Association of NMR metabolic signatures of healthy lifestyle with hypertension: a prospective cohort study.
10 affiliations
- 1Department of Cardiology, Affiliated Minda Hospital of Hubei Minzu University, Enshi, 445000, China.
- 2Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Minda Hospital of Hubei Minzu University, Enshi, 445000, China.
- 3Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443003, China.
- 4Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, 443003, China.
- 5Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, 443003, China.
- 6Hubei Key Laboratory for Translational Research in Traditional Chinese Medicine, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, 445000, China.
- 7Hubei Selenium and Human Health Institute, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China.
- 8Hubei Key Laboratory for Translational Research in Traditional Chinese Medicine, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, 445000, China. [email protected].
- 9Hubei Selenium and Human Health Institute, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China. [email protected].
- 10Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, No. 158 Wuyang Avenue, Enshi, 445000, Hubei, China. [email protected].
Abstract
Background
Lifestyle factors play a critical role in the prevention and management of hypertension, while metabolomics provides valuable insights into the biological mechanisms underlying disease development. However, the relationships among lifestyle-related metabolic signatures, lifestyle behaviors, and hypertension risk remain incompletely understood.Methods
This prospective cohort study used data from the UK Biobank. A composite healthy lifestyle score was calculated, and a lifestyle-related metabolic signature was developed using nuclear magnetic resonance (NMR)-based metabolomics and elastic net regression. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations between the healthy lifestyle score and the metabolic signature and incident hypertension. Causal mediation analysis based on a counterfactual framework (CMAverse package) was performed to quantify the mediating effect of the metabolic signature on the association between lifestyle and hypertension. Subgroup, interaction, and sensitivity analyses were also conducted.Results
A total of 126,677 eligible participants (mean age, 54.92 ± 8.12 years; 46.47% male; 96.09% White) were included. During a median follow-up of 13.43 years, 18,720 participants developed hypertension. A healthy lifestyle-related metabolic signature comprising 76 metabolites was identified and showed a strong correlation with the healthy lifestyle score. Both a higher healthy lifestyle score (HR: 0.927; 95% CI: 0.913-0.940) and a higher metabolic signature level (HR: 0.675; 95% CI: 0.641-0.711) were independently associated with a significantly lower risk of incident hypertension, with significant inverse dose-response trends. These associations remained generally consistent across subgroups stratified by age, education, and income. Mediation analysis indicated that the metabolic signature explained 57.08% (95% CI: 31.89%-83.15%) of the protective association between a healthy lifestyle and hypertension risk. The primary findings remained robust across multiple sensitivity analyses.Conclusion
A healthy lifestyle is associated with a distinct metabolomic profile that substantially mediates its protective association with hypertension. These findings provide new insights into the metabolic mechanisms linking lifestyle behaviors to hypertension risk and highlight the importance of metabolic health in hypertension prevention.
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BibTeX
@article{zhang2026association,
title = {{Association of NMR metabolic signatures of healthy lifestyle with hypertension: a prospective cohort study.}},
author = {Xi Zhang and Li Zhang and Zhixing Fan and Chuying Huang and Jie Xiang},
journal = {BMC cardiovascular disorders},
year = {2026},
month = jul,
doi = {10.1186/s12872-026-06363-x},
url = {https://europepmc.org/article/MED/42928121},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Association of NMR metabolic signatures of healthy lifestyle with hypertension: a prospective cohort study.
AU - Xi Zhang
AU - Li Zhang
AU - Zhixing Fan
AU - Chuying Huang
AU - Jie Xiang
PY - 2026
DA - 2026/07/29
JO - BMC cardiovascular disorders
DO - 10.1186/s12872-026-06363-x
UR - https://europepmc.org/article/MED/42928121
AB - Background Lifestyle factors play a critical role in the prevention and management of hypertension, while metabolomics provides valuable insights into the biological mechanisms underlying disease development. However, the relationships among lifestyle-related metabolic signatures, lifestyle behaviors, and hypertension risk remain incompletely understood.Methods This prospective cohort study used data from the UK Biobank. A composite healthy lifestyle score was calculated, and a lifestyle-related metabolic signature was developed using nuclear magnetic resonance (NMR)-based metabolomics and elastic net regression. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations between the healthy lifestyle score and the metabolic signature and incident hypertension. Causal mediation analysis based on a counterfactual framework (CMAverse package) was performed to quantify the mediating effect of the metabolic signature on the association between lifestyle and hypertension. Subgroup, interaction, and sensitivity analyses were also conducted.Results A total of 126,677 eligible participants (mean age, 54.92 ± 8.12 years; 46.47% male; 96.09% White) were included. During a median follow-up of 13.43 years, 18,720 participants developed hypertension. A healthy lifestyle-related metabolic signature comprising 76 metabolites was identified and showed a strong correlation with the healthy lifestyle score. Both a higher healthy lifestyle score (HR: 0.927; 95% CI: 0.913-0.940) and a higher metabolic signature level (HR: 0.675; 95% CI: 0.641-0.711) were independently associated with a significantly lower risk of incident hypertension, with significant inverse dose-response trends. These associations remained generally consistent across subgroups stratified by age, education, and income. Mediation analysis indicated that the metabolic signature explained 57.08% (95% CI: 31.89%-83.15%) of the protective association between a healthy lifestyle and hypertension risk. The primary findings remained robust across multiple sensitivity analyses.Conclusion A healthy lifestyle is associated with a distinct metabolomic profile that substantially mediates its protective association with hypertension. These findings provide new insights into the metabolic mechanisms linking lifestyle behaviors to hypertension risk and highlight the importance of metabolic health in hypertension prevention.
SN - 1471-2261
ER -