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Non-linear associations of serum and red blood cell folate with risk of cardiovascular and all-cause mortality in hypertensive adults

Hypertension Research volume 46, pages 1504–1515 (2023)Cite this article

Abstract

This study aims to assess the associations of serum and red blood cell (RBC) folate with cardiovascular and all-cause mortality in hypertensive adults. Data on serum and RBC folate from the 1999–2014 National Health and Nutrition Examination Survey were included. Through December 31, 2015, cardiovascular and all-cause mortality were identified from the National Death Index. Multiple Cox regression and restricted cubic spline analyses were used to determine the relationship between folate concentrations and outcomes. A total of 13,986 hypertensive adults were included in the analysis (mean age, 58.5 ± 16.1 years; 6898 [49.3%] men). At a median of 7.0 years of follow-up, 548 cardiovascular deaths and 2726 all-cause deaths were identified. After multivariable adjustment, the fourth quartile of serum folate was associated with cardiovascular (HR = 1.32 [1.02–1.70]) and all-cause (HR = 1.20 [1.07–1.35]) mortality compared to the second quartile, whereas the first quartile was only linked with increased all-cause (HR = 1.29 [1.15–1.46]) mortality. The inflection points for the non-linear associations of serum folate with cardiovascular and all-cause mortality were 12.3 ng/mL and 20.5 ng/mL, respectively. In addition, the highest quartile of RBC folate was associated with cardiovascular (HR = 1.68 [1.30–2.16]) and all-cause (HR = 1.30 [1.16–1.46]) mortality compared to the second quartile, but the lowest quartile was not associated with either outcome. The inflection points for the non-linear associations of RBC folate with cardiovascular and all-cause mortality were 819.7 and 760.1 ng/mL, respectively. The findings suggest non-linear associations between serum and RBC folate levels and the risk of cardiovascular and all-cause mortality in hypertensive adults.

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Acknowledgements

We appreciate the people who contributed to the NHANES data we studied.

Funding

This work was supported by the Science and Technology Talents Support Program of Shaanxi Provincial People’s Hospital (No. 2021BJ-10, No. 2021LJ-03, No. 2021JY-18). Science and technology development incubation fund of Shaanxi Provincial People’s Hospital (2022YJY-06, 2021YJY-08). Health research project of Shaanxi Province (2022B004).

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  1. These authors contributed equally: Jing Xu, Xu Zhu

Authors and Affiliations

  1. Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, 710000, China

    Jing Xu, Gongchang Guan, Yong Zhang, Yujie Xing, Junkui Wang & Ling Zhu

  2. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China

    Xu Zhu

  3. Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China

    Rutai Hui

  4. Department of Cardiology, The Third Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, China

    Ling Zhu

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YX, JW and LZ designed the research, and had primary responsibility for the final content, JX and XZ conducted analyses and wrote the first draft of the paper. JX, XZ, GG, YZ, and RH revised the manuscript, and all authors read and approved the final manuscript and approved the final submitted version.

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Correspondence to Yujie Xing, Junkui Wang or Ling Zhu.

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Xu, J., Zhu, X., Guan, G. et al. Non-linear associations of serum and red blood cell folate with risk of cardiovascular and all-cause mortality in hypertensive adults. Hypertens Res 46, 1504–1515 (2023). https://doi.org/10.1038/s41440-023-01249-3

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