Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction

Bønaa, Kaare Harald; Njølstad, Inger; Ueland, Per Magne; Schirmer, Henrik; Tverdal, Aage; Steigen, Terje K.; Wang, Harald; Nordrehaug, Jan Erik; Arnesen, Egil; Rasmussen, Knut

doi:10.1056/nejmoa055227

Cited by 1,257 publications

(859 citation statements)

References 38 publications

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“…21 Reinforcing this possibility, some recent large-scale studies on reducing tHcy by increasing folate intake, have failed to show any impact of this intervention on CVD risk. [7][8][9] However, renal function did not modify the association of tHcy with PWV or CIMT in our data.…”

Section: Discussionmentioning

confidence: 72%

“…4 There is evidence showing that elevated homocysteine (tHcy) concentrations are a major risk factor for CVD, 5,6 although the etiological meaning of this finding is less clear, since recent studies indicate that lowering tHcy levels does not decrease CVD risk. [7][8][9] There are several mechanisms through which elevated tHcy may play a role in arterial disease, and one of these might be a deleterious effect of tHcy on vascular function. Elevated tHcy levels may result in vascular changes through induction of endothelial dysfunction, 10 arterial wall structural change and arterial stiffness, 11 but these associations were mostly found in persons with existing disease, familial risk, or other risk factors.…”

Section: Introductionmentioning

confidence: 99%

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Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

et al. 2007

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Elevated plasma homocysteine (tHcy) is considered as a risk factor for cardiovascular events, and has been associated with arterial stiffness and subclinical atherosclerosis in subjects with classical cardiovascular risk factors. The aim of this study is to investigate the association of plasma tHcy with functional and structural changes in the large arteries by measuring aortic pulsewave velocity (PWV) and carotid artery intima-media thickness (CIMT). In a population-based sample of 376 middle-aged and elderly men, tHcy levels were measured by using fluorescence polarization immunoassay. Aortic stiffness was assessed non-invasively by measuring carotid-femoral PWV with the use of applanation tonometry. CIMT was measured by ultrasonography. We used multivariate linear regression analysis with the logtransformed value of tHcy as the determinant, and aortic PWV and CIMT as outcomes. In the univariate model, PWV increased with increasing tHcy concentration; PWV increased by 2.64 m/s (95% confidence interval (CI) 1.74; 3.54) per unit change in log tHcy. After adjustment for confounders, no statistically significant association remained; PWV increased by 0.42 m/s (95% CI À0.27; 1.11) per unit change in log tHcy. Furthermore, in the univariate model, CIMT increased significantly with increasing tHcy concentration; CIMT increased by 0.19 mm (95% CI 0.11; 0.26) per unit increase log tHcy. This association was attenuated and did not remain significant after additional adjustment for age and cardiovascular confounders (b ¼ 0.06 (95% CI À0.01; 0.13)). The results of this study do not support the presence of an independent relationship between circulating tHcy levels and large artery stiffness and thickness.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

et al. 2007

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“…25 Other studies, however, have suggested that folic acid intervention, in the presence and absence of vitamin B 6 , does not lower the risk of recurrent cardiovascular disease or death after acute myocardial infarction. 26 This finding is mirrored in studies in which patients with vascular disease showed no decrease in the risk of major cardiovascular events after supplementation with folic acid and vitamin B 6 and B 12 . 27 Despite the many apparently beneficial effects of folate supplementation, and its low incidence of toxicity, 28 some concern has been expressed regarding the interaction between vitamin B 12 and folic acid, primarily in the elderly population.…”

Section: Cardiovascular Diseasementioning

confidence: 90%

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

2009

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“…About two‐thirds of these patients were included in WENBIT (the Western Norway B‐vitamin Intervention Trial), a randomized clinical trial investigating the effect of B‐vitamin treatment on CVD and mortality 15. NORVIT was a randomized clinical trial including 3749 patients hospitalized with acute myocardial infarction in the period 1998‐2002 and randomized to identical treatment protocols as in WENBIT 16. In WECAC, we excluded patients with a history of previous AF from the analyses, whereas we did not have information on previous AF among patients in NORVIT.…”

Section: Methodsmentioning

confidence: 99%

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Zuo

Svingen

Tell

et al. 2018

JAHA

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BackgroundAlthough choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias.Methods and ResultsWe evaluated associations of plasma concentrations and dietary intakes of choline and betaine with long‐term atrial fibrillation (AF) risk in a community‐based cohort, HUSK ([the Hordaland Health Study] n=6949), and validated the findings in 2 patient cohorts: the Western Norway Coronary Angiography Cohort (n=4164) and the NORVIT (Norwegian B‐Vitamin) Trial (n=3733). Information on AF was obtained from the CVDNOR (Cardiovascular Disease in Norway) project. In HUSK, WECAC (Western Norway Coronary Angiography Cohort), and NORVIT, 552, 411, and 663 AF cases were identified during a median follow‐up time of 10.9, 7.3, and, 8.7 years, respectively. Plasma concentrations of choline and betaine were significantly positively associated with later AF risk after multivariable adjustments in HUSK. Such associations were independently replicated in the 2 external prospective patient cohorts. The pooled hazard ratio was 1.13 (95% confidence interval 1.08‐1.19, P<0.001) and 1.16 (95% confidence interval 1.10‐1.22, P<0.001) per SD increment for log‐transformed choline and betaine, respectively. Moreover, dietary intake of choline was marginally associated with AF risk (pooled hazard ratio 1.29, 95% confidence interval 1.01‐1.66, fifth versus first quintile), whereas no significant association was observed between dietary betaine and AF risk.ConclusionsOur findings indicate that plasma concentrations as well as dietary intake of choline, but not betaine, are associated with subsequent risk of AF, suggesting a potential role of choline metabolism in the pathogenesis of AF.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov.Unique identifier: NCT00671346.

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Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction

Abstract: Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).

Cited by 1,257 publications

References 38 publications

Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

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