Folate Therapy and In-Stent Restenosis after Coronary Stenting

Lange, Hans; Suryapranata, Harry; Luca, Giuseppe De; Börner, C; Dille, Joep; Kallmayer, Klaus; Pasalary, M Noor; Scherer, E.; Dambrink, Jan‐Henk E.

doi:10.1056/nejmoa032845

Cited by 300 publications

(145 citation statements)

References 34 publications

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“…But, the Swiss Heart Study demonstrated that homocysteine-lowering therapy did show significant risk reduction in major adverse cardiovascular events in patients treated with angioplasty, with or without stenting [30]. Finally, Lange et al evidenced that the multivitamin therapy, although reduced serum homocysteine levels, was associated with a paradoxical increase of restenosis and major adverse cardiac events at 6 months, particularly in patients with homocysteine levels in the normal range, whereas slight benefits were observed in patients with elevated homocysteine [31]. In the 14-year follow-up, the Nurses' Health Study Researchers suggested that intake of folic acid and vitamin B 6 may have positive impact on the primary prevention of heart disease among women and the maximum benefit would be achieved at folic acid intake of at least 400 lg/day [32].…”

Section: Therapy Of Hyperhomocysteinemiamentioning

confidence: 99%

Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties

Cacciapuoti

2011

J Thromb Thrombolysis

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Increased homocysteine levels can be responsible for arterial ischemic events, such as MI, stroke or peripheral vascular disease. Homocysteine is metabolized by two pathways: re-methylation and trans-sulfuration. Both involve folic acid, and vitamins B(6-12.) Several studies assumed that the folates and vitamins B supplementation or dietary source to normalize plasma homocysteine. But, even if tends to normalize homocysteine levels, lowering homocysteine by B-group vitamins and/or folates does not reduce cardiovascular risk. In fact, recent reports confirmed that hyper-homocysteinemia is not directly responsible for cardiovascular disease, but is merely present in individuals suffering for acute and/or chronic cardiovascular events, as a collateral finding. Reduced methylation potential (MP) [due to decreased S-adenosyl-methionine (AdoMet)/S-adenosyl-homocysteine (AdoHcy) ratio] induced by the elevated plasma homocysteine levels seems to be the true responsible for cardiovascular diseases (CVD). The pathogenic mechanisms responsible for CVD appear to be dependent of DNA hypomethylation inducing an inhibition of cyclin A transcription and a reduction of endothelial cells growth. But, other human studies performed in a wide range are requested.

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Section: Therapy Of Hyperhomocysteinemiamentioning

confidence: 99%

Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties

Cacciapuoti

2011

J Thromb Thrombolysis

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“…Although there was no difference in the frequency of coronary stent placement between the two groups, others have reported that stent placement inhibits the beneficial effects of folic acid. In a subsequent study published by Lange et al [56], 636 patients were randomized to folic acid therapy or placebo after coronary stent placement. At 6 months, luminal diameter was smaller and in-stent restenosis rates higher in the treatment group.…”

Section: Coronary Angioplastymentioning

confidence: 99%

“…Of note, when tHcy levels were greater than 15 μmol/L, this effect was diminished. Explaining these contradictory data is difficult, but it is possible that a folic acid-induced antithrombotic state and improved endothelial function may benefit balloon angioplasty patients, whereas folic acid-induced cell proliferation may harm those receiving coronary stents [56,57].…”

Section: Coronary Angioplastymentioning

confidence: 99%

Should hyperhomocysteinemia be treated in patients with atherosclerotic disease?

Maron¹,

Loscalzo

2007

Curr Atheroscler Rep

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Numerous retrospective and prospective observational studies support an association between elevated homocysteine and increased risk for myocardial infarction, stroke, and peripheral vascular disease. Although folic acid therapy substantially reduces homocysteine levels, recent large, randomized controlled trials failed to translate folic acid-induced homocysteine reduction into clinical benefit for the secondary prevention of cardiovascular events. These studies are compelling and have generated some newfound skepticism regarding a clinical role for folic acid therapy. Because these intervention trials have been limited to patients with mild hyperhomocysteinemia, the results of the trials imply that folic acid therapy may be best suited for individuals with more robustly elevated homocysteine levels. Furthermore, the potential benefit of folic acid therapy for primary prevention in individuals at low- or intermediate-risk for atherothrombotic disease has not been studied to date. Thus, at this time, folic acid therapy for borderline or mild hyperhomocysteinemia is not recommended. However, the role of folic acid therapy in patients with intermediate or severe hyperhomocysteinemia, or for primary prevention of cardiovascular diseases, remains unresolved.

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“…These results have led some interventionalists to adopt this vitamin strategy after coronary interventions, although if analyzed the data deeper, theses vitamin treatment seemed to be more effective after balloon angioplasty than after coronary stenting, being the latter now the method of choice for the vast majority of patients undergoing coronary intervention. This is why Lange et al [125] made a similar study using these vitamin treatment but only after stenting and found that folate therapy had adverse effects on the risk of restenosis in all subgroups except for women, patients with diabetes, and patients with markedly elevated homocysteine levels (15 µmol/L) at baseline, results that make the controversy about folate therapy grow.…”

Section: Hyperhomocysteinemia Treatmentmentioning

confidence: 99%

Metabolism of Homocysteine and its Relationship with Cardiovascular Disease

Aguilar¹,

Rojas²,

Collados³

2004

J Thromb Thrombolysis

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Hyperhomocysteinemia, or the rise of plasmatic homocysteine levels above 15 mug/dL, is accepted nowadays as an independent risk factor for cardiovascular disease in men and women. Homocysteine (Hcy) is a non-protein forming aminoacid (aa) derivated from the loss of the methyl group, found within methionine. Methionine regenerates by retrieving the methyl radical from 5-methyltetrahydrofolate (5-MTHF) creating tetrahydrofolate (THF) which will then regenerate to 5-MTHF through the action of methylentetrahydrofolate reductase (MTHFR). This process is called remethylation. Alternatively, Hcy can follow the transsulfuration route, where through cystationine-beta-syntetase (CBS), it irreversibly converted into cystationine, a precursor of cysteine, glutathione, and other substances that are finally excreted in the urine. Hyperhomocysteinemia results from inhibition of the remethylation route, or inhibition or saturation of the transsulfuration pathway. Main factors causally associated increased plasmatic Hcy are mutations of the enzymes MTHFR and CBS; varying nutritional and health states; demographic factors; and, others. The most accepted hypotheses about Hcy action in cardiovascular disease are direct endothelial and vessel wall damage; oxidative stress generation; and, stimulation of a procoagulant and proinflammatory state of blood components. Since hyperhomocysteinemia can be effectively treated with folic acid, prospective trials are underway to determine if folate therapy is required to lower Hcy levels in plasma. These studies also attempt to address the impact, if any, of folate therapy in the reduction of cardiovascular risk, and to demonstrate if hyperhomocysteinemia is actually an independent risk factor that can be effectively treated.

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Folate Therapy and In-Stent Restenosis after Coronary Stenting

Abstract: Contrary to previous findings, the administration of folate, vitamin B6, and vitamin B12 after coronary stenting may increase the risk of in-stent restenosis and the need for target-vessel revascularization.

Cited by 300 publications

References 34 publications

Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties

Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties

Should hyperhomocysteinemia be treated in patients with atherosclerotic disease?

Metabolism of Homocysteine and its Relationship with Cardiovascular Disease

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