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Introduction: There is limited knowledge about the use of invasive treatment and mortality after acute myocardial infarction (AMI) in prostate cancer (PCa) patients. We therefore wanted to compare rates of invasive treatment and 30-day mortality between AMIs in patients with PCa and AMIs in the general Norwegian male population. Methods: Norwegian population-based registry data from 2013 to 2019 were used in this cohort study to identify AMIs in patients with a preceding PCa diagnosis. We compared invasive treatment rates and 30-day mortality in AMI patients with PCa to the same outcomes in all male AMI patients in Norway. Invasive treatment was defined as performed angiography with or without percutaneous coronary intervention or coronary artery bypass graft surgery. Standardized mortality (SMR) and incidence ratios, and logistic regression were used to evaluate the association between PCa risk groups and invasive treatment. Results: In 1,018 patients with PCa of all risk groups, the total rates of invasive treatment for AMIs were similar to the rates in the general AMI population. In patients with ST-segment elevation AMIs, rates were lower in metastatic PCa compared to localized PCa (OR 0.15, 95% CI: 0.04–0.49). For non-ST-segment elevation AMIs, there were no differences between PCa risk groups. The 30-day mortality after AMI was lower in PCa patients than in the total population of similarly aged AMI patients (SMR 0.77, 95% CI: 0.61–0.97). Conclusion: Except for patients with metastatic PCa experiencing an ST-segment elevation AMI, PCa patients were treated as frequent with invasive treatment for their AMI as the general AMI population. 30-day all-cause mortality was lower after AMI in PCa patients compared to the general AMI population. [ABSTRACT FROM AUTHOR]

Background: Drug-eluting stents (DES) reduce target lesion revascularization (TLR) with no effect on mortality or myocardial infarction (MI) compared to bare-metal stents (BMS) in native vessels. Randomized stent studies in saphenous vein grafts (SVG) are few and the reported effects are ambiguous. The Norwegian Coronary Stent Trial study is the first to randomize lesions to percutaneous coronary intervention in native vessels and SVG. Aims: The aim of this study was to compare the rate of mortality, MI, and TLR across stent and vessel types. Methods: In this substudy, 6,087 patients with a single lesion in native vessels and 164 in SVG were followed for 5 years. Results: MI was more frequent in SVG (subdistributional hazard ratio [SHR] 4.95 (3.75–6.54, p < 0.001), but not affected by stent type. In the first 500 days, DES reduced TLR in native vessels (SHR 0.21 (0.15–0.30) p < 0.001) and SVG (SHR 0.18 (0.04–0.80) p = 0.02). Thereafter, DES and BMS were equivalent in native vessels, but DES had a higher TLR rate than BMS in SVG (SHR 3.31 (1.23–8.94) p = 0.02). After 5 years, the TLR rate was still significantly lower for DES in native vessels (3.2% vs. 7.8%, p < 0.001) but not in SVG (21.4% vs. 18. 4%). Conclusion: In SVG, no difference in TLR between DES and BMS was observed after 5 years in contrast to persistent benefit in native vessels. The high rate of TLR and MI in SVG makes treatment of native vessels a preference whenever feasible and better treatment options for SVG are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study. Patients and Methods: Using the Tromsø Study Cardiovascular Disease Register for 2013– 2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test. Results: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8– 99.2) and a sensitivity of 88.2% (95% CI 82.0– 92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6– 98.8) and the sensitivity was 85.6% (95% CI 79.0– 90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1– 98.9) and a sensitivity of 91.5% (95% CI 85.9– 95.4). Conclusion: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromsø Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area. [ABSTRACT FROM AUTHOR]

Introduction: Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT). Materials and methods: NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008–11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3–5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models. Results: The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15). Conclusions: The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk. Clinical trial registration: Unique identifier NCT00811772; http://www.clinicaltrial.gov. [ABSTRACT FROM AUTHOR]

Background: Disease-specific registers may be used for measuring and improving healthcare and patient outcomes, and for disease surveillance and research, provided they contain valid and reliable data. The aim of this study was to assess the interrater reliability of all variables in a national myocardial infarction register. Methods: We randomly selected 280 patients who had been enrolled from 14 hospitals to the Norwegian Myocardial Infarction Register during the year 2013. Experienced audit nurses, who were blinded to the data about the 280 patients already in the register, completed the Norwegian Myocardial Infarction paper forms for 240 patients by review of medical records. We then extracted all registered data on the same patients from the Norwegian Myocardial Infarction Register. To compare the interrater reliability between the register and the audit nurses, we calculated intraclass correlations coefficient for continuous variables, Cohen's kappa and Gwet's first agreement coefficient (AC1) for nominal variables, and quadratic weighted Cohen's kappa and Gwet's second AC for ordinal variables. Results: We found excellent (AC1 >0.80) or good (AC1 0.61-0.80) agreement for most variables, including date and time variables, medical history, investigations and treatments during hospitalization, medication at discharge, and ST-segment elevation or non-ST-segment elevation acute myocardial infarction. However, only moderate agreement (AC1 0.41-0.60) was found for family history of coronary heart disease, diagnostic electrocardiography, and complications during hospitalization, whereas fair agreement (AC1 0.21-0.40) was found for acute myocardial infarction location. A high percentage of missing data was found for symptom onset, family history, body mass index, infarction location, and new Q-wave. Conclusion: Most variables in Norwegian Myocardial Infarction Register had excellent or good reliability. However, some important variables had lower reliability than expected or had missing data. Precise definitions of data elements and proper training of data abstractors are necessary to ensure that clinical registries contain valid and reliable data. [ABSTRACT FROM AUTHOR]

High blood pressure is a modifiable risk factor for cardiovascular disease. Previous studies showing a blood pressure decline in recent decades lack data to follow individuals born in different decades from early and middle adulthood to older age. We investigated changes in age-specific blood pressure by repeated measurements in 37 973 women and men born 1905 to 1977 (aged 20–89 years) examined ≤5× between 1979 and 2008 in the population-based Tromsø Study. Mixed models were used to estimate time trends. Mean systolic and diastolic blood pressure decreased from 1979 to 2008 in both genders in the age groups 30 to 89 years. The decrease was similar in the 80th percentile and the 20th percentile of the population blood pressure distribution. The decrease in systolic blood pressure in age group 40 to 49 years was 10.6 mm Hg in women and 4.5 mm Hg in men. Systolic blood pressure increased with age in women and men born 1920 to 1949, whereas a decrease or flattening of curve was observed in the younger birth cohorts. Thus, we found both time periodic and cohort effects, and trends were more pronounced in women than in men. The findings suggest changes in blood pressure in the population rather than an effect of treatment of high-risk individuals. [ABSTRACT FROM AUTHOR]

The article discusses a research which examines the association of multiple protein biomarkers with the 10-year risk of incident first-ever myocardial infarction (MI) and identifies a clinically significant risk model in samples from a longitudinal study of men and women in Tromsø, Norway. The study found several clinically significant biomarkers adjusted for traditional risk factors including apolipoprotein B/apolipoprotein A1 ratio, kallikrein, and matrix metalloproteinase 9.

The article focuses on comparison of comparing contemporary bare-metal stents (BMS) and second-generation drug-eluting stents (DES) inpatients with stable or unstable coronary artery disease, done by Norwegian Coronary Stent Trial (NORSTENT). Topics discussed are test conducted on the basis of factors such as sex, age and medical history, European guidelines for safety outcomes, and growing evidence of stent thrombosis in DES stents compared to BMS stents.

The article presents a study on the relationship between blood levels of folate, vitamin B12, homocysteine and vitamin B12 transport proteins, and prostate cancer risk. The case-control study was done by investigating prostate-specific antigen-detected prostate cancer of the Prostate Testing for Cancer and Treatment in Great Britain, which measured 1,461 cases and 1,507 controls. The authors found that increased risk for prostate cancer can be attributed to vitamin B12 and folate based on the cohort studies in Great Britain.

The article offers information on a study which investigated the effects of treatment with B vitamins on cancer outcomes and all-cause mortality. A total of 6837 patients were recruited to participate in two randomized, double-blind, placebo-controlled clinical trials conducted in Norway between 1998 and 2005, and followed up through December 31, 2007. Treatment interventions included oral treatment with folic acid combined with vitamin B12 and vitamin 6, folic acid combined with vitamin B12, vitamin 6 alone and placebo. Presented in details are the research findings.

The article offers information on a study which investigated the effects of treatment with B vitamins on cancer outcomes and all-cause mortality. A total of 6837 patients were recruited to participate in two randomized, double-blind, placebo-controlled clinical trials conducted in Norway between 1998 and 2005, and followed up through December 31, 2007. Treatment interventions included oral treatment with folic acid combined with vitamin B12 and vitamin 6, folic acid combined with vitamin B12, vitamin 6 alone and placebo. Presented in details are the research findings.

Introduction: Diabetes is associated with increased risk of coronary heart disease (CHD). The relative risk has been found to be higher in women than men, and the more pronounced adverse effect has even been claimed to eliminate the female advantage in risk. However, few previous studies have quantified the difference in risk between men and women among individuals with diabetes. Aims: To evaluate interaction between gender and diabetes in relation to the risk of incident myocardial infarction (MI). Methods: Population-based prospective study of 33,859 individuals (51% women) in Tromsø, Norway. Median follow-up time at ages 35-94 years was 17.6 years; 2,746 individuals (854 women) were diagnosed with MI during follow-up. At their last visit, a total of 1063 individuals (3.1%) reported they had diabetes (530 men, 533 women); 170 (74 women) were later diagnosed with MI. Incidence rate ratios (IRR) were calculated as estimates of relative risk in Poisson regression analysis of person-years at risk. Interaction terms were included in the model to evaluate heterogeneity in risk estimates across subgroups. Results: Adjusted for age, gender and established CHD risk factors, diabetes was associated with a doubling in risk of MI (IRR=2.18, 95% CI=1.86-2.55). The adverse effect was slightly more pronounced for women than men (IRR of 2.55 vs. 1.96, p=0.11, test for interaction). Accordingly, the gender contrast in risk was less pronounced among individuals with diabetes (IRR of 1.63 vs 2.11), but the elevated risk in men remained significant. Considering combined categories of interacting factors, women with diabetes had a risk level close to men without diabetes, but men with diabetes had a risk about four times as high as women without diabetes. Some heterogeneity across age groups was seen, but risk estimates were imprecise. These results are preliminary. Gender heterogeneity in associations with adjustment factors may influence risk estimates. Analyses based on data with 5 year extended follow-up are planned. Conclusions: In terms of relative risk, the association between diabetes and risk of MI was more pronounced for women than men, but the female advantage in risk of MI was not erased in persons with diabetes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate determinants of reperfusion within recommended time limits (timely reperfusion) for ST-segment elevation myocardial infarction patients, exploring the impact of geography, patient characteristics and socio-economy., Design: National register-based cohort study., Setting: Multilevel logistic regression models were applied to examine the associations between timely reperfusion and residency in hospital referral areas and municipalities, patient characteristics, and socio-economy., Participants: 7607 Norwegian ST-segment elevation myocardial infarction patients registered in the Norwegian Registry of Myocardial Infarction during 2015-2018., Main Outcome Measures: The odds of timely reperfusion by primary percutaneous coronary intervention (PCI) or fibrinolysis., Results: Among 7607 ST-segment elevation myocardial infarction patients in Norway, 56% received timely reperfusion. The Norwegian goal is 85%. While 81% of the patients living in the Oslo hospital referral area received timely reperfusion, only 13% of the patients living in Finnmark did so.Patients aged 75-84 years had lower odds of timely reperfusion than patients below 55 years of age (OR 0.73, 95% CI 0.61 to 0.87). Patients with moderate or high comorbidity had lower odds than patients without (OR 0.81, 95% CI 0.68 to 0.95 and OR 0.61, 95% CI 0.44 to 0.84). More than 2 hours from symptom onset to first medical contact gave lower odds than less than 30 min (OR 0.63, 95% CI 0.54 to 0.72). 1-2 hours of travel time to a PCI centre (OR 0.39, 95% CI 0.31 to 0.49) and more than 2 hours (OR 0.22, 95% CI 0.16 to 0.30) gave substantially lower odds than less than 1 hour of travel time., Conclusions: The varying proportion of patients receiving timely reperfusion across hospital referral areas implies inequity in fundamental healthcare services, not compatible with established Norwegian health policy. The importance of travel time to PCI centre points at the expanded use of prehospital pharmacoinvasive strategy to obtain the goals of timely reperfusion in Norway., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiovascular disease and cancer have been described as possible risk factors for COVID-19 mortality. The purpose of this study was to investigate whether a history of cardiovascular disease or cancer affects the risk of dying after a COVID-19 diagnosis in Norway., Material and Method: Data were compiled from the Norwegian Surveillance System for Communicable Diseases, the Norwegian Cardiovascular Disease Registry and the Cancer Registry of Norway. Univariable and multivariable regression models were used to calculate both relative and absolute risk., Results: In the first half of 2020, 8 809 people tested positive for SARS-CoV-2 and 260 COVID-19-associated deaths were registered. Increasing age, male sex (relative risk (RR): 1.5; confidence interval (CI): 1.2-2.0), prior stroke (RR: 1.5; CI: 1.0-2.1) and cancer with distant metastasis at the time of diagnosis (RR: 3.0; CI: 1.1-8.2) were independent risk factors for death after a diagnosis of COVID-19. After adjusting for age and sex, myocardial infarction, atrial fibrillation, heart failure, hypertension, and non-metastatic cancer were no longer statistically significant risk factors for death., Interpretation: The leading risk factor for death among individuals who tested positive for SARS-CoV-2 was age. Male sex, and a previous diagnosis of stroke or cancer with distant metastasis were also associated with an increased risk of death after a COVID-19 diagnosis.

Background: ST-elevation myocardial infarction is treated with reperfusion, either in the form of primary percutaneous coronary intervention (PCI) or thrombolytic therapy. The choice of treatment depends on transport time to the nearest PCI centre. Norway's geography means that thrombolytic therapy will be appropriate for many patients. Irrespective of treatment choice, it is important to avoid delays. We wished to compare the outcomes of primary PCI and thrombolytic therapy in our healthcare region and to examine whether reperfusion therapy was administered within the recommended time window., Material and Method: Using registry data and patient medical records, we compared the outcomes of primary PCI and thrombolytic therapy in cases of ST-elevation myocardial infarction in the Central Norway Regional Health Authority in the period 2015-16. The outcomes analysed were 30-day mortality, ejection fraction measured by echocardiography during the hospital stay, incidence of bleeding complications, and time from diagnosis to start of treatment., Results: The study population comprised 648 patients with ST-elevation myocardial infarction. Of these, 382 were treated with primary PCI and 266 received thrombolytic therapy. The 30-day mortality was 5.5 % in the primary PCI group and 5.6 % in the thrombolysis group (p = 1.0). There were no significant differences in ejection fraction and no cases of serious bleeding. In 45 % of the total population, reperfusion therapy was started later than recommended in guidelines., Interpretation: There was no statistically significant difference in mortality or ejection fraction when comparing primary PCI and thrombolytic therapy in an unselected population with ST-elevation myocardial infarction. Many patients experienced delayed start of treatment . It is important to take action to reduce delays at all stages of the therapeutic chain. Thrombolytic therapy should be considered when it is unclear whether transport time to a PCI centre will exceed that recommended in guidelines.

Objectives: Elevated blood cholesterol is a modifiable risk factor for cardiovascular disease. Cholesterol level surveillance is necessary to study population disease burden, consider priorities for prevention and intervention and understand the effect of diet, lifestyle and treatment. Previous studies show a cholesterol decline in recent decades but lack data to follow individuals born in different decades throughout life., Methods: We investigated changes in age-specific and birth cohort-specific total cholesterol (TC) levels in 43 710 women and men born in 1905-1977 (aged 20-95 years at screening) in the population-based Tromsø Study. Fifty-nine per cent of the participants had more than one and up to six repeated TC measurements during 1979-2016. Linear mixed models were used to test for time trends., Results: Mean TC decreased during 1979-2016 in both women and men and in all age groups. The decrease in TC in age group 40-49 years was 1.2 mmol/L in women and 1.0 mmol/L in men. Both the 80th and the 20th percentile of the population TC distribution decreased in both sexes and all age groups. Longitudinal analysis showed that TC increased with age to a peak around middle age followed by a decrease. At any given age, TC significantly decreased with increase in year born. Lipid-lowering drug use was rare in 1994, increased thereafter, but was low (<3% in women and <5% in men) among those younger than 50 years in all surveys. Between 1994 and 2016, lipid-lowering drug treatment in individuals 50 years and older explained 21% and 28% of the decrease in TC levels in women and men, respectively., Conclusions: We found a substantial decrease in mean TC levels in the general population between 1979 and 2016 in all age groups. In birth cohorts, TC increased with age to a peak around middle age followed by a decrease., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Disease-specific registers may be used for measuring and improving healthcare and patient outcomes, and for disease surveillance and research, provided they contain valid and reliable data. The aim of this study was to assess the interrater reliability of all variables in a national myocardial infarction register., Methods: We randomly selected 280 patients who had been enrolled from 14 hospitals to the Norwegian Myocardial Infarction Register during the year 2013. Experienced audit nurses, who were blinded to the data about the 280 patients already in the register, completed the Norwegian Myocardial Infarction paper forms for 240 patients by review of medical records. We then extracted all registered data on the same patients from the Norwegian Myocardial Infarction Register. To compare the interrater reliability between the register and the audit nurses, we calculated intraclass correlations coefficient for continuous variables, Cohen's kappa and Gwet's first agreement coefficient (AC1) for nominal variables, and quadratic weighted Cohen's kappa and Gwet's second AC for ordinal variables., Results: We found excellent (AC1 >0.80) or good (AC1 0.61-0.80) agreement for most variables, including date and time variables, medical history, investigations and treatments during hospitalization, medication at discharge, and ST-segment elevation or non-ST-segment elevation acute myocardial infarction. However, only moderate agreement (AC1 0.41-0.60) was found for family history of coronary heart disease, diagnostic electrocardiography, and complications during hospitalization, whereas fair agreement (AC1 0.21-0.40) was found for acute myocardial infarction location. A high percentage of missing data was found for symptom onset, family history, body mass index, infarction location, and new Q-wave., Conclusion: Most variables in Norwegian Myocardial Infarction Register had excellent or good reliability. However, some important variables had lower reliability than expected or had missing data. Precise definitions of data elements and proper training of data abstractors are necessary to ensure that clinical registries contain valid and reliable data.

Background: A seasonal pattern with higher winter morbidity and mortality has been reported for acute myocardial infarction (MI). The magnitude of the difference between peak and nadir season has been associated with latitude, but results are inconsistent. Studies of seasonal variation of MI in population-based cohorts, based on adjudicated MI cases,are few.We investigated the monthly and seasonal variation in first-ever nonfatal and fatal MI in the population of Tromsø in northern Norway, a region with a harsh climate and extreme seasonal variation in daylight exposure., Design: Prospective population-based cohort study., Methods: A total of 37 392 participants from the Tromsø Study enrolled between 1974 and 2001 were followed throughout 2004. Each incident case of MI was validated by the review of medical records and death certificates. MI incidence rates for months and seasons were analyzed for seasonal patterns with Poisson regression and the Cosinor procedure. All analyses were stratified by sex, age and smoking status., Results: A total of 1893 first-ever MIs were registered, of which 592 were fatal. There was an 11 % (95% confidence interval: 1.00-1.23, P=0.04) increased risk of incident MI during winter (November-January) compared with non-winter seasons, with no statistically significant interaction with sex, age, smoking or calendar year. Other seasonal modelling gave similar but not statistically significant results., Conclusion: We found a small increase in risk of incident MI during the darkest winter months. Populations living in sub-Arctic areas may be adapted to face climate exposure during winter through behavioural protection.

Background: Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B(12), and related metabolites were associated with prostate cancer risk., Methods: Matched case-control study nested within the U.K. population-based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen-detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B(12) (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B(12), and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review., Results: In the ProtecT study, increased B(12) and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B(12) odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); P(trend) = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); P(trend) = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B(12) levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B(12); P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02]., Conclusion: Vitamin B(12) and (in cohort studies) folate were associated with increased prostate cancer risk., Impact: Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations., (Copyright 2010 AACR.)

Background: Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction., Methods: The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease., Results: The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05)., Conclusions: Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.)., (Copyright 2006 Massachusetts Medical Society.)