Plasma markers of endothelial damage/dysfunction, inflammation and thrombogenesis in relation to TIMI risk stratification in acute coronary syndromes

Summary

Risk stratification at presentation with acute coronary syndromes (ACS) on the basis of theTIMI risk score for unstable angina and non-ST-elevation myocardial infarction (UAP/NSTEMI) identifies patients at high risk of recurrent cardiac events and those who benefit from more aggressive treatment strategy. We hypothesised the following: (a) that a high TIMI risk score brings a greater degree of acute changes in endothelial damage/dysfunction (circulating endothelial cells [CECs], von Willebrand factor [vWf]), inflammation (interleukin-6, IL-6) and blood thrombogenicity (plasma tissue factor, TF); and (b) that these indices are higher in those with high TIMI risk score who experienced recurrent cardiac event at day 14 and day 30. TIMI risk scores were determined at admission and 48 hours later in 88 ACS patients (60 male, age 67±12 yrs) with UAP or NSTEMI. CECs, IL-6 andTF levels were measured at both time points and the acute change (Δ) calculated. Patients were split into high (score ≥4) or low (<4) TIMI score groups. The composite end point of death, myocardial infarction, and refractory angina requiring revascularisation following 14 and 30 days’ follow-up was ascertained. Fifty-eight patients with high TIMI risk score (mean 4.7) had significantly higher baseline and 48 h CEC, vWf, IL-6, TF and ΔTF levels, compared to low TIMI risk score (mean 2.4) patients (all p<0.05). Multivariate Cox regression analysis adjusted for clinical variables and TIMI risk score expressed as either continuous or categorical variable identified baseline CECs and ΔvWf levels (both p≤0.01) as independent predictors of subsequent cardiac events at both 14 days and 30 days. TIMI risk score for UA/NSTEMI identifies those patients with more profound vascular insult, inflammation and thrombogenicity that, in the ‘high risk’ patient group, predicts short-term outcomes although vascular damage was the more sensitive predictor. These indices may further refine global risk stratification for short-term adverse cardiac events in these patients.

Keywords

Endothelial damage - inflammation - thrombogenesis - von Willebrand factor - tissue factor - interleukin-6 - TIMI risk score

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