Cardiovascular Morbidity and Mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in Chronic Renal Failure

Zoungas, Sophia; McGrath, Barry P; Branley, Pauline; Kerr, Peter G.; Muske, Christine; Wolfe, Rory; Atkins, Robert C.; Nicholls, Kathy; Fraenkel, Margaret; Hutchison, Brian; Walker, Robert; McNeil, John J

doi:10.1016/j.jacc.2005.10.064

Cited by 206 publications

(165 citation statements)

References 37 publications

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“…For example, the plausibility of a link between the levels of Hcy and the risk of CVD was supported by a number of studies. (12) Folic acid: 5 mg/d or 5 mg, every other day 35·0 13·1 2 15·1 2 49·3 Righetti et al (14) Folic acid: 15 mg/d 27 13·0 2 2·4 2 8·9 Vianna et al (17) Folic acid: 10 mg, three times a week 23·5 15 2 10·5 2 44 Jamison et al (20) Folic Vit, vitamin.…”

Section: Discussionmentioning

confidence: 99%

“…Whether on dialysis or not on dialysis, prescriptions of VitB 6 or VitB 12 , or the degree of Hcy-lowering were potential confounders related to both the outcome and the primary variable of interest. As Fig.…”

Section: Subgroup Analysis Of Relative Risk For Cvdmentioning

confidence: 99%

“…Wrone et al (13) Righetti et al (14) Zoungas et al (12) House et al (21) Heinz et al (22) Overall 0·159537 One report demonstrated that endothelial cells can develop abnormal vasoreactivity and may adopt a prothrombotic phenotype and secrete leucocyte chemotactic factors, adhesion molecules and inflammatory cytokines when exposed to elevated Hcy (23) . Endothelial dysfunction is a key process in atherosclerosis, which independently predicts CVD events (24) ; and it becomes progressively more common as renal function declines (25) .…”

Section: Studymentioning

confidence: 99%

“…Also, to the best of our knowledge, there are no studies that have determined a threshold value for Hcy level for effective prevention of cardiovascular events in the general population or in patients with CKD. Observational data in a meta-analysis show that a 25 % reduction in Hcy was associated with a 32 % lower risk of CVD among Study Righetti et al (16) Wrone et al (13) Righetti et al (14) Zoungas et al (12) Jamison et al (20) Nanayakkara et al (18) Vianna et al (17) Mann et al (19) House et al (21) Heinz et al (22) Overall 0·074931 …”

Section: Studymentioning

confidence: 99%

“…Wrone et al (13) Zoungas et al (12) Righetti et al (14) Jamison et al (20) Heinz et al (22) House et al (21) Overall 0·021215 women and a 15 % lower risk among men (29) . However, the reported decreases in Hcy levels vary substantially; and the ten papers in our meta-analysis reported a wide range of Hcy-lowering from 8·9 % to 53·8 %, which is consistent with the observed range of decrease in patients without CKD.…”

Section: Studymentioning

confidence: 99%

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Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

et al. 2012

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The efficacy of homocysteine (Hcy)-lowering therapy in reducing the risk of CVD among patients with chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to determine whether pooling the data from the few small randomised, controlled trials that address this topic would improve the statistical power of the analysis and resolve some of the inconsistencies in the results. Randomised, controlled clinical trials (RCT) were identified from MEDLINE, EMBASE, www.clinicaltrials.gov, the Cochrane Controlled Clinical Trials Register Database and Nephrology Filters. Independent extraction of articles was performed using predefined data fields. The primary outcome was relative risk (RR) of CVD, CHD, stroke and all-cause mortality for the pooled trials. A stratified analysis was planned, assessing the RR for cardiovascular events between the patients on and not on dialysis. Overall, ten studies met the inclusion criteria. The estimated RR were not significantly different for any outcomes, including CHD (RR 1·00, 95 % CI 0·75, 1·31, P ¼ 0·97), CVD (RR 0·94, 95 % CI 0·84, 1·05, P ¼ 0·30), stroke (RR 0·83, 95 % CI 0·57, 1·19, P ¼ 0·31) and all-cause mortality (RR 1·00, 95 % CI 0·92, 1·09, P ¼ 0·98). In the stratified analysis, the estimated RR were not significantly different for cardiovascular events regardless of dialysis or in combination with vitamin B therapy or the degree of reduction in Hcy levels. Our meta-analysis of RCT supports the conclusion that Hcy-lowering therapy was not associated with a significant decrease in the risk for CVD events, stroke and all-cause mortality among patients with CKD.Key words: CVD: Chronic kidney disease: Folic acid: Homocysteine-lowering therapy: Homocysteine: Meta-analyses CVD is the leading cause of mortality both among the general population and among patients with chronic kidney disease (CKD). The rate of mortality from CVD among patients on haemodialysis (HD) is 20-fold higher than that among the general population (1) , and impaired renal function per se is a very strong cardiovascular prognostic factor (2,3) . Therefore, much attention has been focused on managing risk factors to attempt to reduce the associated CVD risks, especially among patients with CKD. Elevated plasma total homocysteine (Hcy) has been proposed as a risk factor for cardiovascular morbidity and mortality in patients either with normal renal function or with CKD (4,5) . Among patients with CKD, plasma Hcy levels tend to increase with decreasing glomerular filtration rate (6) ; thus, hyperhomocysteinaemia may potentially further increase the risk of CVD in this special population. In the Cardiovascular Risk Extended Evaluation in Dialysis trial, investigators followed-up on 175 patients with kidney failure for 29 months and found that an increase in Hcy of 10 mmol/l was associated with a 20 % increased risk for CVD events (7) . In another study, Hcy was found to be a strong independent predictor of mortality among patients on HD with a 3 % increase in mortality for each 1 mmol...

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Section: Discussionmentioning

confidence: 99%

Section: Subgroup Analysis Of Relative Risk For Cvdmentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

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Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

et al. 2012

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Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women

Christen¹,

Glynn²,

Chew³

et al. 2009

Arch Intern Med

151

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Context Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of homocysteine-lowering in AMD are lacking. Objective To examine incidence of AMD in a trial of folic acid/vitamin B6/vitamin B12. Design Randomized, double-masked, placebo-controlled trial. Participants 5,442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or 3 or more CVD risk factors. A total of 5,205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Intervention Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d), or placebo. Main Outcome Measures Total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually-significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the folic acid/B6/B12 group and 82 in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.02). For visually-significant AMD, there were 26 cases in the folic acid/B6/B12 group and 44 in the placebo group (RR, 0.59; 95% CI, 0.36–0.95; p=0.03). Conclusions These randomized trial data from a large cohort of women at high risk of CVD indicate that daily supplementation with folic acid/B6/B12 may reduce the risk of AMD.

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Effect of Folic Acid Supplementation on Risk of Cardiovascular Diseases

Bazzano¹,

Reynolds²,

Holder³

et al. 2006

JAMA

385

231

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Cardiovascular Morbidity and Mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in Chronic Renal Failure

Abstract: High-dose folic acid does not slow atheroma progression or improve cardiovascular morbidity or mortality in patients with CRF.

Cited by 206 publications

References 37 publications

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women

Effect of Folic Acid Supplementation on Risk of Cardiovascular Diseases

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