Publications by authors named "Alison Offer"
Alzheimer's disease (AD) risk is increased in carriers of the apolipoprotein E (APOE) ε4 allele and decreased in ε2 allele carriers compared with the ε3ε3 genotype. The aim of this study was to determine whether: the APOE genotype affects brain grey (GM) or white matter (WM) structure; and if differences exist, the age when they become apparent and whether there are differential effects by sex. We used cross-sectional magnetic resonance imaging data from ~43,000 (28,494 after pre-processing) white British cognitively healthy participants (7,446 APOE ε4 carriers) aged 45-80 years from the UK Biobank cohort and investigated image-derived phenotypes (IDPs).
View Article and Find Full Text PDFBackground: Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against "gold standard" (GS) methods to study the feasibility of using such methods in clinical trials.
View Article and Find Full Text PDFIntroduction: Populations at increased risk of dementia need to be identified for well-powered trials of preventive interventions. Weight loss, which often occurs in pre-clinical dementia, could identify a population at sufficiently high dementia risk.
Methods: In 12,975 survivors in the Heart Protection Study statin trial of people with, or at high risk of, cardiovascular disease, the association of weight change over 5 years during the trial with post-trial dementia recorded in electronic hospital admission and death records ( = 784) was assessed, after adjustment for age, sex, treatment allocation, and deprivation measures.
Background: Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke.
Methods And Findings: Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations.
Aims: Aspirin is widely used in cardiovascular disease prevention but is also associated with an increased risk of bleeding. The net effect of aspirin on dementia and cognitive impairment is uncertain.
Methods And Results: In the ASCEND trial, 15 480 people from the UK with diabetes and no history of cardiovascular disease were randomized to aspirin 100 mg daily or matching placebo for a mean of 7.
A Biomarker-based Biological Age in UK Biobank: Composition and Prediction of Mortality and Hospital Admissions.
J Gerontol A Biol Sci Med Sci
June 2021
Background: Chronological age is the strongest risk factor for most chronic diseases. Developing a biomarker-based age and understanding its most important contributing biomarkers may shed light on the effects of age on later-life health and inform opportunities for disease prevention.
Methods: A subpopulation of 141 254 individuals healthy at baseline were studied, from among 480 019 UK Biobank participants aged 40-70 recruited in 2006-2010, and followed up for 6-12 years via linked death and secondary care records.
Aims: Statins are widely used to prevent cardiovascular events, but little is known about the impact of different risk factors for statin-related myopathy or their relevance to reports of other types of muscle symptom.
Methods And Results: An observational analysis was undertaken of 171 clinically adjudicated cases of myopathy (defined as unexplained muscle pain or weakness with creatine kinase >10× upper limit of normal) and, separately, of 15 208 cases of other muscle symptoms among 58 390 individuals with vascular disease treated with simvastatin for a mean of 3.4 years.
Importance: Acquisition of reliable randomized clinical trial evidence of the effects of cardiovascular interventions on cognitive decline is a priority.
Objectives: To estimate the association of cognitive aging with the avoidance of vascular events in cardiovascular intervention trials and understand whether reports of nonsignificant results exclude worthwhile benefit.
Design, Setting, And Participants: This secondary analysis of 3 randomized clinical trials in participants with preexisting occlusive vascular disease or diabetes included survivors to final in-trial follow-up in the Heart Protection Study (HPS), Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), and Treatment of HDL (High-Density Lipoprotein) to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trials of lipid modification for prevention of cardiovascular events.
Background: Genetic studies have shown lipoprotein(a) (Lp[a]) to be an important causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the chief determinant of Lp(a) levels, but its impact on the benefits of therapies that lower Lp(a) remains unclear.
Methods: HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized trial of niacin-laropiprant versus placebo on a background of simvastatin therapy.
Aims: Statins reduce LDL cholesterol (LDL-C) and the risk of vascular events, but it remains uncertain whether there is clinically relevant genetic variation in their efficacy. This study of 18 705 individuals aims to identify genetic variants related to the lipid response to simvastatin and assess their impact on vascular risk response.
Methods And Results: A genome-wide study of the LDL-C and apolipoprotein B (ApoB) response to 40 mg simvastatin daily was performed in 3895 participants in the Heart Protection Study, and the nine strongest associations were tested in 14 810 additional participants.
Background: Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol are established risk factors for vascular disease, but lipoprotein particle concentrations may be stronger determinants of risk.
Methods And Results: Associations between vascular events and baseline concentrations of cholesterol fractions, apolipoproteins B and A(1), and lipoprotein particles assessed by nuclear magnetic resonance were considered in the Heart Protection Study randomized trial of simvastatin versus placebo (>5000 vascular events during 5.3 years of follow-up among 20 000 participants).
Background: In China, there have been few large prospective studies of the associations of body mass index (BMI) with overall and cause-specific mortality that have simultaneously controlled for biases that can be caused by pre-existing disease and smoking.
Methods: Prospective cohort study of 224 064 men, of whom 40 700 died during follow-up between 1990-91 and 2006. Analyses restricted to 142 214 men aged 40-79 years at baseline with no disease history and, to further reduce bias from pre-existing disease, at least 5 years of subsequent follow-up, leaving 17 800 deaths [including 4165 stroke, 1297 coronary heart disease (CHD), 3121 chronic obstructive pulmonary disease (COPD)].
Aims: Plasma levels of apolipoprotein B (apoB), the main surface protein on LDL particles, and LDL-C, the amount of cholesterol in those particles, are closely correlated and, considered separately, are positive risk factors. Plasma levels of apolipoprotein A(1), the main surface protein on HDL particles, and HDL-C, the amount of cholesterol in those particles, are also closely correlated with each other and, considered separately, are negative risk factors. The interdependence of these four risk factors is unclear.
View Article and Find Full Text PDFBackground And Purpose: Despite previous investigations, substantial uncertainty remains about the relation between body mass index (BMI) and stroke, especially in populations with a relatively low BMI but a high stroke rate.
Methods: A nationally representative prospective study of mortality included 212,000 Chinese men 40 to 79 years old without known cardiovascular disease in 1990 to 1991 who were followed up for 10 years. Standardized hazard ratios were calculated for stroke mortality by baseline systolic blood pressure (SBP) and BMI.
Several epidemiological studies have reported on the association between body mass index (BMI) and risk of esophageal cancer, but these were mostly in Western populations where many are overweight or obese. There is little direct evidence about the relationship in China where the mean BMI is relatively low and the disease rate is high. We examined the data from a population-based prospective study of 220,000 Chinese men aged 40-79 without a previous history of cancer (mean BMI 21.
View Article and Find Full Text PDFBackground: Increased body mass index (BMI) is known to be related to ischaemic heart disease (IHD) in populations where many are overweight (BMI>or=25 kg/m2) or obese (BMI>or=30). Substantial uncertainty remains, however, about the relationship between BMI and IHD in populations with lower BMI levels.
Methods: We examined the data from a population-based, prospective cohort study of 222,000 Chinese men aged 40-79.