T W Meade's research while affiliated with London School of Hygiene and Tropical Medicine and other places
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Publications (299)
Aims
The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40–69 years in Europe.
Methods and results
We derived risk prediction models using individual-participant data from...
Aims: The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40–69 years in Europe. Methods and results: We derived risk prediction models using individual-participant data from...
Background:
We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.
Methods:
Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized...
Background:
To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adap...
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...
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...
Aims:
There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populatio...
The added value of incorporating information from repeated measurements of blood pressure and cholesterol for cardiovascular disease (CVD) risk prediction has not been rigorously assessed. We used data from the Emerging Risk Factors Collaboration on 191,445 adults (38 cohorts from across 17 countries with data from 1962-2014) with > 1 million measu...
The added value of incorporating information from repeated measurements of blood pressure and cholesterol for cardiovascular disease (CVD) risk prediction has not been rigorously assessed. We used data from the Emerging Risk Factors Collaboration on 191,445 adults (38 cohorts from across 17 countries with data from 1962-2014) with > 1 million measu...
The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million mea...
Aim
To establish whether ECG findings are associated with subsequent risk of sudden death from coronary heart disease (CHD).
Methods and results
Potential risk factors for CHD were measured at entry to the first Northwick Park Heart Study of 2167 men. ECG findings were coded as high or low risk for CHD according to definitions in the Minnesota cod...
Background:
Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial ben...
The prevalence of cardiometabolic multimorbidity is increasing.
To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.
Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; year...
Objective
Numerous studies have reported that chronic obstructive pulmonary disease or impaired lung function are associated with later coronary heart disease (CHD). However, it is unclear if lung function is an independent risk factor, as many of these studies have included only limited measures of other factors associated with CHD.
Methods
In to...
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...
The Northwick Park Heart Study (NPHS) has shown associations of high plasma fibrinogen and factor VII (FVIIc) levels with the risk of death from coronary heart disease (CHD). The finding for fibrinogen has been confirmed in many other studies. While one further study has found a similar prospective association for FVIIc, several have not. Experimen...
Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into
the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies.
Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for...
Background:
There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events.
Methods:
We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding...
Background:
The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods:
We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174374 deaths or major non-fata...
In those who have already survived myocardial infarction (MI) or stroke, or have had a transient ischaemic episode (TIA), daily low dose aspirin (ASA) reduces the risk of recurrences by an amount that greatly exceeds the risk of serious bleeding (secondary prevention). ASA is therefore recommended for these people. However, in primary prevention-re...
Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R sig...
Daily aspirin reduces the long-term incidence of some adenocarcinomas, but effects on mortality due to some cancers appear after only a few years, suggesting that it might also reduce growth or metastasis. We established the frequency of distant metastasis in patients who developed cancer during trials of daily aspirin versus control.
Our analysis...
Daily aspirin reduces the long-term risk of death due to cancer. However, the short-term effect is less certain, especially in women, effects on cancer incidence are largely unknown, and the time course of risk and benefit in primary prevention is unclear. We studied cancer deaths in all trials of daily aspirin versus control and the time course of...
BACKGROUND: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to aff...
Daily aspirin reduces the long-term incidence of some adenocarcinomas, but effects on mortality due to some cancers appear after only a few years, suggesting that it might also reduce growth or metastasis. We established the frequency of distant metastasis in patients who developed cancer during trials of daily aspirin versus control. Methods Our a...
Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus c...
The association between respiratory infection and risk of heart attacks and strokes is well established. However, less evidence exists for an association between respiratory infection and venous thromboembolism (VTE). In this article, we describe the associations between respiratory infection and VTE.
All cases aged ≥18 years of first-time diagnosi...
Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus c...
Daily treatment with aspirin for longer than 5 years reduces the long-term risk of colorectal cancer. A number of studies have suggested that long-term aspirin use may reduce the risk of several noncolorectal solid cancers, but clear evidence for a preventive effect is lacking. This study investigated the possible effect of aspirin on reducing the...
High-dose aspirin (≥500 mg daily) reduces long-term incidence of colorectal cancer, but adverse effects might limit its potential for long-term prevention. The long-term effectiveness of lower doses (75-300 mg daily) is unknown. We assessed the effects of aspirin on incidence and mortality due to colorectal cancer in relation to dose, duration of t...
Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality.
We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration,...
Whether renin is involved in the onset of coronary heart disease (CHD) remains unclear. A case-control study in 1972, suggesting a causal association between renin and CHD, has now been followed by three prospective studies. One was based on 1,717 hypertensive subjects in a Work-Site Program in New York. The main results showed an increased risk of...
Basic and clinical research support the hypothesis that activation of the coagulation and inflammation pathways may affect cancer onset, but there is limited epidemiological data to support this.
We examined a large range of haemostatic and inflammation markers, including fibrinogen, in 19 303 male participants from three English cohorts followed f...
The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis.
A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photogra...
Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances.
We meta-analysed individual records of 160 309 people...
Whether renin is involved in the onset of coronary heart disease (CHD) remains unclear. A case-control study in 1972, suggesting a causal association between renin and CHD, has now been followed by three prospective studies. One was based on 1,717 hypertensive subjects in a Work-Site Program in New York. The main results showed an increased risk of...
Context Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified.
Objective To assess major lipids and apolipoproteins in vascular risk.
Design, Setting, and Participants Individual records were supplied on 302 430 people without initial vascular disease from 68 long-term prospective studi...
Since evidence of a long-term association between routine blood count (Coulter) variables and coronary heart disease (CHD) is inconsistent, the authors analysed white blood cell count (WBC), red blood cell count (RBC), haemoglobin (Hgb), packed cell volume (PCV) and platelet count for their long-term associations with CHD mortality in the first Nor...
Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention.
We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95,000 ind...
Background Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention. Methods We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention...
One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohort...
Previous trials evaluating possible improvements in health-related quality of life (QOL) with combined hormone-replacement therapy (HRT) used generic instruments that did not contain specific items on postmenopausal symptoms, and may have underestimated improvements for a particular outcome or condition. This placebo-controlled, double-blind, rando...
Coronary heart disease is the leading cause of death worldwide affecting millions of people in both developed and developing countries. The dual aims of this book are to review the well-established and emerging risk factors in coronary heart disease (CHD) and to apply this knowledge to public health approaches to disease prevention. The book includ...
Although fibrinogen is known to be an independent population-level risk factor for cardiovascular disease in healthy individuals, less is known about its value for individual-level risk prediction.
To assess the independent contribution of plasma fibrinogen to risk prediction in men with peripheral arterial disease.
We used data from the 785 men ra...
Respiratory infection may be associated with an increased risk of major cardiovascular events. This case-control study describes associations with these events of respiratory infection.
The IMS Disease Analyzer Mediplus primary care database was used to identify all cases of first-time diagnosis of myocardial infarction (MI) or stroke and single ma...
To assess the effect of combined hormone replacement therapy (HRT) on health related quality of life.
Randomised placebo controlled double blind trial.
General practices in United Kingdom (384), Australia (94), and New Zealand (24).
Postmenopausal women aged 50-69 at randomisation; 3721 women with a uterus were randomised to combined oestrogen and...
To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy).
Multicentre, randomised, placebo controlled, double blind trial.
General practices in UK (384), Australia (91), and New Zealand (24).
Postmenopausal women aged 50-69 years at rando...
Objective To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy).Design Multicentre, randomised, placebo controlled, double blind trial.Setting General practices in UK (384), Australia (91), and New Zealand (24).Participants Postmenopau...
The long-term associations of established risk factors for coronary heart disease (CHD), for example cholesterol, are well known, but not for the less familiar hemostatic variables.
To establish whether associations between hemostatic variables and CHD first identified nearly three decades ago have persisted long-term.
The first Northwick Park Hear...
WISDOM data collection summary. Table summarising information collected at different stages of the WISDOM trial.
At the time of feasibility work and final design of the trial there was no randomised control trial evidence for the long-term risks and benefits of hormone replacement therapy. Observational studies had suggested that long term use of estrogen was likely to be associated, amongst other things, with reduced risks of osteoporosis and ischaemic heart...
Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration h...
As with 'conventional' risk factors such as cholesterol and smoking, there is a need for large, long-term prospective studies on hemostatic factors.
To investigate the prospective relationship of fibrinogen and factor VII clotting activity (FVIIc) with risk of coronary heart disease (CHD) and stroke in a study with a large number of outcomes over a...
It is unclear wheather the association between C-reactive protein (CRP) and incident coronary events is free from bias and confounding. Individuals homozygous for a +1444C>T polymorphism in the CRP gene have higher circulating concentrations of CRP. Since the distribution of this polymorphism occurs at random during gamete formation, its associatio...
To examine the effect of baseline body mass index (BMI) and skinfold thickness (ST) on fatal coronary heart disease (CHD) and all cause mortality after 30 years of follow up.
Prospective cohort study.
Northwick Park heart study (NPHS) designed to investigate the role of haemostatic variables on CHD.
1511 men and 691 women enrolled in NPHS aged 40 t...
Mounting interest over the past 10 or 15 years in the possible role of infection in the risk of myocardial infarction (MI) has mainly centred on serological evidence of infection that often has occurred several years or months previously.1 However, recent rather than distant infection may be more strongly associated with coronary events, as shown b...
Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke.
To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data.
Relevant studies were identified by computer-assisted searches, hand searches of reference lists...
CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches...
In the Thrombosis Prevention Trial (TPT), low-intensity warfarin reduced the risk of first coronary events only when the achieved international normalized ratio (INR) was > or =1.4. To validate the likely mechanism of action of low-intensity warfarin we measured its effects on plasma markers of thrombin generation, fibrin turnover and low-grade inf...
Background Many long-term studies have reported on associations of plasma fibrinogen concentration with cardiovascular disease, but few have been large enough to provide reliable estimates in different circumstances. Moreover, most published prospective studies have related disease risk only to baseline values of plasma fibrinogen (which can lead t...
The Thrombosis Prevention Trial was a primary prevention factorial trial that reported a reduction in the risk of coronary heart disease (CHD) with warfarin and/or aspirin. This article examines compliance (duration of treatment) with warfarin treatment and whether warfarin has a retained effect.
Risk of CHD while complying with warfarin treatment...
In 1989, the UK Medical Research Council (MRC) agreed that, if feasible, a randomized controlled trial to assess the long-term risks and benefits of hormone replacement therapy (HRT) was a priority. Feasibility work began in 1990 and demonstrated that a large-scale multicenter trial was possible. An application for funding for a main trial was subm...
To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease.
Double blind placebo controlled randomised trial.
85 general practices and nine hospital vascular clinics.
1568 men, mean age 68.2 years (range 35 to 92) at recruitment.
Bezafibrate 400 mg daily (783 men) or placebo (78...
Genetic determinants of baseline levels and the fall in plasma triglyceride and fibrinogen levels in response to bezafibrate treatment were examined in 853 men taking part in the lower extremity arterial disease event reduction (LEADER) trial. Three polymorphisms in the peroxisome proliferator activated receptor alpha (PPARalpha) gene were investig...
In primary prevention, anticoagulation with warfarin sodium to an international normalized ratio of 1.5 and 75 mg of aspirin per day each reduced the incidence of coronary heart disease (CHD). Effects on the development of angina pectoris and total CHD (resulting from angina, myocardial infarction, and coronary death) have been assessed, particular...
The impact of randomised controlled trials on subsequent practice has only occasionally been assessed. Doing so is particularly necessary when unusual and possibly controversial treatments are being used. The aim of this study was to assess the practical implications of the results of the placebo-controlled primary prevention thrombosis prevention...
OBJECTIVE: To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease. DESIGN: Double blind placebo controlled randomised trial. SETTING: 85 general practices and nine hospital vascular clinics. PARTICIPANTS: 1568 men, mean age 68.2 years (range 35 to 92) at recruitment. INTERVE...
Coronary heart disease (CHD) in the form of myocardial infarction first came to attention early in the 20th century. Mortality from CHD increased dramatically after the First World War and had assumed epidemic proportions, particularly in the USA, by 1945. The ensuing research stemmed almost exclusively from the lipid infiltration hypothesis for at...
To determine the relation between psychological characteristics and subsequent fatal ischaemic heart disease (IHD) events.
Prospective study of participants in the Northwick Park heart study (NPHS) recruited between 1972 and 1978 and followed up for fatal events until 1997.
Three occupational groups in north west London.
1408 white men without a hi...
Editor—By implying disagreements with our study1 which are largely misplaced or non-existent, Ramsay et al may have confused doctors who are deciding about aspirin in the primary prevention of coronary heart disease.2 We pointed out that the British Hypertension Society,3 the hypertension optimal treatment trial,4 and our trial1 all say that aspiri...
A prospective study of 7079 people aged 45-74 recruited through general practices in South Wales, Herefordshire and Edinburgh, Scotland was undertaken to test the hypothesis that faecal bile acids are implicated in the causation of large bowel cancer. The population was recruited between 1974 and 1980 and the response rate for stool collection was...
There is mounting evidence that low-intensity oral anticoagulation is effective, particularly in primary prevention of thrombosis, with important implications for safety and the practicalities of using warfarin. Because it is desirable to know possible benefits for different indications so that optimal therapy can be administered in as wide a range...