G.D.O. Lowe's research while affiliated with University of Glasgow and other places

Publications (864)

Article
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We examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60–79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow‐up period of 18 years, there were 149 confirmed cases of fatal or non‐fatal V...
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The associations of plasma levels of haemostatic factors, other than fibrinogen, with risks of cardiovascular disease and all-cause mortality are not well defined. In two phases of the Glasgow MONICA Study, we assayed coagulation factors (VII, VIII, IX and von Willebrand factor, VWF), coagulation inhibitors (antithrombin, protein C, protein S), coa...
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The associations of plasma levels of hemostatic factors, other than fibrinogen, with risks of cardiovascular disease (CVD) and all-cause mortality are not well defined. In two phases of the Glasgow MONICA study, we assayed coagulation factors (VII, VIII, IX, and von Willebrand factor), coagulation inhibitors (antithrombin, protein C, protein S), co...
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eAppendix. Outcome definitions. eTable 1. Cohort-specific summaries of selected characteristics and recorded outcomes. eTable 2. Hazard ratios for VTE per 1-SD higher usual risk factor value or group contrast, with and without adjustment for BMI. eFigure 1. Hazard ratios for fatal/nonfatal VTE by alcohol consumption among current drinkers in UK Bio...
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Importance It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants This study included individual participant data...
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Objective To examine the long-term predictive value of 28 biomarkers for subsequent non-ischaemic congestive heart failure (CHF) and separately for other cardiovascular outcomes (myocardial infarction (MI) and stroke). Methods The Caerphilly Prospective Study recruited 2171 men aged 55–69 years from the general population in 1989–1993; men were sc...
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Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by divers...
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Genomic inflation factors by study and imputation panel. (XLSX)
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Quantile-Quantile (QQ) plots comparing the HapMap and 1000G GWA studies. (DOCX)
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Regional plots of overlapping signals that were significant in both the HapMap (red) and 1000G (green) GWA studies. (DOCX)
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Differences between HapMap and 1000G for loci with a correlation R2 < 0.8 between imputed dosages of the HapMap and 1000G lead variants. (XLSX)
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Comparison of lead variants of the HapMap and 1000G GWA studies of significant loci. (DOCX)
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Annotation of loci significant in the HapMap GWA study, 1000G GWA study, or both. (XLSX)
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Characteristics of the included studies and their participants. (XLSX)
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Loci that were significant in either the HapMap or 1000G GWA studies with genomic control corrections. (XLSX)
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Sample and array type used for the fibrinogen measurement in each of the included studies. (XLSX)
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Genotyping and imputation methods of the included studies. (XLSX)
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An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap...
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Correlation between the lead variants from the HapMap and 1000G GWA studies. (XLSX)
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Manhattan plot comparing the HapMap (red) and 1000G (green) GWA studies. (DOCX)
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Analysis software and covariates used by the included studies. (XLSX)
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Loci that were significant in either the HapMap or 1000G GWAS excluding studies that did not use the same imputation software, analysis software, or covariates. (XLSX)
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Aims: Chronic heart failure (HF) is associated with activation of blood coagulation but there is a lack of prospective studies on the association between coagulation markers and incident HF in general populations. We have examined the association between the coagulation markers fibrinogen, von Willebrand Factor (VWF), Factors VII, VIII and IX, D-d...
Article
Introduction: Studies on the prevalence of cardiovascular disease (CVD) and risk factors in patients with haemophilia (PWH) in comparison to the general population have generated inconsistent results. The ADVANCE Working Group collected data on CV comorbidities in PWH aged ≥40 years (H(3) Study). Aim: Identification of German epidemiological dat...
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We have previously shown that there is a complex and dynamic biological interaction between acute mental stress and acute release of inflammatory factors into the blood stream in relation to heart disease. We now hypothesize that the presence of chronic psychosocial stress may modify the weight of single test results for inflammation as a predictor...
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Background and objective: Recent studies suggest perivascular spaces are a marker of small vessel disease, blood-brain barrier permeability, and inflammation, but little is known about their risk factors and associations with peripheral blood markers. Materials and methods: In prospectively recruited patients with recent minor ischemic stroke, w...
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Objective: Higher systemic levels of proinflammatory biomarkers and low adiponectin are associated with increased risk for type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers associated with 5-year changes in glucos...
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Background: Heightened blood pressure (BP) responses to mental stress predict raised BP levels over subsequent years, but evidence for associations with incident hypertension is limited, and the significance of inflammatory responses is uncertain. Purpose: We investigated the relationship between BP and plasma fibrinogen responses to stress and...
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The European Journal of Human Genetics is the official Journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports, News and Commentary articles and reviews in the rapidly expanding field of human genetics and genomics.
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Funding for this study was provided by the Academy of Finland (41071, 117787, 118065, 121584, 124282, 126925, 129494, 129322, 129378, 130326, 134309, 134791, 136895, 139635, 250207, 263836, 286284 and 263924); Ahokas Foundation; ALF/LUA research grant in Gothenburg; Amgen; Augustinus Foundation; Becket Foundation; Bristol-Myers Squibb; British Hear...
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Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association s...
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Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34...
Article
Low von Willebrand factor (VWF) levels are associated with bleeding symptoms and are a diagnostic criterion for von Willebrand disease, the most common inherited bleeding disorder. To date, it is unclear which genetic loci are associated with reduced VWF levels. Therefore, we conducted a meta-analysis of genome-wide association studies to identify...
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The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It...
Article
To examine a panel of 28 biomarkers for prediction of cardiovascular disease (CVD) and non-CVD mortality in a population-based cohort of men. Starting in 1979, middle-aged men in Caerphilly underwent detailed medical examination. Subsequently 2171 men were re-examined during 1989-1993, and fasting blood samples obtained from 1911 men (88%). Fibrino...
Article
Low levels of ADAMTS13 have been repeatedly associated with an increased risk of ischemic stroke but results for risk of myocardial infarction (MI) are inconclusive. To perform an individual patient data meta-analysis from observational studies investigating the association between ADAMTS13 levels and MI. A one step meta-analytic approach with rand...
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Plasma fibrinogen is considered as a positive mediator between mental stress and cardiovascular disease because it is an acute-phase protein released in response to mental stress and a coagulation factor. However those three factors have never been studied together within a single integrated framework, using cardiac troponin T as a marker of cardio...
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Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear. We examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress. Relative to high IL-6 levels, low level...
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Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is...
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Background: Hypercoagulability may be an important contributor to the pathophysiology of atherosclerosis and atherothrombosis. As thrombin fulfills a central role in coagulation and links to several cellular mechanisms involved in arterial disease, we hypothesized that thrombin generation is associated with cardiovascular events in elderly patient...
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Objectives To examine the independent relationships between fibrin D-dimer, interleukin 6 (IL-6), C-reactive protein (CRP), and fibrinogen and incident mobility limitation and mortality.DesignProspective.SettingGeneral practice in 24 British towns.ParticipantsMen aged 60 to 79 without prevalent heart failure followed up for an average of 11.5 years...
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Background Inflammation plays an important role in the cause of cardiovascular diseases and may contribute to the association linking an unhealthy diet to chronic age-related diseases. However, to date the long-term associations between diet and inflammation have been poorly described. Our aim was to assess the extent to which adherence to a health...
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Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916...
Article
Several haemostatic factors have been associated with incident arterial cardiovascular disease in prospective studies and meta-analyses. Plasma fibrinogen shows a strong and consistent association with risk; however, this may reflect its inflammatory marker status, and causality remains to be proven. The common haemostatic gene polymorphisms for fa...
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The aim is to examine the association of lifecourse socioeconomic position (SEP) on circulating levels of D-dimer. Data from the 1958 British birth cohort were used, social class was determined at three stages of respondents' life: at birth, at 23 and at 42 years. A cumulative indicator score of SEP (CIS) was calculated ranging from 0 (always in th...
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Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagul...
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Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide associa...
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C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6), are associated with cardiovascular disease and death in general populations. However, studies in type 2 diabetes are limited. We studied their associations with risk of major macrovascular events, microvascular complications and mortality in patients with type 2 diabetes who participat...
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Coagulation phenotypes show strong intercorrelations, affect cardiovascular disease risk and are influenced by genetic variants. The objective of this study was to search for novel genetic variants influencing the following coagulation phenotypes: factor VII levels, fibrinogen levels, plasma viscosity and platelet count. We genotyped the British Wo...
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Background: The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in...
Article
Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta-analysis of prospective studies. Interleukin-6 (IL-...
Article
Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease (CVD), range from 34 to 50%. Genetic variants so far identified by genome-wide association (GWA) studies only explain a small proportion (< 2%) of its variation. We conducted a meta-analysis of 28 GWA studies, including more than 90,...
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Purpose: There are few data assessing the relationship between circulating levels of C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) and the risk of vascular complications in individuals with type 2 diabetes mellitus (T2DM). We studied the associations between these inflammatory markers and the risk of major CV events (CV death, myoc...
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Thrombin is a key protease in coagulation also implicated in complex pathology including atherosclerosis. To address the role of thrombin in relation to myocardial infarction (MI) we explored thrombin generation analysis in plasma from patients and controls that had participated in the Glasgow MI Study (GLAMIS). Thrombin generation at 1 and 2 pM TF...
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Patients with bleeding disorders previously frequently became infected with hepatitis C virus. We identified the number of patients infected in Scotland and assessed several aspects of the outcomes of HCV infection and its treatment comparing these with cohorts infected for other reasons. We calculated the number of individuals infected in Scotland...
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There is strong evidence from meta-analyses of prospective epidemiological studies that increasing plasma fibrinogen levels are associated with an increasing risk of cardiovascular disease (CVD) and all-cause mortality. However, there are few published direct comparisons of the several different available fibrinogen assays in association with CVD o...
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Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
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Whiteley et al.(1) reported that higher level of circulating markers of the acute inflammatory response in acute stroke were associated with higher temperatures in normal brain. They found no association between blood markers of inflammation and brain temperature in different regions of brain. The authors measured 3 markers of inflammation: C-react...
Data
Estimated within-person variability of t-PA antigen, D-dimer and VWF by time since baseline measurement in the published literature. Abbreviations: ARIC, Atherosclerosis Risk in Communities Study; BRHS, British Regional Heart Study; EAS, Edinburgh Artery Study; Fletcher, Fletcher Challenge Study; Reykjavik, Reykjavik Study. Each point represents un...
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Search strategy used in the updated meta-analyses. (PDF)
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Funnel plots of reported associations of t-PA antigen, D-dimer and VWF with coronary heart disease risk. The dotted lines show 95% confidence intervals around the overall summary estimate calculated using fixed effect models. Egger’s test for regression asymmetry: t-PA antigen, P = 0.086; D-dimer, P = 0.004; VWF, P = 0.290. (PDF)
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Within-person variability of t-PA antigen, D-dimer and VWF plus other measured markers (mean time between repeated measurements, 11.6 years). (PDF)
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PRISMA 2009 Checklist. From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097. For more information, visit: www.prisma-statement.org. (PDF)
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Flow-chart of the Reykjavik Study. (PDF)
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Explorative analysis of effect modification of the associations of baseline levels of t-PA antigen, D-dimer and VWF with coronary heart disease risk in the Reykjavik study. Continuous variables were categorized based on tertile cut-offs in controls. All models are adjusted for age, sex, period of recruitment, smoking status, body mass index, systol...
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Cross-sectional correlates of baseline levels of D-dimer. (PDF)
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Meta-analyses of reported associations of t-PA antigen, D-dimer and VWF with coronary heart disease risk in population-based prospective studies. Where studies reported more than one odds ratio, the least adjusted estimate was used. Study acronyms are explained in the legend of Table 3. Summary estimates were calculated using random effects models....
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Systematic review and updated meta-analysis. (PDF)
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Investigation of sources of possible heterogeneity in reported associations of t-PA antigen, D-dimer and VWF with coronary heart disease risk, according to various study-level characteristics. Summary estimates were calculated using random effects models. *P values are from meta-regression for differences in odds ratios across studies in different...
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Cross-sectional correlates of baseline levels of t-PA antigen. (PDF)
Article
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Activation of blood coagulation and fibrinolysis may be associated with increased risk of coronary heart disease. We aimed to assess associations of circulating tissue plasminogen activator (t-PA) antigen, D-dimer and von Willebrand factor (VWF) with coronary heart disease risk. Prospective case-control study, systematic review and meta-analyses. M...
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Comparison of baseline characteristics of coronary heart disease cases, randomly selected controls and the overall Reykjavik cohort. *Controls were matched to coronary heart disease cases by sex and age (in five-year age bands) and therefore differ from the remainder of the Reykjavik cohort. (PDF)
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Cross-sectional correlates of baseline levels of VWF. (PDF)