher in VHR compared to non-VHR patients (0.054±0.03 vs. 0.039±0.02, p<0.0001). There was no significant difference in TACE gene expression between ACS-VHR and ELEC-VHR patients. sTNFRI levels were higher in VHR patients compared to non-VHR patients (1247 pg/ml ± 724.2 vs. 815.5 pg/ml ± 210.2, p<0.0001) and higher in ACS-VHR patients versus ELEC-VHR patients (1359 pg/ml ± 775 vs. 1103 pg/ml ± 629, p=0.0002). sTNFRII were higher in VHR patients versus non-VHR patients (2839 pg/ml ± 1314 v/s 2099 pg/ml ± 620.1, p<0.0001) but were not significantly higher in ACS-VHR patients versus ELEC-VHR patients. TACE gene expression, sTNFR1 and sTNFR2 levels increased significantly with increasing cardiovascular risk p<0.0001.
Conclusion: These results indicate that TACE, sTNFRI and sTNFRII can potentially differentiate between VHR and non-VHR patients as well as discriminate between acute and elective VHR patients. Such biomarkers may help to further stratify very high risk patients at risk of major adverse cardiovascular events.
|Title of host publication||TACE gene expression and soluble receptors TNFRI and TNFRII levels identifies very high risk cardiovascular patients|
|Number of pages||6229|
|Publication status||Published (in print/issue) - 29 Aug 2017|
|Event||European Society for Cardiology - Barcelona, Spain|
Duration: 23 Aug 2017 → 30 Aug 2017
|Conference||European Society for Cardiology|
|Period||23/08/17 → 30/08/17|