Author Identifier (ORCID)
Enoch Odame Anto: https://orcid.org/0000-0001-9023-6612
Zhuoqiao He: https://orcid.org/0009-0000-5016-0684
Abstract
Background: Postpartum cardiovascular disease (CVD) following hypertensive disorders of pregnancy (HDP) involves multifactorial mechanisms linking metabolic susceptibility to vascular damage. Identifying predictive biomarkers and modifiable risk factors is crucial for early stratification in the context of predictive, preventive, and personalized medicine (PPPM). We aimed to investigate the association of triglyceride-glucose (TyG) indices with incident CVD in women with prior HDP and to assess the causal relationship using Bayesian weighted Mendelian randomization (BWMR) analysis, with a focus on the implications for PPPM strategies in postpartum management. Methods: In this longitudinal cohort study, 1,642 women with prior HDP from the UK Biobank were followed for a median of 14.05 years postpartum. TyG and modified TyG indices were assessed at enrollment. Associations with incident CVD were evaluated using Cox proportional hazards models and restricted cubic spline regression, while predictive performance was assessed with Harrell’s C-index. BWMR was further used to validate causal relationships. Results: During follow-up, 466 (28.4%) women developed postpartum CVD (mean age 51.05 ± 8.28 years). Elevated baseline TyG indices were associated with an increased risk of CVD. The highest TyG tertile had an adjusted hazard ratio (HR) of 1.35 for CVD (95% CI, 1.04–1.74; P = 0.023), with similar associations for modified TyG indices (adjusted HRs for the highest tertile ranging from 1.31 to 1.39 [P < 0.05]). C-indices were around 0.6. The stratified analysis showed more pronounced associations in younger, normotensive, and non-obese subgroups. The BWMR analysis supported a significant causal effect of genetically predicted TyG levels on CVD risk (P < 0.05), confirming the observational findings. Conclusions: Elevated TyG indices are significantly associated with increased postpartum CVD risk in women with prior HDP, particularly in subgroups without overt clinical risk factors. Integration of observational and genetic evidence supports a causal role of insulin resistance in this multifactorial pathology. TyG indices may serve as promising predictive biomarkers for early risk stratification and potential targets for personalized metabolic interventions, in line with PPPM strategies. Our findings highlight the importance of monitoring metabolic trajectories for effective PPPM-guided postpartum CVD prevention and management.
Keywords
CVD prevention and management, hypertensive disorders of pregnancy, Insulin resistance, Mendelian randomization, monitoring metabolic trajectories, obesity indicators, paradigm change from reactive to proactive medicine, postpartum cardiovascular disease, predictive preventive personalized medicine (PPPM / 3PM), triglyceride glucose index
Document Type
Journal Article
Date of Publication
1-1-2026
Publication Title
EPMA Journal
Publisher
Springer
School
Nutrition and Health Innovation Research Institute / School of Medical and Health Sciences
Funders
National Natural Science Foundation of China (82073659) / Special Fund from the Central Government for Guiding Local Scientific and Technological Development in 2024 (STKJ2024068) / Overseas Exchange and Cooperation Program for Graduate Students at Shantou University Medical College, China (002–18124704) / Funding for Guangdong Medical Leading Talent / First Affiliated Hospital of Shantou University Medical College, China (2019–2022) / Shantou University Medical College Scientific Research Initiation Grant (009–510858071) / Science and Technology Special Fund Projects of Guangdong Province (20211231071–2) / Edith Cowan University / Provincial Science and Technology Special Fund of Guangdong in 2021 (2021–88-53) / Provincial Science and Technology Special Fund of Guangdong in 2022 (2022–124-6) / Fund from National Health Commission Medical and Health Science and Technology Development and Research Center (WKZX2022JG0138) / Innovation Team Project of Guangdong Universities, China (2024KCXTD019) / Key Disciplinary Project of Clinical Medicine under the High-level University Development Program, Guangdong, China (2024–2025)
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Lin, D., Tang, H., Anto, E. O., Zhou, Y., Zhang, S., Deng, X., Tian, C., Cao, W., He, Z., Chen, Z., Ying, P., Chen, Y., & Tan, X. (2026). Triglyceride glucose index and modified triglyceride glucose indices are instrumental to optimize 3P medical management for postpartum cardiovascular disease. EPMA Journal, 17, 105–120. https://doi.org/10.1007/s13167-026-00437-8