Metabolic vulnerability index and Life's Essential 8 with risk of major adverse cardiovascular events

Area of Science:

• Cardiovascular Medicine
• Metabolic Health
• Biomarker Research

Background:

• The metabolic vulnerability index (MVX) assesses metabolic-inflammatory status.
• Life's Essential 8 (LE8) measures cardiovascular health (CVH).
• The combined predictive value of MVX and LE8 for major adverse cardiovascular events (MACE) requires investigation.

Purpose of the Study:

• To evaluate the joint relevance of MVX and LE8 in predicting MACE.
• To explore the interaction and mediation effects between MVX, LE8, and MACE.
• To assess the potential of combined MVX and LE8 assessment for cardiovascular risk stratification.

Main Methods:

• Analysis of 239,135 UK Biobank participants without baseline MACE.
• Calculation of MVX using six NMR-based biomarkers.
• Classification of LE8 scores into low, moderate, and high CVH categories.
• Application of Cox models, joint-effect, interaction, counterfactual, and mediation analyses.

Main Results:

• Higher MVX was associated with increased MACE risk (HR=1.08).
• High CVH (LE8 ≥80) was associated with reduced MACE risk compared to low CVH (HR=0.44).
• The highest MACE risk was observed in participants with low CVH and high MVX (Q4) (HR=2.84).
• Additive interaction was found between MVX and LE8 for MACE and myocardial infarction.
• Mediation analysis indicated that improved CVH could prevent events partly by reducing metabolic vulnerability.

Conclusions:

• Combined assessment of MVX and LE8 offers enhanced cardiovascular risk stratification.
• Targeted prevention strategies can be supported by understanding the interplay between metabolic vulnerability and CVH.
• MVX and LE8 are valuable tools for predicting MACE and guiding cardiovascular health interventions.