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Background The Perivascular Fat Attenuation Index (FAI) has emerged as a novel non-invasive biomarker for predicting major adverse cardiovascular events (MACE) and assessing coronary plaque vulnerability. Elevated FAI values are associated with key clinical factors including Type 2 Diabetes Mellitus (T2DM), young age, coronary in-stent restenosis (ISR), stress-related neural activity, non-ST elevation acute coronary syndrome (NSTE-ACS), and high-risk plaque features. This meta-analysis aims to comprehensively evaluate the predictive value of lesion-specific FAI for MACE across these variables, ultimately enhancing cardiovascular risk stratification and clinical decision-making.
Methods A systematic analysis of studies published between 2018 and 2025 was conducted using PubMed and Embase. Hazard Ratios (HRs) associated with elevated FAI for MACE were collected and compared across high-risk patient subgroups, including individuals with type 2 diabetes mellitus (T2DM), in-stent restenosis (ISR), young adults, stress-related neural activity (NSR), non-ST elevation acute coronary syndrome (NSTE-ACS), high-risk plaque features, and cardiac transplant recipients.
Results Seven studies (n>6,000 patients) found that elevated lesion specific FAI values were significantly associated with a higher risk of MACE across all subgroups. The CRISP-CT study confirmed these findings, revealing that high-risk plaque features combined with elevated FAI values significantly increased the risk of cardiac mortality (HR = 7.33, p < 0.001). In patients with T2DM, those with lesion-specific FAI values higher than -83.5 Hounsfield Units (HU) exhibited a significantly increased risk of MACE (HR = 2.40, p = 0.001) and a higher prevalence of high-risk plaques. Young patients (≤45 years) with elevated FAI (≥ -75.2 HU) demonstrated a significantly increased risk of MACE (HR = 19.257, p = 0.004). Stress-related neural activity correlated positively with higher FAI values (r = 0.49, p < 0.001), suggesting that stress-induced activation may increase plaque vulnerability. Patients with ISR showed significantly higher peri-stent FAI values compared to those without ISR (-87.2 ± 7.3 HU vs -78.1 ± 6.2 HU, p < 0.001). In the NSTE-ACS and cardiac transplant subgroups, FAI values ≥ -70.1 HU were associated with increased plaque vulnerability and ultimately a higher risk of adverse cardiovascular outcomes.
Conclusion Lesion-specific FAI is a unique non-invasive biomarker for predicting MACE in high-risk populations, including T2DM patients, young adults, ISR patients, those with stress-induced neural activity, NSTE-ACS, and cardiac transplant recipients. The strong correlation with high-risk plaque features suggests that FAI can significantly enhance cardiovascular risk stratification and guide personalized intervention strategies. Integrating FAI into clinical practice may improve predictive accuracy and enable more precise and effective management of cardiovascular risk.
