Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

Lonn, Eva; Yusuf, Salim; Arnold, Jane; Pogue, Janice; Micks, Mary; McQueen, Matthew; Probstfield, Jeffrey L.

doi:10.1056/nejmoa060900

Cited by 1,424 publications

(240 citation statements)

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“…Recently, several large randomized studies showed that although homocysteine can be lowered, there is not necessarily a reduced risk of major cardiovascular events [16, 17, 29]. This raises the questions whether any benefit can be gained from lowering homocysteine and what role homocysteine actually plays in contributing towards cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

“…Although supplementation with folic acid, B 6 and B 12 usually decreases homocysteine in patients with vascular disease [16, 17], it often remains elevated in ESRD patients despite supplementation of folic acid, B 6 and B 12 . Several studies have reported only moderate effects, even with very high doses of folic acid (up to 15 mg/daily) [18].…”

Section: Introductionmentioning

confidence: 99%

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5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

et al. 2008

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“…Of these, 2573 (61.8%) were subsequently enrolled in the WENBIT (Western Norway B‐vitamin Intervention Trial; NCT00354081) and received either (1) folic acid, vitamin B12 and vitamin B6 (n=642), (2) folic acid and vitamin B12 (n=642), (3) vitamin B6 (n=643), or (4) placebo (n=646) 14. Because B‐vitamin supplementation has been reported to lower the risk of stroke in some studies,15, 16 we excluded patients who received supplementation with B‐vitamins in the WENBIT. In addition, patients with missing baseline data on cystathionine and 1 patient with an extremely high cystathionine level (20 μmol/L) were excluded, leaving 2036 patients eligible for the current analyses (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

Dhar

Svingen

Ueland

et al. 2018

JAHA

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BackgroundCystathionine is an intermediate product in the transsulfuration pathway and formed during the B6‐dependent conversion of methionine to cysteine. Elevated plasma cystathionine has been related to atherosclerosis, which is a major etiological factor for ischemic stroke. However, the role of cystathionine in stroke development is unknown. Therefore, we prospectively assessed the association of circulating levels of cystathionine with risk of total and ischemic stroke.Methods and ResultsTwo‐thousand thirty‐six patients (64% men; median age, 62 years) undergoing coronary angiography for suspected stable angina pectoris were included. Stroke cases were identified by linkage to the CVDNOR (Cardiovascular Disease in Norway) project. Hazard ratios with confidence intervals (95% confidence interval) were estimated by using Cox‐regression analyses. During 7.3 years of median follow‐up, 124 (6.1%) incident strokes were ascertained, which comprised 100 cases of ischemic stroke. There was a positive association of plasma cystathionine with risk of total stroke and ischemic stroke. Comparing the fourth versus the first cystathionine quartiles, age‐ and sex‐adjusted hazard ratios (95% confidence interval) were 2.11 (1.19–3.75) and 2.56 (1.31–4.99) for total and ischemic stroke, respectively. Additional adjustment for major stroke risk factors only slightly attenuated the associations, which tended to be stronger in patients without previous or existing atrial fibrillation at baseline (hazard ratio [95% confidence interval], 2.43 [1.27–4.65] and 2.88 [1.39–5.98] for total and ischemic stroke, respectively).ConclusionsIn patients with suspected stable angina pectoris, plasma cystathionine was independently related to increased risk of total stroke and, in particular, ischemic stroke.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354081.

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“…Consequently, it can be suggested that lowering homocysteine levels with B12, B6 and folic acid would prevent cardiovascular events. However, in the three large prospective trials (VISP, HOPE-2 and NORVIT) in patients with established cardiovascular disease [10,11,12], there was no clinical benefit of treatment with folic acid and B vitamins for prevention of recurrent cardiovascular events and mortality. Although our population is a small group of 211 patients, the results are in accordance with the results of the three large studies.…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinaemia and Vitamin B12 Deficiency: The Long-Term Effects in Cardiovascular Disease

Oijen¹,

Vlemmix²,

Laheij³

et al. 2006

Cardiology

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Background: An elevated plasma homocysteine level is an established risk factor for cardiovascular disease. Vitamin B12 plays a key role in homocysteine metabolism and could be the main factor in causing cardiovascular disease as well. Objectives: The aim of this study was to assess whether vitamin B12 deficiency or hyperhomocysteinaemia is associated with recurrent cardiovascular events. Methods: Overall, 211 patients discharged alive from our Coronary Care Unit were recruited from February till May 1998. Serum vitamin B12 and plasma homocysteine levels were measured in fasting blood samples. Patient characteristics, medical information and cardiovascular risk factors were assessed from medical files. Patients were followed for 5 years and the prevalence of cardiovascular mortality and morbidity was collected. Results: In the follow-up period of 810 person-years, 48 (21%) of the patients experienced a nonfatal recurrent cardiovascular event and another 14 (7%) died of a cardiovascular cause. Among those with ischaemic heart disease at discharge, no difference in survival was found between the patients with a low (<250 pmol/l) or a high vitamin B12 level (p = 0.21). In patients with hyperhomocysteinaemia (>16 µmol/l), an increased risk of a recurrent cardio vascular event (p = 0.05) in comparison to those with normal plasma homocysteine levels was proven (adjusted hazard ratio of 2.22 (95% CI: 1.40–3.04). Conclusions: In conclusion, high plasma homocysteine concentration, but not a low serum vitamin B12 concentration, increases the risk of cardiovascular morbidity and mortality in patients with ischaemic heart disease.

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Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

Abstract: Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).

Cited by 1,424 publications

References 18 publications

5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

Hyperhomocysteinaemia and Vitamin B12 Deficiency: The Long-Term Effects in Cardiovascular Disease

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