Early and late changes of multi-marker panel in patients with STEMI after angioplasty

Abstract

Background: Post-infarction remodeling is strongly linked with collagen turnover which is influenced mostly by oxidative stress and inflammation, the last being, according to our previous data, triggered by early infiltrated neutrophils (24–48 h) followed by accumulation of macrophages M1 (72 h) and M2 (7–14 days).

Aim: Evaluation of circulating markers of inflammation and oxidative stress in the different periods of 1 year follow up post-infarct evolution: first 2 weeks (each day), 1st month (synthesis of collagen type III), 3rd month (synthesis of collagen type I), 6 and 12 months.

Material and methods: Study was performed in 47 patients (age range of 37–68 years) with STEMI exposed to angioplasty (<12 hours). Circulating levels of 28 markers were determined at admission, 1, 2, 3 ... 14 days, 1, 3, 6 and 12 months. Obtained results were compared with control value of markers determined in 17 apparently healthy persons and admission level (before PCI).

Results: The earliest (first 24 h) significant change was inherent to MMP-8, whose double elevation (averagely from 3,1 up to 6,4 ng/ml) corresponded to period of neutrophil infiltration (24–48 h). Serum levels of IL-1, IL-6 have raised significantly since 48 h, followed by authentic increase of TNF-alpha, IL-8, CRPhs and phospholipase A2 since 72 h. Up to a period of 7 days these markers remained increased, but toward 14th day fell by 24–46% arguably due to macrophage M2 activation. This is consistent to dynamics of anti-inflammatory markers, IL-4 and IL-10 which decreased till 7th, elevated toward 14th day although remained below control. Inflammation boosting was associated by oxidative stress activation during 1st week manifested by malonic dialdehyde (MAD) rise and total antioxidant activity fall. To be noted that markers improvement till 3rd month was poor and a conspicuous dynamics began since 6th month with nearing to control level toward 12th month. However, at this time following markers significantly differed from control value: TNF-alpha (+29,6%), IL-4 (-31,7%), S-nitrosothiols (-17,8%), CRPhs exceeded 3,0 g/L (4,77±0,38) and MAD (+23,6%).

Conclusions: (1). Dynamics of inflammation markers in patients with STEMI during first 14 days after angioplasty conclusive reflect chronologic accumulation of inflammatory cells in necrotic zone. (2). Maximal serum plateau of MMP-8, IL-1, IL-6, IL-6, TNF-alpha and CRPhs goes till 7th day of post-infarct evolution, associated with lowest IL-4 and IL-10. (3). Marker improvements begin since 3rd month with nearing to control toward 12th month, excepting IL-4, TNF-alpha, CRPhs and MAD indicating thus a late statement of inflammation dissemination.