期刊
AMERICAN JOURNAL OF CLINICAL NUTRITION
卷 113, 期 5, 页码 1157-1167出版社
OXFORD UNIV PRESS
DOI: 10.1093/ajcn/nqaa432
关键词
homocysteine; vitamin B12; folate; cardiovascular disease risk; thromboembolic manifestations; inborn errors of metabolism; 1-carbon metabolism
资金
- FHU ARRIMAGE
- French Agence Nationale de la Recherche, PIA project, Lorraine Universite d'Excellence [ANR-15-IDEX-04-LUE]
The study found an association between intermediate/severe HHcy and cardiovascular diseases outcomes, highlighting the importance of diagnosing and treating nutritional deficiencies and inherited disorders.
Background: The association of moderate hyperhomocysteinemia (HHcy) (15-30 mu mol/L) with cardiovascular diseases (CVD) has been challenged by the lack of benefit of vitamin supplementation to lowering homocysteine. Consequently, the results of interventional studies have confused the debate regarding the management of patients with intermediate/severe HHcy. Objective: We sought to evaluate the association of intermediate (30-100 mu mol/L) and severe (>100 mu mol/L) HHcy related to vitamin deficiencies and/or inherited disorders with CVD outcomes. Methods: We performed a retrospective cross-sectional study on consecutive patients who underwent a homocysteine assay in a French University Regional Hospital Center. Patients with CVD outcomes were assessed for vitamin B12, folate, Hcy, methylmalonic acid, and next-generation clinical exome sequencing. Results: We evaluated 165 patients hospitalized for thromboembolic and other cardiovascular (CV) manifestations among 1006 patients consecutively recruited. Among them. 84% (138/165) had Hcy >30 mu mol/L, 27% Hcy >50 mu mol/L, (44/165) and 3% Hcy >100 mu mol/L (5/165). HHcy was related to vitamin 1312 and/or folate deficiency in 55% (87/165), mutations in one or more genes of one-carbon and/or vitamin B12 metabolisms in 11% (19/165), and severe renal failure in 15% (21/141) of the studied patients. HHcy was the single vascular risk retrieved in almost 9% (15/165) of patients. Sixty % (101/165) of patients received a supplementation to treat HHcy, with a significant decrease in median Hcy from 41 to 17 mu mol/L, (IQR: 33.6-60.4 compared with 12.1-28). No recurrence of thromboembolic manifestations was observed after supplementation and antithrombotic treatment of patients who had HHcy as a single risk, after similar to 4 y of follow-up. Conclusion: The high frequency of intermediate/severe HHcy differs from the frequent moderate HHcy reported in previous observational studies of patients with pre-existing CVD. Our study points out the importance of diagnosing and treating nutritional deficiencies and inherited disorders to reverse intermediate/severe HHcy associated with CVD outcomes.
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