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Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis

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Abstract

Purpose

We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality.

Methods

We searched PubMed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events [including total CVD, CVD mortality, total coronary heart disease (CHD), fatal CHD, nonfatal myocardial infarction (MI), and stroke] and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis.

Results

Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I2 = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I2 = 32.1%; two studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality, or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I2 = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I2 = 0%; two studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD.

Conclusions

Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.

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Acknowledgements

We thank Geertje W. Dalmeijer and Sabine R. Zwakenberg (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands) for providing re-analyzed data on dp-ucMGP and total CVD.

Funding

The work was supported by the National Key Research and Development Program of China (2017YFC0907500 and 2017YFC0907504), and Hubei Province Science Fund for Distinguished Young Scholars (2018CFA033).

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China

    Heng-Gui Chen, Li-Ting Sheng, Yan-Bo Zhang, An-Lan Cao, Yu-Wei Lai, Limiao Jiang & An Pan

  2. Translational Health Sciences, Bristol Medical School, University of Bristol Southmead Hospital, Bristol, UK

    Setor K. Kunutsor

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Contributions

H-GC performed the statistical analysis; contributed to the discussion, wrote the manuscript, and reviewed and edited the manuscript. H-GC and L-TS conducted the research, screened the references and extracted the data. Y-BZ, A-LC, and Y-WL researched and proofed the data. SKK transformed the data to comparison of top third with bottom third. LJ and AP planned and designed the study. H-GC and AP had full access to the data in this study and take complete responsibility for the integrity of the data and the accuracy of the data analysis. All authors critically reviewed, discussed, and approved the final manuscript.

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Correspondence to An Pan.

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AP reported receiving a research grant from the BY-HEALTH CO., LTD, outside the submitted work. Other authors declare no conflict of interest.

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Chen, HG., Sheng, LT., Zhang, YB. et al. Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis. Eur J Nutr 58, 2191–2205 (2019). https://doi.org/10.1007/s00394-019-01998-3

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