PMID- 33693455
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20230214
IS  - 1938-3207 (Electronic)
IS  - 0002-9165 (Linking)
VI  - 113
IP  - 5
DP  - 2021 May 8
TI  - Cardiovascular manifestations of intermediate and major hyperhomocysteinemia due 
      to vitamin B12 and folate deficiency and/or inherited disorders of one-carbon 
      metabolism: a 3.5-year retrospective cross-sectional study of consecutive 
      patients.
PG  - 1157-1167
LID - 10.1093/ajcn/nqaa432 [doi]
AB  - BACKGROUND: The association of moderate hyperhomocysteinemia (HHcy) (15-30 
      mumol/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 mumol/L) and severe (>100 mumol/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 mumol/L, 27% Hcy >50 mumol/L 
      (44/165) and 3% Hcy >100 mumol/L (5/165). HHcy was related to vitamin B12 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 micromol/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  approximately 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.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      American Society for Nutrition.
FAU - Levy, Julien
AU  - Levy J
AD  - Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, 
      Nutrition, and Metabolism, University Hospital (CHRU) of Nancy, Nancy, France.
AD  - Reference Centre for Inborn Errors of Metabolism (ORPHA67872), University 
      Hospital (CHRU) of Nancy, Nancy, France.
FAU - Rodriguez-Gueant, Rosa-Maria
AU  - Rodriguez-Gueant RM
AD  - Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, 
      Nutrition, and Metabolism, University Hospital (CHRU) of Nancy, Nancy, France.
AD  - Reference Centre for Inborn Errors of Metabolism (ORPHA67872), University 
      Hospital (CHRU) of Nancy, Nancy, France.
AD  - INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), 
      Faculty of Medicine of Nancy, University of Lorraine, INSERM, Nancy, France.
FAU - Oussalah, Abderrahim
AU  - Oussalah A
AD  - Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, 
      Nutrition, and Metabolism, University Hospital (CHRU) of Nancy, Nancy, France.
AD  - Reference Centre for Inborn Errors of Metabolism (ORPHA67872), University 
      Hospital (CHRU) of Nancy, Nancy, France.
AD  - INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), 
      Faculty of Medicine of Nancy, University of Lorraine, INSERM, Nancy, France.
FAU - Jeannesson, Elise
AU  - Jeannesson E
AD  - Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, 
      Nutrition, and Metabolism, University Hospital (CHRU) of Nancy, Nancy, France.
AD  - Reference Centre for Inborn Errors of Metabolism (ORPHA67872), University 
      Hospital (CHRU) of Nancy, Nancy, France.
FAU - Wahl, Denis
AU  - Wahl D
AD  - INSERM UMR_S 1116 DCAC and CHRU-Nancy, Vascular Medicine Division and Regional 
      Competence Center for Rare Auto-Immune Diseases, University of Lorraine, INSERM, 
      University Hospital (CHRU) of Nancy, Nancy, France.
FAU - Ziuly, Stephane
AU  - Ziuly S
AD  - INSERM UMR_S 1116 DCAC and CHRU-Nancy, Vascular Medicine Division and Regional 
      Competence Center for Rare Auto-Immune Diseases, University of Lorraine, INSERM, 
      University Hospital (CHRU) of Nancy, Nancy, France.
FAU - Gueant, Jean-Louis
AU  - Gueant JL
AUID- ORCID: 0000-0002-5067-042X
AD  - Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, 
      Nutrition, and Metabolism, University Hospital (CHRU) of Nancy, Nancy, France.
AD  - Reference Centre for Inborn Errors of Metabolism (ORPHA67872), University 
      Hospital (CHRU) of Nancy, Nancy, France.
AD  - INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), 
      Faculty of Medicine of Nancy, University of Lorraine, INSERM, Nancy, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Clin Nutr
JT  - The American journal of clinical nutrition
JID - 0376027
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 8LL8S712J7 (Methylmalonic Acid)
RN  - 935E97BOY8 (Folic Acid)
RN  - P6YC3EG204 (Vitamin B 12)
SB  - IM
CIN - Am J Clin Nutr. 2021 May 8;113(5):1081-1082. PMID: 33851207
MH  - Adult
MH  - Cardiovascular Diseases/*etiology
MH  - Child, Preschool
MH  - Cross-Sectional Studies
MH  - Female
MH  - Folic Acid/*therapeutic use
MH  - Folic Acid Deficiency/*complications
MH  - Homocysteine/blood/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*complications
MH  - Male
MH  - Metabolism, Inborn Errors/*blood/genetics/metabolism
MH  - Methylmalonic Acid/blood/metabolism
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Vitamin B 12/blood/metabolism
OTO - NOTNLM
OT  - 1-carbon metabolism
OT  - cardiovascular disease risk
OT  - folate
OT  - homocysteine
OT  - inborn errors of metabolism
OT  - thromboembolic manifestations
OT  - vitamin B12
EDAT- 2021/03/12 06:00
MHDA- 2021/06/22 06:00
CRDT- 2021/03/11 06:42
PHST- 2020/08/25 00:00 [received]
PHST- 2020/12/16 00:00 [accepted]
PHST- 2021/03/12 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/03/11 06:42 [entrez]
AID - S0002-9165(22)00691-8 [pii]
AID - 10.1093/ajcn/nqaa432 [doi]
PST - ppublish
SO  - Am J Clin Nutr. 2021 May 8;113(5):1157-1167. doi: 10.1093/ajcn/nqaa432.