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Background: Whether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown.Objective: To assess whether oral multivitamins reduce cardiovascular events and are safe.Design: Double-blind, placebo-controlled, 2 x 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) SETTING: 134 U.S. and Canadian academic and clinical sites.Patients: 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 mol/L (2.0 mg/dL) or less.Intervention: Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo.Measurements: The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina.Results: The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events.Limitation: There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety).Conclusion: High-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: Whether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown. Objective: To assess whether oral multivitamins reduce cardiovascular events and are safe. Design: Double-blind, placebo-controlled, 2 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) Setting: 134 U.S. and Canadian academic and clinical sites. Patients: 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 μmol/L (2.0 mg/dL) or less. Intervention: Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo. Measurements: The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. Results: The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P 0.23).Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events. Limitation: There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety). Conclusion: High-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate. Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

The article presents a study which was conducted to determine if the polyamino carboxylic acid ethylenediaminetetraacetic acid (EDTA)-based chelation regimen can reduce cardiovascular events. The study was conducted as disodium EDTA was used to treat atherosclerosis without proof of efficacy. The study involved the use of double-blind, placebo-controlled factorial randomized clinical trial which enrolled 1708 patients in the age group of 50-years who were experiencing myocardial infarction. The result revealed that the use of disodium EDTA by these patients had reduced risks of adverse cardiovascular outcomes.

Importance: Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.Objective: To determine if an EDTA-based chelation regimen reduces cardiovascular events.Design, Setting, and Participants: Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial.Interventions: Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events.Main Outcome Measures: The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036.Results: Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.Conclusions and Relevance: Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.Trial Registration: clinicaltrials.gov Identifier: NCT00044213. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5-29.9 kg/m²) adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0. 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE - RMR - 0.1 * TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity. [ABSTRACT FROM AUTHOR]

Context It is unclear if blood transfusion in anemic patients with acute coronary syndromes is associated with improved survival. Objective To determine the association between blood transfusion and mortality among patients with acute coronary syndromes who develop bleeding, anemia, or both during their hospital course. Design, Setting, and Patients We analyzed 24,112 enrollees in 3 large international trials of patients with acute coronary syndromes (the GUSTO IIb, PURSUIT, and PARAGON B trials). Patients were grouped according to whether they received a blood transfusion during the hospitalization. The association between transfusion and outcome was assessed using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate and the propensity to receive blood, and a landmark analysis. Main Outcome Measure Thirty-day mortality. Results Of the patients included, 2401 (10.0%) underwent at least 1 blood transfusion during their hospitalization. Patients who underwent transfusion were older and had more comorbid illness at presentation and also had a significantly higher unadjusted rate of 30-day death (8.00% vs 3.08%; P<.001), myocardial infarction (MI) (25.16% vs 8.16%; P<.001), and death/MI (29.24% vs 10.02%; P<.001) compared with patients who did not undergo transfusion. Using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate, transfusion was associated with an increased hazard for 30-day death (adjusted hazard ratio [HR], 3.94; 95% confidence interval [CI], 3.26-4.75) and 30-day death/MI (HR, 2.92; 95% CI, 2.55-3.35). In the landmark analysis that included procedures and bleeding events, transfusion was associated with a trend toward increased mortality. The predicted probability of 30-day death was higher with transfusion at nadir hematocrit values above 25%. Conclusions Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality, and th... [ABSTRACT FROM AUTHOR]

Infectious diseases have influenced population genetics and the evolution of the structure of the human genome in part by selecting for host susceptibility alleles that modify pathogenesis. Norovirus infection is associated with ~90% of epidemic non-bacterial acute gastroenteritis worldwide. Here, we show that resistance to Norwalk virus infection is multifactorial. Using a human challenge model, we showed that 29% of our study population was homozygous recessive for the a(1,2)fucosyltransferase gene (FUT2) in the ABH histo-blood group family and did not express the H type-1 oligosaccharide ligand required for Norwalk virus binding. The FUT2 susceptibility allele was fully penetrant against Norwalk virus infection as none of these individuals developed an infection after challenge, regardless of dose. Of the susceptible population that encoded a functional FUT2 gene, a portion was resistant to infection, suggesting that a memory immune response or some other unidentified factor also affords protection from Norwalk virus infection. [ABSTRACT FROM AUTHOR]

An abstract of the study "Disodium EDTA Chelation for Post Myocardial Infarction Patients" by Gervasio A. Lamas and colleagues is presented.

An abstract of the article "Oral High-Dose Multivitamins and Minerals Alone and in Combination with Chelation Therapy for Coronary Disease: A Randomized Clinical Trial" by Gervasio A. Lamas, Robin Boineau, Christine Goertz, Daniel B. Mark, Yves Rosenberg and Mario Stylianou is presented.