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Published on: October 6, 2023
Metabolomic signatures connect and mediate sedentary time-driven mortality risk in patients with cardiovascular
Min Zhu1,2, Keke Ding1, Peiyang Luo1
1Center for Translational Medicine, Shanghai Sixth People's Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
Sedentary behavior increases cardiovascular disease (CVD) mortality risk. Metabolomics pathways, including fatty acid and amino acid metabolism, mediate this risk, offering targets for personalized CVD management.
Area of Science:
- Cardiovascular Science
- Metabolomics
- Epidemiology
Background:
- Sedentary behavior is linked to cardiovascular disease (CVD), but underlying molecular mechanisms, particularly metabolomic pathways, are not fully understood.
- Clarifying these links is crucial for developing targeted interventions to mitigate CVD risks associated with inactivity.
Purpose of the Study:
- To investigate the mediating role of the metabolome in the association between sedentary behavior and all-cause mortality in individuals with CVD.
- To provide novel metabolic insights for improved CVD management strategies.
Main Methods:
- Utilized UK Biobank data (2006-2010) from 13,561 CVD participants, analyzing 249 serum metabolites and sedentary time.
- Employed Cox proportional hazards and elastic network regression models to identify metabolic signatures associated with sedentary behavior and mortality risk.
- Conducted mediation analysis to quantify the role of specific metabolites in the sedentary behavior-mortality link, with validation using follow-up data.
Main Results:
- Identified 35 metabolites associated with sedentary behavior; 24 of these were also linked to increased all-cause mortality risk.
- Both sedentary time (HR 1.08) and an integrated metabolic feature (HR 1.16) independently predicted higher mortality.
- Key mediating metabolites included those in fatty acid metabolism, branched-chain amino acid metabolism, and inflammatory-related glycoproteins.
Conclusions:
- Revealed significant metabolic pathways mediating the link between sedentary behavior and mortality in CVD patients.
- Highlighted specific metabolites (e.g., glycoprotein acetyls, lipid ratios) as potential targets for personalized interventions to reduce CVD mortality.
- Findings underscore the importance of considering metabolic profiles in managing sedentary behavior-related risks in cardiovascular health.
Background:
Increasing evidence highlights the association between sedentary behavior and cardiovascular disease (CVD). However, the molecular mechanisms that link sedentary behavior to adverse cardiovascular outcomes, especially the metabolomics pathways, remain unclear.
Methods:
Participants with CVD at baseline from 2006 to 2010 in the UK Biobank were involved. The all-cause mortality outcome was obtained through the National Death Registry System. Cox proportional hazards model and the elastic network regression model were employed to identify metabolic signatures related to both sedentary time and the risk of all-cause mortality. Mediation analysis was conducted to examine the mediating effects of selected metabolic signatures to the association of sedentary behavior and mortality. The follow-up data was used for validationt.
Objectives:
This study aims to explore the mediating role of the metabolome in the association between sedentary behavior and all-cause mortality among individuals with CVD, providing metabolic insights for CVD management.
Results:
The study included 13,561 baseline CVD participants with concentrations of 249 serum metabolites and sedentary time. Thirty-five metabolites were associated with sedentary behavior. Both sedentary time [hazard ratio (HR), 1.08 (95% CI, 1.04-1.13)] and the integrated metabolic feature which was derived from the 35 identified metabolites were associated with an increased risk of all-cause mortality [HR, 1.16 (95% CI, 1.10-1.21)]. Out of the 35 metabolites selected by elastic net regression, 24 were significantly associated with all-cause mortality. These included metabolites involved in fatty acid metabolism, branched-chain amino acid metabolism and inflammatory-related glycoproteins. The integrated metabolic feature, glycoprotein acetyls, phospholipids to total lipids in very small VLDL percentage, and monounsaturated fatty acids to total fatty acids percentage played 36.3%, 35%, 22%, 20% mediating roles respectively between sedentary behavior and all-cause mortality risk.
Conclusion:
Our research has revealed the metabolic effects associated with sedentary behavior and all-cause mortality in patients with CVD, highlighting possible targets for personalized intervention and management.
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