## 4 Discussion  
Despite plenty of research and novel therapeutic options in intensive care medicine, such as extracorporeal membrane oxygenation (ECMO) or different new antimicrobial agents, mortality rates in sepsis remain high. Early diagnosis and therapy, as well as source control, remain to be cornerstones in the treatment of sepsis patients [7]. However, hardly any diagnostic milestones in sepsis care were set over the last years, especially considering the progress in other (acute) disease entities, such as cardiovascular disease. Numerous analyses on novel cardiac biomarkers targeting the cardiovascular field emerged over the last decade, with new markers entering guidelines as well as clinical applications. As  
Figure 3: ROC curve—sepsis vs. STEMI. \begin{table}
\begin{tabular}{l l} \hline \hline
**Optimal Cut-Off Values for Sepsis** \\ \hline
**Biomarker** & **Cut-Off** \\ \hline sST2 & 15,909 pg/mL \\ GDF-15 & 2090 pg/mL \\ suPAR & 5414 pg/mL \\ H-FABP & 4 ng/mL \\ \hline \hline \end{tabular}
\end{table} 
Table 5: Optimal biomarker cut-off values for sepsis. these markers are well studied in numerous cardiovascular pathologies (especially myocardial infarction and heart failure) and since a considerable cardiovascular involvement in sepsis patients is assumed, we aimed for a head-to-head analysis of biomarker levels in cardiovascular disease and sepsis. Baseline characteristics showed typical findings and associated risk profiles for heart failure and STEMI patients. With regards to sepsis patients, a significant increase in kidney parameters and CRP was observed, indicating renal damage and considerable inflammatory activity at the time of blood sampling. This finding is of major importance, as many cardiovascular biomarkers, including troponin and natriuretic peptides, are elevated in the context of renal failure [8]. To date, data on tested biomarkers in CKD patients remain scarce. Still, a prognostic impact for cardiovascular disease in the context of CKD has been shown for H-FABP, especially sST2 [8]. Similar, a prognostic value of GDF-15 in addition to BNP was shown in the context of CKD [8]. In contrast, elevated suPAR levels are linked to acute kidney injury (AKI) as well as CKD, due to its interaction with renal podocytes [9]. Accordingly, the interaction of tested biomarkers and renal function has to be considered when interpreting the present study. With regards to H-FABP, a highly sensitive marker for myocardial ischemia, patients with sepsis evidenced significantly higher serum concentrations than individuals with STEMI, HF or patients in the control group [10]. H-FABP constitutes a protein, which is involved in the fatty acid metabolism of cardiomyocytes and is thus highly sensitive for myocardial ischemia [11]. Similarly, recent studies also reported a correlation of H-FABP levels and disease severity in COVID-19 [12]. As no relevant involvement in inflammatory processes is reported for H-FABP, the predominant part of the observed elevation must be attributed to myocardial ischemia and damage, based on our findings [13]. This is emphasized by the fact, that H-FABP levels in sepsis by far exceeded the levels observed for STEMI. Moreover, in our analyses, H-FABP remained predictive for sepsis even after correction for possible confounders. Accordingly, myocardial ischemia and damage in the course of sepsis might be of even higher relevance than currently accepted. Thus, based on our results and its pathophysiological role in myocardial ischemia, H-FABP represents a promising new target with regards to sepsis patients. GDF-15, representing a marker of inflammation and oxidative stress, was also significantly elevated in the sepsis group. GDF-15 was also reported to act as an immune regulator, emphasizing its potential role as a marker in inflammatory diseases [14]. GDF-15 is elevated in response to tissue damage of various kinds [14]. Thus, in the context of sepsis, reflection of disease severity by GDF-15 seems plausible [14].