ORCID Profile
0000-0003-2279-0624
Current Organisations
Nottingham Trent University
,
Health Data Research UK
,
University College London
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: BMJ
Date: 26-05-2009
Abstract: High job strain has been linked with cardiovascular outcomes. This study aimed to examine whether job strain is associated with angina pectoris symptoms among British and Finnish non-manual employees. Postal questionnaire survey data among 40-60-year-old employees of the British Whitehall II Study (n = 4551, 27% women) and the Finnish Helsinki Health Study (n = 7605, 83% women) cohort were analysed. Angina pectoris symptoms were the outcome in logistic regression analysis. Karasek's job strain was examined. Models were adjusted first for age, second for occupational class and finally for smoking, heavy drinking, physical inactivity, unhealthy food habits and obesity. Angina pectoris symptoms were reported by 5% of women and 3% of men in Britain, and by 6% of women and 4% of men in Finland. High job strain was associated with angina pectoris symptoms among men in Britain (OR 2.08 CI 95% 1.07 to 4.02) and women in Finland (OR 1.90 CI 95% 1.36 to 2.63) independent of age, occupational class, and behavioural risk factors. However, similar associations between job strain and angina pectoris symptoms were not observed among men in Finland or women in Britain. The results yielded partial support for the association between job strain and angina pectoris symptoms across national contexts.
Publisher: Wiley
Date: 11-1997
Publisher: Elsevier BV
Date: 02-1999
DOI: 10.1016/S0021-9150(98)00239-1
Abstract: This study compares risk factors for cardiovascular disease in civil servants of three ethnic groups screened as part of the Whitehall II cohort study. Previously identified risk factors for cardiovascular disease in 360 Afro-Caribbean and 577 South Asian subjects are compared with the 8973 white Caucasian subjects. Controlling for socio-economic status is more precise than in most previous studies of cardiovascular differences between ethnic groups. After controlling for socio-economic confounding factors, age and sex, South Asian subjects were found to have increased prevalence of hypertension (defined as either having systolic pressure of > 160, diastolic pressure of > 95 or being on antihypertensives) OR 2.3 (95% CI 1.6-3.3), diabetes OR 4.2 (95%, CI 3.0-5.8) and a high risk lipid profile, although total cholesterol was lower than in the white population. Afro-Caribbean subjects had more hypertension OR 4.0 (95% CI 2.8-5.7) and diabetes OR 2.8 (95% CI 1.7-4.6), but this was accompanied by a favourable lipid profile with low cholesterol and high HDL. Afro-Caribbean alcohol and smoking habits were low-risk. Socio-economic status was found to be an important confounding factor for ethnic differences in biochemical risk factors for cardiovascular disease. However, adjusting for socioeconomic class only attenuates observed differences it does not abolish them.
Publisher: Springer Science and Business Media LLC
Date: 06-09-2008
Publisher: Elsevier BV
Date: 05-2014
Publisher: SAGE Publications
Date: 27-07-2016
Abstract: The Mindful Attention Awareness Scale was developed to measure in idual differences in the tendency to be mindful. The current study examined the psychometric properties of the Mindful Attention Awareness Scale in a heterogeneous s le of 565 nonmeditators and 612 meditators using the polytomous Rasch model. The results showed that some items did not function the same way for these two groups. Overall, meditators had higher mean estimates than nonmeditators. The analysis identified a group of items as highly discriminating. Using a different model, Van Dam, Earleywine, and Borders in 2010 identified the same group of items as highly discriminating, and concluded that they were the items with the most information. Multiple pieces of evidence from the Rasch analysis showed that these items discriminate highly because of local dependence, hence do not supply independent information. We discussed how these different conclusions, based on similar findings, result from two very different paradigms in measurement.
Publisher: Oxford University Press (OUP)
Date: 10-2001
Abstract: To determine the seasonal effect on all-cause and cause-specific mortality and to identify high-risk groups. A 25-year follow-up of 19,019 male civil servants aged 40-69 years. All-cause mortality was seasonal (ratio of highest mortality rate during winter versus lowest rate during summer 1.22, 95% CI : 1.1-1.3), largely due to the seasonal nature of ischaemic heart disease. Participants at high risk based on age, employment grade, blood pressure, cholesterol, forced expiratory volume, smoking and diabetes did not have higher seasonal mortality, although participants with ischaemic heart disease at baseline did have a higher seasonality effect (1.38, 95% CI : 1.2-1.6) than those without (1.18, 95% CI : 1.1-1.3) (P = 0.03). Seasonal mortality differences were greater among those with prevalent ischaemic heart disease and at older ages, but were not greater in in iduals of lower socioeconomic status or with a high multivariate risk score. Since seasonal differences showed no evidence of declining over time, elucidating their causes and preventive strategies remains a public health challenge.
Publisher: Springer Science and Business Media LLC
Date: 28-10-2014
DOI: 10.1038/NCOMMS6068
Abstract: Statins effectively lower LDL cholesterol levels in large studies and the observed interin idual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1 , not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
Publisher: Elsevier BV
Date: 09-2016
Publisher: SAGE Publications
Date: 04-05-2016
Abstract: Synthetic impact surrogates are widely used in the sporting goods industry in the evaluation of personal protective equipment. Existing surrogates, exemplified by those used in safety standards, have many shortcomings, primarily relating to their mass, stiffness, geometries and levels of constraint which limit their biofidelity and subsequent usefulness in personal protective equipment evaluations. In sports, absence from competition is a primary severity measure for injuries consequently, blunt trauma injuries, such as contusions and lacerations, become pertinent and serious concerns. It is important, therefore, that synthetic surrogates provide an adequate description of these soft tissues to effectively evaluate injury risk. A novel, multi-material human thigh surrogate has been presented with consideration to the tissue structures, geometries and simulant materials used. This study presents the detailed development stages undertaken to fabricate a multi-material synthetic soft tissue surrogate with skin, subcutaneous adipose and muscle tissue components. The resultant surrogate demonstrates the successful use of sequential moulding techniques to construct a full-scale anatomical human impact surrogate which can be used in personal protective equipment testing.
Publisher: Informa UK Limited
Date: 03-07-2018
Publisher: Oxford University Press (OUP)
Date: 07-09-2018
Publisher: Wiley
Date: 03-09-2021
DOI: 10.1002/EHF2.13517
Abstract: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological s les and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 in idual studies enrolled participants of both sexes in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate s le, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P 5 × 10 −8 under an additive genetic model. HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization and (iii) develop genomic tools for disease stratification and risk prediction.
Publisher: Springer Science and Business Media LLC
Date: 22-06-2014
DOI: 10.1038/NG.3014
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.IJCARD.2015.03.075
Abstract: Electronic health records (EHRs) offer the opportunity to ascertain clinical outcomes at large scale and low cost, thus facilitating cohort studies, quality of care research and clinical trials. For acute myocardial infarction (AMI) the extent to which different EHR sources are accessible and accurate remains uncertain. Using MEDLINE and EMBASE we identified thirty three studies, reporting a total of 128658 patients, published between January 2000 and July 2014 that permitted assessment of the validity of AMI diagnosis drawn from EHR sources against a reference such as manual chart review. In contrast to clinical practice, only one study used EHR-derived markers of myocardial necrosis to identify possible AMI cases, none used electrocardiogram findings and one used symptoms in the form of free text combined with coded diagnosis. The remaining studies relied mostly on coded diagnosis. Thirty one studies reported positive predictive value (PPV)≥ 70% between AMI diagnosis from both secondary care and primary care EHRs and the reference. Among fifteen studies reporting EHR-derived AMI phenotypes, three cross-referenced ST-segment elevation AMI diagnosis (PPV range 71-100%), two non-ST-segment elevation AMI (PPV 91.0, 92.1%), three non-fatal AMI (PPV range 82-92.2%) and six fatal AMI (PPV range 64-91.7%). Clinical coding of EHR-derived AMI diagnosis in primary care and secondary care was found to be accurate in different clinical settings and for different phenotypes. However, markers of myocardial necrosis, ECG and symptoms, the cornerstones of a clinical diagnosis, are underutilised and remain a challenge to retrieve from EHRs.
Publisher: American Physiological Society
Date: 11-2022
DOI: 10.1152/AJPREGU.00149.2022
Abstract: Skin wetness sensing is important for thermal stress resilience. In iduals with multiple sclerosis (MS) present greater vulnerability to thermal stress yet, it is unclear whether they present wetness-sensing abnormalities. We investigated the effects of MS on wetness sensing and their modulation with changes in mean skin temperature (T sk ). Twelve participants with MS [5 males (M)/7 females (F) 48.3 ± 10.8 yr Expanded Disability Status Scale (EDSS) range: 1–7] and 11 healthy controls (4 M/7 F 47.5 ± 11.3 yr) undertook three trials, during which they performed a quantitative sensory test with either a thermoneutral (30.9°C), warm (34.8°C), or cold (26.5°C) mean T sk . Participants reported on visual analog scales local wetness perceptions arising from the static and dynamic application of a cold-, neutral-, and warm-wet probe (1.32 cm 2 water content: 0.8 mL), to the index finger pad, forearm, and forehead. Data were analyzed for the group-level effect of MS, as well as for its in idual variability. Our results indicated that MS did not alter skin wetness sensitivity at a group level, across the skin sites and temperature tested, neither under normothermia nor under conditions of shifted thermal state. However, when taking an in idualized approach to profiling wetness-sensing abnormalities in MS, we found that 3 of the 12 participants with MS (i.e., 25% of the s le) presented a reduced wetness sensitivity on multiple skin sites and to different wet stimuli (i.e., cold, neutral, and warm wet). We conclude that some in iduals with MS may possess reduced wetness sensitivity however, this sensory symptom may vary greatly at an in idual level. Larger-scale studies are warranted to characterize the mechanisms underlying such in idual variability.
Publisher: Elsevier BV
Date: 07-2016
Publisher: Elsevier BV
Date: 11-2012
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/S0002-9149(03)00985-8
Abstract: Social position and psychosocial factors are associated with coronary disease, but the underlying pathophysiologic mechanisms remain unclear. In a s le of 283 nonsmokers, we found that social position was inversely associated with interleukin-6 and C-reactive protein and that participants with mild depression had impaired endothelial function.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2012
DOI: 10.1038/NATURE11725
Publisher: Elsevier BV
Date: 03-2014
Publisher: American Public Health Association
Date: 09-1997
Abstract: OBJECTIVES: This study measured the association between socioeconomic status and the eight scale scores of the Medical Outcomes Study short form 36 (SF-36) general health survey in the Whitehall II study of British civil servants. It also assessed, for the physical functioning scale, whether this association was independent of disease. METHODS: A questionnaire containing the SF-36 was administered at the third phase of the study to 5766 men and 2589 women aged 39 through 63 years. Socioeconomic status was measured by means of six levels of employment grades. RESULTS: There were significant improvements with age in general mental health, role-emotional, vitality, and social functioning scale scores. In men, all the scales except vitality showed significant age-adjusted gradients across the employment grades (lower grades, worse health). Among women, a similar relationship was found for the physical functioning, pain, and social functioning scales. For physical functioning, the effect of grade was found in those with and without disease. CONCLUSIONS: Low socioeconomic status was associated with poor health functioning, and the effect sizes were comparable to those for some clinical conditions. For physical functioning, this association may act both via and independently of disease.
Publisher: Elsevier BV
Date: 11-1997
Publisher: BMJ
Date: 15-11-1997
DOI: 10.1136/BMJ.315.7118.1273
Abstract: To measure within-person change in scores on the short form general health survey (SF-36) by age, sex, employment grade, and disease status. Longitudinal study with a mean of 36 months (range 23-59 months) follow up, with screening examination and questionnaire to detect physical and psychiatric morbidity. 20 civil service departments originally located in London. 5070 male and 2197 female office based civil servants aged 39-63 years. Change in the eight scales of the SF-36 (adjusted for baseline score and length of follow up) and effect sizes (adjusted change standard deviation of differences). Within-person declines (worsening health) with age were greater than estimated by cross sectional data alone. General mental health showed greater declines among younger participants (P for linear trend < 0.001). Employment grade was inversely related to change lower grades had greater deteriorations than higher grades (P < 0.001 for each scale in men P < 0.05 for each scale in women except general health perceptions and role limitations due to physical problems). The greatest declines were seen among participants with disease at baseline, with the effects of physical and psychiatric morbidity being additive. Effect sizes ranged from 0.20 to 0.65 in participants with both physical and psychiatric morbidity. Health functioning, as measured by the SF-36, changed in hypothesised directions with age, employment grade, and disease status. These changes occurred within a short follow up period, in an occupational, high functioning cohort which has not been the subject of intervention, suggesting that the SF-36 is sensitive to changes in health in general populations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-12-2005
Publisher: Elsevier BV
Date: 07-2014
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.AMJCARD.2007.03.056
Abstract: Previous cross-sectional studies have shown that heart rate (HR) and HR variability (HRV) are influenced by several behavioral, biologic, and psychosocial factors. There are very few longitudinal studies that enable analyses of changes in HRV over time at an in idual level. This study aimed to describe changes in HR and HRV in a general population setting and to determine predictors of HR and HRV at follow-up. From 1997 to 2004, 1,999 participants (29% women) in the United Kingdom Whitehall II Cohort Study had 2 measurements of cardiac autonomic function (mean time between measurements 5.47 years, range 4.07 to 6.93). The mean +/- SD age at the first measurement was 55.6 +/- 6.0 years. At baseline, men showed higher low-frequency power than women, suggesting that they may have higher sympathetic activity. Conversely, women had higher high-frequency power, indicating higher parasympathetic tone. Over the 5-year follow-up period, men and women had decreases in HR. Men had reductions in HRV in time and frequency dimensions, whereas women showed increases in HRV. In conclusion, the probability of being in the adverse quartile of HRV function and HR at follow-up was related to baseline exercise, body mass index, cholesterol, and blood pressure.
Publisher: F1000 Research Ltd
Date: 17-01-2019
DOI: 10.12688/WELLCOMEOPENRES.15007.1
Abstract: Background: In 2017, 15.6% of the people living in England were born abroad, yet we have a limited understanding of their use of health services and subsequent health conditions. This linked population-based cohort study aims to describe the hospital-based healthcare and mortality outcomes of 1.5 million non-European Union (EU) migrants and refugees in England. Methods and analysis: We will link four data sources: first, non-EU migrant tuberculosis pre-entry screening data second, refugee pre-entry health assessment data third, national hospital episode statistics and fourth, Office of National Statistics death records. Using this linked dataset, we will then generate a population-based cohort to examine hospital-based events and mortality outcomes in England between Jan 1, 2006, and Dec 31, 2017. We will compare outcomes across three groups in our analyses: 1) non-EU international migrants, 2) refugees, and 3) general population of England. Ethics and dissemination: We will obtain approval to use unconsented patient identifiable data from the Secretary of State for Health through the Confidentiality Advisory Group and the National Health Service Research Ethics Committee. After data linkage, we will destroy identifying data and undertake all analyses using the pseudonymised dataset. The results will provide policy makers and civil society with detailed information about the health needs of non-EU international migrants and refugees in England.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2019
DOI: 10.1186/S12872-019-1187-Z
Abstract: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Published and in idual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57 1.22) for the GS, compared to 0.85 (95% CI 0.78 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11 1.50) for the GS, as compared to 1.00 (95% CI 0.96 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown although precision was moderate.
Publisher: Oxford University PressOxford
Date: 30-06-2002
DOI: 10.1093/ACPROF:OSO/9780198525738.003.0025
Abstract: This chapter assesses the relative strength of the epidemiological evidence for causal links between psychosocial factors and coronary heart disease (CHD) incidence among healthy populations and prognosis among CHD patients. Prospective studies published up until 2001 identified seventy reports of aetiological effects and ninety-two reports of prognostic effects by psychosocial factors. Based on prospective epidemiological data, there was indication for an association between depression, social support, and psychosocial work characteristics with CHD aetiology and prognosis. The randomized trials, to date, have been negative. Evidence for an effect of anxiety or type A behaviour was less consistent.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2013
DOI: 10.1161/STROKEAHA.113.002186
Abstract: Visit-to-visit variability in blood pressure (vBP) is associated with ischemic stroke. We sought to determine whether such variability has genetic causes and whether genetic variants associated with BP variability are also associated with ischemic stroke. A Genome Wide Association Study (GWAS) for loci influencing BP variability was undertaken in 3802 in iduals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study, in which long-term visit-to-visit and within-visit BP measures were available. Because BP variability is strongly associated with ischemic stroke, we genotyped the sentinel single nucleotide polymorphism in an independent ischemic stroke population comprising 8624 cases and 12 722 controls and in 3900 additional (Scandinavian) participants from the ASCOT study to replicate our findings. The ASCOT discovery GWAS identified a cluster of 17 correlated single nucleotide polymorphisms within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 ( P =1.4×10 −8 ). Conditional analysis of rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in patients with ischemic stroke found no association for overall stroke (odds ratio, 1.02 95% CI, 0.97–1.07 P =0.52) or its subtypes: cardioembolic (odds ratio, 1.07 95% CI, 0.97–1.16 P =0.17), large vessel disease (odds ratio, 0.98 95% CI, 0.89–1.07 P =0.60), and small vessel disease (odds ratio, 1.07 95% CI, 0.97–1.17 P =0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants ( P =0.18). We identified a cluster of single nucleotide polymorphisms at the NLGN1 locus showing significant association with BP variability. Follow-up analyses did not support an association with risk of ischemic stroke and its subtypes.
Publisher: American Public Health Association
Date: 2005
Abstract: Objectives. Although sick, some people take no time off work, a phenomenon called “sickness presenteeism.” This study examined the association between sickness presenteeism and incidence of serious coronary events. Methods. The analyses were based on a cohort of 5071 male British civil servants without previous myocardial infarction. Baseline screening included measurements of health status and coronary risk factors. Absence records were assessed for the 3 years subsequent to baseline screening. The outcome of interest was incident nonfatal myocardial infarction or fatal coronary heart disease (mean length of follow-up=9.1 years). Results. Seventeen percent of unhealthy employees took no absence during the 3-year follow-up. Their incidence of serious coronary events was twice as high as that of the unhealthy employees with moderate levels of sickness absenteeism (after adjustment for conventional risk factors, hazard ratio 1.97, 95% confidence interval=1.02, 3.83). Conclusions. Employers and employees should be aware of the potential harmful effects caused by sickness presenteeism.
Publisher: Oxford University Press (OUP)
Date: 03-2008
Abstract: To determine the biological and behavioural factors linking work stress with coronary heart disease (CHD). A total of 10 308 London-based male and female civil servants aged 35-55 at phase 1 (1985-88) of the Whitehall II study were studied. Exposures included work stress (assessed at phases 1 and 2), and outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7), and incident CHD (phases 2-7) on the basis of CHD death, non-fatal myocardial infarction, or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17-2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome. Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.SOCSCIMED.2007.12.010
Abstract: Symptoms play a crucial part in the formulation of medical diagnoses, yet the construction and interpretation of symptom narratives is not well understood. The diagnosis of angina is largely based on symptoms, but a substantial minority of patients diagnosed with "non-cardiac" chest pain go on to have a heart attack. In this ethnographic study our aims were to understand: (1) how the patients' accounts are performed or enacted in consultations with doctors (2) the ways in which ambiguity in the symptom narrative is managed by doctors and (3) how doctors reach or do not reach a diagnostic decision. We observed 59 consultations of patients in a UK teaching hospital with new onset chest pain who had been referred for a specialist opinion in ambulatory care. We found that patients rarely gave a history that, without further interrogation, satisfied the doctors, who actively restructured the complex narrative until it fitted a diagnostic canon, detaching it from the patient's interpretation and explanation. A minority of doctors asked about chest pain symptoms outside the canon. Re-structuring into the canonical classification was sometimes resisted by patients who contested key concepts, like exertion. Symptom narratives were sometimes unstable, with central features changing on interrogation and re-telling. When translation was required for South Asian patients, doctors considered the history less relevant to the diagnosis. Diagnosis and effective treatment could be enhanced by research on the diagnostic and prognostic value of the terms patients use to describe their symptoms.
Publisher: Oxford University Press (OUP)
Date: 04-2007
Publisher: Springer Science and Business Media LLC
Date: 09-08-2022
DOI: 10.1038/S41467-022-32095-5
Abstract: In iduals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi in iduals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry in iduals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.
Publisher: BMJ
Date: 18-10-2003
Publisher: Elsevier BV
Date: 07-2022
Publisher: Georg Thieme Verlag KG
Date: 2002
DOI: 10.1055/S-2002-35401
Abstract: The extent to which the associations between psychosocial factors and coronary heart disease (CHD) are causal has seldom been the subject of systematic enquiry. We are updating our previous systematic review up to 2001. The objective of this study is to assess the relative strength of the epidemiological evidence for causal links between psychosocial factors and CHD incidence among healthy populations, and prognosis among CHD patients. Our methods were to systematically review prospective cohort studies identified through the Science Citation index, which met pre-specified quality criteria. We found that the proportion of etiologic studies reporting a strong or moderate association was: 6/18 for Type A behavior and hostility, 15/22 for depression, 4/8 for anxiety, 10/13 for psychosocial work characteristics and 6/9 for social support. For prognostic studies the proportions were: 2/15 for type A behavior and hostility, 18/34 for depression, 8/18 for anxiety, 2/4 for psychosocial work characteristics and 14/21 for social support. Positive studies were more likely to be cited by other papers than negative studies. We concluded that, based on prospective epidemiological data, there was evidence for an association between depression, social support and psychosocial work characteristics and CHD aetiology and prognosis. Evidence for an effect of anxiety or type A behavior was less consistent. Methods to address bias in the reporting of psychosocial data are required.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-06-2005
DOI: 10.1161/CIRCULATIONAHA.104.497347
Abstract: Background— Laboratory and clinical studies suggest that the autonomic nervous system responds to chronic behavioral and psychosocial stressors with adverse metabolic consequences and that this may explain the relation between low social position and high coronary risk. We sought to test this hypothesis in a healthy occupational cohort. Methods and Results— This study comprised 2197 male civil servants 45 to 68 years of age in the Whitehall II study who were undergoing standardized assessments of social position (employment grade) and the psychosocial, behavioral, and metabolic risk factors for coronary disease previously found to be associated with low social position. Five-minute recordings of heart rate variability (HRV) were used to assess cardiac parasympathetic function (SD of N-N intervals and high-frequency power [0.15 to 0.40 Hz]) and the influence of sympathetic and parasympathetic function (low-frequency power [0.04 to 0.15 Hz]). Low employment grade was associated with low HRV (age-adjusted trend for each modality, P ≤0.02). Adverse behavioral factors (smoking, exercise, alcohol, and diet) and psychosocial factors (job control) showed age-adjusted associations with low HRV ( P .03). The age-adjusted mean low-frequency power was 319 ms 2 among those participants in the bottom tertile of job control compared with 379 ms 2 in the other participants ( P =0.004). HRV showed strong ( P .001) linear associations with components of the metabolic syndrome (waist circumference, systolic blood pressure, HDL cholesterol, triglycerides, and fasting and 2-hour postload glucose). The social gradient in prevalence of metabolic syndrome was explained statistically by adjustment for low-frequency power, behavioral factors, and job control. Conclusions— Chronically impaired autonomic function may link social position to different components of coronary risk in the general population.
Publisher: Oxford University Press (OUP)
Date: 15-07-2003
DOI: 10.1093/AJE/KWG120
Abstract: Physical inactivity and low resting heart rate variability (HRV) are associated with increased coronary heart disease incidence. In the Whitehall II study of civil servants aged 45-68 years (London, United Kingdom, 1997-1999), the strength of the association of moderate and vigorous activity with higher HRV was examined. Five-minute recordings of heart rate and HRV measures were obtained from 3328 participants. Calculated were time domain (standard deviation of NN intervals) and high-frequency-power measures as indicators of cardiac parasympathetic activity and low-frequency power of parasympathetic-sympathetic balance. Leisure-time physical activity (metabolic equivalent-hours per week) was categorized as moderate (>or=3- or=5). Moderate and vigorous physical activity were associated with higher HRV and lower heart rate. For men, linear trends of higher low-frequency power with increasing quartile of vigorous activity (304.6 (low), 329.0, 342.4, 362.5 (high) p < 0.01) and lower heart rate with increasing quartile of moderate activity (69.6 (low), 69.2, 68.9, 67.8 (high) p 25 kg/m(2), vigorous activity was associated with HRV levels similar to those for normal-weight men who engaged in no vigorous activity. Vigorous activity was associated with higher HRV, representing a possible mechanism by which physical activity reduces coronary heart disease risk.
Publisher: Cold Spring Harbor Laboratory
Date: 19-01-2018
DOI: 10.1101/250712
Abstract: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture however, genomic risk scores have not yet leveraged the totality of genetic information available nor been externally tested at population-scale to show potential utility in primary prevention. Using a meta-analytic approach to combine large-scale genome-wide and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS), consisting of 1.7 million genetic variants. We externally tested metaGRS, in idually and in combination with available conventional risk factors, in 22,242 CAD cases and 460,387 non-cases from UK Biobank. In UK Biobank, a standard deviation increase in metaGRS had a hazard ratio (HR) of 1.71 (95% CI 1.68–1.73) for CAD, greater than any other externally tested genetic risk score. In iduals in the top 20% of the metaGRS distribution had a HR of 4.17 (95% CI 3.97–4.38) compared with those in the bottom 20%. The metaGRS had higher C-index (C=0.623, 95% CI 0.615–0.631) for incident CAD than any of four conventional factors (smoking, diabetes, hypertension, and body mass index), and addition of the metaGRS to a model of conventional risk factors increased C-index by 3.7%. In in iduals on lipid-lowering or anti-hypertensive medications at recruitment, metaGRS hazard for incident CAD was significantly but only partially attenuated with HR of 2.83 (95% CI 2.61– 3.07) between the top and bottom 20% of the metaGRS distribution. Recent genetic association studies have yielded enough information to meaningfully stratify in iduals using the metaGRS for CAD risk in both early and later life, thus enabling targeted primary intervention in combination with conventional risk factors. The metaGRS effect was partially attenuated by lipid and blood pressure-lowering medication, however other prevention strategies will be required to fully benefit from earlier genomic risk stratification. National Health and Medical Research Council of Australia, British Heart Foundation, Australian Heart Foundation.
Publisher: Elsevier BV
Date: 10-2018
Publisher: BMJ
Date: 05-2001
Abstract: To determine the relative contribution of adult compared with early life socioeconomic status as predictors of morbidity attributable to coronary heart disease (CHD), chronic bronchitis and depression in the Whitehall II study of British civil servants. Prospective observational study with mean 5.3 years (range 3.7-7.6) follow up. 20 civil service departments originally located in London. 6895 male and 3413 female office-based civil servants aged 35-55 years at baseline. New cases at follow up of CHD, chronic bronchitis and depression defined using validated questionnaires. Employment grade was inversely associated with CHD, chronic bronchitis and depression in men (odds ratio per unit decrease in grade 1.30, 1.44 and 1.20 respectively). Employment grade was strongly related to father's social class. Chronic bronchitis, in women, and depression, in men, were more common among those with fathers of higher social class. When mutual adjustment was made for father's social class, grade at entry to the civil service and current grade, the strongest effects on adult morbidity were found for current grade. Among participants in whom neither parent had died < or =70 years of age the inverse association with adult SES was maintained. Adult socioeconomic status was a more important predictor of morbidity attributable to coronary disease, chronic bronchitis and depression than measures of social status earlier in life. In this population, the importance of social circumstances early in life may be in the way they influence employment and social position and thus exposures in adult life.
Publisher: Cold Spring Harbor Laboratory
Date: 10-07-2019
DOI: 10.1101/682013
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide 1 . A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained 2–4 . We report the largest GWAS meta-analysis of HF to-date, comprising 47,309 cases and 930,014 controls. We identify 12 independent variant associations with HF at 11 genomic loci, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function suggesting shared genetic aetiology. Expression quantitative trait analysis of non-CAD-associated loci implicate genes involved in cardiac development ( MYOZ1, SYNPO2L ), protein homeostasis ( BAG3 ), and cellular senescence ( CDKN1A ). Using Mendelian randomisation analysis we provide new evidence supporting previously equivocal causal roles for several HF risk factors identified in observational studies, and demonstrate CAD-independent effects for atrial fibrillation, body mass index, hypertension and triglycerides. These findings extend our knowledge of the genes and pathways underlying HF and may inform the development of new therapeutic approaches.
Publisher: BMJ
Date: 02-10-1999
Publisher: BMJ
Date: 07-08-2015
DOI: 10.1136/BMJ.H3913
Abstract: To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom. Population based longitudinal cohort study using nationwide clinical registries. Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87 119,786 patients) and the UK (NICOR/MINAP, n=242 391,077 patients), 2004-10. Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction. Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% v 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% v 6.6% in Sweden 12.7% v 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals' use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries. Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction. Clinical trials registration Clinical trials NCT01359033.
Publisher: Public Library of Science (PLoS)
Date: 10-09-2015
Publisher: BMJ
Date: 04-1999
Abstract: To explore the previously stated hypothesis that risk factors for atherothrombotic disease are associated with back pain. Prospective (mean of four years of follow up) and retrospective analyses using two main outcome measures: (a) short ( 7 days) spells of sickness absence because of back pain reported separately in men and women (b) consistency of effect across the resulting four duration of spell and sex cells. 14 civil service departments in London. 3506 male and 1380 female white office-based civil servants, aged 35-55 years at baseline. In age adjusted models, low apo AI was associated with back pain across all four duration-sex cells and smoking was associated across three cells. Six factors were associated with back pain in two cells: low exercise and high BMI, waist-hip ratio, triglycerides, insulin and Lp(a). On full adjustment (for age, BMI, employment grade and back pain at baseline), each of these factors retained a statistically significant effect in at least one duration-sex cell. Triglycerides were associated with short and long spells of sickness absence because of back pain in men in fully adjusted models with rate ratios (95% confidence intervals) of 1.53 (1.1, 2.1) and 1.75 (1.0, 3.2) respectively. There was little or no evidence of association in age adjusted models with: fibrinogen, glucose tolerance, total cholesterol, apoB, hypertension, factor VII, von Willebrand factor, electrocardiographic evidence of coronary heart disease and reported angina. In this population of office workers, only modest support was found for an atherothrombotic component to back pain sickness absence. However, the young age of participants at baseline and the lack of distinction between different types of back pain are likely to bias the findings toward null. Further research is required to ascertain whether a population sub-group of atherothrombotic back pain can be identified.
Publisher: BMJ
Date: 29-05-1999
Publisher: Oxford University Press (OUP)
Date: 02-11-2010
Publisher: BMJ
Date: 06-1998
Abstract: (1) To identify behavioural and biological correlates of poor physical functioning and (2) to determine whether such associations are independent of disease. Potential correlates were obtained from questionnaires and screening visits at baseline and five year follow up. Physical functioning was measured at follow up using the 10 item scale from the short-form 36 health survey. London offices at baseline. 10,308 civil servants (6895 men and 3413 women), with a median age (range) of 49 years (39-63) at follow up. Multiple logistic regression showed that cigarette smoking, physical activity, body mass index (BMI), triglycerides, fibrinogen, and insulin were independently associated with poor physical functioning for men. For women, physical activity, eating habits, body mass index, fibrinogen, and insulin were independently associated with poor physical functioning. For ex le, among men, current smokers who had smoked more than 20 pack years were 1.89 (95% CI 1.35 to 2.67) times as likely to have poor physical functioning as never smokers. Men with BMI of 30 kg/m2 or more were 1.71 (95% CI 1.13 to 2.59) times as likely to have poor physical functioning as those with BMI < 20 kg/m2. The corresponding odds ratio for women was 2.66 (95% CI 1.80 to 3.93). With the exceptions of fibrinogen and insulin, associations remained on exclusion of subjects with physical disease. Risk factors established for physical diseases are associated with poor physical functioning in a population of working age. These associations may be independent of current disease.
Publisher: Scandinavian Journal of Work, Environment and Health
Date: 04-1997
DOI: 10.5271/SJWEH.189
Abstract: The relation between psychosocial work characteristics, employment grade, and sickness absence due to back pain was studied among office workers. Base-line questionnaire data and sickness absence data collected continuously with a mean of 4 years of follow-up were analyzed. The subjects were 6894 men and 3414 women aged 35 to 55 years at recruitment. The main outcome measures were short ( 7 days) absences due to back pain. There was a strong inverse association between employment grade and rate of absences due to back pain (P for linear trend < 0.001) for ex le, the rate ratio for short absences among the men in a comparison of lowest versus highest employment grade was 8.21. The age adjusted rate ratio for the effect of low versus high control over work among the men was 2.22 [95% confidence interval (95% CI) 1.77-2.79] for short and 1.61 (95% CI 1.01-2.58) for long absences due to back pain. For short absences due to back pain among the men in high grades of employment, the rate ratio for low control was 3.42 compared with 0.78 for the lower grades (P for interaction < 0.001). For the women the corresponding rate ratios were 0.80 and 1.35, respectively (P for interaction 0.08). Absence from work due to back pain was strongly inversely related to employment grade. The effects of psychosocial work characteristics-particularly control-differed by grade and gender in magnitude and direction. The psychosocial work environment represents a potentially reversible cause of ill health.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-04-2016
Abstract: On average, most people's genomes contain approximately 100 completely nonfunctional genes. These loss-of-function (LOF) mutations tend to be rare and/or occur only as a single copy within in iduals. Narasimhan et al. investigated LOF in a Pakistani population with high levels of consanguinity. Examining LOF alleles that were identical by descent, they found, as expected, an absence of homozygote LOF for certain protein-coding genes. However, they also identified many homozygote LOF alleles with no apparent deleterious phenotype, including some that were expected to confer genetic disease. Indeed, one family had lost the recombination-associated gene PRDM9 . Science , this issue p. 474
Publisher: Springer Science and Business Media LLC
Date: 09-01-2020
DOI: 10.1038/S41467-019-13690-5
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development ( MYOZ1 , SYNPO2L ), protein homoeostasis ( BAG3 ), and cellular senescence ( CDKN1A ). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
Publisher: BMJ
Date: 05-07-2004
Publisher: Springer Science and Business Media LLC
Date: 23-12-2012
DOI: 10.1038/NG.2500
Publisher: BMJ
Date: 02-05-1998
DOI: 10.1136/BMJ.316.7141.1353
Abstract: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP-cancer pain, NCP-non-cancer pain, MP-mixed pain intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7-10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0% MP: 18.5%). PMI was 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy). Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.
Publisher: Elsevier BV
Date: 11-1997
Publisher: American Medical Association (AMA)
Date: 13-09-2016
Abstract: International studies report a decline in mortality following non-ST-elevation myocardial infarction (NSTEMI). Whether this is due to lower baseline risk or increased utilization of guideline-indicated treatments is unknown. To determine whether changes in characteristics of patients with NSTEMI are associated with improvements in outcomes. Data on patients with NSTEMI in 247 hospitals in England and Wales were obtained from the Myocardial Ischaemia National Audit Project between January 1, 2003, and June 30, 2013 (final follow-up, December 31, 2013). Baseline demographics, clinical risk (GRACE risk score), and pharmacological and invasive coronary treatments. Adjusted all-cause 180-day postdischarge mortality time trends estimated using flexible parametric survival modeling. Among 389 057 patients with NSTEMI (median age, 72.7 years [IQR, 61.7-81.2 years] 63.1% men), there were 113 586 deaths (29.2%). From 2003-2004 to 2012-2013, proportions with intermediate to high GRACE risk decreased (87.2% vs 82.0%) proportions with lowest risk increased (4.2% vs 7.6% P= .01 for trend). The prevalence of diabetes, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, chronic renal failure, previous invasive coronary strategy, and current or ex-smoking status increased (all P < .001). Unadjusted all-cause mortality rates at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio [HR], 0.968 [95% CI, 0.966-0.971] difference in absolute mortality rate per 100 patients [AMR/100], -1.81 [95% CI, -1.95 to -1.67]). These findings were not substantially changed when adjusted additively by baseline GRACE risk score (HR, 0.975 [95% CI, 0.972-0.977] AMR/100, -0.18 [95% CI, -0.21 to -0.16]), sex and socioeconomic status (HR, 0.975 [95% CI, 0.973-0.978] difference in AMR/100, -0.24 [95% CI, -0.27 to -0.21]), comorbidities (HR, 0.973 [95% CI, 0.970-0.976] difference in AMR/100, -0.44 [95% CI, -0.49 to -0.39]), and pharmacological therapies (HR, 0.972 [95% CI, 0.964-0.980] difference in AMR/100, -0.53 [95% CI, -0.70 to -0.36]). However, the direction of association was reversed after further adjustment for use of an invasive coronary strategy (HR, 1.02 [95% CI, 1.01-1.03] difference in AMR/100, 0.59 [95% CI, 0.33-0.86]), which was associated with a relative decrease in mortality of 46.1% (95% CI, 38.9%-52.0%). Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies.
Publisher: Elsevier BV
Date: 08-1999
DOI: 10.1016/S0277-9536(99)00135-5
Abstract: Continuous decline in functioning is not an inevitable consequence of ageing, as some in iduals maintain high levels of functioning to old age. The origins of functional problems in old age are not only related to current circumstances, but may be traced back to earlier life-experiences. Previous analyses show that change in functioning is related to socioeconomic status, but it is uncertain to what extent these differences can be accounted for by the same health behaviours and material and psychosocial factors that are related to socioeconomic differences in morbidity and mortality. This paper investigates socioeconomic differences in change in mental and physical functioning in a relatively young and healthy population over a three year follow-up period. The data come from the Whitehall II Study of London based civil servants aged 39-63 in 1991-93. We measured functioning with the Short Form 36 (SF-36) General Health Survey and socioeconomic status by civil service employment grade. Among lower employment grade men the odds ratio of being in the quartile of rapid decline in mental and physical functioning was 1.79 and 1.56 respectively. For women the odds ratio for physical functioning was 1.34, but employment grade differences in mental functioning were inconsistent. Among men health behaviours were the most important determinants of employment grade differences in physical functioning change. In addition, material problems and job decision latitude accounted for employment grade differences in physical as well as mental functioning change. However, among women employment grade differences in change in physical functioning can not be accounted for with these risk factors. Analyses of change in determinants may provide further insight into the underlying pathways. Early detection of functional decline and intervention may be a key to better functioning in ageing populations.
Publisher: Oxford University Press (OUP)
Date: 06-1998
Abstract: To examine the association of radiographic measures of heart size with mortality from coronary heart disease. One thousand, one hundred and ninety-one male civil servants aged 40-69 years were followed-up for mortality over 25 years in relation to cardiothoracic ratio and relative heart volume. A high cardiothoracic ratio and relative heart volume predicted coronary (n = 196 deaths) and all-cause mortality, but not respiratory or malignant mortality. After adjustment for age, systolic and diastolic blood pressure, the highest (> or = 0.47) compared to the lowest quintile of the cardiothoracic ratio (< 0.40) was associated with a rate ratio of 1.84 (95% CI 1.14-2.97) for the effect on coronary heart disease mortality. Further adjustment for heart rate, smoking, cholesterol, angina and ECG ischaemia had little effect, reducing the rate ratio to 1.65 (95% CI 1.01-2.70). Similar rate ratios were observed for relative heart volume. Cardiothoracic ratio within the range considered 'normal' in clinical practice predicted coronary heart disease mortality independent of established coronary heart disease risk factors. The relative heart volume, which uses measurements from the lateral as well as the posteroanterior chest X-ray, did not predict coronary heart disease any better than the cardiothoracic ratio. The extent to which left ventricular mass and systolic dysfunction-- pathophysiological correlates of the cardiothoracic ratio and relative heart volume--are independent risk factors for coronary heart disease should be further investigated.
Publisher: Cold Spring Harbor Laboratory
Date: 25-05-2018
DOI: 10.1101/329052
Abstract: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Published and in idual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Fourteen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95%CI 0.42 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95%CI 0.86 0.93). For ischemic stroke ORs were 0.84 (95%CI 0.57 1.22) for the GS, compared to 0.85 (95%CI 0.78 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11 1.50) for the GS, as compared to 1.00 (95%CI 0.96 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. Apparent discordance between genetic associations and trial outcome for T2DM might be explained lack by a of statistical precision, or differences in the nature and duration of genetic versus pharmacological perturbation of PCSK9. This research was funded by the British Heart Foundation (SP/13/6/30554, RG/10/12/28456, FS/18/23/33512), UCL Hospitals NIHR Biomedical Research Centre, by the Rosetrees and Stoneygate Trusts. Evidence on the long-term efficacy and safety of therapeutic inhibition of PCSK9 is lacking. To explore potential long-term effects of PCSK9 inhibition, we characterised the phenotypic consequence of LDL-cholesterol lowering variants at the PCSK9 locus. A PCSK9 gene score comprising 4 SNPs recapitulated the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and risk of myocardial infarction, and was associated with an increased risk of type 2 diabetes. No associations with safety outcomes such as cancer, COPD, Alzheimer’s disease or atrial fibrillation were identified. Our findings suggest PCSK9 inhibition may be safe and effective during prolonged use.
Publisher: Oxford University Press (OUP)
Date: 07-2001
Publisher: Springer Science and Business Media LLC
Date: 18-12-1998
Abstract: (i) To investigate the effects of current obesity, steady weight change and weight fluctuation on physical functioning and (ii) to determine whether associations are independent of coronary heart disease. Prospective cohort study with body mass index (BMI) measurements at four time points between the ages of 25 and 63 y. British civil servants based in London offices at baseline. 6895 men and 3413 women aged 35-55 y at baseline. Physical functioning was assessed using the 10-item scale from the Short Form 36 Health Survey, with a score in the lowest quartile indicating poor physical functioning. After adjustment for age and confounders (employment grade, smoking, alcohol, exercise and menopausal status), current BMI was monotonically associated with poor physical functioning in women whereas a threshold effect at a BMI of 27 kg/m2 was seen in men. The odds ratio of poor physical functioning was 1.55 (95% confidence interval (CI) 1.02-2.35) amongst women and 1.04 (95% CI 0.77-1.41) amongst men with BMI 23-24.9 kg/m2 compared to those with BMI < 21 kg/m2. Women in the upper, compared to the lower, tertile of steady weight change, had an odds ratio of poor physical functioning of 1.79 (1.24-2.60) after adjustment for age, confounders, current BMI and weight fluctuation. Women in the upper, compared to the lower, tertile of weight fluctuation had an odds ratio of poor physical functioning of 1.70 (1.23-2.34) adjusting for age, confounders, current BMI and steady weight change. Adjustment for the presence of coronary heart disease did not substantially alter any of these associations. Steady weight change and weight fluctuation had no independent effects in men. Among women, current obesity, steady weight change and weight fluctuation are independently and monotonically associated with poor physical functioning. Development of overt coronary heart disease is unlikely to be the mechanism for these associations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1998
DOI: 10.1097/00006842-199805000-00004
Abstract: To assess whether work characteristics and social support are predictors of physical, psychological, and social functioning. Work characteristics (Karasek and Siegrist models) and social support at baseline were used to predict health functioning measured by the SF-36 General Health Survey 5 years later in a prospective cohort study of 10,308 British male and female civil servants. Effort-reward imbalance and negative aspects of close relationships predicted poor physical, psychological, and social functioning after adjustment for the potential confounding effects of age, employment grade, baseline ill health, and negative affectivity. These psychosocial characteristics seem to act in a similar way in the healthy and those with existing illness. Psychological demands at work in women, and low confiding/emotional support in men, also predicted poor functioning. Etiologically. these effects are not mediated through health-related behaviors. Negative aspects of work (high demands and effort-reward imbalance) and negative aspects of close relationships are independent powerful predictors of poor health functioning. They may have an etiological role, which is independent of baseline illness.
Publisher: Wiley
Date: 30-07-2014
DOI: 10.1002/SIM.6265
Publisher: BMJ
Date: 07-2000
Abstract: To determine the impact of socioeconomic status (SES) on coronary heart disease (CHD) mortality in people with and without prevalent CHD at baseline. Cohort study with 25 year follow up prevalent CHD was defined by Q, ST or T wave electrocardiographic (ECG) abnormalities or symptoms (defined by the Rose chest pain questionnaire and self reported doctor diagnosis) or both. SES was defined by four civil service employment grades. London. 17 907 male civil servants aged 40-69 years. CHD mortality (n=2695 deaths). The lowest versus highest employment grade was associated with increased CHD mortality (age adjusted hazard ratio 1.56 (95% CI 1.2, 2.1)), prevalence of symptoms and, among symptomatic participants only, the prevalence of Q, ST or T abnormalities. Thirty one per cent of CHD deaths occurred in participants with prevalent CHD at baseline. Among participants without Q, ST or T abnormality employment grade was associated with CHD mortality the hazard ratios (lowest v highest grade) adjusted for age, systolic and diastolic blood pressure were 1.72 (95% CI 1.4, 2.1) for asymptomatic and 1.52 (95% CI 1.1, 2.1) for symptomatic participants among participants with Q, ST or T abnormality the corresponding hazard ratios were 1.46 (95% CI 0.7, 2.9) and 1.14 (95% CI 0.6, 2.0) respectively. SES was inversely associated with CHD mortality in civil servants with and without prevalent CHD at baseline. Further distinguishing the relative contribution of SES to the initiation and progression of CHD requires repeated measures studies of pre-clinical and clinical measures of CHD.
Publisher: Elsevier BV
Date: 07-1997
DOI: 10.1016/S0140-6736(97)04244-X
Abstract: The first Whitehall Study showed an inverse social gradient in mortality from coronary heart disease (CHD) among British civil servants--namely, that there were higher rates in men of lower employment grade. About a quarter of this gradient could be attributed to coronary risk factors. We analysed 5-year CHD incidence rates from the Whitehall II study to assess the contribution to the social gradient of psychosocial work environment, social support, coronary risk factors, and physical height. Data were collected in the first three phases of examination of men and women in the Whitehall II study. 7372 people were contacted on all three occasions. Mean length of follow-up was 5.3 years. Characteristics from the baseline, phase 1, questionnaire, and examination were related to newly reported CHD in people without CHD at baseline. Three self-reported CHD outcomes were examined: angina and chest pain from the Rose questionnaire, and doctor-diagnosed ischaemia. The contribution of different factors to the socioeconomic differences in incident CHD was assessed by adjustment of odds ratios. Compared with men in the highest grade (administrators), men in the lowest grade (clerical and office-support staff) had an age-adjusted odds ratio of developing any new CHD of 1.50. The largest difference was for doctor-diagnosed ischaemia (odds ratio for the lowest compared with the highest grade 2.27). For women, the odds ratio in the lowest grade was 1.47 for any CHD. Of factors examined, the largest contribution to the socioeconomic gradient in CHD frequency was from low control at work. Height and standard coronary risk factors made smaller contributions. Adjustment for all these factors reduced the odds ratios for newly reported CHD in the lowest grade from 1.5 to 0.95 in men, and from 1.47 to 1.07 in women. Much of the inverse social gradient in CHD incidence can be attributed to differences in psychosocial work environment. Additional contributions were made by coronary risk factors--mainly smoking--and from factors that act early in life, as represented by physical height.
Publisher: Springer Science and Business Media LLC
Date: 09-02-2014
DOI: 10.1038/NG.2897
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-11-2002
DOI: 10.1161/01.CIR.0000038364.26310.BD
Abstract: Background— The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. Methods and Results— This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both −0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output ( r =−0.19 P =0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. Conclusions— Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.
Publisher: Cold Spring Harbor Laboratory
Date: 24-06-2021
DOI: 10.1101/2021.06.22.21259323
Abstract: In iduals with South Asian ancestry have higher risk of heart disease than other groups in Western countries however, most genetic research has focused on European-ancestry (EUR) in iduals. It is unknown whether reported genetic loci and polygenic scores (PGSs) for cardiometabolic traits are transferable to South Asians, and whether PGSs have utility in clinical settings. Using data from 22,000 British Pakistani and Bangladeshi in iduals with linked electronic health records from the Genes & Health cohort (G& H), we conducted genome-wide association studies (GWAS) and characterised the genetic architecture of coronary artery disease (CAD), body mass index (BMI), lipid biomarkers and blood pressure. We applied a new technique to assess the extent to which loci from GWAS in EUR s les were transferable. We tested how well existing findings from EUR studies performed in genetic risk prediction and Mendelian randomisation in G& H. Trans-ancestry genetic correlations between G& H and EUR s les for the tested traits were not significantly lower than 1, except for BMI (r g =0.85, p=0.02). We found evidence for transferability for the vast majority of loci from EUR discovery studies that were sufficiently powered to replicate in G& H. PGSs showed variable transferability in G& H, with the relative accuracy compared to EUR (ratio of incremental r 2 /AUC) ≥0.95 for HDL-C, triglycerides, and blood pressure, but lower for BMI (0.78) and CAD (0.42). We observed significant improvement in categorical net reclassification in G& H (NRI=3.9% 95% CI 0.9–7.0) when adding a previously developed CAD PGS to clinical risk factors (QRISK3). We used transferable loci as genetic instruments in trans-ancestry Mendelian randomisation and found evidence of an increased CAD risk for higher LDL-C and BMI, and for lower HDL-C in G& H, consistent with our findings for EUR s les. The genetic loci for CAD and its risk factors are largely transferable from EUR studies to British Pakistanis and Bangladeshis, whereas the transferability of PGSs varies greatly between traits. Our analyses suggest clinical utility for addition of PGS to existing clinical risk prediction tools for this population. This is the first study to explore the transferability of GWAS findings and PGSs for CAD and related cardiometabolic traits in British Pakistani and Bangladeshi in iduals from a cohort with real-world electronic clinical data. We propose a new approach to assessing transferability of GWAS loci between populations, which can serve as a new methodological standard in this developing field. We find evidence of overall high transferability of GWAS loci in British Pakistanis and Bangladeshis. BMI, lipids and blood pressure show the highest transferability of loci, and CAD the lowest. The transferability of PGSs varied between traits, being high for HDL-C, triglycerides and blood pressure but more modest for CAD, BMI and LDL-C. Our results suggest that, for some traits, the use of transferable GWAS loci improves the robustness of Mendelian randomisation estimates in non-Europeans. The polygenic score for CAD derived from genetic studies of European in iduals improves reclassification on top of clinical risk factors in British Pakistanis and Bangladeshis. The improvement was driven by identification of more cases in younger in iduals (25–54 years old), and of controls in older in iduals (55–84 years old). Incorporation of the polygenic score for CAD into risk prediction models is likely to prevent cardiovascular events and deaths in this population.
Publisher: BMJ
Date: 22-02-1997
Abstract: To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants. Prospective cohort study (Whitehall II study). At the baseline examination (1985-8) and twice during follow up a self report questionnaire provided information on psychosocial factors of the work environment and coronary heart disease. Independent assessments of the work environment were obtained from personnel managers at baseline. Mean length of follow up was 5.3 years. London based office staff in 20 civil service departments. 10,308 civil servants aged 35-55 were examined-6895 men (67%) and 3413 women (33%). New cases of angina (Rose questionnaire), severe pain across the chest, diagnosed ischaemic heart disease, and any coronary event. Men and women with low job control, either self reported or independently assessed, had a higher risk of newly reported coronary heart disease during follow up. Job control assessed on two occasions three years apart, although intercorrelated, had cumulative effects on newly reported disease. Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 (95% confidence interval 1.34 to 2.77) compared with subjects with high job control at both occasions. This association could not be explained by employment grade, negative affectivity, or classic coronary risk factors. Job demands and social support at work were not related to the risk of coronary heart disease. Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices. The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease.
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2019-032165
Abstract: For non-ST-segment elevation acute coronary syndrome (NSTEACS) there is a gap between the use of class I guideline recommended therapies and clinical practice. The Global Registry of Acute Coronary Events (GRACE) risk score is recommended in international guidelines for the risk stratification of NSTEACS, but its impact on adherence to guideline-indicated treatments and reducing adverse clinical outcomes is unknown. The objective of the UK GRACE Risk Score Intervention Study (UKGRIS) trial is to assess the effectiveness of the GRACE risk score tool and associated treatment recommendations on the use of guideline-indicated care and clinical outcomes. The UKGRIS, a parallel-group cluster randomised registry-based controlled trial, will allocate hospitals in a 1:1 ratio to manage NSTEACS by standard care or according to the GRACE risk score and associated international guidelines. UKGRIS will recruit a minimum of 3000 patients from at least 30 English National Health Service hospitals and collect healthcare data from national electronic health records. The co-primary endpoints are the use of guideline-indicated therapies, and the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospitalisation or cardiovascular readmission at 12 months. Secondary endpoints include duration of inpatient hospital stay over 12 months, EQ-5D-5L responses and utilities, unscheduled revascularisation and the components of the composite endpoint over 12 months follow-up. The study has ethical approval (North East - Tyne & Wear South Research Ethics Committee reference: 14/NE/1180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder’s open access policy. ISRCTN29731761 Pre-results.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Harry Hemingway.