Abstract
Background
The independent and interactive associations of abdominal obesity and fatty acids with the risk of microvascular diseases (MVDs) are still unclear.
Methods
We conducted a prospective cohort study of 88,571 participants aged 40-69 years from the UK Biobank. Plasma fatty acids were quantified at baseline using high-throughput nuclear magnetic resonance spectroscopy and were analyzed in quartiles, with the lowest quartile of each fatty acid subtype as the reference. Cox regression models were employed to assess the associations between fatty acid levels and incident MVDs, with adjustment for relevant covariates.
Results
Over a median follow-up of 13.7 years, higher levels of total polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-6 PUFAs are associated with a significantly lower risk of MVDs. The hazard ratios (HRs) for the highest versus lowest quartile (Q4 vs. Q1) are 0.81 (95% CI: 0.75-0.87), 0.89 (95% CI: 0.83-0.96), and 0.85 (95% CI: 0.79-0.91), respectively. Conversely, higher levels of saturated and monounsaturated fatty acids are associated with a higher risk of MVDs. Furthermore, an antagonistic additive interaction is observed between n-3 PUFAs and abdominal obesity (RERI: −0.14, 95% CI: −0.25- −0.03).
Conclusion
Higher plasma PUFAs are associated with a lower risk of MVDs. Furthermore, the association between n-3 PUFAs and a lower risk of MVDs is more pronounced among individuals with abdominal obesity. These findings contribute to the limited prospective evidence on the associations between plasma-specific fatty acids and MVDs.
Plain language summary
Microvascular diseases (like kidney or nerve issues from small blood vessel damage) are common, and obesity and fatty acids may affect their risks. We studied 88,571 people over 13.7 years to see how belly fat, also termed abdominal obesity (measured by the ratio of waist over hip circumference) and blood fatty acids relate to microvascular diseases risk. We found that higher levels of polyunsaturated fatty acids lowered microvascular diseases risk, while saturated and monounsaturated fatty acids raised it. For people with abdominal obesity, n-3 PUFAs were especially protective. These findings suggest that public health strategies should emphasize the intake of n-3 fatty acids and the management of belly fat, particularly for individuals at risk of microvascular diseases.
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Data availability
The UK Biobank data are protected by privacy regulations and governance policies. Access to the raw data requires an application submitted directly to the UK Biobank (www.ukbiobank.ac.uk). The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request. The source data for Fig. 1 are provided in Supplementary Table 4.
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Acknowledgements
The authors thank all the participants and professionals contributing to the UK Biobank. This work was supported by the National Natural Science Foundation of China (Grant Nos. 82173519, 82473721, and 81500330) as well as the National Key R&D Program of China (Grant No. 2022YFC2503605).
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Ruidie Shi and Lan Yu contributed equally to this work, wrote the manuscript and researched the data. Ruidie Shi, Lan Yu, Shengnan Liu, and Guangbin Sun were involved in data management and analysis. Dongfang Zhang, Xinyue Li, Qiang Zhang, Xiaolong Xing, Xumei Zhang, and Xueli Yang provided expert knowledge on microvascular diseases and methodology. All authors edited, reviewed, and approved the final version of the manuscript. Xueli Yang is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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Shi, R., Yu, L., Liu, S. et al. Associations of abdominal obesity and plasma fatty acids with microvascular diseases. Commun Med (2026). https://doi.org/10.1038/s43856-025-01333-4
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DOI: https://doi.org/10.1038/s43856-025-01333-4
