Homocysteine-lowering interventions for preventing cardiovascular events

Martí‐Carvajal, Arturo J; Solà, Iván; Lathyris, Dimitrios; Karakitsiou, Despoina-Elvira; Simancas‐Racines, Daniel

doi:10.1002/14651858.cd006612.pub3

Cited by 127 publications

(150 citation statements)

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“…26 Indeed, a substantial body of evidence supports a role of plasma homocysteine in the pathogenesis of hypertension. 27 However, an updated Cochrane review demonstrated that clinical trials using low and high doses of folic acid, vitamin B12, and vitamin B6 had not shown any clinical benefit 28 and claimed that the effects of folate might be influenced by the duration of treatment. 29 The average duration of folic acid supplementation in our study was 2.5 years, which reduced the tHcy level by an average of 6.7 μmol/L (27.92%).…”

Section: Discussionmentioning

confidence: 99%

Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients

Han

Wang

et al. 2015

Stroke

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Stroke is the leading cause of permanent disability in China, 1 and ischemic stroke (IS) accounts for almost 80% of all strokes, 2 whereas coronary heart disease (CHD) is a major worldwide health threat. In tandem with the economic success of China, the number of individuals in China with IS and CHD has increased significantly in recent years, with stroke resulting in 301 million disability-adjusted life-years. 3CHD in Chinese adults aged 35 to 84 years is predicted to increase by 64% during the period 2020-2029. 4 Although numerous epidemiology studies have researched the association between hyperhomocysteinemia and IS or CHD, the results have been conflicting. Most studies have been retrospective and focused on healthy populations in the developed world, whereas data from developing countries remains limited.Vitamins B12 and B6 and folate are involved in the metabolism of methionine, and deficiency of these B vitamins can cause elevation of total homocysteine (tHcy) levels.5 Deficiencies in these nutrients are more prevalent in developing countries. A meta-analysis of randomized trials demonstrated that homocysteine-lowering interventions for stroke seem not to have a significant effect in geographic regions with high dietary folate intake, but may have a substantial effect in regions with low folate intake, such as Asia. 6 Regarding public health guidelines,Background and Purpose-Total homocysteine level (tHcy) is a risk factor of ischemic stroke (IS) and coronary heart disease. However, the results are conflicting and mainly focused on healthy individuals in developed countries. Methods-A prospective, population-based cohort study was conducted among 5935 participants from 60 communities in the city of Shenzhen, China. A Cox regression analysis was applied to evaluate the contribution of tHcy to the risk of IS and coronary heart disease. The effect of folic acid supplementation on tHcy levels was also evaluated among 501 patients with essential hypertension, who received an average of 2.5 years of folic acid supplementation. Results-After adjustment for confounding factors, the hazard ratios (95% confidence intervals) of IS caused by hyperhomocysteinemia were 2.18 (1.65-2.89), 2.40 (1.56-3.67), and 2.73 (1.83-4.08) in the total, male, and female participants, respectively. Compared with normal levels of tHcy (<15 μmol/L), the hazard ratios (95% confidence intervals) for IS in the highest tHcy category (≥30 μmol/L) were 4.96 (3.03-8.12), 6.11 (3.44-10.85), and 1.84 (0.52-6.46) in the total, males, and females participants, respectively. However, we did not observe a significant relationship between tHcy and the risk of coronary heart disease. The 2.5 years of folic acid supplementation reduced tHcy levels by 6.7 μmol/L (27.92%) in patients with essential hypertension. Conclusions-Hyperhomocysteinemia in Chinese hypertensive patients is significantly associated with IS risk but not coronary heart disease susceptibility, and folic acid supplementation can efficiently reduce tHcy levels.

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Section: Discussionmentioning

confidence: 99%

Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients

Han

Wang

et al. 2015

Stroke

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“…1), are the main precursors of vitamins. Nitrogen status (deprivation, fertilization) or different N sources (ammonia, nitrate) have therefore an impact on the amino acid profile (Scheible et al 2004;Foyer 2010;Marschner 2012). Besides, although the de novo synthesis of purines is tightly regulated, it dynamically varies with developmental and environmental cues (Zrenner et al 2006).…”

Section: Variation In Vitamin Contentsmentioning

confidence: 99%

Plant amino acid-derived vitamins: biosynthesis and function

Miret

Munné‐Bosch

2013

Amino Acids

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Vitamins are essential organic compounds for humans, having lost the ability to de novo synthesize them. Hence, they represent dietary requirements, which are covered by plants as the main dietary source of most vitamins (through food or livestock's feed). Most vitamins synthesized by plants present amino acids as precursors (B1, B2, B3, B5, B7, B9 and E) and are therefore linked to plant nitrogen metabolism. Amino acids play different roles in their biosynthesis and metabolism, either incorporated into the backbone of the vitamin or as amino, sulfur or one-carbon group donors. There is a high natural variation in vitamin contents in crops and its exploitation through breeding, metabolic engineering and agronomic practices can enhance their nutritional quality. While the underlying biochemical roles of vitamins as cosubstrates or cofactors are usually common for most eukaryotes, the impact of vitamins B and E in metabolism and physiology can be quite different on plants and animals. Here, we first aim at giving an overview of the biosynthesis of amino acid-derived vitamins in plants, with a particular focus on how this knowledge can be exploited to increase vitamin contents in crops. Second, we will focus on the functions of these vitamins in both plants and animals (and humans in particular), to unravel common and specific roles for vitamins in evolutionary distant organisms, in which these amino acid-derived vitamins play, however, an essential role.

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“…This has led to a number of studies exploring the possible mechanisms by which HHcy may impair vascular function [2,3] and the effects of interventions targeting a lowering of the plasma homocysteine concentration [8]. In contrast, surprisingly little work has been carried out investigating the acute effects of Hcy on cardiac performance during ischaemia reperfusion and on calcium homeostasis and the contractile properties of the individual cardiomyocytes during oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of studies conducted so far have either concentrated on the efficacy of strategies targeting a reduction in plasma Hcy [2,8] or have used vascular endothelial cells, smooth muscle cells, monocytes [2,4] or podocytes [7]. In contrast, the effect of Hcy and HHcy on the myocardium and functional contractile cardiomyocytes has been little studied.…”

Section: Introductionmentioning

confidence: 99%

Homocysteine Exposure Impairs Myocardial Resistance to Ischaemia Reperfusion and Oxidative Stress

Almashhadany

Shackebaei

Touw

et al. 2015

Cell Physiol Biochem

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Background/Aims: Hyperhomocysteinaemia is recognised as a strong independent risk factor for developing cardiovascular disease. This study investigated how an acute homocysteine dose affected cardiac performance during ischaemia reperfusion and cardiomyocyte contractility and morphology under normal conditions and during oxidative stress. Methods: Cardiac function was measured in isolated and perfused rat hearts before and after 40 minutes' global normothermic ischaemia. Where used, 0.1 mM L-homocysteine was present prior to, and throughout ischaemia, before wash out after 10 minutes' reperfusion. Calcium transients under normal conditions and changes in contractile synchronicity during oxidative stress (exposure to 0.2 mM H₂O₂) were measured in freshly isolated rat cardiomyocytes incubated for 60 minutes ± 0.1 mM L-homocysteine. Results: During ischaemia reperfusion 0.1 mM L-homocysteine significantly reduced the rate pressure product during reperfusion (10,038 ± 749 vs. 5955 ± 567 mmHg bpm, p < 0.001), but did not affect time to ischaemic contracture. Incubation of freshly isolated cardiomyocytes with 0.1 mM L-homocysteine significantly decreased the amplitude of the calcium transient and slowed the time to half relaxation. Conclusions: These findings suggest that homocysteine exposure affected myocardial recovery from ischaemia and contractile homeostasis although the exact mechanisms for these changes remain to be determined.

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Homocysteine-lowering interventions for preventing cardiovascular events

Cited by 127 publications

References 130 publications

Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients

Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients

Plant amino acid-derived vitamins: biosynthesis and function

Homocysteine Exposure Impairs Myocardial Resistance to Ischaemia Reperfusion and Oxidative Stress

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