Homocysteine and Peripheral Arterial Disease: Systematic Review and Meta-analysis

Khandanpour, Nader; Loke, Yoon K.; Meyer, Felicity J.; Jennings, Barbara; Armon, Matthew P.

doi:10.1016/j.ejvs.2009.05.007

Cited by 112 publications

(76 citation statements)

References 45 publications

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“…The vitamin amount in standard food fails to lower homocysteine levels. Recent literature information is consistent with our data concerning the lack of benefit from folate supplementation [24] Statistical analysis (AnOVA-one-way) indicated significant differences within groups (*p < 0.0001, when compared to the initial measurement), but no significant differences between groups.…”

Section: Resultssupporting

confidence: 79%

Hyperhomocysteinemia’s effect on antioxidant capacity in rats

et al. 2010

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AbstractHyperhomocysteinemia represents elevated homocysteine (Hcys) concentrations in blood above the normal range. In humans, the normal range of homocysteine is 5.0–15.9 mM/ml. High levels of homocysteine disturb the normal epithelial functions and correlate with cardiovascular diseases even at slightly increased concentrations. In homocysteine metabolism, vitamins play an important role. The mechanism through which homocysteine triggers these effects is not yet elucidated, but the involvement of reactive species may be the answer. It is not known whether the intra- or extracellular antioxidant system is more affected by elevated homocysteine levels. We studied the effects of hyperhomocysteinemia on the intra- and extracellular antioxidant defense systems in two different types of diet in rats. Type I was food with low folic acid and vitamin B12 content and type II was food with normal amounts of these two vitamins. Hyperhomocysteinemia was experimentally induced by oral administration of methionine 2 mg/kg body weight, single daily dose, for a 15-day period. Plasma concentrations of homocysteine were measured using an HPLC method. In the response of the intracellular antioxidant defense system against hyperhomocysteinemia, we determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in red blood cells, using RANDOX kits for manual use. For the extracellular response we determined the plasma total antioxidant status (TAS) also using a RANDOX kit for manual use. Our data show that methionine load induces hyperhomocysteinemia despite normal vitamin supply in rats. SOD activity rose with simultaneous decrease in GPx activity independently of diet; this might suggest that the intracellular defense system was disturbed by the rise in homocysteine level. TAS decrease suggests that the extracellular antioxidant defense was also affected. We assume that hyperhomocysteinemia is directly linked to reactive species generation and the intracellular space seems to be more affected than the extracellular one.

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Section: Resultssupporting

confidence: 79%

Hyperhomocysteinemia’s effect on antioxidant capacity in rats

et al. 2010

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“…Os autores dessas revisões enfatizaram que a homocisteína é fácil de ser avaliada e, mais importante, fácil e barata de ser tratada, muito embora alguns estudos clínicos interroguem os efeitos benéficos dessa terapêutica 90 . Por outro lado, o declínio da mortalidade cardiovascular nos Estados Unidos…”

Section: Efeitos Do Tratamento Da Hiper-homocisteinemia Sobre a Morbiunclassified

Tratamento dietético da hiper-homocisteinemia na doença arterial periférica

Venâncio

Burini²,

Yoshida

2010

J. vasc. bras.

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IntroduçãoA doença arterial periférica (DAP) é definida como uma doença arterial das extremidades que reduz o fluxo sanguíneo durante o exercício ou, em estágios avançados, mesmo em repouso 1 . Estudos epidemiológicos mostram que a prevalência de DAP varia de 1,6 a 12% 2,3 .As doenças do aparelho circulatório foram as principais causas de morte entre os brasileiros em 2007 (28,2%) 4 e na população mundial (18 milhões) 5 ; dentre as várias etiologias, a aterosclerose foi a causa mais comum. Entre os pacientes com doença aterosclerótica sintomática, 15,9% têm doença polivascular sintomáti-ca (DAP, doença cardiovascular e cerebrovascular) 6 .Além disso, na fase de claudicação intermitente, cerca de 65% dos indivíduos apresentam comprometimento simultâneo e importante dos setores coronariano e cerebrovascular, e 30% dos pacientes com doença vascular coronariana ou cerebral apresentam DAP 7 . Desse modo, a DAP está associada a um aumento da morbimortalidade por doenças cardiovasculares (aproximadamente 30%) e cerebrovasculares 8 , sendo um importante preditor das mesmas. ARTIGO DE REVISÃO ResumoA homocisteína está envolvida na gênese da aterosclerose e, assim, é considerada um importante e prevalente fator de risco na doença arterial periférica. O estado nutricional vitamínico deficiente, em especial do folato, é a principal causa de hiper-homocisteinemia nesses casos. Embora ainda não haja consenso sobre a dose exata e a forma de utilização do folato em suplementos e sobre adequação alimentar ou fortificação de cereais para o tratamento da hiper-homocisteinemia, diversos estudos realizados em pacientes com doença vascular periférica mostraram que o folato, isoladamente, pode reduzir as concentrações de homocisteína, bem como a concentração de alguns marcadores biológicos do processo de aterosclerose. No entanto, estudos recentes não comprovaram esse benefício sobre o processo inflamatório associado à hiper-homocisteinemia. Desta forma, embora a utilização isolada do folato seja uma terapêutica custo-efetiva no controle da hiper-homocisteinemia, seu impacto na evolução das doenças arteriais ainda persiste inconclusivo. Esta revisão abordará os efeitos obtidos com as diversas formas de utilização do folato no tratamento da hiper-homocisteinemia.Palavras-chave: Homocisteína, aterosclerose, vitamina, ácido fó-lico. AbstractHomocysteine plays a role in the genesis of atherosclerosis and, thus, it is considered an important and prevalent risk factor for peripheral arterial disease. Impaired vitamin nutritional status, especially regarding folate, may be mainly attributed to hyperhomocysteinemia. Although there is still no consensus as to the exact dose and method of use of folate in supplements, dietary adjustment or cereal fortification for the treatment of hyperhomocysteinemia, several studies conducted in patients with peripheral vascular disease have shown that isolated folate may reduce homocysteine levels, as well as the levels of some biological markers in the atherosclerotic process. However, recent studies ha...

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“…The prevalence of aspirin, clopido- high-sensitivity C-reactive protein, Total-C: total cholesterol, LDL-C: low-density lipoprotein cholesterol, HDL-C: high-density lipoprotein cholesterol, RLP-C: remnant-like particle cholesterol, TAT: thrombin-antithrombin complex, PIC: plasmin-2 plasmin inhibitor complex, BNP: brain natriuretic peptide, ACE: angiotensin-converting enzyme, ARB: angiotensin receptor blocker tion, the fibrinogen level is particularly associated with the severity and potential for the further development of PAD 26) and functions as an independent risk factor for CAD 25) . Hyperhomocysteinemia is an independent risk factor for atherosclerosis and a stronger risk factor for PAD than for CAD 16,17) , with an association with death or severe vascular events in patients with PAD 27) . We previously found that a high plasma homocysteine level is also a risk factor for CLI as well as PAD 17) .…”

Section: Discussionmentioning

confidence: 99%

“…Homocysteine is an intermediate metabolite of methionine that contributes to cardiovascular disease via mechanisms such as endothelial dysfunction, increased lipid permeability and vascular inflammation 14,15) . Hyperhomocysteinemia is an independent risk factor for PAD and CAD 16,17) . Hence, the combination of high homocysteine and Lp(a) levels synergistically increases the likelihood of developing CAD 15) .…”

Section: Introductionmentioning

confidence: 99%

High-sensitivity C-reactive Protein, Lipoprotein(a) and Homocysteine are Risk Factors for Coronary Artery Disease in Japanese Patients with Peripheral Arterial Disease

Kumakura

Fujita

Kanai

et al. 2015

JAT

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Aim:The goal of the study was to investigate the relationships between coronary artery disease (CAD) and risk factors, including the serum levels of high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) (Lp(a)) and homocysteine, in Japanese patients with peripheral arterial disease (PAD). Methods: Coronary angiography was performed in 451 patients with PAD, among whom the prevalence and clinical characteristics of CAD were analyzed. A multiple logistic analysis was used to evaluate the relationships between CAD and the risk factors. The relationships between the severity of coronary arterial lesions and the risk factors were evaluated using multiple regression analysis. Results: The prevalence of CAD (≥ 70% luminal diameter narrowing or a history of CAD) and coronary artery stenosis (≥ 50%) was 55.9% and 74.1%, respectively, and the rate of CAD (≥ 70%) with single-, double-and triple-vessel disease was 25.9%, 13.5% and 10.6%, respectively. The prevalence of diabetes was higher among the patients with CAD than among those without. The serum levels of hs-CRP, Lp(a), and homocysteine were higher in the patients with CAD, whereas the estimated glomerular filtration rates and HDL-cholesterol levels were lower in these patients. According to the multiple logistic analysis, CAD was related to diabetes (hazard ratio [

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Homocysteine and Peripheral Arterial Disease: Systematic Review and Meta-analysis

Abstract: Patients with PAD have significantly higher Hcy levels than unaffected controls. However, we did not find any robust evidence on clinically beneficial effects of folate supplementation in PAD.

Cited by 112 publications

References 45 publications

Hyperhomocysteinemia’s effect on antioxidant capacity in rats

Hyperhomocysteinemia’s effect on antioxidant capacity in rats

Tratamento dietético da hiper-homocisteinemia na doença arterial periférica

High-sensitivity C-reactive Protein, Lipoprotein(a) and Homocysteine are Risk Factors for Coronary Artery Disease in Japanese Patients with Peripheral Arterial Disease

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