Heart Failure Complicating Acute Myocardial Infarction; Burden and Timing of Occurrence: A Nation-wide Analysis Including 86 771 Patients From the Cardiovascular Disease in Norway (CVDNOR) Project

Background: Coronary heart disease (CHD) represents often the underlying conditions for the development of heart failure (HF). We aimed at exploring the burden and timing of HF complicating an acute myocardial infarction (AMI), using the total population of AMI patients hospitalized during 2001–2009 in Norway. Methods and Results: A total of 86 771 patients with a first AMI during 2001–2009 and without previous HF were identified in the “Cardiovascular Disease in Norway” project and followed until HF development, death, or December 31, 2009. In 16 219 patients (18.7%), HF was present on admission or developed during hospitalization for the incident AMI. HF occurrence varied according to age (8.9%, 15.2%, and 25.6% among men and 10.2%, 16.8%, and 27.1% among women ages 25–54, 55–74, and 75–85 years). Among 63 853 patients discharged alive without HF, 8058 (12.6%) were hospitalized with or died because of HF during a median follow‐up time of 3.2 years. HF incidence rates (IRs) per 1000 person‐years during follow‐up were 31 (95% CI, 30–32) for men and 46 (95% CI, 44–47) for women (P<0.01). IRs of HF were highest during the first 6 months of follow‐up, after which they leveled off and remained stable until the end of follow‐up. Conclusions: In this nation‐wide cohort study, we observed that HF remains a frequent complication of the first AMI; both during the acute phase and shortly after the discharge from the hospital.publishedVersio

Interrelation between rifting, faulting, sedimentation, and mantle serpentinization during continental margin formation-including examples from the Norwegian Sea

The conditions permitting mantle serpentinization during continental rifting are explored within 2-D thermotectonostratigraphic basin models, which track the rheological evolution of the continental crust, account for sediment blanketing effects, and allow for kinetically controlled mantle serpentinization processes. The basic idea is that the entire extending continental crust has to be brittle for crustal scale faulting and mantle serpentinization to occur. The isostatic and latent heat effects of the reaction are fully coupled to the structural and thermal solutions. A systematic parameter study shows that a critical stretching factor exists for which complete crustal embrittlement and serpentinization occurs. Increased sedimentation rates shift this critical stretching factor to higher values as sediment blanketing effects result in higher crustal temperatures. Sediment supply has therefore, through the temperature-dependence of the viscous flow laws, strong control on crustal strength and mantle serpentinization reactions are only likely when sedimentation rates are low and stretching factors high. In a case study for the Norwegian margin, we test whether the inner lower crustal bodies (LCB) imaged beneath the Møre and Vøring margin could be serpentinized mantle. Multiple 2-D transects have been reconstructed through the 3-D data set by Scheck-Wenderoth and Maystrenko (2011). We find that serpentinization reactions are possible and likely during the Jurassic rift phase. Predicted thicknesses and locations of partially serpentinized mantle rocks fit to information on LCBs from seismic and gravity data. We conclude that some of the inner LCBs beneath the Norwegian margin may be partially serpentinized mantle

Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials

Homocysteine-lowering clinical trials in Norway. Cardiovascular and cancer outcomes in the Western Norway B Vitamin Intervention Trial and the Norwegian Vitamin Trial

Introduction: Observational studies have reported associations between levels of the amino acid homocysteine in the circulation and risk of cardiovascular disease. Oral administration of the synthetic B vitamins folic acid and cyanocobalamin (vitamin B12) can lower plasma total homocysteine levels. In the Western Norway B Vitamin Intervention Trial (WENBIT) and the Norwegian Vitamin Trial (NORVIT), patients with ischemic heart disease were randomized to groups receiving folic acid plus vitamin B12, or no such treatment, to assess whether they would benefit from lowered homocysteine levels with respect to major adverse clinical events, such as myocardial infarction, stroke, cardiovascular death or all-cause death. Using a 2 x 2 factorial design, participants were also randomized to groups receiving vitamin B6 or no vitamin B6. Aims: The overall aim of the present dissertation was to investigate the clinical effects of B vitamin treatment in patients with established ischemic heart disease. Materials and methods: We used clinical and laboratory data on 6837 patients with ischemic heart disease, recruited from 36 hospitals in Norway (1998 to 2004) collected during in-trial followup, and data on cancer incidence and cause-specific and all-cause mortality on these patients collected during extended follow-up throughout the year 2007. Clinical outcomes were analyzed for groups assigned to folic acid plus vitamin B12 treatment vs no folic acid/vitamin B12, and for groups assigned to vitamin B6 treatment vs no vitamin B6. Survival curves were constructed using the Kaplan-Meier method, and estimates of hazard ratios with confidence intervals were obtained using Cox proportional hazards regression. Results: Folic acid plus vitamin B12 treatment lowered plasma total homocysteine substantially in both trial populations. In the WENBIT study population, this treatment was not associated with the incidence of major adverse cardiovascular events or all-cause mortality during in-trial follow-up of median 38 months. In the combined NORVIT-WENBIT study population, it was not associated with the incidence of major adverse cardiovascular events or any of its constituents (myocardial infarction, stroke or cardiovascular death) during in-trial follow-up of median 39 months, or associated with long-term cardiovascular mortality during extended follow-up of median 78 months. However, among NORVIT-WENBIT participants with hyperhomocysteinemia at baseline, treatment with folic acid plus vitamin B12 was associated with increased risk of in-trial major cardiovascular events, and of long-term cardiovascular mortality. Exploratory analyses in NORVITWENBIT showed that baseline plasma total homocysteine was not independently associated with cardiovascular outcomes, whereas homocysteine measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of in-trial major cardiovascular events. In the combined NORVIT-WENBIT study population, folic acid plus vitamin B12 treatment was associated with increased cancer incidence, cancer mortality and allcause mortality during extended follow-up of median 78 months. These findings were consistent in both trial populations, among patients with age below or above the median, in both genders, among never and ever smokers and among patients with baseline serum folate level below or above the median. However, hazard ratios for folic acid plus vitamin B12 treatment vs no such treatment were higher among individuals with the TT genotype than among those with the CC or CT genotypes of the methylenetetrahydrofolate reductase 677C→T polymorphism. Vitamin B6 treatment led to a 10-fold increase in plasma levels of pyridoxal 5’ phosphate in both trial populations, but was not associated with outcomes during intrial follow-up in the WENBIT study population, or with any outcomes during in-trial or extended follow-up of the combined NORVIT-WENBIT study population. Discussion and conclusions: Our findings with respect to cardiovascular outcomes are consistent with the null effects of homocysteine-lowering B vitamin treatment demonstrated in large randomized controlled trials to date. The increased risk of cardiovascular outcomes by folic acid plus vitamin B12 among patients with baseline hyperhomocysteinemia was contrary to what would be expected if homocysteine has a causal role in cardiovascular disease progression. Thus, B vitamins to lower homocysteine should not be recommended for patients with cardiovascular disease. The increased cancer incidence and cancer mortality during extended follow-up observed in the groups who received folic acid plus vitamin B12 for median 39 months may be explained by the so-called acceleration phenomenon; that this treatment influenced growth in cancers that were silent at baseline or during trials, leading to excess subsequent clinical surfacing and diagnosis during extended followup. However, reports on cancer outcomes from other completed homocysteinelowering B vitamin treatment trials to date do not support our findings, and our results need confirmation in other populations