The association between triglyceride-glucose index;  atherogenic index of plasma;  systemic immune-inflammation index;  and mortality in patients with acute coronary syndrome: the direct effects of glucose-lipid metabolism and U-shaped immune modulation in mortality risk

Weichen Luo

doi:10.3389/fcvm.2025.1604284

The association between triglyceride-glucose index; atherogenic index of plasma; systemic immune-inflammation index; and mortality in patients with acute coronary syndrome: the direct effects of glucose-lipid metabolism and U-shaped immune modulation in mortality risk

2025-08-11

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DOI：10.3389/fcvm.2025.1604284

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BackgroundCardiovascular disease (CVD) remains the leading global cause of death; with inflammation and glycolipid dysregulation as key drivers of atherosclerosis progression. While triglyceride-glucose index (TyG) and Atherogenic Index of Plasma (AIP) are linked to cardiovascular risk; their prognostic value in Acute Coronary Syndrome (ACS) patients; particularly Acute Myocardial Infarction (AMI) patients; and mediating role of systemic inflammation remain unclear. This study investigates the relationship between glycolipid metabolism; systemic inflammation; and mortality in ACS patients.MethodsIn this single-center retrospective study; 3; 861 ACS patients were analyzed. Glycolipid metabolism was assessed using the TyG and AIP index; while the systemic immune-inflammation index (SII) evaluated inflammatory status. Missing data were addressed with random forest multiple imputation. Statistical analyses included the Least Absolute Shrinkage and Selection Operator (LASSO) regression for variable selection; generalized linear modeling; restricted cubic splines (RCS) for nonlinear associations; and the Mantel test for correlations between glycolipid metabolism and inflammatory markers. Additionally; multivariable logistic regression; RCS models; and mediation analysis were used to assess associations and pathways.ResultsElevated TyG index linearly increased mortality risk in ACS patients (Odds Ratio (OR) = 1.64; 95% Confidence Interval (CI):1.07–2.52) and AMI subgroups (OR = 1.56; 95% CI:1.00–2.42); with minimal SII mediation (ACS:3.97%; AMI: non-significant).The AIP index directly increased mortality risk (ACS: Beta coefficient (β) = 0.076; AMI: β = 0.091; p < 0.001); partially offset by SII's negative mediation (ACS:−6.6%; AMI:−7.8%). SII showed U-shaped mortality associations in ACS and AMI patients; with the lowest risk around 450–900 × 10⁹/L. Age ≥ 75 (ACS: OR = 8.35; AMI: OR = 10.12); STEMI diagnosis (ACS: OR = 1.46; AMI: OR = 1.53); and elevated total cholesterol (ACS: OR = 1.50; AMI: OR = 1.40) were independent mortality predictors. Increased HDL-C (ACS: OR = 0.198; AMI: OR = 0.280) was an independent protective factor.ConclusionThe TyG and AIP index independently predict mortality in ACS and AMI patients through direct metabolic toxicity rather than inflammatory mediation.SII exhibits a U-shaped mortality association; reflecting bidirectional immune regulation (tissue repair vs. damage); with an optimal threshold range of 450–900 × 109/L to guide anti-inflammatory strategies. Findings support metabolic-inflammatory risk stratification; prioritizing glycolipid metabolic dysregulation intervention in acute events while dynamically monitoring SII to balance immune homeostasis.Trial registrationApproved by Zhongda Hospital Ethics Committee (2020ZDSYLL164-P01); retrospectively registered.

Keywords:

Triglyceride-glucose index

Atherogenic Index of Plasma

Systemic inflammation

Acute Coronary Syndrome

Mortality risk

The association between triglyceride-glucose index; atherogenic index of plasma; systemic immune-inflammation index; and mortality in patients with acute coronary syndrome: the direct effects of glucose-lipid metabolism and U-shaped immune modulation in mortality risk

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