Biomarker-based risk scores for predicting mortality and major cardiovascular events in patients with myocardial infarction

Abstract Aims The incidence of adverse events after a myocardial infarction (MI) remains high despite therapeutic advancements. Inflammatory biomarkers may assist in risk stratification due to the role of inflammation in the pathophysiology of MI. We aimed to develop a combined index incorporating high-sensitivity troponin T, inflammatory biomarkers and endothelial dysfunction biomarkers to predict mortality and major adverse cardiovascular events (MACE) in patients with MI. Methods Prospective study of 124 MI patients admitted to our hospital between 2022-2023, who underwent coronary angiography, consented to participate, and completed biological sample collection. hs-CRP, IL-6, TNFα, ADMA, and high sensitivity troponin-T were measured within the first 24 hours. The events studied included mortality and MACE (cardiovascular mortality, rehospitalization, reinfarction, and stroke). Associations were analyzed using Cox proportional hazard models adjusted for age and sex. Individual indices and a combined index were developed and optimized to maximize the iAUC, comparing their prognostic performance. In the individual system, five cut-off points were estimated for each biomarker and event, generating a score ranging from 0 (best) to 5 (worst). In the combined system, five cut-off points were estimated for each biomarker for each event, generating a score from 0 (best) to 25 (worst). Results The patients had a mean age of 67 years (SD 13.3), with 67.7% being male. During a median follow-up of 13 months (IQR 6-23), 21 patients died, and 28 experienced MACE. Older patients and those with comorbidities had higher mortality and MACE rates. Logistic regression models adjusted for age and sex showed a significant association between the admission levels of hs-CRP, IL-6, TNFα and mortality. Higher IL-6 and TNFα levels were associated with an increased risk of both events, while higher ADMA levels to lower mortality. Each one-point increase in the combined index increased the risk of mortality by 1.5-fold (95%CI: 1.27-1.75;p<0.001) and the risk of MACE by 1.8-fold (95%CI: 1.47-2.28;p<0.001). The combined index demonstrated the strongest predictive value, with an iAUC of 0.97 for mortality, significantly outperforming individual biomarkers (iAUCs ranging from 0.83 to 0.88) and indices (0.86-0.92). For MACE, the combined index also achieved the highest discrimination (iAUC 0.87; p<0.05). Table 1 shows the indices of each individual biomarker and the combined index of the 5 biomarkers, in relation to mortality and MACE risks, iAUCs, and p-values. Figure 1 illustrates the iAUCs for the different models. Panel A: Models predicting mortality. Panel B: Models predicting MACE. Conclusions The incidence of adverse events was higher in patients with elevated levels of inflammatory biomarkers at admission. The combined biomarker index demonstrated outstanding predictive capacity for mortality and MACE in patients with MI, significantly outperforming individual biomarkers.Table 1 Figure 1