Project description:The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in whole blood samples from 540 samples, of which 266 were samples taken from postmenopausal women with ovarian cancer and 274 were from age-matched healthy controls Keywords: DNA methylation
Project description:The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in whole blood samples from 540 samples, of which 266 were samples taken from postmenopausal women with ovarian cancer and 274 were from age-matched healthy controls Keywords: DNA methylation Bisulphite converted DNA from the 540 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
Project description:BackgroundPrevious studies have yielded conflicting results on the association between human cytomegalovirus (HCMV) and cardiovascular disease (CVD). This study examined associations between HCMV and incident CVD, ischaemic heart disease (IHD) and stroke.MethodsThis study included 8531 women and men of predominantly white ethnic background, aged 40-69 without prevalent CVD from the population-based UK Biobank study, recruited between 2006-2010 with HCMV antibody levels measured. CVD was ascertained via linkage to health administrative records collected until 2020. Multivariate Cox proportional-hazards models were used to determine associations between HCMV seropositivity and incident CVD, IHD and stroke. HCMV seropositive antibody levels in tertiles were used to assess dose-response associations.ResultsOver a mean follow-up period of 10.2 years, HCMV seropositivity was not significantly associated with CVD (Cases = 626, Hazard Ratio [HR] =1.01, 95% confidence interval [CI], .86-1.20), IHD (Cases = 539, HR=1.03, 95% CI, .87-1.24) or stroke (Cases = 144, HR = 0.96, 95% CI, .68-1.36). There was no evidence of dose-response associations with any outcome.ConclusionsWe found no significant association between HCMV seropositivity and risk of CVD, IHD or stroke. Further research within understudied populations, such as those of non-white ethnicity, and CVD subtypes is warranted.
Project description:BackgroundLimited evidence suggests elevated risks of cardiovascular disease (CVD) among people diagnosed with tuberculosis (TB) disease, though studies have not adjusted for preexisting CVD risk. We carried out a cohort study using 2 separate datasets, estimating CVD incidence in people with TB versus those without.MethodsUsing data from the United States (Veterans Health Administration) and the United Kingdom (Clinical Practice Research Datalink) for 2000-2020, we matched adults with incident TB disease and no CVD history 2 years before TB diagnosis (US, n = 2121; UK, n = 15 820) with up to 10 people without TB on the basis of age, sex, race/ethnicity and healthcare practice. Participants were followed beginning 2 years before TB diagnosis and for 2 years subsequently. The acute period was defined as 3 months before/after TB diagnosis. TB, CVD, and covariates were identified from electronic routinely collected data (primary and secondary care; mortality). Poisson models estimated incident rate ratios for CVD events in people with TB compared to those without.ResultsCVD incidence was consistently higher in people with TB, including during the baseline period (pre-TB) and particularly in the acute period: incident rate ratios were US, 3.5 (95% confidence interval, 2.7-4.4), and UK, 2.7 (2.2-3.3). Rate ratios remained high after adjusting for differences in preexisting CVD risk: US, 3.2 (2.2-4.4); UK, 1.6 (1.2-2.1).ConclusionsIncreased CVD incidence was observed in people with TB versus those without, especially within months of TB diagnosis, persistent after adjustment for differences in preexisting risk. Enhancing CVD screening and risk management may improve long-term outcomes in people with TB.
Project description:ObjectivesOur objective was to describe the prevalence of cardiovascular disease (CVD) risk factors in people of African ancestry with HIV in the UK.MethodsWe conducted a cross-sectional analysis of CVD risk factors in Black people with HIV aged ≥40 years and estimated the 10-year CVD risk using QRISK®3-2018. Correlations between body mass index (BMI) and CVD risk factors were described using Pearson correlation coefficients, and factors associated with 10-year CVD risk ≥5% were described using logistic regression.ResultsWe included 833 Black people with HIV and a median age of 54 years; 54% were female, 50% were living with obesity (BMI ≥30 kg/m2), 61% had hypertension, and 19% had diabetes mellitus. CVD risk >5% ranged from 2% in female participants aged 40-49 years to 99% in men aged ≥60 years, and use of statins ranged from 7% in those with CVD risk <2.5% to 64% in those with CVD risk ≥20%. BMI was correlated (R2 0.1-0.2) with triglycerides and diastolic blood pressure in women and with glycated haemoglobin, systolic and diastolic blood pressure, and total:high-density lipoprotein (HDL) cholesterol ratio in men. In both female and male participants, older age, blood pressure, diabetes mellitus, and kidney disease were strongly associated with CVD risk ≥5%, whereas obesity, total:HDL cholesterol, triglycerides, and smoking status were variably associated with CVD risk ≥5%.ConclusionsWe report a high burden of CVD risk factors, including obesity, hypertension, and diabetes mellitus, in people of African ancestry with HIV in the UK. BMI-focused interventions in these populations may improve CVD risk while also addressing other important health issues.
Project description:BackgroundDespite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.Methods and resultsData on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539).ConclusionsStroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.
Project description:This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.
Project description:BackgroundVaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed.MethodsIn a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN.ResultsAmong 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year.ConclusionThis first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK.