Inflammatory cytokine signatures and factors associated with cardiogenic shock in acute coronary syndrome: Insights from an observational study

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Acute coronary syndrome (ACS) with and without cardiogenic shock (CS) (n=150). Intervention: Cardiogenic shock (ACS-CS) and 13-analyte serum inflammatory cytokine signature vs. Acute coronary syndrome without cardiogenic shock (ACS-noCS). Primary outcome: Identification of cardiogenic shock (CS) and in-hospital mortality (OR 2.63 (for TNF-α independent association with CS); 13-cytokine RF model AUC 0.958, 95% CI 1.33-5.20, p=0.005).

Q: What does this research mean for the field?

A 13-cytokine panel discriminates cardiogenic shock complicating acute coronary syndrome with high diagnostic accuracy, with IL-6, IL-10, and TNF-alpha independently associated with shock. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Deven Mittal; Kraticka Singhal; Monika Sharma; Akash Batta; Yash Sharma

doi:10.21542/gcsp.2026.45

October 30, 2026Global Cardiology Science and PracticeOpen Access

Inflammatory cytokine signatures and factors associated with cardiogenic shock in acute coronary syndrome: Insights from an observational study

View Full Paper

Ask AI

Bookmark

Share

Key result

Elevated TNF-α is linked to ~2.6-fold higher odds of cardiogenic shock in ACS.

OR 2.63 (for TNF-α independent association with CS); 13-cytokine RF model AUC 0.958
95% CI 1.33-5.20
P=0.005
n=150

Why the study?

Cardiogenic shock complicating ACS is a leading cause of in-hospital cardiovascular mortality, and the systemic inflammatory cytokines that may contribute to its pathophysiology remain incompletely characterized.

Does a 13-analyte serum inflammatory cytokine signature discriminate cardiogenic shock and predict in-hospital mortality in patients presenting with acute coronary syndrome?

Key Points

To characterize inflammatory cytokine profiles in acute coronary syndrome patients with and without cardiogenic shock and evaluate their discriminatory utility.
Conducted a single-center observational study with a comparator sampling design enrolling 150 acute coronary syndrome patients (ACS-CS, n = 60; ACS-noCS, n = 90) between August 2024 and December 2025.
Quantified a bioinformatically selected 13-analyte cytokine panel in serum using Luminex multiplex immunoassay within 24 hours of admission and prior to definitive therapy.
Evaluated biomarkers using Benjamini–Hochberg false discovery rate correction, receiver operating characteristic analysis, random-forest modeling, and multivariable logistic regression.
In-hospital mortality was 35.0% (21/60) in ACS-CS versus 6.7% (6/90) in ACS-noCS (p < 0.001), alongside lower median systolic blood pressure (85 vs 127 mmHg; p < 0.001) and reduced left ventricular ejection fraction (27.5% vs 44.5%).
Eleven cytokines met pre-specified criteria (FDR < 0.05 and log₂FC > 0.5), with IL-6 serving as the strongest individual discriminator (log₂FC 2.62; AUC 0.870).
A random-forest model based on the 13-cytokine panel achieved an internally cross-validated AUC of 0.958 (95% CI 0.92-0.98), and IL-6, IL-10, and TNF-α remained independently associated with shock after adjusting for age and sex.

Study Design

Type

Observational (n=150)

Blinding

Single-blind (laboratory personnel were blinded to the clinical group allocation)

Multicenter

No

Structured PICO

Does a 13-analyte serum inflammatory cytokine signature discriminate cardiogenic shock and predict in-hospital mortality in patients presenting with acute coronary syndrome?

P

Population

150 adults aged 18-85 years with confirmed acute coronary syndrome (60 with cardiogenic shock and 90 without) at a single tertiary care hospital in North India, free of admission acute kidney injury or sepsis, evaluated for in-hospital outcomes.

E

Exposure

Quantification of an a priori selected 13-analyte serum cytokine panel (GM-CSF, IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-9, IL-10, IL-12p70, IL-18, MCP-1, M-CSF, and TNF-α) by Luminex multiplex immunoassay within 24 hours of hospital admission and prior to definitive therapy.

C

Comparator

ACS patients presenting without cardiogenic shock (ACS-noCS, n=90) undergoing identical baseline clinical, laboratory, and serum cytokine profiling within 24 hours of admission.

O

Outcome

Differential serum cytokine expression (pre-specified criteria: FDR < 0.05 and log2FC > 0.5) and discriminatory performance (ROC AUC and random-forest classification) for identifying cardiogenic shock in ACS within 24 hours of admission.surrogate

Main Result

Odds Ratio: 2.63 (95% CI 1.33–5.2)

Absolute Event Rate: 35% vs 6.7%

p-value: p=0.005

Cardiogenic shock in acute coronary syndrome is characterized by marked systemic inflammatory cytokine activation—particularly IL-6, IL-10, and TNF-α—which shows high exploratory discrimination for shock identification.

Limitations

Single-centre observational study design
No formal power-based sample size calculation was performed
Internal cross-validation only; performance estimates are likely optimistic and require external validation
Events-per-variable ratio in multivariable logistic regression (8.6) was below the conventional threshold of 10, with cross-validated calibration slope (0.770) indicating some overfitting
Cytokine cut-offs are specific to serum measured by the study Luminex assay and are not transferable to plasma or other platforms without re-derivation
Single-centre observational study with no formal power-based sample size calculation
Two-group comparator sampling design does not reflect the true population prevalence or incidence of CS in ACS
Model performance estimates are derived from internal cross-validation only, are potentially optimistic, and lack external validation
Events-per-variable ratio in multivariable regression was below the conventional threshold of 10 (EPV = 8.6), and cross-validated calibration slope (0.770) indicated some overfitting
Cytokine cut-offs are specific to serum on the Luminex platform and are not transferable to plasma or other platforms without re-derivation

Implication

May aid early shock detection in ACS; leaves open external validation before clinical use.

Abstract

Background: Cardiogenic shock (CS) complicating acute coronary syndrome (ACS) remains a leading cause of in-hospital cardiovascular mortality. Systemic inflammatory cytokines may contribute to CS pathophysiology but remain incompletely characterized. We aimed to delineate profiles of ACS patients with and without CS and evaluate their utility for CS identification. Methods: In this single-centre observational study with a comparator sampling design, 150 ACS patients (August 2024-December 2025) were enrolled as ACS-CS (n = 60) and ACS-noCS (n = 90). A 13-analyte cytokine panel, selected a priori from an independent bioinformatics analysis of six GEO datasets, was quantified in serum by Luminex multiplex immunoassay within 24 hours of admission and before definitive therapy. Analyses comprised group comparison with Benjamini–Hochberg false discovery rate (FDR) correction, receiver operating characteristic (ROC) analysis, random-forest classification and multivariable logistic regression with Firth-penalised sensitivity analysis. Results: ACS-CS patients were more frequently female (46.7% vs 22.2%; p = 0.002) and had higher diabetes prevalence (68.3% vs 37.8%; p < 0.001). Median SBP was lower (85 vs 127 mmHg; p < 0.001), LVEF reduced (27.5% vs 44.5%), BNP elevated (1009 vs 237.5 pg/mL; p < 0.001) and in-hospital mortality higher (35.0% vs 6.7%; p < 0.001). Eleven cytokines met both pre-specified criteria (FDR < 0.05 and log₂FC > 0.5). IL-6 was the strongest individual discriminator (log₂FC 2.62; AUC 0.870). A random-forest model incorporating the 13-cytokine panel achieved an internally cross-validated AUC of 0.958 (95% CI 0.92-0.98). IL-6, IL-10 and TNF-α remained independently associated with CS after adjustment for age and sex. Conclusion: CS complicating ACS is accompanied by broad, coordinated systemic immune activation alongside hemodynamic failure. Multi-cytokine modelling showed high discrimination within this cohort, but all performance estimates are internal and potentially optimistic. These findings are hypothesis-generating and support prospective external validation of inflammatory profiling for risk stratification and as a rationale for immunomodulatory strategies.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Mittal et al. (2026) conducted an observational in Acute coronary syndrome (ACS) with and without cardiogenic shock (CS) (n=150). Cardiogenic shock (ACS-CS) and 13-analyte serum inflammatory cytokine signature vs. Acute coronary syndrome without cardiogenic shock (ACS-noCS) was evaluated on Identification of cardiogenic shock (CS) and in-hospital mortality (OR 2.63 (for TNF-α independent association with CS); 13-cytokine RF model AUC 0.958, 95% CI 1.33-5.20, p=0.005). A 13-cytokine panel identified cardiogenic shock in ACS with an AUC of 0.958 (95% CI 0.92-0.98), with TNF-α (OR 2.63), IL-10 (OR 2.01), and IL-6 (OR 1.81) independently associated with shock.

synapsesocial.com/papers/6ae682bde432e7a5c4ef36e2 https://doi.org/10.21542/gcsp.2026.45

View Full Paper

Ask AI

Bookmark

Share

Inflammatory cytokine signatures and factors associated with cardiogenic shock in acute coronary syndrome: Insights from an observational study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Inflammatory cytokine signatures and factors associated with cardiogenic shock in acute coronary syndrome: Insights from an observational study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading