Homocysteine lowering interventions for preventing cardiovascular events

Iberoamerican Cochrane Network, Valencia, Edo. Carabobo, Venezuela, 2001.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2009; 1(4):CD006612. DOI: 10.1002/14651858.CD006612.pub2
Source: PubMed

ABSTRACT Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease.
To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease.
We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search.
We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease.
We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings.
We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I(2) = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I(2) = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I(2): 0%), respectively.
Results from available published trials suggest that there is no evidence to support the use of HLI to prevent cardiovascular events.

  • Source
    • "IL-6- knockout mice exhibit impaired immune and acute-phase responses [15]. Homocysteineis an í µí»¼-amino acid [16]. It is not obtained from the diet; it is biosynthesized from methionine [17]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Chronic inflammation may play a role in psoriasis pathogenesis. Lipocalin 2, clusterin, soluble tumor necrosis factor receptor-1 (sTNFR-1), interleukin-6, homocysteine, and uric acid are inflammatory and/or biochemical markers. However, both the roles of these markers and the pathogenesis of psoriasis are unknown. Objective. The aim of this study was to investigate serum levels of lipocalin 2, clusterin, sTNFR-1, interleukin-6, homocysteine, and uric acid in patients and controls groups. Methods. Fifty-six patients with psoriasis and 33 healthy controls were included in the study. Serum concentrations of the markers were evaluated by ELISA. The Psoriasis Area and Severity Index (PASI) was evaluated in all psoriasis patients. Body mass index (BMI) was calculated by dividing weight (kg) by height (m) squared. Results. The serum value of lipocalin and sTNFR-1 were significantly higher in psoriasis patients than in controls (resp., P < 0.001, P < 0.05). The others showed no significant differences between psoriasis and the control groups (all of them P > 0.05). The mean PASI score in the patient group was 8.3 ± 6.5. Conclusions. These findings suggest that lipocalin 2 and sTNFR-1 might play a role in the pathogenesis of psoriasis and can be used as markers of the disease.
    Disease markers 04/2014; 2014:541709. DOI:10.1155/2014/541709 · 2.17 Impact Factor
  • Source
    • "Similarly, HS-indomethacin and HS-naproxen are more GI sparing than their traditional counterparts [12,14]. HS-mesalamin exhibits a marked increase in antiinflammatory activity and potency in a murine model of colitis, compared to mesalamine [15] [16], while GYY4137, a slow-releasing H 2 S donor, has anti-inflammatory properties in a mouse model of endotoxic shock [17]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (HS-NSAIDs) are an emerging novel class of compounds with significant anti-inflammatory properties. They consist of a traditional NSAID to which an H(2)S-releasing moiety is covalently attached. We examined the effects of four different HS-NSAIDs on the growth properties of eleven different human cancer cell lines of six different tissue origins. Human colon, breast, pancreatic, prostate, lung, and leukemia cancer cell lines were treated with HS-aspirin, -sulindac, -iburofen, -naproxen, and their traditional counterparts. HS-NSAIDs inhibited the growth of all cancer cell lines studied, with potencies of 28- to >3000-fold greater than that of their traditional counterparts. HS-aspirin (HS-ASA) was consistently the most potent. HS-NSAIDs inhibited cell proliferation, induced apoptosis, and caused G(0)/G(1) cell cycle block. Metabolism of HS-ASA by colon cells showed that the acetyl group of ASA was hydrolyzed rapidly, followed by hydrolysis of the ester bond linking the salicylate anion to the H(2)S releasing moiety, producing salicylic acid and ADT-OH from which H(2)S is released. In reconstitution studies, ASA and ADT-OH were individually less active than the intact HS-ASA towards cell growth inhibition. Additionally, the combination of these two components representing a fairly close approximation to the intact HS-ASA, was 95-fold less active than the intact HS-ASA for growth inhibition. Taken together, these results demonstrate that HS-NSAIDs have potential anti-growth activity against a wide variety of human cancer cells.
    Biochemical pharmacology 03/2012; 83(6):715-22. DOI:10.1016/j.bcp.2011.12.018 · 4.65 Impact Factor
  • Source
    • "It is well known that low folate intake, low folate status, or high plasma homocysteine concentrations are independent risk factors for a number of adverse health outcomes including, among others: cardiovascular diseases, some cancers, cognitive decline in the elderly, adverse pregnancy outcomes, and congenital malformations. Although it is well known that an FA supplementation effectively lower the homocysteine concentration [1], up to date, the expected risk decrease of the cardiovascular events, cancers, adverse pregnancy outcomes, or other adverse health outcomes has not been supported by the available studies [2] [3] [4] [5] [6] [7] [8] [9] [10]. The only well-documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies including pre–post evaluation after mandatory fortification, is the risk reduction of neural tube defects (NTDs). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, a number of studies have been performed to evaluate the possible health benefits of an increased intake of folic acid (FA) on human health. However, the only well-documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies is the risk reduction of neural tube defects (NTDs). NTDs are congenital malformations that include anencephaly, encephalocele, and spina bifida caused by the failure of fusion of the neural tube that normally closes between 22nd and 28th day since conception (on an average 40-42th day after the first day of last menstrual period). The occurrence of NTDs varies among population between 0.8 and 3 per 1,000, and it is estimated that 324,000 pregnancies are affected every year worldwide. More FA can decrease the NTDs risk up to 0.6 per 1,000 births. Other malformations as congenital heart defects, cleft lip, and limb deficiencies can be most probably also reduced. To decrease the NTDs risk, it is recommended that all women capable of becoming pregnant should have more FA. The goal is that every woman could start her pregnancy with an optimal folate status, estimated today to be as more than 906 nmol/L of red blood cell folate concentration. More FA can be obtained through a strict Mediterranean pattern of nutrition and healthy life style, fortified food, supplements. Women and health authorities can choose the most appropriate strategy. Monitoring folate status of women during the periconceptional period is an essential way to evaluate the success of the preferred strategy.
    BioFactors 07/2011; 37(4):272-9. DOI:10.1002/biof.172 · 3.00 Impact Factor
Show more