Abstract

Introduction: Metabolic Vulnerability Index (MVX) is a novel spectroscopic multimarker of mortality risk. MVX reflects components of nutrition and systemic inflammation status and is hypothesized to enhance disease and mortality risk stratification. As Studies Targeting Risk Reduction Interventions through Defined Exercise (STRRIDE) has previously demonstrated the ability of aerobic exercise training to improve traditional markers of cardiometabolic health, we hypothesized that aerobic exercise intervention also would result in beneficial changes in the components of MVX. Methods: Participants (n=222, previously sedentary, overweight men and women with mild to moderate dyslipidemia from STRRIDE) were randomized to either a 6-month control group or to one of three supervised aerobic exercise groups for 8-months: 1) low amount moderate intensity (LM): 14 kcal/kg/wk at 40-55% VO 2peak ; 2) low amount vigorous intensity (LV): 14 kcal/kg/wk at 65-80% VO 2peak ; 3) high amount vigorous intensity (HV): 21 kcal/kg/wk at 65-80% VO 2peak . Blood samples were obtained after an overnight fast at both baseline and study completion (16-24 hr after the final training bout for exercisers). Nuclear magnetic resonance spectroscopy was performed on the Vantera ® clinical analyzer at LabCorp to determine MVX score. MVX has two components: inflammation index [INFX; combined concentrations of GlycA and small HDL particle subspecies (diameters < 9 nm)] and metabolic malnutrition index (MALNX; combined concentrations of total branched chain amino acids and ketone bodies). MVX, INFX, and MALNX are all scaled from 1 (lowest risk) to 100 (highest risk). Paired t-tests determined whether the post- minus pre- intervention change scores within each group were significant (p<0.05). We used analysis of covariance accounting for baseline values to determine difference between groups. Results: The inactive control group did not exhibit significant changes in any of the multimarkers. After 8-months of exercise training, the LM group experienced significant decreases in all three scores: INFX (-2.1 ± 5.2), MALNX (-3.1 ± 11.3), and MVX (-3.9 ± 9.1). The LV group significantly decreased their INFX score (-1.5 ± 3.8), yet significantly increased MALNX (2.2 ± 6.8). The HV group significantly decreased their INFX (-1.6 ± 4.8) and MVX scores (-1.9 ± 5.6). For the LM group, the beneficial changes in MALNX and MVX were significantly greater than the LV group. Conclusion: Aerobic exercise improved components of the novel risk-prediction multimarker MVX, with the LM group displaying the best responses across all three scores. As ongoing research investigates the clinical utility of these mulitmarkers, this study provides evidence for the ability of exercise intervention to beneficially change MVX score.

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