Key result
The median Metabolic Vulnerability Index score was lower in the clinical trial population (50) compared to the matched community cohort (66), with distinct clinical correlates observed in each setting.
Why the study?
The Metabolic Vulnerability Index (MVX) predicts mortality in heart failure, but its distribution and clinical correlates in matched clinical trial and community populations were unknown.
Cross-Sectional (n=389)
Yes
Absolute Event Rate: 50% vs 66%
The Metabolic Vulnerability Index (MVX) distribution and its clinical correlates differ significantly between clinical trial and community heart failure cohorts, highlighting the need to account for population heterogeneity when applying risk scores.
MVX thresholds require population-specific calibration in HF; cross-sectional data leave open generalizability to community cohorts.
BACKGROUND: The Metabolic Vulnerability Index (MVX) is a novel multi-marker risk score derived from nuclear magnetic resonance (NMR) measures and has shown predictive value for mortality in heart failure. Hence, we aimed to evaluate the distribution of MVX and its clinical correlates within a clinical trial population and a comparable subpopulation of patients with heart failure with reduced ejection fraction and ischemic heart disease within a community cohort. METHODS: We studied a clinical trial (2016-2018) and a community cohort (2003-2012), matched based on ejection fraction category and presence of ischemic heart failure. NMR LipoProfile analyses of plasma from both populations provided measures of valine, leucine, isoleucine, citrate, GlycA, and small high-density lipoprotein particles used to compute sex-specific MVX scores. Univariable and multivariable regression models assessed the relationship between MVX (modeled continuously), and selected demographic and clinical covariates. RESULTS: Clinical trial patients (N = 101, median age: 63, 93% male, median EF: 28%) were younger and predominantly male compared to the cohort (N = 288, median age: 75, 70% male, median EF: 30%). The median MVX score was lower in the clinical trial (50, 42-61) compared to the cohort (66, 58-73). Male sex and hyperlipidemia were linked to higher MVX scores in the clinical trial, while obesity and NT-proBNP were linked to lower and higher MVX scores, respectively, in the cohort (p <.05). After adjusting for significant covariates from univariable analyses and age in multivariable analyses, only the associations between male sex and MVX scores in the clinical trial, and NT-proBNP levels with MVX in the cohort remained significant. CONCLUSION: This study highlights significant differences in MVX distribution and its clinical correlates between a clinical trial and a community cohort despite matched heart failure subtypes. These findings have important implications for interpreting and applying the score in diverse study settings.
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Kuku et al. (2025) conducted a cross-sectional in Heart failure with reduced ejection fraction and ischemic heart disease (n=389). Clinical trial setting vs. Community cohort setting was evaluated on Metabolic Vulnerability Index (MVX) score. The median Metabolic Vulnerability Index score was lower in the clinical trial population (50) compared to the matched community cohort (66), with distinct clinical correlates observed in each setting.
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