Metabolic vulnerability index strongly predicts mortality after cardiac catheterization
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A composite biomarker score derived from six metabolites that indicate malnutrition or inflammation provided strong stratification of all-cause mortality in two large, independent cohorts that underwent cardiac catheterization, data show.
“Our results suggest that survival might be more dependent on previously unrecognized causal factors distinct from those responsible for development of the diseases or vulnerabilities considered to be the causes of death,” James D. Otvos, PhD, of the Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch at the NHLBI, and colleagues wrote. “If supported by future research, treating the underlying metabolic dysfunctions of the overlapping syndromes of cachexia, sarcopenia, malnutrition and frailty with anti-inflammatory, nutritional or alternative therapies might provide greater survival benefit than targeting conventional disease risk factors.”
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In a prospective, observational study, Otvos and colleagues analyzed data from 5,876 participants from the CATHGEN biorepository and 2,888 participants from the Intermountain Heart study, followed for a median of 6.2 years and 8.2 years, respectively.
Participants underwent coronary angiography and had clinical nuclear magnetic resonance metabolomic profiling done on frozen plasma obtained at catheterization. Researchers aggregated six mortality risk biomarkers — GlycA, small HDL, valine, leucine, isoleucine and citrate concentrations — into sex-specific metabolic vulnerability index scores using coefficients from predictive models for all-cause mortality in the CATHGEN cohort. Researchers then assessed the associations of biomarkers and metabolic vulnerability index with mortality in both cohorts.
The findings were published in The Lancet Healthy Longevity.
Researchers found that the six nuclear magnetic resonance biomarkers and metabolic vulnerability index made strong, independent contributions to 5-year mortality risk prediction in both cohorts, with an HR of 2.18 in the CATHGEN cohort (95% CI, 2.03-2.34) and an HR of 1.67 for the Intermountain Heart cohort (95% CI, 1.5-1.87).
In subgroup analyses, the CATHGEN cohort showed similar metabolic vulnerability index associations for men vs. women and for older vs. younger individuals for death from CV or non-CV causes. The metabolic vulnerability index associations were also similar in those who had multiple comorbidities and those who did not.
“Our findings in a patient subpopulation that was not previously linked to malnutrition-inflammation syndromes suggest a degree of biological universality to the contribution the associated metabolic dysfunctions make to mortality risk,” the researchers wrote. “Particularly noteworthy was the dominance of the predictive contribution of metabolic vulnerability index scores to multivariable models of 5-year mortality, exceeding or similar to that of age, and surpassing the importance of such established risk factors as smoking, diabetes, heart failure and renal function. Together, these variables in the CATHGEN cohort accounted for more than half of the mortality prediction of a Cox model that did not include metabolic vulnerability index score. However, the addition of metabolic vulnerability index score to the model greatly attenuated the mortality risks from heart failure and renal dysfunction, suggesting a largely metabolic basis for these associations, and overall mortality prediction improved so substantially that the predictive contribution of metabolic vulnerability index dwarfed those of the covariates.”
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