Publications by authors named "John Deanfield"

286 Publications

Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years.

Hypertension 2021 Jul 19:HYPERTENSIONAHA12117396. Epub 2021 Jul 19.

From the School of Human Development and Health, Institute of Developmental Sciences Building, Faculty of Medicine, University of Southampton, United Kingdom (R.M., N.K., E.A., G.C.B., K.M.G., M.A.H.).

Increases in aortic pulse wave velocity, a measure of arterial stiffness, can lead to elevated systolic blood pressure and increased cardiac afterload in adulthood. These changes are detectable in childhood and potentially originate in utero, where an adverse early life environment can alter DNA methylation patterns detectable at birth. Here, analysis of epigenome-wide methylation patterns using umbilical cord blood DNA from 470 participants in the Southampton's Women's Survey identified differential methylation patterns associated with systolic blood pressure, pulse pressure, arterial distensibility, and descending aorta pulse wave velocity measured by magnetic resonance imaging at 8 to 9 years. Perinatal methylation levels at 16 CpG loci were associated with descending aorta pulse wave velocity, with identified CpG sites enriched in pathways involved in DNA repair (=9.03×10). The most significant association was with cg20793626 methylation (within protein phosphatase, Mg2+/Mn2+ dependent 1D; β=-0.05 m/s/1% methylation change, [95% CI, -0.09 to -0.02]). Genetic variation was also examined but had a minor influence on these observations. Eight pulse wave velocity-linked dmCpGs were associated with prenatal modifiable risk factors, with cg08509237 methylation (within palmitoyl-protein thioesterase-2) associated with maternal oily fish consumption in early and late pregnancy. Lower oily fish consumption in early pregnancy modified the relationship between methylation and pulse wave velocity, with lower consumption strengthening the association between cg08509237 methylation and increased pulse wave velocity. In conclusion, measurement of perinatal DNA methylation signatures has utility in identifying infants who might benefit from preventive interventions to reduce risk of later cardiovascular disease, and modifiable maternal factors can reduce this risk in the child.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17396DOI Listing
July 2021

Quality of acute myocardial infarction care in England and Wales during the COVID-19 pandemic: linked nationwide cohort study.

BMJ Qual Saf 2021 Jun 22. Epub 2021 Jun 22.

Leeds Institute for Data analytics, University of Leeds, Leeds, UK.

Background And Objective: The impact of the COVID-19 pandemic on the quality of care for patients with acute myocardial infarction (AMI) is uncertain. We aimed to compare quality of AMI care in England and Wales during and before the COVID-19 pandemic using the 2020 European Society of Cardiology Association for Acute Cardiovascular Care quality indicators (QIs) for AMI.

Methods: Cohort study of linked data from the AMI and the percutaneous coronary intervention registries in England and Wales between 1 January 2017 and 27 May 2020 (representing 236 743 patients from 186 hospitals). At the patient level, the likelihood of attainment for each QI compared with pre COVID-19 was calculated using logistic regression. The date of the first national lockdown in England and Wales (23 March 2020) was chosen for time series comparisons.

Results: There were 10 749 admissions with AMI after 23 March 2020. Compared with before the lockdown, patients admitted with AMI during the first wave had similar age (mean 68.0 vs 69.0 years), with no major differences in baseline characteristics (history of diabetes (25% vs 26%), renal failure (6.4% vs 6.9%), heart failure (5.8% vs 6.4%) and previous myocardial infarction (22.9% vs 23.7%)), and less frequently had high Global Registry of Acute Coronary Events risk scores (43.6% vs 48.6%). There was an improvement in attainment for 10 (62.5%) of the 16 measured QIs including a composite QI (43.8% to 45.2%, OR 1.06, 95% CI 1.02 to 1.10) during, compared with before, the lockdown.

Conclusion: During the first wave of the COVID-19 pandemic in England and Wales, quality of care for AMI as measured against international standards did not worsen, but improved modestly.
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http://dx.doi.org/10.1136/bmjqs-2021-013040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228654PMC
June 2021

Case-ascertainment of acute myocardial infarction hospitalisations in cancer patients: a cohort study using English linked electronic health data.

Eur Heart J Qual Care Clin Outcomes 2021 Jun 22. Epub 2021 Jun 22.

Biostatistics Research Group, Department of Health Sciences, University of Leicester, Leicester, UK.

Aims: To assess the recording and accuracy of acute myocardial infarction (AMI) hospital admissions between two electronic health record databases within an English cancer population over time and understand the factors that affect case-ascertainment.

Methods And Results: We identified 112,502 hospital admissions for AMI in England 2010-2017 from the Myocardial Ischaemia National Audit Project (MINAP) disease registry and Hospital Episode Statistics (HES) for 95,509 patients with a previous cancer diagnosis up to 15 years prior to admission. Cancer diagnoses were identified from the National Cancer Registration Dataset (NCRD). We calculated the percentage of AMI admissions captured by each source and examined patient characteristics associated with source of ascertainment. Survival analysis assessed whether differences in survival between case-ascertainment sources could be explained by patient characteristics.57,265 (50.9%) AMI admissions in patients with a prior diagnosis of cancer were captured in both MINAP and HES. Patients captured in both sources were younger, more likely to have ST-segment elevation MI and had better prognosis, with lower mortality rates up to 9 years after AMI admission compared with patients captured in only one source. The percentage of admissions captured in both data sources improved over time. Cancer characteristics (site, stage and grade) had little effect on how AMI was captured.

Conclusion: MINAP and HES define different populations of patients with AMI. However, cancer characteristics do not substantially impact on case-ascertainment. These findings support a strategy of using multiple linked data sources for observational cardio-oncological research into AMI.
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http://dx.doi.org/10.1093/ehjqcco/qcab045DOI Listing
June 2021

Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial.

Arterioscler Thromb Vasc Biol 2021 Aug 10;41(8):e417-e426. Epub 2021 Jun 10.

Periodontology Unit, UCL Eastman Dental Institute and Hospital (M.O., Y.L., F.D.), University College London, United Kingdom.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.316388DOI Listing
August 2021

Substantial decline in hospital admissions for heart failure accompanied by increased community mortality during COVID-19 pandemic.

Eur Heart J Qual Care Clin Outcomes 2021 Jul;7(4):378-387

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute for Primary Care and Health Sciences, Keele University, Stoke-on-Trent, UK.

Aims: We hypothesized that a decline in admissions with heart failure during COVID-19 pandemic would lead to a reciprocal rise in mortality for patients with heart failure in the community.

Methods And Results: We used National Heart Failure Audit data to identify 36 974 adults who had a hospital admission with a primary diagnosis of heart failure between February and May in either 2018, 2019, or 2020. Hospital admissions for heart failure in 2018/19 averaged 160/day but were much lower in 2020, reaching a nadir of 64/day on 27 March 2020 [incidence rate ratio (IRR): 0.40, 95% confidence interval (CI): 0.38-0.42]. The proportion discharged on guideline-recommended pharmacotherapies was similar in 2018/19 compared to the same period in 2020. Between 1 February-2020 and 31 May 2020, there was a 29% decrease in hospital deaths related to heart failure (IRR: 0.71, 95% CI: 0.67-0.75; estimated decline of 448 deaths), a 31% increase in heart failure deaths at home (IRR: 1.31, 95% CI: 1.24-1.39; estimated excess 539), and a 28% increase in heart failure deaths in care homes and hospices (IRR: 1.28, 95% CI: 1.18-1.40; estimated excess 189). All-cause, inpatient death was similar in the COVID-19 and pre-COVID-19 periods [odds ratio (OR): 1.02, 95% CI: 0.94-1.10]. After hospital discharge, 30-day mortality was higher in 2020 compared to 2018/19 (OR: 1.57, 95% CI: 1.38-1.78).

Conclusion: Compared with the rolling daily average in 2018/19, there was a substantial decline in admissions for heart failure but an increase in deaths from heart failure in the community. Despite similar rates of prescription of guideline-recommended therapy, mortality 30 days from discharge was higher during the COVID-19 pandemic period.
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http://dx.doi.org/10.1093/ehjqcco/qcab040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244536PMC
July 2021

Study Protocol: The Heart and Brain Study.

Front Physiol 2021 31;12:643725. Epub 2021 Mar 31.

Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.

Background: It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart-brain association remain unclear. Recent evidence suggests that impairments in vascular phenotypes and cerebrovascular reactivity (CVR) may play an important role in cognitive decline. The combines state-of-the-art vascular ultrasound, cerebrovascular magnetic resonance imaging (MRI) and cognitive testing in participants of the long-running Whitehall II Imaging cohort to examine these processes together. This paper describes the study protocol, data pre-processing and overarching objectives.

Methods And Design: The 775 participants of the Whitehall II Imaging cohort, aged 65 years or older in 2019, have received clinical and vascular risk assessments at 5-year-intervals since 1985, as well as a 3T brain MRI scan and neuropsychological tests between 2012 and 2016 (Whitehall II Wave MRI-1). Approximately 25% of this cohort are selected for the , which involves a single testing session at the University of Oxford (Wave MRI-2). Between 2019 and 2023, participants will undergo ultrasound scans of the ascending aorta and common carotid arteries, measures of central and peripheral blood pressure, and 3T MRI scans to measure CVR in response to 5% carbon dioxide in air, vessel-selective cerebral blood flow (CBF), and cerebrovascular lesions. The structural and diffusion MRI scans and neuropsychological battery conducted at Wave MRI-1 will also be repeated. Using this extensive life-course data, the will examine how 30-year trajectories of vascular risk throughout midlife (40-70 years) affect vascular phenotypes, cerebrovascular health, longitudinal brain atrophy and cognitive decline at older ages.

Discussion: The study will generate one of the most comprehensive datasets to examine the longitudinal determinants of the heart-brain association. It will evaluate novel physiological processes in order to describe the optimal window for managing vascular risk in order to delay cognitive decline. Ultimately, the will inform strategies to identify at-risk individuals for targeted interventions to prevent or delay dementia.
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http://dx.doi.org/10.3389/fphys.2021.643725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046163PMC
March 2021

Revascularisation strategies in patients with significant left main coronary disease during the COVID-19 pandemic.

Catheter Cardiovasc Interv 2021 Mar 25. Epub 2021 Mar 25.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Keele University, Keele, UK.

Background: There are limited data on the impact of the COVID-19 pandemic on left main (LM) coronary revascularisation activity, choice of revascularisation strategy, and post-procedural outcomes.

Methods: All patients with LM disease (≥50% stenosis) undergoing coronary revascularisation in England between January 1, 2017 and August 19, 2020 were included (n = 22,235), stratified by time-period (pre-COVID: 01/01/2017-29/2/2020; COVID: 1/3/2020-19/8/2020) and revascularisation strategy (percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). Logistic regression models were performed to examine odds ratio (OR) of 1) receipt of CABG (vs. PCI) and 2) in-hospital and 30-day postprocedural mortality, in the COVID-19 period (vs. pre-COVID).

Results: There was a decline of 1,354 LM revascularisation procedures between March 1, 2020 and July 31, 2020 compared with previous years' (2017-2019) averages (-48.8%). An increased utilization of PCI over CABG was observed in the COVID period (receipt of CABG vs. PCI: OR 0.46 [0.39, 0.53] compared with 2017), consistent across all age groups. No difference in adjusted in-hospital or 30-day mortality was observed between pre-COVID and COVID periods for both PCI (odds ratio (OR): 0.72 [0.51. 1.02] and 0.83 [0.62, 1.11], respectively) and CABG (OR 0.98 [0.45, 2.14] and 1.51 [0.77, 2.98], respectively) groups.

Conclusion: LM revascularisation activity has significantly declined during the COVID period, with a shift towards PCI as the preferred strategy. Postprocedural mortality within each revascularisation group was similar in the pre-COVID and COVID periods, reflecting maintenance in quality of outcomes during the pandemic. Future measures are required to safely restore LM revascularisation activity to pre-COVID levels.
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http://dx.doi.org/10.1002/ccd.29663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292673PMC
March 2021

Place and Underlying Cause of Death During the COVID-19 Pandemic: Retrospective Cohort Study of 3.5 Million Deaths in England and Wales, 2014 to 2020.

Mayo Clin Proc 2021 04 16;96(4):952-963. Epub 2021 Feb 16.

Leeds Institute for Data Analytics, University of Leeds, United Kingdom; Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, United Kingdom; Leeds Teaching Hospitals NHS Trust, United Kingdom. Electronic address:

Objective: To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.

Methods: This national death registry included all adult (aged ≥18 years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.

Results: Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.

Conclusion: The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.
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http://dx.doi.org/10.1016/j.mayocp.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885692PMC
April 2021

Incidence and mortality due to thromboembolic events during the COVID-19 pandemic: Multi-sourced population-based health records cohort study.

Thromb Res 2021 06 8;202:17-23. Epub 2021 Mar 8.

Leeds Institute for Data Analytics, University of Leeds, UK; Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK; Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Background: Evidence supports an excess of deaths during the COVID-19 pandemic. We report the incidence and mortality of thrombo-embolic events (TE) during the COVID-19 pandemic.

Methods: Multi-sourced nationwide cohort study of adults (age ≥18 years) admitted to hospital with TE and deaths from TE in England (hospital and community) between 1st February 2018 and 31st July 2020. Relative risks, adjusted for age, sex, atrial fibrillation, co-morbidities and time trend comparing before and during the COVID-19 pandemic were estimated using Poisson regression.

Findings: Of 272,423 patients admitted with TE to 195 hospitals, 86,577 (31.8%) were admitted after 2nd March 2020 (first COVID-19 death in the UK). The incidence of TE hospitalised increased during the COVID-19 pandemic from 1090 to 1590 per 100,000 (absolute risk change 45.9% [95% CI 45.1-46.6%], adjusted relative risk [ARR] 1.43 [95% CI 1.41-1.44]) driven particularly by pulmonary embolism; 1.49, 95% CI 1.46-1.52. TE were more frequent among those with COVID-19; 1.9% vs. 1.6%, absolute risk change 21.7%, 95% CI 21.0-22.4%, ARR 1.20, 95% CI 1.18-1.22. There was an increase in the overall mortality from TE during the pandemic (617, 6.7% proportional increase compared with the historical baseline), with more TE deaths occurring in the community compared with the historical rate (44% vs. 33%).

Interpretation: The COVID-19 pandemic has resulted in an increase in the incidence of hospitalised TE. There were more deaths from TE in the community highlighting a number of mechanisms including the hypercoagulable state associated with COVID-19 infection and potential impact of delays in seeking help.

Research In Context: Evidence before this study We searched PubMed on 16 November 2020 for articles that documented the incidence and mortality of thrombo-embolic events (TE) during the COVID-19 pandemic using the search terms "COVID-19" OR "Coronavirus*" OR "2019-nCOV" OR "SARS-CoV" AND ("Thromboembolism" OR "Venous Thromboembolism" OR "thromboembol*") with no language or time restrictions. The majority of data on TE in COVID-19 pertains to hospitalised patients from retrospective cohort studies. One study found that TE in hospitalised patients was associated with an increased mortality rate (adjusted hazard ratio 1.82; 95% CI 1.54-2.15). A systematic review and meta-analysis of 35 studies in 9249 hospitalised patients calculated an overall pooled incidence of TE of 17.8% (95% CI: 9.9-27.4%), rising to 22.9% (95% CI: 14.5-32.4%) in patients admitted to intensive care (ICU). The most contemporary data are from a cohort of 1114 patients (715 outpatient, 399 hospitalised, 170 admitted to ICU). With robust COVID-19-specific therapies and widespread thromboprophylaxis the prevalence of venous TE in ICU patients was reported as 7% (n = 12) when catheter-/device-related events were excluded, and among the outpatients there was no TE reported. No published studies have used nationwide data to investigate TE during the pandemic or the effect of the pandemic on outcomes of patients with TE but without Covid-19. Added value of this study This retrospective multi-sourced nationwide unlinked cohort study compares the overall incidence and mortality of TE prior to and during the COVID-19 pandemic. We found an increased incidence of TE despite only a small proportion having a diagnosis of COVID-19. This may highlight the lack of testing, particularly in the community during the initial phase of the pandemic, and the possibility of other factors contributing to TE risk, such as decreased daily activity mandated by home quarantine and alterations in medication concordance. Mortality from TE was higher in the community during the pandemic and this highlights that adverse societal effects of the pandemic, such as aversion to seeking medical assessment, may precipitate worse outcomes related to TE. Implications of all the available evidence Evidence suggests that COVID-19 produces a hypercoagulable state and thromboprophylaxis is recommended in hospitalised patients to prevent excess mortality from TE. Whether to anticoagulate non-hospitalised ambulatory patients with COVID-19 will be answered by ongoing trials. Clinicians should consider the risks posed by decreased daily activity and fear of medical contact, and provide appropriate advice to patients.
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http://dx.doi.org/10.1016/j.thromres.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938753PMC
June 2021

Racial differences in management and outcomes of acute myocardial infarction during COVID-19 pandemic.

Heart 2021 05 8;107(9):734-740. Epub 2021 Mar 8.

Keele Cardiovascular Research Group, School of Medicine, Keele University, Keele, UK

Objective: There are concerns that healthcare and outcomes of black, Asian and minority ethnic (BAME) communities are disproportionately impacted by the COVID-19 pandemic. We investigated admission rates, treatment and mortality of BAME with acute myocardial infarction (AMI) during COVID-19.

Methods: Using multisource national healthcare records, patients hospitalised with AMI in England during 1 February-27 May 2020 were included in the COVID-19 group, whereas patients admitted during the same period in the previous three consecutive years were included in a pre-COVID-19 group. Multilevel hierarchical regression analyses were used to quantify the changes in-hospital and 7-day mortality in BAME compared with whites.

Results: Of 73 746 patients, higher proportions of BAME patients (16.7% vs 10.1%) were hospitalised with AMI during the COVID-19 period compared with pre-COVID-19. BAME patients admitted during the COVID-19 period were younger, male and likely to present with ST-elevation acute myocardial infarction. COVID-19 BAME group admitted with non-ST-elevation acute myocardial infarction less frequently received coronary angiography (86.1% vs 90.0%, p<0.001) and had a longer median delay to reperfusion (4.1 hours vs 3.7 hours, p<0.001) compared with whites. BAME had higher in-hospital (OR 1.68, 95% CI 1.27 to 2.28) and 7-day mortality (OR 1.81 95% CI 1.31 to 2.19) during COVID-19 compared with pre-COVID-19 period.

Conclusion: In this multisource linked cohort study, compared with whites, BAME patients had proportionally higher hospitalisation rates with AMI, less frequently received guidelines indicated care and had higher early mortality during COVID-19 period compared with pre-COVID-19 period. There is a need to develop clinical pathways to achieve equity in the management of these vulnerable populations.
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http://dx.doi.org/10.1136/heartjnl-2020-318356DOI Listing
May 2021

Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction.

Circ Genom Precis Med 2021 04 2;14(2):e003304. Epub 2021 Mar 2.

Genomics plc, Oxford, United Kingdom (F.R.-M., M.E.W., R.M., S.S., E.K., R.M.S., W.A.T., P.S., A.S.L., J.A.G., A.S., C.C.A.S., V.P., P.D.).

Background: There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment.

Methods: Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals.

Results: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7-7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%-15.4%), with the best performance in 40- to 54-year-old men (15.4% [95% CI, 11.6-19.3]). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period.

Conclusions: An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person's polygenic risk.
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http://dx.doi.org/10.1161/CIRCGEN.120.003304DOI Listing
April 2021

Outcomes of COVID-19-positive acute coronary syndrome patients: A multisource electronic healthcare records study from England.

J Intern Med 2021 07 13;290(1):88-100. Epub 2021 Mar 13.

From the, Keele Cardiovascular Research Group, Institute for Prognosis Research, School of Primary Care, Keele University, Keele, UK.

Background: Patients with underlying cardiovascular disease and coronavirus disease 2019 (COVID-19) infection are at increased risk of morbidity and mortality.

Objectives: This study was designed to characterize the presenting profile and outcomes of patients hospitalized with acute coronary syndrome (ACS) and COVID-19 infection.

Methods: This observational cohort study was conducted using multisource data from all acute NHS hospitals in England. All consecutive patients hospitalized with diagnosis of ACS with or without COVID-19 infection between 1 March and 31 May 2020 were included. The primary outcome was in-hospital and 30-day mortality.

Results: A total of 12 958 patients were hospitalized with ACS during the study period, of which 517 (4.0%) were COVID-19-positive and were more likely to present with non-ST-elevation acute myocardial infarction. The COVID-19 ACS group were generally older, Black Asian and Minority ethnicity, more comorbid and had unfavourable presenting clinical characteristics such as elevated cardiac troponin, pulmonary oedema, cardiogenic shock and poor left ventricular systolic function compared with the non-COVID-19 ACS group. They were less likely to receive an invasive coronary angiography (67.7% vs 81.0%), percutaneous coronary intervention (PCI) (30.2% vs 53.9%) and dual antiplatelet medication (76.3% vs 88.0%). After adjusting for all the baseline differences, patients with COVID-19 ACS had higher in-hospital (adjusted odds ratio (aOR): 3.27; 95% confidence interval (CI): 2.41-4.42) and 30-day mortality (aOR: 6.53; 95% CI: 5.1-8.36) compared to patients with the non-COVID-19 ACS.

Conclusion: COVID-19 infection was present in 4% of patients hospitalized with an ACS in England and is associated with lower rates of guideline-recommended treatment and significant mortality hazard.
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http://dx.doi.org/10.1111/joim.13246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013521PMC
July 2021

Associations between arterial stiffening and brain structure, perfusion, and cognition in the Whitehall II Imaging Sub-study: A retrospective cohort study.

PLoS Med 2020 12 29;17(12):e1003467. Epub 2020 Dec 29.

Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.

Background: Aortic stiffness is closely linked with cardiovascular diseases (CVDs), but recent studies suggest that it is also a risk factor for cognitive decline and dementia. However, the brain changes underlying this risk are unclear. We examined whether aortic stiffening during a 4-year follow-up in mid-to-late life was associated with brain structure and cognition in the Whitehall II Imaging Sub-study.

Methods And Findings: The Whitehall II Imaging cohort is a randomly selected subset of the ongoing Whitehall II Study, for which participants have received clinical follow-ups for 30 years, across 12 phases. Aortic pulse wave velocity (PWV) was measured in 2007-2009 (Phase 9) and at a 4-year follow-up in 2012-2013 (Phase 11). Between 2012 and 2016 (Imaging Phase), participants received a multimodal 3T brain magnetic resonance imaging (MRI) scan and cognitive tests. Participants were selected if they had no clinical diagnosis of dementia and no gross brain structural abnormalities. Voxel-based analyses were used to assess grey matter (GM) volume, white matter (WM) microstructure (fractional anisotropy (FA) and diffusivity), white matter lesions (WMLs), and cerebral blood flow (CBF). Cognitive outcomes were performance on verbal memory, semantic fluency, working memory, and executive function tests. Of 542 participants, 444 (81.9%) were men. The mean (SD) age was 63.9 (5.2) years at the baseline Phase 9 examination, 68.0 (5.2) at Phase 11, and 69.8 (5.2) at the Imaging Phase. Voxel-based analysis revealed that faster rates of aortic stiffening in mid-to-late life were associated with poor WM microstructure, viz. lower FA, higher mean, and radial diffusivity (RD) in 23.9%, 11.8%, and 22.2% of WM tracts, respectively, including the corpus callosum, corona radiata, superior longitudinal fasciculus, and corticospinal tracts. Similar voxel-wise associations were also observed with follow-up aortic stiffness. Moreover, lower mean global FA was associated with faster rates of aortic stiffening (B = -5.65, 95% CI -9.75, -1.54, Bonferroni-corrected p < 0.0125) and higher follow-up aortic stiffness (B = -1.12, 95% CI -1.95, -0.29, Bonferroni-corrected p < 0.0125). In a subset of 112 participants who received arterial spin labelling scans, faster aortic stiffening was also related to lower cerebral perfusion in 18.4% of GM, with associations surviving Bonferroni corrections in the frontal (B = -10.85, 95% CI -17.91, -3.79, p < 0.0125) and parietal lobes (B = -12.75, 95% CI -21.58, -3.91, p < 0.0125). No associations with GM volume or WMLs were observed. Further, higher baseline aortic stiffness was associated with poor semantic fluency (B = -0.47, 95% CI -0.76 to -0.18, Bonferroni-corrected p < 0.007) and verbal learning outcomes (B = -0.36, 95% CI -0.60 to -0.12, Bonferroni-corrected p < 0.007). As with all observational studies, it was not possible to infer causal associations. The generalisability of the findings may be limited by the gender imbalance, high educational attainment, survival bias, and lack of ethnic and socioeconomic diversity in this cohort.

Conclusions: Our findings indicate that faster rates of aortic stiffening in mid-to-late life were associated with poor brain WM microstructural integrity and reduced cerebral perfusion, likely due to increased transmission of pulsatile energy to the delicate cerebral microvasculature. Strategies to prevent arterial stiffening prior to this point may be required to offer cognitive benefit in older age.

Trial Registration: ClinicalTrials.gov NCT03335696.
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http://dx.doi.org/10.1371/journal.pmed.1003467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771705PMC
December 2020

In-Hospital and 30-Day Mortality After Percutaneous Coronary Intervention in England in the Pre-COVID and COVID Eras.

J Invasive Cardiol 2021 03 22;33(3):E206-E219. Epub 2020 Dec 22.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute for Primary Care and Health Sciences, Keele University, UK.

Background: Public reporting of percutaneous coronary intervention (PCI) outcomes is a performance metric and a requirement in many healthcare systems. There are inconsistent data on the causes of death after PCI, and the proportion of these deaths that are attributable to cardiac causes.

Methods: All patients undergoing PCI in England between January 1, 2017 and May 10, 2020 (n = 273,141) were retrospectively analyzed according to their outcome from the date of PCI: no death, in-hospital death, postdischarge death, and total 30-day death. The present study examined short-term primary causes of death after PCI in a national cohort before and during COVID-19.

Results: The overall rates of in-hospital and 30-day death were 1.9% and 2.8%, respectively. The rate of 30-day death declined between 2017 (2.9%) and February 2020 (2.5%), mainly due to lower in-hospital death (2.1% vs 1.5%), before rising again from March 1, 2020 (3.2%) due to higher rates of postdischarge mortality. Only 59.6% of 30-day deaths were due to cardiac causes, with the most common causes being acute coronary syndrome, cardiogenic shock, and heart failure, and this persisted throughout the study period. In the 30-day death group, 10.4% after March 1, 2020 were due to confirmed COVID-19.

Conclusions: In this nationwide study, we show that 40% of 30-day deaths are due to non-cardiac causes. Non-cardiac deaths have increased even more from the start of the COVID-19 pandemic, with 1 in 10 deaths from March 2020 being COVID-19 related. These findings raise a question of whether public reporting of PCI outcomes should be cause specific.
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March 2021

Evaluation of the uptake and delivery of the NHS Health Check programme in England, using primary care data from 9.5 million people: a cross-sectional study.

BMJ Open 2020 11 5;10(11):e042963. Epub 2020 Nov 5.

Public Health England, London, UK.

Objectives: To describe the uptake and outputs of the National Health Service Health Check (NHSHC) programme in England.

Design: Observational study.

Setting: National primary care data extracted directly by NHS Digital from 90% of general practices (GP) in England.

Participants: Individuals aged 40-74 years, invited to or completing a NHSHC between 2012 and 2017, defined using primary care Read codes.

Intervention: The NHSHC, a structured assessment of non-communicable disease risk factors and 10-year cardiovascular disease (CVD) risk, with recommendations for behavioural change support and therapeutic interventions.

Results: During the 5-year cycle, 9 694 979 individuals were offered an NHSHC and 5 102 758 (52.6%) took up the offer. There was geographical variation in uptake between local authorities across England ranging from 25.1% to 84.7%. Invitation methods changed over time to incorporate greater digitalisation, opportunistic delivery and delivery by third-party providers.The population offered an NHSHC resembled the English population in ethnicity and deprivation characteristics. Attendees were more likely to be older and women, but were similar in terms of ethnicity and deprivation, compared with non-attendees. Among attendees, risk factor prevalence reflected population survey estimates for England. Where a CVD risk score was documented, 25.9% had a 10-year CVD risk ≥10%, of which 20.3% were prescribed a statin. Advice, information and referrals were coded as delivered to over 2.5 million individuals identified to have risk factors.

Conclusion: This national analysis of the NHSHC programme, using primary care data from over 9.5 million individuals offered a check, reveals an uptake rate of over 50% and no significant evidence of inequity by ethnicity or deprivation. To maximise the anticipated value of the NHSHC, we suggest continued action is needed to invite more eligible people for a check, reduce geographical variation in uptake, prioritise engagement with non-attendees and promote greater use of evidence-based interventions especially where risk is identified.
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http://dx.doi.org/10.1136/bmjopen-2020-042963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646358PMC
November 2020

Impact of the COVID-19 Pandemic on Percutaneous Coronary Intervention in England: Insights From the British Cardiovascular Intervention Society PCI Database Cohort.

Circ Cardiovasc Interv 2020 11 3;13(11):e009654. Epub 2020 Nov 3.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute for Primary Care and Health Sciences, Keele University, Stoke-on-Trent, United Kingdom (C.S.K., M.A.M.).

Background: The objective of the study was to evaluate changes in percutaneous coronary intervention (PCI) practice in England by analyzing procedural numbers, changes in the clinical presentation, and characteristics of patients and their clinical outcomes during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: We conducted a retrospective cohort study of all patients who underwent PCI in England between January 2017 and April 2020 in the British Cardiovascular Intervention Society database.

Results: Forty-four hospitals reported PCI procedures for 126 491 patients. There were ≈700 procedures performed each week before the lockdown. After the March 23, 2020 lockdown (11th/12th week in 2020), there was a 49% fall in the number of PCI procedures after the 12th week in 2020. The decrease was greatest in PCI procedures performed for stable angina (66%), followed by non-ST-segment-elevation myocardial infarction (45%), and ST-segment-elevation myocardial infarction (33%). Patients after the lockdown were younger (64.5 versus 65.5 years, <0.001) and less likely to have diabetes (20.4% versus 24.6%, <0.001), hypertension (52.0% versus 56.8%, =0.001), previous myocardial infarction (23.5% versus 26.7%, =0.008), previous PCI (24.3% versus 28.3%, =0.001), or previous coronary artery bypass graft (4.6% versus 7.2%, <0.001) compared with before the lockdown.

Conclusions: The lockdown in England has resulted in a significant decline in PCI procedures. Fewer patients underwent PCI for stable angina. This enabled greater capacity for urgent and emergency cases, and a reduced length of stay was seen for such patients. Significant changes in the characteristics of patients towards a lower risk phenotype were observed, particularly for non-ST-segment-elevation myocardial infarction, reflecting a more conservative approach to this cohort.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009654DOI Listing
November 2020

Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes.

Hypertension 2020 12 26;76(6):1734-1743. Epub 2020 Oct 26.

From the Institute of Cardiovascular Science, University College London, United Kingdom (S.T.C., J.E.D.).

An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0-7.2] versus 5.3% [4.7-5.9]; =0.005), whereas no effect was observed following statin use (6.2% [5.5-6.8] versus 5.8% [5.1-6.4]; =0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8-5.9] versus 6.3% [5.8-6.7] for high-risk versus low-risk groups; =0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment (>0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03-0.12]; =0.001 and 0.5 m/s [0.4-0.6]; <0.001 for reactive hyperemia index and pulse wave velocity, respectively). ACE inhibitors improve endothelial function in high-risk adolescents as they transition through puberty. The longer-term protective effects of this intervention at this early age remain to be determined. Registration- URL: https://www.clinicaltrials.gov; Unique identifier NCT01581476.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15721DOI Listing
December 2020

Excess mortality in England and Wales during the first wave of the COVID-19 pandemic.

J Epidemiol Community Health 2021 03 15;75(3):213-223. Epub 2020 Oct 15.

Department of Health Sciences, University of York, York, UK.

Background: Deaths during the COVID-19 pandemic result directly from infection and exacerbation of other diseases and indirectly from deferment of care for other conditions, and are socially and geographically patterned. We quantified excess mortality in regions of England and Wales during the pandemic, for all causes and for non-COVID-19-associated deaths.

Methods: Weekly mortality data for 1 January 2010 to 1 May 2020 for England and Wales were obtained from the Office of National Statistics. Mean-dispersion negative binomial regressions were used to model death counts based on pre-pandemic trends and exponentiated linear predictions were subtracted from: (i) all-cause deaths and (ii) all-cause deaths minus COVID-19 related deaths for the pandemic period (week starting 7 March, to week ending 8 May).

Findings: Between 7 March and 8 May 2020, there were 47 243 (95% CI: 46 671 to 47 815) excess deaths in England and Wales, of which 9948 (95% CI: 9376 to 10 520) were not associated with COVID-19. Overall excess mortality rates varied from 49 per 100 000 (95% CI: 49 to 50) in the South West to 102 per 100 000 (95% CI: 102 to 103) in London. Non-COVID-19 associated excess mortality rates ranged from -1 per 100 000 (95% CI: -1 to 0) in Wales (ie, mortality rates were no higher than expected) to 26 per 100 000 (95% CI: 25 to 26) in the West Midlands.

Interpretation: The COVID-19 pandemic has had markedly different impacts on the regions of England and Wales, both for deaths directly attributable to COVID-19 infection and for deaths resulting from the national public health response.
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http://dx.doi.org/10.1136/jech-2020-214764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892396PMC
March 2021

Impact of Coronavirus Disease 2019 Pandemic on the Incidence and Management of Out-of-Hospital Cardiac Arrest in Patients Presenting With Acute Myocardial Infarction in England.

J Am Heart Assoc 2020 11 7;9(22):e018379. Epub 2020 Oct 7.

Keele Cardiovascular Research Group Institute for Prognosis Research School of Primary Care Keele University Newcastle UK.

Background Studies have reported significant reduction in acute myocardial infarction-related hospitalizations during the coronavirus disease 2019 (COVID-19) pandemic. However, whether these trends are associated with increased incidence of out-of-hospital cardiac arrest (OHCA) in this population is unknown. Methods and Results Acute myocardial infarction hospitalizations with OHCA during the COVID-19 period (February 1-May 14, 2020) from the Myocardial Ischaemia National Audit Project and British Cardiovascular Intervention Society data sets were analyzed. Temporal trends were assessed using Poisson models with equivalent pre-COVID-19 period (February 1-May 14, 2019) as reference. Acute myocardial infarction hospitalizations during COVID-19 period were reduced by >50% (n=20 310 versus n=9325). OHCA was more prevalent during the COVID-19 period compared with the pre-COVID-19 period (5.6% versus 3.6%), with a 56% increase in the incidence of OHCA (incidence rate ratio, 1.56; 95% CI, 1.39-1.74). Patients experiencing OHCA during COVID-19 period were likely to be older, likely to be women, likely to be of Asian ethnicity, and more likely to present with ST-segment-elevation myocardial infarction. The overall rates of invasive coronary angiography (58.4% versus 71.6%; <0.001) were significantly lower among the OHCA group during COVID-19 period with increased time to reperfusion (mean, 2.1 versus 1.1 hours; =0.05) in those with ST-segment-elevation myocardial infarction. The adjusted in-hospital mortality probability increased from 27.7% in February 2020 to 35.8% in May 2020 in the COVID-19 group (<.001). Conclusions In this national cohort of hospitalized patients with acute myocardial infarction, we observed a significant increase in incidence of OHCA during COVID-19 period paralleled with reduced access to guideline-recommended care and increased in-hospital mortality.
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http://dx.doi.org/10.1161/JAHA.120.018379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763705PMC
November 2020

Sex Differences in Mortality Rates and Underlying Conditions for COVID-19 Deaths in England and Wales.

Mayo Clin Proc 2020 10 23;95(10):2110-2124. Epub 2020 Jul 23.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Institutes of Applied Clinical Science and Primary Care and Health Sciences, Keele University, Keele, United Kingdom; Department of Cardiology, Royal Stoke University Hospital, Stoke-on-Trent, United Kingdom. Electronic address:

Objective: To address the issue of limited national data on the prevalence and distribution of underlying conditions among COVID-19 deaths between sexes and across age groups.

Patients And Methods: All adult (≥18 years) deaths recorded in England and Wales (March 1, 2020, to May 12, 2020) were analyzed retrospectively. We compared the prevalence of underlying health conditions between COVID and non-COVID-related deaths during the COVID-19 pandemic and the age-standardized mortality rate (ASMR) of COVID-19 compared with other primary causes of death, stratified by sex and age group.

Results: Of 144,279 adult deaths recorded during the study period, 36,438 (25.3%) were confirmed COVID deaths. Women represented 43.2% (n=15,731) of COVID deaths compared with 51.9% (n=55,980) in non-COVID deaths. Overall, COVID deaths were younger than non-COVID deaths (82 vs 83 years). ASMR of COVID-19 was higher than all other common primary causes of death, across age groups and sexes, except for cancers in women between the ages of 30 and 79 years. A linear relationship was observed between ASMR and age among COVID-19 deaths, with persistently higher rates in men than women across all age groups. The most prevalent reported conditions were hypertension, dementia, chronic lung disease, and diabetes, and these were higher among COVID deaths. Pre-existing ischemic heart disease was similar in COVID (11.4%) and non-COVID (12%) deaths.

Conclusion: In a nationwide analysis, COVID-19 infection was associated with higher age-standardized mortality than other primary causes of death, except cancer in women of select age groups. COVID-19 mortality was persistently higher in men and increased with advanced age.
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http://dx.doi.org/10.1016/j.mayocp.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377724PMC
October 2020

Place and causes of acute cardiovascular mortality during the COVID-19 pandemic.

Heart 2021 01 28;107(2):113-119. Epub 2020 Sep 28.

Leeds Institute for Data Analytics, University of Leeds, Leeds, UK

Objective: To describe the place and causes of acute cardiovascular death during the COVID-19 pandemic.

Methods: Retrospective cohort of adult (age ≥18 years) acute cardiovascular deaths (n=5 87 225) in England and Wales, from 1 January 2014 to 30 June 2020. The exposure was the COVID-19 pandemic (from onset of the first COVID-19 death in England, 2 March 2020). The main outcome was acute cardiovascular events directly contributing to death.

Results: After 2 March 2020, there were 28 969 acute cardiovascular deaths of which 5.1% related to COVID-19, and an excess acute cardiovascular mortality of 2085 (+8%). Deaths in the community accounted for nearly half of all deaths during this period. Death at home had the greatest excess acute cardiovascular deaths (2279, +35%), followed by deaths at care homes and hospices (1095, +32%) and in hospital (50, +0%). The most frequent cause of acute cardiovascular death during this period was stroke (10 318, 35.6%), followed by acute coronary syndrome (ACS) (7 098, 24.5%), heart failure (6 770, 23.4%), pulmonary embolism (2 689, 9.3%) and cardiac arrest (1 328, 4.6%). The greatest cause of excess cardiovascular death in care homes and hospices was stroke (715, +39%), compared with ACS (768, +41%) at home and cardiogenic shock (55, +15%) in hospital.

Conclusions And Relevance: The COVID-19 pandemic has resulted in an inflation in acute cardiovascular deaths, nearly half of which occurred in the community and most did not relate to COVID-19 infection suggesting there were delays to seeking help or likely the result of undiagnosed COVID-19.
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http://dx.doi.org/10.1136/heartjnl-2020-317912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523172PMC
January 2021

Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design.

Am Heart J 2020 11 17;229:61-69. Epub 2020 Jul 17.

Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH. Electronic address:

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.
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http://dx.doi.org/10.1016/j.ahj.2020.07.008DOI Listing
November 2020

Impact of COVID-19 on percutaneous coronary intervention for ST-elevation myocardial infarction.

Heart 2020 12 31;106(23):1805-1811. Epub 2020 Aug 31.

Keele Cardiovascular Research Group, Keele University, Keele, Staffordshire, UK

Background: The objective of the study was to identify any changes in primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in England by analysing procedural numbers, clinical characteristics and patient outcomes during the COVID-19 pandemic.

Methods: We conducted a retrospective cohort study of patients who underwent PCI in England between January 2017 and April 2020 in the British Cardiovascular Intervention Society-National Institute of Cardiovascular Outcomes Research database. Analysis was restricted to 44 hospitals that reported contemporaneous activity on PCI. Only patients with primary PCI for STEMI were included in the analysis.

Results: A total of 34 127 patients with STEMI (primary PCI 33 938, facilitated PCI 108, rescue PCI 81) were included in the study. There was a decline in the number of procedures by 43% (n=497) in April 2020 compared with the average monthly procedures between 2017 and 2019 (n=865). For all patients, the median time from symptom to hospital showed increased after the lockdown (150 (99-270) vs 135 (89-250) min, p=0.004) and a longer door-to-balloon time after the lockdown (48 (21-112) vs 37 (16-94) min, p<0.001). The in-hospital mortality rate was 4.8% before the lockdown and 3.5% after the lockdown (p=0.12). Following adjustment for baseline characteristics, no differences were observed for in-hospital death (OR 0.87, 95% CI 0.45 to 1.68, p=0.67) and major adverse cardiovascular events (OR 0.71, 95% CI 0.39 to 1.32, p=0.28).

Conclusions: Following the lockdown in England, we observed a decline in primary PCI procedures for STEMI and increases in overall symptom-to-hospital and door-to-balloon time for patients with STEMI. Restructuring health services during COVID-19 has not adversely influenced in-hospital outcomes.
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http://dx.doi.org/10.1136/heartjnl-2020-317650DOI Listing
December 2020

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes.

Pediatr Diabetes 2020 11 17;21(7):1322-1332. Epub 2020 Aug 17.

Department of Paediatrics, University of Cambridge, Cambridge, UK.

Objectives: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D.

Methods: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource.

Results: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10 ; -0.18 [-0.26, -0.11], P = 5.1 × 10 ; -0.12 [-0.20, -0.05], P = 1.6 × 10 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR.

Conclusions: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.
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http://dx.doi.org/10.1111/pedi.13095DOI Listing
November 2020

Patient response, treatments, and mortality for acute myocardial infarction during the COVID-19 pandemic.

Eur Heart J Qual Care Clin Outcomes 2021 05;7(3):238-246

Leeds Institute for Data Analytics, University of Leeds, Worsley Building, Level 11, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK.

Aims: COVID-19 might have affected the care and outcomes of hospitalized acute myocardial infarction (AMI). We aimed to determine whether the COVID-19 pandemic changed patient response, hospital treatment, and mortality from AMI.

Methods And Results: Admission was classified as non-ST-elevation myocardial infarction (NSTEMI) or STEMI at 99 hospitals in England through live feeding from the Myocardial Ischaemia National Audit Project between 1 January 2019 and 22 May 2020. Time series plots were estimated using a 7-day simple moving average, adjusted for seasonality. From 23 March 2020 (UK lockdown), median daily hospitalizations decreased more for NSTEMI [69 to 35; incidence risk ratios (IRR) 0.51, 95% confidence interval (CI) 0.47-0.54] than STEMI (35 to 25; IRR 0.74, 95% CI 0.69-0.80) to a nadir on 19 April 2020. During lockdown, patients were younger (mean age 68.7 vs. 66.9 years), less frequently diabetic (24.6% vs. 28.1%), or had cerebrovascular disease (7.0% vs. 8.6%). ST-elevation myocardial infarction more frequently received primary percutaneous coronary intervention (81.8% vs. 78.8%), thrombolysis was negligible (0.5% vs. 0.3%), median admission-to-coronary angiography duration for NSTEMI decreased (26.2 vs. 64.0 h), median duration of hospitalization decreased (4 to 2 days), secondary prevention pharmacotherapy prescription remained unchanged (each > 94.7%). Mortality at 30 days increased for NSTEMI [from 5.4% to 7.5%; odds ratio (OR) 1.41, 95% CI 1.08-1.80], but decreased for STEMI (from 10.2% to 7.7%; OR 0.73, 95% CI 0.54-0.97).

Conclusion: During COVID-19, there was a substantial decline in admissions with AMI. Those who presented to hospital were younger, less comorbid and, for NSTEMI, had higher 30-day mortality.
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http://dx.doi.org/10.1093/ehjqcco/qcaa062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454506PMC
May 2021

COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.

Lancet 2020 08 14;396(10248):381-389. Epub 2020 Jul 14.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, UK; Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, Oxford, UK. Electronic address:

Background: Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.

Methods: We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.

Findings: Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.

Interpretation: Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.

Funding: UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.
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http://dx.doi.org/10.1016/S0140-6736(20)31356-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429983PMC
August 2020

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Circulation 2020 Aug 13;142(6):546-555. Epub 2020 Jul 13.

Department of Cardiology, Division Heart and Lungs (V.T., A.F.S., J.v.S., A.O.K., F.W.A.), UMC Utrecht, Utrecht University, the Netherlands.

Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.

Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.

Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; =28%; -heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.

Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493828PMC
August 2020

Effects of tobacco cigarettes, e-cigarettes, and waterpipe smoking on endothelial function and clinical outcomes.

Eur Heart J 2020 11;41(41):4057-4070

Center for Cardiology-Cardiology I, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.

Tobacco smoking is a leading cause of non-communicable disease globally and is a major risk factor for cardiovascular disease (CVD) and lung disease. Importantly, recent data by the World Health Organizations (WHO) indicate that in the last two decades global tobacco use has significantly dropped, which was largely driven by decreased numbers of female smokers. Despite such advances, the use of e-cigarettes and waterpipes (shisha, hookah, narghile) is an emerging trend, especially among younger generations. There is growing body of evidence that e-cigarettes are not a harm-free alternative to tobacco cigarettes and there is considerable debate as to whether e-cigarettes are saving smokers or generating new addicts. Here, we provide an updated overview of the impact of tobacco/waterpipe (shisha) smoking and e-cigarette vaping on endothelial function, a biomarker for early, subclinical, atherosclerosis from human and animal studies. Also their emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and the circadian clock are summarized. We briefly discuss heat-not-burn tobacco products and their cardiovascular health effects. We discuss the impact of the toxic constituents of these products on endothelial function and subsequent CVD and we also provide an update on current recommendations, regulation and advertising with focus on the USA and Europe. As outlined by the WHO, tobacco cigarette, waterpipe, and e-cigarette smoking/vaping may contribute to an increased burden of symptoms due to coronavirus disease 2019 (COVID-19) and to severe health consequences.
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http://dx.doi.org/10.1093/eurheartj/ehaa460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454514PMC
November 2020