Author
Maarten Leusink
Other affiliations: University Medical Center Utrecht
Bio: Maarten Leusink is an academic researcher from Utrecht University. The author has contributed to research in topics: Odds ratio & Population. The author has an hindex of 13, co-authored 19 publications receiving 1988 citations. Previous affiliations of Maarten Leusink include University Medical Center Utrecht.
Topics: Odds ratio, Population, Genome-wide association study, Asthma, Statin
Papers
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University College London1, University of Cambridge2, University of Cologne3, Leiden University4, Utrecht University5, National Institutes of Health6, University of Pennsylvania7, University of Glasgow8, University of Edinburgh9, Mayo Clinic10, University of London11, University of Bristol12, Cardiff University13, University of Oxford14, University of Ioannina15, University of Hamburg16, Lithuanian University of Health Sciences17, Jagiellonian University18, Russian Academy19, Karolinska Institutet20, Memorial Hospital of South Bend21, University of Groningen22, MedStar Washington Hospital Center23, Swansea University24, Brown University25, University of Iowa26, Harvard University27, University of Exeter28, University of North Carolina at Chapel Hill29, Boston University30, Medical Research Council31, University of California, San Diego32, University of Mississippi33, Fred Hutchinson Cancer Research Center34
TL;DR: IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials and could help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses.
891 citations
TL;DR: In this article, the causal role of alcohol consumption in cardiovascular disease was investigated using a Mendelian randomisation meta-analysis of 56 epidemiological studies, including 20 259 coronary heart disease cases and 10 164 stroke events.
Abstract: OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.
571 citations
Marcel den Hoed1, Mark Eijgelsheim2, Tõnu Esko3, Bianca J. J. M. Brundel4 +264 more•Institutions (85)
TL;DR: A 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci, providing fresh insights into the mechanisms regulating heart rate.
Abstract: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
332 citations
University College London1, French Institute of Health and Medical Research2, Pierre-and-Marie-Curie University3, Karolinska Institutet4, Utrecht University5, University of Edinburgh6, Utah System of Higher Education7, Brigham and Women's Hospital8, University of Amsterdam9, University of Pennsylvania10, Leiden University11, Erasmus University Rotterdam12, University of Leicester13, German Cancer Research Center14, University of Ulm15, Leipzig University16, University of Copenhagen17, University of Cambridge18, University of London19, University of Oxford20, Cyprus University of Technology21, University of Milan22, Ludwig Maximilian University of Munich23, University Medical Center Groningen24, Swansea University25, University of Leeds26, Linköping University27, Imperial College London28, University of Bristol29, University of Glasgow30, University of California, San Diego31, University of Colorado Denver32, Children's Hospital of Philadelphia33, McMaster University34, University of Warwick35
TL;DR: In this paper, the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease was investigated by using a Mendelian randomization meta-analysis of 19 general population studies and 10 acute coronary syndrome (ACS) cohorts.
109 citations
University of London1, University of Bern2, Lancaster University3, University of Warwick4, University College London5, University of Pennsylvania6, Wellcome Trust Centre for Human Genetics7, University of Glasgow8, University Medical Center Utrecht9, University of North Carolina at Chapel Hill10, St George's, University of London11, University of Bristol12, Fred Hutchinson Cancer Research Center13, University of Edinburgh14, Western General Hospital15, Heidelberg University16, University of Graz17, Lund University18, Utrecht University19, Clinical Trial Service Unit20, UCL Institute of Child Health21, University of Tromsø22
TL;DR: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.
Abstract: Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis.
Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D.
Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index (P < 0.001), triglycerides (P < 0.001), non high-density (non-HDL) cholesterol (P < 0.001), C-reactive protein (P = 0.042), and systolic blood pressure (P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity (P < 0.001 for both).
Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.
108 citations
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5,737 citations
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
Brigham and Women's Hospital1, Novartis2, Baylor College of Medicine3, Federal University of São Paulo4, Technische Universität München5, University of Amsterdam6, St. John's University7, University of Pavol Jozef Šafárik8, McGill University9, First Faculty of Medicine, Charles University in Prague10, University of Szeged11, Iuliu Hațieganu University of Medicine and Pharmacy12, University of East Anglia13, Tohoku University14, Sahlgrenska University Hospital15
TL;DR: Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid‐level lowering.
Abstract: BackgroundExperimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. MethodsWe conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. ResultsAt 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in t...
5,660 citations
TL;DR: This year's edition of the Statistical Update includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association’s 2020 Impact Goals.
Abstract: Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovas...
5,078 citations
TL;DR: ABI is ankle-brachial (blood pressure) index and ABPM is ambulatory blood pressure monitoring as mentioned in this paper ; ACCORD is action to control cardiovascular risk in Diabetes and Vascular disease.
Abstract: ABI
: ankle–brachial (blood pressure) index
ABPM
: ambulatory blood pressure monitoring
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ACE-I
: angiotensin-converting enzyme inhibitor
ACS
: acute coronary syndromes
ADVANCE
: Action in Diabetes and Vascular disease: PreterAx
4,352 citations