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Sci Rep. 2017 Jul 6;7(1):4769. doi: 10.1038/s41598-017-05205-3.

Association between Homocysteine Levels and All-cause Mortality: A Dose-Response Meta-Analysis of Prospective Studies.

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Department of medical quality, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, Zhejiang, 315042, China.
Department of chronic disease control and prevention, Zhenhai Center for Disease Control and Prevention, Ningbo, Zhejiang, 315200, China.
The Central Blood Station of Ningbo, Ningbo, Zhejiang, 315099, China.


Plasma homocysteine (Hcy) levels may be associated with all-cause mortality risk. However, the results of this association are conflicting and the dose-response relationship between them has not been clearly defined. In this meta-analysis, we conducted a systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library for the relevant articles dated up to February 2017. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the estimates, and the dose-response relationship was estimated using a restricted cubic spline model. Eleven prospective studies (4,110 deaths among 27,737 individuals) were included. The summary RR of all-cause mortality for the highest Hcy category vs. the lowest Hcy category was 1.80 (95% CI: 1.51, 2.14) with the random effects model. In dose-response meta-analysis, Hcy levels were significantly associated with all-cause mortality risk in a linear fashion (p nonlinearity = 0.255), and the risk of all-cause mortality increased by 33.6% for each 5 µmol/L increase in Hcy levels (RR = 1.336, 95% CI: 1.254-1.422, p < 0.001). Findings from this dose-response meta-analysis suggest that Hcy levels are linearly and positively associated with risk of all-cause mortality.

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