{ "abstract": "Background\n\nLifestyle 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\n\nThis 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\n\nA 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\n\nA 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.", "abstract_shown": true, "affiliations": [ "Department of Cardiology, Affiliated Minda Hospital of Hubei Minzu University, Enshi, 445000, China.", "Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Minda Hospital of Hubei Minzu University, Enshi, 445000, China.", "Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443003, China.", "Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang, 443003, China.", "Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, 443003, China.", "Hubei 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.", "Hubei Selenium and Human Health Institute, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China.", "Hubei 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. xiangjie0101@126.com.", "Hubei Selenium and Human Health Institute, the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China. xiangjie0101@126.com.", "Cardiovascular 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. xiangjie0101@126.com." ], "article_type": "research article", "arxiv": null, "author_total": 5, "authors": [ { "affs": [ 0 ], "name": "Xi Zhang" }, { "affs": [ 1 ], "name": "Li Zhang" }, { "affs": [ 2, 3, 4 ], "name": "Zhixing Fan" }, { "affs": [ 5, 6 ], "name": "Chuying Huang" }, { "affs": [ 7, 8, 9 ], "name": "Jie Xiang", "orcid": "0000-0001-5912-2019" } ], "bibtex": "https://research.draconitic.com/paper/70vvk7fe9awh8.bib", "cited_by": 0, "doi": "10.1186/s12872-026-06363-x", "fulltext_url": "https://europepmc.org/articles/PMC13700337", "id": "70vvk7fe9awh8", "issns": [ "1471-2261" ], "landing_url": "https://europepmc.org/article/MED/42928121", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "1312|Metabolomics and Mass Spectrometry Studies" ] ], "openalex": "W7171631176", "pdf_url": "https://europepmc.org/articles/PMC13700337?pdf=render", "pmcid": "PMC13700337", "pmid": "42928121", "published": "2026-07-29", "publisher": null, "ris": "https://research.draconitic.com/paper/70vvk7fe9awh8.ris", "sources": [ { "first_seen": "2026-10-30T12:21:20Z", "native_id": "MED:42928121", "source": "europepmc", "url": "https://europepmc.org/article/MED/42928121" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|Metabolomics and Mass Spectrometry Studies", "subfield": "molecular-biology" } ], "title": "Association of NMR metabolic signatures of healthy lifestyle with hypertension: a prospective cohort study.", "title_text": "Association of NMR metabolic signatures of healthy lifestyle with hypertension: a prospective cohort study.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:21:20Z", "url": "https://research.draconitic.com/paper/70vvk7fe9awh8", "venue": "BMC cardiovascular disorders", "versions": [] }