Serum magnesium and the risk of death from coronary heart disease and sudden cardiac death

Background-Low serum magnesium has been implicated in cardiovascular mortality, but results are conflicting and the pathway is unclear. We studied the association of serum magnesium with coronary heart disease (CHD) mortality and sudden cardiac death (SCD) within the prospective population-based Rotterdam Study, with adjudicated end points and long-term follow-up. Methods and Results-Nine-thousand eight-hundred and twenty participants (mean age 65.1 years, 56.8% female) were included with a median follow-up of 8.7 years. We used multivariable Cox proportional hazard models and found that a 0.1 mmol/L increase in serum magnesium level was associated with a lower risk for CHD mortality (hazard ratio: 0.82, 95% CI 0.70-0.96). Furthermore, we divided serum magnesium in quartiles, with the second and third quartile combined as reference group (0.81-0.88 mmol/L). Low serum magnesium (=0.80 mmol/L) was associated with an increased risk of CHD mortality (N=431, hazard ratio: 1.36, 95% CI 1.09-1.69) and SCD (N=217, hazard ratio: 1.54, 95% CI 1.12-2.11). Low serum magnesium was associated with accelerated subclinical atherosclerosis (expressed as increased carotid intima-media thickness: +0.013 mm, 95% CI 0.005-0.020) and increased QT-interval, mainly through an effect on heart rate (RR-interval: -7.1 ms, 95% CI -13.5 to -0.8). Additional adjustments for carotid intima-media thickness and heart rate did not change the associations with CHD mortality and SCD. Conclusions-Low serum magnesium is associated with an increased risk of CHD mortality and SCD. Although low magnesium was associated with both carotid intima-media thickness and heart rate, this did not explain the relationship between serum magnesium and CHD mortality or SCD. Future studies should focus on why magnesium associates with CHD mortality and SCD and whether intervention reduces these risks

The effect of methionine on the uptake, distribution, and binding of the convulsant methionine sulfoximine in the rat

The effect of methionine on the uptake, distribution, and binding of the convulsant methionine sulfoximine (MSO) in 7 rat brain regions, the spinal cord, the liver, and the kidney was investigated. The administration of methionine decreased the uptake of MSO in all brain regions. The uptake of MSO by and its distribution in the nervous tissue was uniform and failed to result in any preferential accumulation of the drug. Methionine decreased the amount of MSO bound to cerebral structures and to the spinal cord. MSO bound to the spinal cord was less susceptible to release by Triton X-100 than was brain-bound MSO.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45398/1/11064_2004_Article_BF00965631.pd

Sudden cardiac death prediction in arrhythmogenic right ventricular cardiomyopathy: a multinational collaboration

Background:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD.Methods:We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (>= 30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping.Results:A total of 864 patients with definite ARVC (40 +/- 16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism.Conclusions:LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.Cardiolog

Validated inference of smoking habits from blood with a finite DNA methylation marker set

Inferring a person’s smoking habit and history from blood is relevant for complementing or replacing self-reports in epidemiological and public health research, and for forensic applications. However, a finite DNA methylation marker set and a validated statistical model based on a large dataset are not yet available. Employing 14 epigenome-wide association studies for marker discovery, and using data from six population-based cohorts (N = 3764) for model building, we identified 13 CpGs most suitable for inferring smoking versus non-smoking status from blood with a cumulative Area Under the Curve (AUC) of 0.901. Internal fivefold cross-validation yielded an average AUC of 0.897 ± 0.137, while external model validation in an independent population-based cohort (

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Combined influence of proton-pump inhibitors, calcium-channel blockers and CYP2C19*2 on on-treatment platelet reactivity and on the occurrence of atherothrombotic events after percutaneous coronary intervention

Background: The carriage of CYP2C19*2 and the use of proton-pump inhibitors (PPIs) and calcium-channel blockers (CCBs) has been associated with the diminished efficacy of clopidogrel. However, previous studies have only assessed the isolated impact of these risk factors for clopidogrel poor response. Objectives: The aim of the present study was to investigate the impact of the combined presence of three risk factors for clopidogrel poor response, that is, the use of CCBs, PPIs and the carriage of CYP2C19*2, on on-treatment platelet reactivity and the occurrence of atherothrombotic events in 725 patients on dual antiplatelet therapy undergoing elective coronary stenting. Methods: In a prospective, follow-up study, on-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. The clinical study endpoint was the composite of all-cause mortality, myocardial infarction, stent thrombosis and stroke at 1year after stenting. Results: Patients with either one or more than one risk factor exhibited increased platelet reactivity (mean relative increase one risk factor: 11% and >1 risk factor: 22%, respectively). Sixty-four events occurred during follow-up (8.8% of the study population). Patients with one risk factor for clopidogrel poor response did not have an increased risk of the composite endpoint. However, patients using both CCBs and PPIs and carriers of CYP2C19*2 who used CCBs had a statistically significant increased risk of the composite endpoint [hazard ratio(HR)adj2.2 95% CI, 1.0-5.3, P=0.044 and HRadj3.3 95% CI, 1.1-9.8, P=0.032, respectively]. Conclusions: The presence of more than one of the three investigated risk factors for clopidogrel poor response is associated with an increased risk of adverse cardiovascular events within 1year after elective coronary stenting. © 2011 International Society on Thrombosis and Haemostasis