British Regional Heart Study (BRHS)- linkage of established cohort to NHS England datasets (HES, MHMDS, DIDS)

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Objective for processing

The lawful basis for processing personal data (Article 6.1) e: Public task: the processing is necessary for the data controller to perform a task in the public interest or for their official functions, and the task or function has a clear basis in law. and GDPR article 10 and Part 1 of the DPA 2018 for sensitive/special category personal data. University College London (UCL) and University of Newcastle require access to NHS England data for the purpose of the following research project: British Regional Heart Study (BRHS). Legal basis for processing special category data: (Article 9.2) j: Processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The following is a summary of the aims of the research programme: The Data Protection Act 2018 s7(1)(a) defines ‘public bodies’ for the purpose of the GDPR as “a public authority as defined by the Freedom of Information Act 2000”. The FOI Act 2000 Part 1, section 3 (1)(a)(i) specifies that a public authority means anybody which is listed in Schedule 1. Schedule 1 of the FOI Act 2000 lists “Maintained schools and further and higher education institutions” as public authorities. The overarching purpose is to enhance the BRHS cohort study by obtaining more robust detailed data on disease outcomes in order to research ways to prevent CVD, types of heart failure, dementia and disability in older ages. The British Regional Heart Study (BRHS) is an established, long-term cohort study of cardiovascular disease and other common chronic diseases - the study comprises older men, currently aged 75-94 years, who originally joined the study in 1978. The BRHS currently obtain cancer registration data, mortality data and use the tracing service under NIC-148411-Q64H8 (MR104). Morbidity rates in this study population are exceptionally high, with many study participants developing cardiovascular disease (CVD) and other physical illnesses; fractures and dementia are also major health problems. In order to obtain an accurate assessment of chronic disease outcomes, the researchers are seeking to supplement information on the cohort with disease information from hospital consultations and admissions (HES Data, MHMDS data and DIDs data). The following NHS England Data will be accessed: The British Regional Heart Study (BRHS) is a cohort of men recruited from 1978-80. DARS-NIC-148411-Q64H8 relies on S251 support under this agreement UCL receive mortality, cancer notifications and demographic data to trace participants for the entire cohort. DARS-NIC-28591-H5Q3X- is a subset of the overall BRHS cohort of men who have provided written consent, under this agreement the subset is linked to NHS HES, MMHDS and DIDS data sets • Diagnostic Imaging dataset Using these data UCL will examine trends in cardiovascular disease (CVD) mortality, CVD of morbidity and burden of disability, frailty and functional and cognitive decline in older adults. This rich scientific study resource will facilitate research on the development of novel CVD preventive strategies and for improving the cardiovascular health of older adults • Emergency Care Dataset The additional data provided by NHS England will be used to inform and develop a larger programme of research on the prevention of CVD (CHD and stroke), types of heart failure and CVD related ageing conditions including dementia, frailty and physical disability. For example, there is growing evidence that dementia and CVD share common risk factors. BRHS data resource now includes a wide range of novel risk factors measured at both 60-79 years and at 72-91 years (with blood stored for the measurement of further markers). The data from NHS England will enhance the study and will lay the ground for investigation into the aetiology, mechanisms and prevention of these age-related conditions in older men and allow us to test new hypotheses in cardiovascular ageing. • Hospital Episodes Statistics Accidents & Emergency Linking the NHS England data with the BRHS cohort database will strengthen/enhance the data on chronic disease diagnoses and on health service use. The researchers will use these NHS England data, using Study ID, along with data already available in the cohort study on social, biological, behavioural and environmental determinants of health - this will allow the researchers to undertake detailed research on the determinants of cardiovascular disease and other chronic diseases in later life. • Hospital Episodes Statistics Admitted Patient Care The overarching objectives/purpose of this data request is to enhance the BRHS cohort study by obtaining more robust detailed data on disease outcomes in order to research ways to prevent CVD, types of heart failure, dementia and disability in older ages. The researchers will link the NHS England data to pseudonymised data in the BRHS cohort study, which has been obtained (from the cohort) over the last 40 years - this includes mortality, cancer, postal questionnaire data completed by the participants, questionnaire data collected from General Practice and data collected during the physical assessments in 1978-1980, 1998-2000 and 2010-2012. • Hospital Episodes Statistics Critical Care The BRHS study team is housed within the Institute of Public Health and Epidemiology at University College London (UCL). The Institute produces internationally recognised quality research on the determinants of health and health behaviour across the life-course, develops and evaluates cross-sectoral policies and strategies to improve health, and optimise healthcare delivery and practice. University College London and Newcastle University are joint data controllers, who also process the data for the purpose outlined within this Agreement. The British Heart Foundation (BHF) fund the BRHS cohort study, as well as the data linkage which forms the basis of this Data Sharing Agreement (DSA). • Hospital Episodes Statistics Outpatients The BRHS study team has a 5-year British Heart Foundation core-funded program of research to study the causes, pathways and prevention of cardiovascular disease and disability among older British men. Core funding has been in place since 1985 and is renewed every five years after a scientific review. • Mental Health Minimum dataset The following scientific/research objectives will be investigated in the BRHS data based on the detailed disease outcomes data from NHS Digital - • Mental Health Services dataset 1. Prediction of CVD risk in older people - To investigate the use of non-invasive arterial markers and novel blood markers reflecting a range of biological pathways in improving CVD risk prediction in older men. The level of the Data will be Identifiable. 2. Lifestyle determinants of CVD in older age - To assess patterns of key health behaviour (physical activity, obesity, diet) in influencing CVD morbidity and mortality in both men with and without established CVD. The Data will be minimised as follows: 3. Modifiable risk factors and dementia - To investigate lifestyle factors measured in mid-life and older age (obesity, smoking, physical activity) as well as diet quality and nutritional markers in older age and risk of developing dementia. • Limited to a study cohort identified by UCL 4. Socioeconomic determinants of cardiovascular aging - To investigate the impact of socioeconomic factors that are important in preventing CVD and dementia in older people. • Restricted to cohort of 4123 male participants. This cohort is a subset of the overall BRHS cohort of men who have provided written consent. 5. Dementia and CVD – To investigate shared risk factors and mechanistic pathways underlying CVD and dementia and improving early identification of CVD and dementia. This research will help develop strategies to prevent dementia and CVD. UCL is the research sponsor. UCL and University of Newcastle are joint controllers as the organisations responsible for ensuring that the Data will only be processed for the purpose described above. 6. Determinants of Heart failure – (i) To investigate pathways to prevention of heart failure distinguishing between different types of heart failure; (ii) to develop prediction risk scores for use in clinical practice to identify older adults at high risk of developing any type of heart failure. The lawful basis for processing personal data under the UK GDPR is: 7. Later life determinants of stroke – To differentiate subtypes of strokes and distinguish risk factors for ischaemic and hemorrhagic strokes. Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; 8. Physical disability and frailty – To identify social, lifestyle and biological factors that affect physical functioning and frailty and identify common pathways underlying CVD and frailty which can inform efforts to prevent the development of disability in older people with CVD. The lawful basis for processing special category data under the UK GDPR is: 9. Type 2 Diabetes, CVD and dementia - To examine the influence of duration of diabetes on CVD risk and dementia and identify metabolic pathways linking diabetes with dementia. Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. 10. Improving clinical outcome – To identify and inform ways of evaluating and improving clinical outcomes in patients with CVD and/or dementia such as reducing hospitalisations and mortality. This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care. 11. Enhancing BRHS data- To develop a new source of data in an established population-based cardiovascular cohort study to facilitate the development of ways to improve strategies for preventions of CVD, heart failure, dementia and disability. The funding is provided by The British Heart Foundation. The funding is specifically for the project described. The funder(s) will have no ability to suppress or otherwise limit the publication of findings. Pulsant provides a backup data storage facility, this is a storage location for the Newcastle University servers and no Pulsant employees can access the data. Pulsant is therefore not considered to be acting as a data processor. University College London and Newcastle University are joint controllers. The British Heart Foundation (BHF) fund the BRHS cohort study, as well as the data linkage which forms the basis of this DSA. [1 paragraph unchanged] UCL uses offsite data centre services provided by VIRTUS data centre. VIRTUS does not have access to the data. Data will be accessed by substantive employees of UCL and University of Newcastle. Data will be accessed by Undergraduate, Masters or PhD students enrolled with UCL and University Newcastle Upon Tyne. Any student working with the Data held under this DSA must have completed relevant data protection and confidentiality training and are subject to UCL and University Newcastle Upon Tyne policies on data protection and confidentiality. Any students accessing the Data will do so under the supervision of a substantive employee of UCL and University Newcastle. UCL and University Newcastle would be responsible and liable for any work carried out by students. These students would only work on the Data for the purposes described in this DSA.

Processing activities

The BRHS currently receives data from three sources: UCL will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, Postcode, Gender, Family Name and a unique Study ID) for the cohort to be linked with NHS England data. 1. Study participants- Physical Examinations - 1978-80, 1998-2000, 2010-2012 and regular postal questionnaires - no further personal identifiers are collected. Participants are asked to provide their date of birth when returning the postal questionnaire, to ensure the form is completed by the intended recipient. NHS England will provide the relevant records from the datasets to UCL. 2. GP record review - data collected annually directly from participants' GP using a questionnaire sent to the GP. An update of the participant address is requested so that the researchers can continue to contact cohort members. The Data will contain no direct identifying data items but will contain a unique study ID which can be used to link the Data with other record level data already held by the recipient. 3. NHS England -Participants flagged in 1978-80 and the study receives Mortality notification & Cancer registration on a monthly basis via the Data Exchange Service (received under NIC-148411-Q64H8). This cohort is the original cohort, no new participants are added. UCL will extract the data received under this DSA and securely transfer it to University of Newcastle. 4. NHS England - Pseudonymised HES, MHMDS and DIDs data is received under DARS-NIC-28591-H5Q3X. The data will be stored on the UCL Data Safe Haven on servers at UCL and stored on servers at University of Newcastle. UCL uses offsite back-up services provided by VIRTUS Data Centres. UCL stores data on the Cloud provided by Amazon Web Services as contracted by UCL. GP Record review more information- The Data will be accessed onsite at the premises of UCL and University of Newcastle . GP data is collected through the BRHS record review – this is a bespoke collection of data from GP records of BRHS cohort participants. The BRHS record Review has been a central part of the BRHS morbidity data collection. Since 1978, at regular intervals, the BRHS research team send a survey form to the study participants GP, information on specific health events is ascertained The Data will also be accessed by authorised personnel via remote access. NHS England Data – (HES, MHSDS and DIDs) Linkage has already been established and data has been received by UCL and is retained. An annual refresh of this data is required. The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract. The BRHS cohort has been followed up since 1978. The researchers are requesting historic NHS England data (HES, MHSDS and DIDs) as far back as possible for this cohort i.e. all the available years of data) and on an annual basis going forward. Only those members of the cohort who have provided consent will be followed up for the research purposes mentioned in the objective for processing section. These data will be used to enhance the data already held in the cohort and help to produce robust research findings. Data are requested for this cohort going as far back as possible because this will provide detailed information necessary for research on cardiovascular disease and dementia. A key feature of a cohort study is that health outcomes are assessed over time which provides information on incidence (development) of disease. Therefore data on all available years are requested so as to have complete information on development of diseases - this is needed in order to investigate the research objectives which are to investigate determinants and prevention of diseases. For remote access: Without all the retrospective data requested, the research will be limited to only assessing the prevalence of diseases and lead to biased and limited data analysis. - Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA; Processing of data for the linkage requested: - Access controls granting users the minimum level of access required are in place; The BRHS will provide NHS Digital with Study ID, NHS number, DOB, Sex & last known postcode for linkage to the data requested from NHS Digital for 4,123 consented participants. - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; NHS Digital will return a pseudonymised dataset to the applicant containing study ID and match rank code. - Multifactor authentication (MFA) is required for remote access; Data received under DARS-NIC-28591-H5Q3X and DARS-NIC-148411-Q64H8 are linked to form a pseudonymised database. The Data manager from UCL will link the NHS Digital pseudonymised dataset to the BRHS cohort data base. This is done by matching the Study ID to the BRHS cohort data. The NHS Digital data will not be linked back to any personal identifiers. - Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access; Prior to linkage all identifiers are removed and stored on a separate database, the pseudonymised information received under both Agreements is then linked on a pseudo-ID. The identifiers are obtained for the purpose of maintaining contact with study members. - All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy. Identifiable data received under DARS-NIC-148411-Q64H is kept separately from the study database and is only used for the purpose of maintaining contact with study members. The linked data will be processed in a way that allows the study to address its key aims. The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose). The pseudonymised linked dataset, containing the NHS Digital data and the BRHS cohort data, will be stored on UCL’s Sync & Share network drives. The dataset created is robustly pseudonymised, and it was previously agreed by the NHSD Security team that the data could be stored on UCL’s Sync and share drive which are only accessible with a UCL user ID and password. To prevent any re-identification the identifiable information received under DARS-NIC-148411-Q64H8 is stored separately to the linked dataset, with access to the identifiers restricted to one named individual. The Data will not leave England/Wales at any time. Data is downloaded securely from NHS Digital SEFT and provides data security during transmission appropriate encryption into UCL Data Safe Haven via the DSH Data Ingress Desktop. Access is restricted to employees of UCL and University of Newcastle who have authorisation from the Principal Investigator. The BRHS team at UCL are responsible for the downloading, processing and storing of data. Pseudonymised BRHS data will be transferred securely to the BRHS team based at Newcastle University via their encrypted secure file drop. This data will be used only for analytical and analysis purposes. All personnel accessing the Data have been appropriately trained in data protection and confidentiality. The pseudonymised data containing the NHS Digital data and the BRHS cohort data, will then be made available to the research team of Medical Statisticians, Epidemiologists and Public Health clinicians, to carry out their research analysis. All the researchers working on the data are substantive employees of UCL / Newcastle University or hold honorary contracts with UCL. The terms ‘students’ include MSc Students, PhD Students, Clinical Academic Teaching Fellows (Medical Doctors in academic training). ‘Students’ are closely supervised by the study directors. All researchers are substantive employees of UCL or Newcastle University, their work is supervised by the study directors and students are registered with UCL or Newcastle University The Data will be linked at person record level with the BRHS cohort database from UCL. Student access -The number of students involved will vary each year, approximately five students and two medical academic fellows will require access to the data. All researchers will hold formal UCL contracts or honorary UCL contracts with the addendum contract for NHSD data. Students will be working within the agreed scope of the previously approved protocol and no students have accessed the data under this DSA previously. ‘Students’ include MSc Students, PhD Students, Clinical Academic Teaching Fellows (Medical Doctors in academic training). 'Students’ are closely supervised by the study directors. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset. All researchers must undergo annual Information Governance training. Researchers are able to access the data via remote access by logging onto UCLs VPN. Researchers from the UCL and University of Newcastle will analyse the Data for the purposes described above. For data from the Mental Health (MHSDS, MHLDDS, MHMDS) data sets, and any Mental Health data linked to HES or SUS, the following disclosure control rules must be applied: • National-level figures only may be presented unrounded, without small number suppression • Suppress all numbers between 0 and 5 • Round all other numbers to the nearest 5 • Percentages can be calculated based on unrounded values, but need to be rounded to the nearest integer in any outputs • In addition for Learning Disability data in Mental Health (MHSDS, MHLDDS, MHMDS), the England-level data also must apply the suppression of all numbers between 0 and 5, and rounding of other numbers to the nearest All small numbers under 5 must be suppressed in line with the HES analysis guide. All outputs will be restricted to aggregated data with small numbers suppressed in line with the HES analysis guide. No publications/outputs from the BRHS have ever presented or will present data which allow the identification of individuals. All data presented is based on groups of subjects (generally >50 subjects, often considerably larger numbers). Amazon Web Services provides cloud hosting services to UCL and will store the data as contracted by UCL.

Expected output

Short term goals - 1 year The expected outputs of the processing will be: Enhancing the BRHS cohort study with detailed data on disease outcomes based on HES, MHSDS and DIDs data requested under this iteration of the Data Sharing Agreement- This has been achieved Peer reviewed publications from the research in specialty journals in cardiovascular disease, heart failure, diabetes, stroke, public health and geriatric medicine. It may also provide research directly to funding bodies and policy makers (Department of Health, British Heart Foundation, National Institute of Health Research, Medical Research Council, UK Health Forum), clinicians, public health specialists and other health researchers who then use the evidence to develop preventive strategies Medium term goals - 2-5 years Abstracts submitted for presentation include: Peer reviewed publications in scientific and clinical journals based on research objectives mentioned in objective for processing section. (i) Associations between CVD health and types of heart failure in older British men: findings from the BRHS study has been presented at the Society of Social Medicine (September 2021). Long term goals - 5 years and over (ii) Prospective associations of NT-proBNP and troponin T with stroke events in older men free of CVD has been presented at the European Society of Cardiology meeting (September 2021). Adding to the scientific evidence base and knowledge to inform clinical guidelines and health policy. (iii) “Associations between diet quality, dietary components, and risk of cardiometabolic multimorbidity in older British men has been accepted for presentation for the Society Social Medicine meeting in September 2022. The specific outputs from the use of the data will be to generate further high quality research evidence about prevention of chronic diseases and to improve the health of older populations. Importantly, the NHS England data linkage requested will substantially strengthen and enhance the BRHS data on chronic disease events and diagnosis and on health service use. The new data linkage will substantially increase the quality of data relating to treatment and management of disease events permitting the researchers to investigate the disease endpoints in greater detail than has been done previously (e.g. understanding treatment received, recurrence of events and categorising sub-types of cardio vascular events). Linking the existing BRHS database to NHS England data will permit the research into a wide range of public health relevant topics. The potential benefits for the prevention of cardiovascular disease, diabetes, dementia and other chronic diseases and disability in later life are substantial. (iv) Abstract on associations between oral health and incident diabetes has been accepted for presentation for the Society Social Medicine meeting in September 2022. The BRHS has a track record of providing high quality evidence to improve the health of the public in the UK and internationally. To date (using data received under NIC-148411-Q64H8), the study has published over 600 peer reviewed research papers, providing high quality evidence about the epidemiology of these conditions and improving understanding on how to manage, treat and prevent them. Importantly, these papers have informed evidence based strategies to reduce the health and social care burden in older populations, as outlined in detail in section “Specific output” above. The researchers have contributed to a range of influential UK and international clinical guidelines for management and treatment of important chronic conditions including CHD, stroke, angina, arrhythmias, and diabetes which together cause substantial burdens of ill health in UK and globally. The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived. The BRHS have also contributed to public health guidelines and clinical guidelines about the modification of important cardiovascular disease risk factors (e.g. lipids, obesity, alcohol use, physical activity, smoking and passive smoking). Outputs are expected within1-5 years of the DSA commencing. Outputs are expected to continue beyond 5 years.

Expected measurable benefits

Enhanced data on The BRHS has a track record of providing high quality evidence to improve health and disease outcomes in the BRHS cohort study will allow further detailed research on ways to prevent chronic diseases in older ages. It is hoped this will lead to development of the research evidence-based that is needed to inform clinical guidelines public in UK and health policies to improve the health of ageing populations. internationally. Global trends of ageing populations will acutely increase the health and social [10 words unchanged] as cardiovascular disease, diabetes, dementia, other chronic diseases and disability in later life - these chronic diseases present both health and social care challenges in older populations. life. Therefore, research in this a cohort study BRHS of older men aims to establish the contributions of potentially important factors (obesity, diabetes, health [6 words unchanged] prevent cardiovascular disease, diabetes, dementia, other chronic diseases and disability in later life - this research evidence is crucially needed to inform health policies and clinical guidelines to reduce the health and social care burden of chronic diseases in older people. The long term goal (>5 years) of the research is to lead to improved care and prevention of chronic diseases and disability in older people. life. It is hoped data from NHS England will allow the following area of research to be addressed which will have potential implications for clinical practice: It is hoped the specific benefits from the use of the data will be to generate further high-quality research evidence about prevention of chronic diseases and to improve the health of older populations and management of multiple health conditions. As the population ages, an increasing proportion are living with multiple health conditions and frailty. The management of these patients conditions is complex. To meet this challenge, new ways of supporting clinical decision making need to be developed. Modifiable lifestyle factors and cardiometabolic multimorbidity Linking the existing BRHS databases to NHS England data will permit the researcher to study a wider range of public health relevant topics including multimorbidity which is an increasing concern for healthcare systems globally. The potential benefits for prevention of cardiovascular disease, diabetes, dementia, other age-related chronic diseases, multimorbidity and disability in later life are substantial to achieve healthier ageing and improve the quality of life in older people. Multimorbidity is generally understood to be the presence of two or more chronic conditions in one individual. Cardiometabolic multimorbidity (CMM) is a common pattern of multimorbidity, defined as the co-existence of two or more cardiometabolic diseases, including myocardial infarction (MI), stroke, type 2 diabetes (T2D), and related diseases. The prevalence of CMM increases with age, and with population aging worldwide, CMM is becoming an increasing global health concern. CMM contributes to decline in mobility, which impacts the physical, psychological and social aspects of the lives of older people, and any combination of cardio-metabolic disease is associated with multiplicative mortality risk. We are currently investigating the role of diet in the prevention of cardiometabolic multimorbidity including exploring the role of diet quality, fatty acids (particularly circulating omega-3 and omega-6 fatty acids), and blood lipids with risk of CMM. Work will be extended to the role of obesity and physical activity. This will help understand how people can stay healthier for longer. It is hoped this will enable clinicians to provide evidence-based personalised care to patients, by identifying which lifestyle modifications are most effective at reducing risk of cardio-metabolic multi-morbidity in older age. Healthcare costs relating to heart and circulatory diseases are estimated at £9 billion each year. It is estimated that the CVD’s cost to the UK economy (including premature death, disability and other costs) is estimated to be £19billion each year. Given the rapidly growing proportion of older people in the UK population, the health burden attributable to people living longer with CVD will continue to rise. There is a clear need to foster successful cardiovascular aging and to increase healthy life expectancy through improvements in CVD assessment, prevention, management and care at advanced age. Arterial stiffness and cardiovascular disease in older age Moreover, CVD and cancers are two leading causes of morbidity and mortality in the developed world. Advances in cancer therapeutics and diagnostics have led to improved survival of cancer patients. As survival from cancer increases, CVD in survivors has become increasingly prevalent. Although commonly thought of as 2 separate disease entities. The emerging field of cardio-oncology suggests common pathophysiological linkages owing to shared modifiable risk factors and overlapping molecular mechanisms. As a result, interest has increased in understanding the fundamental biological mechanism that are central to the relationship between CVD and cancer. With the continued collection of CVD and cancer events, the study is thus uniquely placed to study the modifiable risk factors and biological mechanisms common to CVD and cancer. It is hoped these findings will lay the foundation for developing prevention strategies and provide opportunities to improve the care of the growing cancer survivors. Arterial stiffness, represented as carotid-femoral pulse wave velocity (cfPWV), predicts cardiovascular disease. (CVD). Arterial stiffness occurs with ageing but in older populations, however, the association between arterial stiffness and risk of CVD seems attenuated. This research will investigate whether measurement of pulse wave velocity improves the performance of cardiovascular risk stratification tools in older adults aged >70 years which has potential to improve cost-effectiveness of cardiovascular disease prevention in the elderly in primary care. Research from the BRHS has already been used to shape and change many policies on cardiovascular disease prevention, both nationally and internationally, for example, in developing initiatives for primary prevention of CVD and dementia in South East London. Researchers have drawn on their expertise, established through working with BRHS data to develop independent initiatives for primary prevention of cardiovascular disease (CVD) and dementia in South East London. This was part of work undertaken in 2010. It was through evidence in the form of published peer-reviewed papers from the BRHS which were included as part of evidence for making a case for primary prevention of CVD in the work of the local Primary Care Trust. The study plans for future findings to be disseminated via national conference presentations including The Society for Social Medicine, the Nutrition Society, the British Geriatric Society, and Public Health England and via international conference presentations including the AHA Epidemiology and Prevention | Lifestyle and Cardiometabolic Health and The International Society of Behavioural Nutrition and Physical Activity meetings. The Study findings may also be cited in reports by a range of influential national and international public sector bodies including the UK House of Commons Health Select Committee, the UK Department of Health, the U.S. Surgeon General (whose reports inform health policies both in USA and other countries around the world) and the World Health Organisation (e.g. their Guidelines for assessment and management of cardiovascular risk).

Benefits reported

The BRHS is a unique cohort study of men with detailed assessments of risk factor exposure across the adult life from middle age into very old ages (90+) and is uniquely placed to study healthy cardiovascular ageing. The immediate benefits are to advance our research capability by enhancing the BRHS cohort with detailed phenotyped disease outcome from HES linkage. This has enabled us to investigate many [6 words unchanged] recently been published and have potential implications in clinical practice including: - 1. The influence of orthostatic hypotension on cardiovascular health. 1.Healthy lifestyle and survival free of cardiometabolic diseases and heart failure (HF) Exaggerated postural change in blood pressure, in particular, postural hypotension, is found in 1 in 5 community-dwelling older adults. Its association with falls and fractures is well-known but there is emerging evidence that it may also increase cardiovascular morbidity and mortality. We have shown that both orthostatic hypotension and systolic orthostatic hypertension (rise in blood pressure on standing) is associated with many cardiovascular risk factors and increased risk of developing types of heart failure. This work was published in the journal Hypertension (2021). This work led to a practice clinical update in the BMJ on postural hypotension (BMJ 2021; 373) and emphasises the important role in screening and detection of postural hypotension in primary care and in helping patients make shared treatment decisions to improve symptoms and reduce risk. Life’s Simple 7 (LS7) recommended by the American Heart Association (AHA) are 7 risk factors (smoking, physical activity, obesity, blood pressure, blood cholesterol, blood glucose and diet) that people can manage through lifestyle changes to improve health. The study team have estimated that life expectancy free of cardiometabolic disease (CHD, stroke and diabetes) was up to 4.5 years longer in men engaging in a healthier lifestyle compared to those who had a poor healthy lifestyle score. The findings have been published in Commun Med (Lond). 2024. The study team have also shown that a consistently healthy lifestyle, as reflected in a better cardiovascular health score (life’s simple 7) maintained over an adult lifetime, is associated with lower HF risk in older men. Results of the study have been published in the Eur J Preventive Cardiology 2025 with an accompanying editorial. These findings emphasise the importance of life’s simple 7 and through this insight, help the healthcare system to implement preventive measures for the benefit of the individual and the society. 2. The relationship between frailty and different types of heart failure 2. Subclinical vascular disease and incident CVD Heart failure (HF) and frailty are associated in cross-sectional studies, and probably share common pathophysiological determinants. Longitudinal data are very limited; We have determined whether frailty as measured by three different measures of frailty (based on Fried, Gill and HABC) is prospectively associated with HF risk in older men. We found an association between frailty—as measured by a novel score combining low gait speed, slow sit-stand time and subjective balance impairment—and incident HF risk, that persisted despite adjustment for comorbidities, known risk factors for HF and biomarkers of inflammation. Frailty as defined by the Fried frailty index showed a weaker association with HF risk and no associations was observed between a score based on the Gill index and HF. These findings published in OPEN HEART (2021 ) has potential impact on clinical practice. People who are frail should be considered at higher risk of developing HF. Further work might lead to frailty assessment, based on the criteria as describe here, being used as part of HF risk prediction scores. Interventions to prevent or ameliorate frailty might help to reduce the subsequent development of HF. Carotid intima-media thickness (CIMT) and carotid distensibility are markers of arterial change and indicators of subclinical vascular disease. The study team have shown that lower carotid distensibility (least flexible carotid arteries) and higher CIMT (thicker carotid artery walls) were also associated with an increased risk of incident heart failure (HF). These findings have been published in the Journal of the American Heart Association 2025. The carotid ultrasound is a safe, cheap and painless investigation, and the findings suggest it may be able to provide an early warning sign for HF. 3. Trajectories of physical activity from midlife to old age with subsequent cardiovascular disease and all-cause mortality. 3. The Mediterranean diet and cardiometabolic multimorbidity It is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear. A dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive. The findings published in the J Epidemiol Community Health 2020 has important implications for promoting physical activity. Promoting a light sustained level of PA across adulthood may be a feasible intervention target for the most inactive. Cardiometabolic multimorbidity (CMM) (having at least two of CHD, stroke or diabetes) contributes significantly to mortality and disability. The study team have shown that fish /seafood consumption, a dietary component of the mediterranean diet was significantly inversely related to the risk of CMM. These results are in keeping with the AHA and traditional Mediterranean diet recommendations of consuming nonfried fish/seafood 1–2 days/week, and further the potential health benefits towards reducing the risk of CMM. The findings are published in the European J Clinical Nutrition 2023. 4. Oral health and incident frailty 4. Socioeconomic deprivation, individual social class and diabetes Oral health problems, including tooth loss, periodontal disease, and dry mouth, accumulate throughout adult life and worsen with increasing age. The presence of oral health problems was associated with greater risks of being frail and developing frailty in older age (J Am Geriatr Soc. 2018). The identification and management of poor oral health in older people could be important in preventing frailty. This study investigated the prospective associations of neighborhood-level deprivation and individual socioeconomic position (SEP) with T2DM incidence in older age. Inequalities in T2DM risk persist in later life, both in relation to neighborhood-level and individual-level socioeconomic factors largely due to obesity and family history of diabetes. The findings are published in BMJ Open Diabetes Res Care. 2023. Underlying modifiable risk factors continue 5. Ideal cardiovascular health and prevention of stroke and CVD related outcomes in older men. to need to be addressed in deprived older age populations to reduce diabetes and disease burden. The European Stroke Organisation and Stroke Alliance for Europe emphasize both risk factor modification and improved stroke risk assessment as means to improve primary prevention in their latest European Stroke Action Plan. As part of the US 2020 strategic impact goal to improve the CVD health by 20%, the American Heart Association (AHA) charted a new strategy for CVD risk assessment and prevention by introducing the concept of ideal Cardiovascular Health (CVH) which comprises 7 metrics, including 4 ideal health behaviours (healthy diet, physical activity, non-smoking, and normal body weight) and 3 risk factors (cholesterol, glucose and blood pressure) commonly referred to as `Life’s simple 7’ . Less is known about its impact on stroke in older ages. We have addressed the impact of maintaining as well as changes in a positive AHA risk profile (`Life’s simple 7’) in older age on risk of stroke. We have shown that CVH is weakly associated with stroke at older ages. The findings published in STROKE (2020) suggests that prevention strategies for older adults should prioritize BP control but also enhance focus beyond traditional risk factors towards better detection and management of wider causes, including atrial fibrillation. We will extend this work to address the impact of life’s simple 7 on other disease endpoints including its impact on heart failure and dementia. 5. Social engagement and loneliness and health outcomes 6. Identifying older adults at high risk of developing venous thromboembolism Loneliness is recognized as a significant public health concern, affecting quality of life and a wide range of health outcomes. Our findings published in the American Journal of Epidemiology 2024 provides evidence that social inactivity and loneliness are potentially important factors that increase the risk of developing frailty as well as hinder its reversal and highlight the importance of considering social connections as a crucial and modifiable factor in interventions to promote healthy ageing. Venous thromboembolism (VTE; deep vein thrombosis and pulmonary embolism) is the third most common cause of cardiovascular death in the UK and other developed countries. Each year, over half a million people die from VTE in the United States and Europe; and 50% of survivors have long-term complications. For the half of VTE episodes which are non-provoked, there is a need to establish further risk predictors, in addition to age, obesity and smoking as assessed by Thrombosis risk score. We examined the associations between haematological and inflammatory variables with future VTE. Our findings suggest that the combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores. Both tests are routinely performed in UK haematology laboratories, to assess bleeding risk and VTE risk. This work is published online in the British Journal Haematology (2022). 6. Sporting leisure time activity and cognition in mid and later life. The study has an established track record of providing high quality evidence about the epidemiology of cardiovascular-related conditions, and improving understanding on how to manage, treat and prevent them (published >600 peer-reviewed research papers). Importantly, these papers have informed evidence-based strategies to reduce the health and social care burden in older populations. The research findings have been published and presented to scientific community at conferences. Some of the research findings have received national and international press attention. Research from this data linkage may provide similar benefits in the long-term of research outputs and producing evidence to influence practice. Consensus statement on PA and aging highlights moderate intensity physical activity (PA) as being favourable but concedes a lack of evidence exists as to the importance of PA context (social, physical, and mental domains) in relation to cognitive reserve. The study has shown that sports with team/partner elements were strongly positively associated with cognition in the older BRHS men. The findings have implications for physical activity guidelines. PA guidelines encouraging group‐based sporting activities may yield additional benefits for reducing cognitive decline in older age. The findings have been published in the Scand J Med Sci Sports 2023. Some particular examples of evidence generated of relevance to the wider health and social care system are – the importance of oral health and its influence on improving health outcomes in later life; persistent protective effects of physical activity in later life and potential protective effects of vitamin D in reducing the risk of mortality from respiratory disease 7. Orthostatic hypotension and risk of incident dementia Research from the BRHS has been used to shape and change many policies on cardiovascular disease prevention, both nationally and internationally. The BRHS provide outputs in the form of peer reviewed publications from the research to directly funding bodies and policy makers (Department of Health, British Heart Foundation, National Institute of Health Research, Medical Research Council, UK Health Forum), clinicians, public health specialists and other health researchers who then use the evidence to develop preventive strategies. The researchers have a track record of research findings informing health policies on a range of issues related to primary and secondary prevention of cardiovascular disease (CVD), management of stroke, angina, arrhythmias, and diabetes and modification of risk factors e.g. lipids, obesity, alcohol use, physical activity, smoking and passive smoking. Orthostatic hypotension (OH) (drop in BP on standing), is common in older adults; Its association with CVD, falls and fractures is well-known. The study has shown that diastolic OH in the elderly (>70 years) (drop in DBP on standing) is associated with risk of developing dementia which was not due to known risk factors. These findings emphasise the important role in screening and detection of OH in primary care. Given that OH is a modifiable condition, it represents a promising target for dementia prevention efforts. These findings will be presented at the WONCA (World Organization of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians) conference in September 2025. The Study findings will be cited in reports by a range of influential national and international public sector bodies including the UK House of Commons Health Select Committee, the UK Department of Health, the U.S. Surgeon General (whose reports inform health policies both in USA and other countries around the world) and the World Health Organisation (e.g. their Guidelines for assessment and management of cardiovascular risk). Contribution to cardiovascular and public health research Previous research is also cited in guidelines produced by professional organisations for treatment of specific chronic conditions, e.g. NICE guidelines, American Heart Association guidelines for prevention of stroke and transient ischemic attack, for management of cardiovascular disease, and management of ventricular arrhythmias condition, Australian guidelines for management of cardiovascular disease risk, Joint British Societies management of cardiovascular disease guidelines, Endocrine Society guidelines on hypertriglyceridemia and obesity. Evidence generated from the research has also been used to support local public health programmes, for example, in developing initiatives for primary prevention of CVD and dementia in South East London. The research findings have been published in open-access peer-reviewed scientific journals related to public health. Researchers have drawn on their expertise, established through working with BRHS data to develop independent initiatives for primary prevention of cardiovascular disease (CVD) and dementia in South East London. This was part of work undertaken in 2010. It was through evidence in the form of published peer-reviewed papers from the BRHS which were included as part of evidence for making a case for primary prevention of CVD in the work of the local Primary Care Trusts The study has an established track record of providing high quality evidence about the epidemiology of CVD and CVD-related conditions, and improving understanding on how to manage, treat and prevent them (published >600 peer-reviewed research papers). Importantly, these papers have informed evidence-based strategies to reduce the health and social care burden in older populations. The research findings have been published and presented to scientific community at conferences; some have received national and international press attention. Some particular recent examples of evidence generated of relevance to the wider health and social care system are the importance of maintaining a healthy lifestyle in improving life expectancy free of cardiometabolic diseases and HF risk and that it is never too late to adopt a healthy lifestyle for health benefits. Underlying modifiable risk factors continue to need to be addressed intensively in deprived older age populations to reduce disease burden. It highlights the potential use of carotid ultrasound which is a safe, cheap and painless investigation to help better understand the risk of future HF in older adults as well as the importance of screening for orthostatic hypotension in the elderly to identify those at high risk of dementia who may benefit from intervention. Encouraging group/team sport in the elderly may be important in reducing cognitive decline and preventing dementia. These published findings can be used as key messages to educate the public and inform policymakers. Retaining this linked data with HES will allow the study to continue to contribute to the global efforts to improve risk assessment and prediction of CVD and CVD-related morbidity including frailty and dementia and to developing CVD preventive strategies to improving the health of older adults. It will provide new knowledge on heathy ageing, specifically seeking to identify factors that determine why some older individuals remain physically and cognitively healthy well into their late 80s and 90s, whereas others show decline much earlier. Through these efforts, the BRHS has the potential to contribute to reducing the burden of CVD and related morbidity and improve social care and to refinement of clinical guidelines for improved management of CVD at advanced ages. Improved detection and management of CVD and related morbidity would yield substantial cost savings and health benefit. Contribution to policies and guidelines Research from the BRHS has been used to shape and change many policies on CVD prevention, both nationally and internationally. The BRHS provide outputs in the form of peer reviewed publications from the research to directly funding bodies and policy makers (Department of Health, British Heart Foundation, National Institute of Health Research, Medical Research Council, UK Health Forum), clinicians, public health specialists and other health researchers who then use the evidence to develop preventive strategies. The researchers have a track record of research findings informing health policies on a range of issues related to primary and secondary prevention of CVD, management of stroke, diabetes and modification of risk factors e.g. lipids, obesity, alcohol use, physical activity, smoking and passive smoking. The study findings have been cited in reports by a range of influential national and international public sector bodies including the UK House of Commons Health Select Committee , the UK Department of Health, the U.S. Surgeon General and the World Health Organisation (e.g. their Guidelines for assessment and management of cardiovascular risk) as well as in guidelines produced by professional organisations for treatment of specific chronic conditions, e.g. NICE guidelines, American Heart Association guidelines for prevention of stroke and management of cardiovascular disease, Joint British Societies management of cardiovascular disease guidelines, Endocrine Society guidelines on hypertriglyceridemia and obesity.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

On 1 February 2023, NHS Digital merged with NHS England. NHS England has assumed responsibility for all activities previously undertaken by NHS Digital. The merger was completed by a statute change. Any reference made to NHS Digital within this Data Sharing Agreement is in reference to the merged organisation known as NHS England. [6 paragraphs unchanged] The additional data provided by NHS Digital England will be used to inform and develop a larger programme of research [59 words unchanged] blood stored for the measurement of further markers). The data from NHS Digital England will enhance the study and will lay the ground for investigation into [10 words unchanged] older men and allow us to test new hypotheses in cardiovascular ageing. Linking the NHS Digital England data with the BRHS cohort database will strengthen/enhance the data on chronic disease diagnoses and on health service use. The researchers will use these NHS Digital England data, using Study ID, along with data already available in the cohort [21 words unchanged] the determinants of cardiovascular disease and other chronic diseases in later life. The overarching objectives/purpose of this data request is to enhance the BRHS [23 words unchanged] dementia and disability in older ages. The researchers will link the NHS Digital England data to pseudonymised data in the BRHS cohort study, which has been [27 words unchanged] and data collected during the physical assessments in 1978-1980, 1998-2000 and 2010-2012. The BRHS study team is housed within the Institute of Public Health [73 words unchanged] as well as the data linkage which forms the basis of this DSA. Data Sharing Agreement (DSA). [14 paragraphs unchanged] University College London and Newcastle University are joint data controllers, who also process the data for the purpose outlined within this Agreement. controllers. The British Heart Foundation (BHF) fund the BRHS cohort study, as well as the data linkage which forms the basis of this DSA DSA. Amazon Web Services (AWS) is a processor acting under the instructions of UCL. AWS’ role is limited to secure back-up of data stored in UCL’s Data Safe Haven. UCL uses offsite data centre services provided by VIRTUS data centre. VIRTUS does not have access to the data.

Processing activities

[3 paragraphs unchanged] 3. NHS Digital England -Participants flagged in 1978-80 and the study receives Mortality notification & Cancer [12 words unchanged] NIC-148411-Q64H8). This cohort is the original cohort, no new participants are added. 4. NHS Digital- England - Pseudonymised HES, MHMDS and DIDs data is received under DARS-NIC-28591-H5Q3X. [2 paragraphs unchanged] NHS Digital England Data – (HES, MHSDS and DIDs) Linkage has already been established and [5 words unchanged] UCL and is retained. An annual refresh of this data is required. The BRHS cohort has been followed up since 1978. The researchers are requesting historic NHS Digital England data (HES, MHSDS and DIDs) as far back as possible for this [136 words unchanged] the research objectives which are to investigate determinants and prevention of diseases. [21 paragraphs unchanged] The data from NHS Digital will not be used for any other purpose other than that outlined in this Agreement. Amazon Web Services provides cloud hosting services to UCL and will store the data as contracted by UCL. All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data).

Expected output

[6 paragraphs unchanged] The specific outputs from the use of the data will be to [10 words unchanged] diseases and to improve the health of older populations. Importantly, the NHS Digital England data linkage requested will substantially strengthen and enhance the BRHS data on [54 words unchanged] sub-types of cardio vascular events). Linking the existing BRHS database to NHS Digital England data will permit the research into a wide range of public health [12 words unchanged] dementia and other chronic diseases and disability in later life are substantial. [2 paragraphs unchanged]

Expected measurable benefits

[1 paragraph unchanged] It is hoped Data data from NHS digital England will allow us to address the following area of research to be addressed which will have potential implications for clinical practice practice: [4 paragraphs unchanged]

Unchanged: Benefits reported.

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Data controllers: + UNIVERSITY OF NEWCASTLE UPON TYNE

Objective for processing

The British Regional Heart Study (BRHS) is an established, long-term cohort study of cardiovascular disease and other common chronic diseases - the study comprises older men, currently aged 75-94 years, who originally joined the study in 1978. The BRHS currently obtain cancer registration data, mortality data and use the tracing service under NIC-148411-Q64H8 (MR104). The data held under NIC-148411-Q64H8 will not be linked to the data disseminated under this agreement. Morbidity rates in this study population are exceptionally high, with many study participants developing cardiovascular disease (CVD) and other physical illnesses; fractures and dementia are also major health problems. In order to obtain an accurate assessment of chronic disease outcomes, the researchers are seeking to supplement information on the cohort with disease information from hospital consultations and admissions (HES Data, MHMDS data and DIDs data). On 1 February 2023, NHS Digital merged with NHS England. NHS England has assumed responsibility for all activities previously undertaken by NHS Digital. The merger was completed by a statute change. Any reference made to NHS Digital within this Data Sharing Agreement is in reference to the merged organisation known as NHS England. The additional data provided by NHS Digital will be used to inform and develop a larger programme of research on the prevention of CVD (CHD and stroke), heart failure and CVD related ageing conditions including dementia, frailty and physical disability. For example, there is growing evidence that dementia and CVD share common risk factors. BRHS data resource now includes a wide range of novel risk factors measured at both 60-79 years and at 72-91 years (with blood stored for the measurement of further markers). The data from NHS Digital will enhance the study and will lay the ground for investigation into the aetiology, mechanisms and prevention of these age-related conditions in older men and allow us to test new hypotheses in cardiovascular ageing. The lawful basis for processing personal data (Article 6.1) e: Public task: the processing is necessary for the data controller to perform a task in the public interest or for their official functions, and the task or function has a clear basis in law. and GDPR article 10 and Part 1 of the DPA 2018 for sensitive/special category personal data. Legal basis for processing special category data: (Article 9.2) j: Processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The Data Protection Act 2018 s7(1)(a) defines ‘public bodies’ for the purpose of the GDPR as “a public authority as defined by the Freedom of Information Act 2000”. The FOI Act 2000 Part 1, section 3 (1)(a)(i) specifies that a public authority means anybody which is listed in Schedule 1. Schedule 1 of the FOI Act 2000 lists “Maintained schools and further and higher education institutions” as public authorities. The British Regional Heart Study (BRHS) is an established, long-term cohort study of cardiovascular disease and other common chronic diseases - the study comprises older men, currently aged 75-94 years, who originally joined the study in 1978. The BRHS currently obtain cancer registration data, mortality data and use the tracing service under NIC-148411-Q64H8 (MR104). Morbidity rates in this study population are exceptionally high, with many study participants developing cardiovascular disease (CVD) and other physical illnesses; fractures and dementia are also major health problems. In order to obtain an accurate assessment of chronic disease outcomes, the researchers are seeking to supplement information on the cohort with disease information from hospital consultations and admissions (HES Data, MHMDS data and DIDs data). The British Regional Heart Study (BRHS) is a cohort of men recruited from 1978-80. DARS-NIC-148411-Q64H8 relies on S251 support under this agreement UCL receive mortality, cancer notifications and demographic data to trace participants for the entire cohort. DARS-NIC-28591-H5Q3X- is a subset of the overall BRHS cohort of men who have provided written consent, under this agreement the subset is linked to NHS HES, MMHDS and DIDS data sets Using these data UCL will examine trends in cardiovascular disease (CVD) mortality, CVD of morbidity and burden of disability, frailty and functional and cognitive decline in older adults. This rich scientific study resource will facilitate research on the development of novel CVD preventive strategies and for improving the cardiovascular health of older adults The additional data provided by NHS Digital will be used to inform and develop a larger programme of research on the prevention of CVD (CHD and stroke), types of heart failure and CVD related ageing conditions including dementia, frailty and physical disability. For example, there is growing evidence that dementia and CVD share common risk factors. BRHS data resource now includes a wide range of novel risk factors measured at both 60-79 years and at 72-91 years (with blood stored for the measurement of further markers). The data from NHS Digital will enhance the study and will lay the ground for investigation into the aetiology, mechanisms and prevention of these age-related conditions in older men and allow us to test new hypotheses in cardiovascular ageing. [1 paragraph unchanged] The overarching objectives/purpose of this data request is to enhance the BRHS [7 words unchanged] data on disease outcomes in order to research ways to prevent CVD, types of heart failure, dementia and disability in older ages. The researchers will link [42 words unchanged] and data collected during the physical assessments in 1978-1980, 1998-2000 and 2010-2012. The BRHS study team is housed within the Institute of Public Health and Epidemiology at University College London (UCL). The Institute produces internationally recognised quality research on the determinants of health and health behaviour across the life-course, develops and evaluates cross-sectoral policies and strategies to improve health, and optimise healthcare delivery and practice. University College London and Newcastle University are joint data controllers, who also process the data for the purpose outlined within this Agreement. The British Heart Foundation (BHF) fund the BRHS cohort study, as well as the data linkage which forms the basis of this DSA. The BRHS study team has a 5-year British Heart Foundation core-funded program of research to study the causes, pathways and prevention of cardiovascular disease and disability among older British men. Core funding has been in place since 1985 and is renewed every five years after a scientific review. [6 paragraphs unchanged] 6. Determinants of Heart failure – (i) To investigate pathways to prevention of heart failure distinguishing between reduced ejection different types of heart failure and preserved ejection heart failure which is more common in older adults; failure; (ii) to develop prediction risk scores for use in clinical practice to identify older adults at high risk of developing any type of heart failure. [4 paragraphs unchanged] 11. Enhancing BRHS data- To develop a new source of data in an established population-based cardiovascular cohort study to facilitate the development of ways to improve strategies for preventions of CVD, heart failure, dementia and disability. Pulsant provides a backup data storage facility, this is a storage location for the Newcastle University servers and no Pulsant employees can access the data. Pulsant is therefore not considered to be acting as a data processor. University College London and Newcastle University are joint data controllers, who also process the data for the purpose outlined within this Agreement. The British Heart Foundation (BHF) fund the BRHS cohort study, as well as the data linkage which forms the basis of this DSA

Processing activities

[1 paragraph unchanged] 1. Study participants- Physical Examinations - 1978-80, 1998-2000, 2010-2012 and regular postal [14 words unchanged] date of birth when returning the postal questionnaire, to ensure the form in is completed by the intended recipient. [2 paragraphs unchanged] 4. NHS Digital- Pseudonymised HES, MHMDS and DIDs data is received under DARS-NIC-28591-H5Q3X. GP Record review more information- GP data is collected through the BRHS record review – this is a bespoke collection of data from GP records of BRHS cohort participants. The BRHS record Review has been a central part of the BRHS morbidity data collection. Since 1978, at regular intervals, the BRHS research team send a survey form to the study participants GP, information on specific health events is ascertained NHS Digital Data – (HES, MHSDS and DIDs) Linkage has already been established and data has been received by UCL and is retained. An annual refresh of this data is required. [5 paragraphs unchanged] Data received under DARS-NIC-28591-H5Q3X and DARS-NIC-148411-Q64H8 are linked to form a pseudonymised database. The Data manager from UCL will then link this the NHS Digital pseudonymised dataset, using the Study ID, dataset to the BRHS cohort data base. This is done by matching the Study ID for analysis. to the BRHS cohort data. The NHS Digital data will not be linked back to any personal identifiers. The pseudonymised dataset will be stored on UCL’s Sync & Share network drives which are only accessible with a UCL user ID and password. The pseudonymised data will then be made available to the research team of Medical Statisticians, Epidemiologists and Public Health clinicians, to carry out their research analysis. All the researchers working on the data are substantive employees of UCL. Prior to linkage all identifiers are removed and stored on a separate database, the pseudonymised information received under both Agreements is then linked on a pseudo-ID. The identifiers are obtained for the purpose of maintaining contact with study members. Identifiable data received under DARS-NIC-148411-Q64H is kept separately from the study database and is only used for the purpose of maintaining contact with study members. The linked data will be processed in a way that allows the study to address its key aims. The pseudonymised linked dataset, containing the NHS Digital data and the BRHS cohort data, will be stored on UCL’s Sync & Share network drives. The dataset created is robustly pseudonymised, and it was previously agreed by the NHSD Security team that the data could be stored on UCL’s Sync and share drive which are only accessible with a UCL user ID and password. To prevent any re-identification the identifiable information received under DARS-NIC-148411-Q64H8 is stored separately to the linked dataset, with access to the identifiers restricted to one named individual. Data is downloaded securely from NHS Digital SEFT and provides data security during transmission appropriate encryption into UCL Data Safe Haven via the DSH Data Ingress Desktop. The BRHS team at UCL are responsible for the downloading, processing and storing of data. Pseudonymised BRHS data will be transferred securely to the BRHS team based at Newcastle University via their encrypted secure file drop. This data will be used only for analytical and analysis purposes. The pseudonymised data containing the NHS Digital data and the BRHS cohort data, will then be made available to the research team of Medical Statisticians, Epidemiologists and Public Health clinicians, to carry out their research analysis. All the researchers working on the data are substantive employees of UCL / Newcastle University or hold honorary contracts with UCL. The terms ‘students’ include MSc Students, PhD Students, Clinical Academic Teaching Fellows (Medical Doctors in academic training). ‘Students’ are closely supervised by the study directors. All researchers are substantive employees of UCL or Newcastle University, their work is supervised by the study directors and students are registered with UCL or Newcastle University Student access -The number of students involved will vary each year, approximately five students and two medical academic fellows will require access to the data. All researchers will hold formal UCL contracts or honorary UCL contracts with the addendum contract for NHSD data. Students will be working within the agreed scope of the previously approved protocol and no students have accessed the data under this DSA previously. ‘Students’ include MSc Students, PhD Students, Clinical Academic Teaching Fellows (Medical Doctors in academic training). 'Students’ are closely supervised by the study directors. All researchers must undergo annual Information Governance training. Researchers are able to access the data via remote access by logging onto UCLs VPN. [5 paragraphs unchanged] • In addition for Learning Disability data in Mental Health (MHSDS, MHLDDS, [12 words unchanged] between 0 and 5, and rounding of other numbers to the nearest 5. [1 paragraph unchanged] All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data). All outputs will be restricted to aggregated data with small numbers suppressed in line with the HES analysis guide. No publications/outputs from the BRHS have ever presented or will present data which allow the identification of individuals. All data presented is based on groups of subjects (generally >50 subjects, often considerably larger numbers). All outputs will be restricted to aggregated data with small numbers suppressed in line with the HES analysis guide. No publications/outputs from the BRHS have ever presented or will present data which allow the identification of individuals. All data presentation is based on groups of subjects (generally >50 subjects, often considerably larger numbers). [1 paragraph unchanged] All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data).

Expected output

[1 paragraph unchanged] Enhancing the BRHS cohort study with detailed data on disease outcomes based on HES, MHSDS and DIDs data requested under this iteration of the Data Sharing Agreement. Agreement- This has been achieved [4 paragraphs unchanged] The specific outputs from the use of the data will be to [126 words unchanged] dementia and other chronic diseases and disability in later life are substantial. Target dates will run from the time of acquiring the data until 2019 with plans to further extend funding for the study. The BRHS cohort study has previously led to the development of evidence, knowledge and translation of evidence into health policies, as described below: The BRHS has a track record of providing high quality evidence to improve the health of the public in the UK and internationally. To date (using data received under NIC-148411-Q64H8), the study has published over 600 peer reviewed research papers, providing high quality evidence about the epidemiology of these conditions and improving understanding on how to manage, treat and prevent them. Importantly, these papers have informed evidence based strategies to reduce the health and social care burden in older populations, as outlined in detail in section “Specific output” above. The researchers have contributed to a range of influential UK and international clinical guidelines for management and treatment of important chronic conditions including CHD, stroke, angina, arrhythmias, and diabetes which together cause substantial burdens of ill health in UK and globally. More than 500 peer-reviewed reports have already been published based on the study which uses mortality data from NHS Digital. It is hoped that research from this new study will be published and utilised in the same way. The BRHS have also contributed to public health guidelines and clinical guidelines about the modification of important cardiovascular disease risk factors (e.g. lipids, obesity, alcohol use, physical activity, smoking and passive smoking). Research from the BRHS has been used to shape and change many policies on cardiovascular disease prevention, both nationally and internationally. The BRHS provide outputs in the form of peer reviewed publications from the research to directly funding bodies and policy makers (Department of Health, British Heart Foundation, National Institute of Health Research, Medical Research Council, UK Health Forum), clinicians, public health specialists and other health researchers who then use the evidence to develop preventive strategies. The researchers have a track record of research findings informing health policies on a range of issues related to primary and secondary prevention of cardiovascular disease (CVD), management of stroke, angina, arrhythmias, and diabetes and modification of risk factors e.g. lipids, obesity, alcohol use, physical activity, smoking and passive smoking. The Study findings will be cited in reports by a range of influential national and international public sector bodies including the UK House of Commons Health Select Committee, the UK Department of Health, the U.S. Surgeon General (whose reports inform health policies both in USA and other countries around the world) and the World Health Organisation (e.g. their Guidelines for assessment and management of cardiovascular risk). Previous research is also cited in guidelines produced by professional organisations for treatment of specific chronic conditions, e.g. NICE guidelines, American Heart Association guidelines for prevention of stroke and transient ischemic attack, for management of cardiovascular disease, and management of patients with ventricular arrhythmias, Australian guidelines for management of cardiovascular disease risk, Joint British Societies management of cardiovascular disease guidelines, Endocrine Society guidelines on hypertriglyceridemia and obesity. Evidence generated from the research has also been used to support local public health programmes, for example, in developing initiatives for primary prevention of CVD and dementia in South East London. The research findings have been published in open access peer-reviewed scientific journals related to public health.

Expected measurable benefits

Enhanced data on health and disease outcomes in the BHRS cohort study will allow further detailed research on ways to prevent chronic diseases in older ages. Enhanced data on health and disease outcomes in the BRHS cohort study will allow further detailed research on ways to prevent chronic diseases in older ages. It is hoped this will lead to development of the research evidence-based that is needed to inform clinical guidelines and health policies to improve the health of ageing populations. Global trends of ageing populations will acutely increase the health and social care burdens on individuals and society from chronic diseases such as cardiovascular disease, diabetes, dementia, other chronic diseases and disability in later life - these chronic diseases present both health and social care challenges in older populations. Therefore, research in this cohort study BRHS aims to establish the contributions of potentially important factors (obesity, diabetes, health behaviours, environmental and social factors) to prevent cardiovascular disease, diabetes, dementia, other chronic diseases and disability in later life - this research evidence is crucially needed to inform health policies and clinical guidelines to reduce the health and social care burden of chronic diseases in older people. The long term goal (>5 years) of the research is to lead to improved care and prevention of chronic diseases and disability in older people. This will lead to development of the research evidence-based that is needed to inform clinical guidelines and health policies to improve the health of ageing populations. It is hoped Data from NHS digital will allow us to address the following area of research which will have potential implications for clinical practice Global trends of ageing populations will acutely increase the health and social care burdens on individuals and society from chronic diseases such as cardiovascular disease, diabetes, dementia, other chronic diseases and disability in later life - these chronic diseases present both health and social care challenges in older populations. Therefore, research in this cohort study BRHS aims to establish the contributions of potentially important factors (obesity, diabetes, health behaviours, environmental and social factors) to prevent cardiovascular disease, diabetes, dementia, other chronic diseases and disability in later life - this research evidence is crucially needed to inform health policies and clinical guidelines to reduce the health and social care burden of chronic diseases in older people. The long term goal (>5 years) of the research is to lead to improved care and prevention of chronic diseases and disability in older people. Modifiable lifestyle factors and cardiometabolic multimorbidity The BRHS has a track record of providing high quality evidence to improve the health of the public in the UK and internationally. To date (using data received under NIC-148411-Q64H8), the study has published over 600 peer reviewed research papers, providing high quality evidence about the epidemiology of these conditions and improving understanding on how to manage, treat and prevent them. Importantly, these papers have informed evidence based strategies to reduce the health and social care burden in older populations, as outlined in detail in section “Specific output” above. The researchers have contributed to a range of influential UK and international clinical guidelines for management and treatment of important chronic conditions including CHD, stroke, angina, arrhythmias, and diabetes which together cause substantial burdens of ill health in UK and globally. Multimorbidity is generally understood to be the presence of two or more chronic conditions in one individual. Cardiometabolic multimorbidity (CMM) is a common pattern of multimorbidity, defined as the co-existence of two or more cardiometabolic diseases, including myocardial infarction (MI), stroke, type 2 diabetes (T2D), and related diseases. The prevalence of CMM increases with age, and with population aging worldwide, CMM is becoming an increasing global health concern. CMM contributes to decline in mobility, which impacts the physical, psychological and social aspects of the lives of older people, and any combination of cardio-metabolic disease is associated with multiplicative mortality risk. We are currently investigating the role of diet in the prevention of cardiometabolic multimorbidity including exploring the role of diet quality, fatty acids (particularly circulating omega-3 and omega-6 fatty acids), and blood lipids with risk of CMM. Work will be extended to the role of obesity and physical activity. This will help understand how people can stay healthier for longer. It is hoped this will enable clinicians to provide evidence-based personalised care to patients, by identifying which lifestyle modifications are most effective at reducing risk of cardio-metabolic multi-morbidity in older age. The BRHS have also contributed to public health guidelines and clinical guidelines about the modification of important cardiovascular disease risk factors (e.g. lipids, obesity, alcohol use, physical activity, smoking and passive smoking). Arterial stiffness and cardiovascular disease in older age Arterial stiffness, represented as carotid-femoral pulse wave velocity (cfPWV), predicts cardiovascular disease. (CVD). Arterial stiffness occurs with ageing but in older populations, however, the association between arterial stiffness and risk of CVD seems attenuated. This research will investigate whether measurement of pulse wave velocity improves the performance of cardiovascular risk stratification tools in older adults aged >70 years which has potential to improve cost-effectiveness of cardiovascular disease prevention in the elderly in primary care.

Benefits reported

This research is on-going, and findings have not yet been published in respect of the HES Data. The immediate benefits are to advance our research capability by enhancing the BRHS cohort with detailed phenotyped disease outcomes outcome from HES linkage. Researchers This has enabled us to investigate many important topics many of which have undertaken data linkage to the rest of the cohort study. recently been published and have potential implications in clinical practice including: - The study has an established track record of providing high quality evidence about the epidemiology of cardiovascular-related conditions, and improving understanding on how to manage, treat and prevent them (published >600 peer reviewed research papers). Importantly, these papers have informed evidence-based strategies to reduce the health and social care burden in older populations. Research from this data linkage may provide similar benefits in the long-term of research outputs and producing evidence to influence practice. 1. The influence of orthostatic hypotension on cardiovascular health. Exaggerated postural change in blood pressure, in particular, postural hypotension, is found in 1 in 5 community-dwelling older adults. Its association with falls and fractures is well-known but there is emerging evidence that it may also increase cardiovascular morbidity and mortality. We have shown that both orthostatic hypotension and systolic orthostatic hypertension (rise in blood pressure on standing) is associated with many cardiovascular risk factors and increased risk of developing types of heart failure. This work was published in the journal Hypertension (2021). This work led to a practice clinical update in the BMJ on postural hypotension (BMJ 2021; 373) and emphasises the important role in screening and detection of postural hypotension in primary care and in helping patients make shared treatment decisions to improve symptoms and reduce risk. 2. The relationship between frailty and different types of heart failure Heart failure (HF) and frailty are associated in cross-sectional studies, and probably share common pathophysiological determinants. Longitudinal data are very limited; We have determined whether frailty as measured by three different measures of frailty (based on Fried, Gill and HABC) is prospectively associated with HF risk in older men. We found an association between frailty—as measured by a novel score combining low gait speed, slow sit-stand time and subjective balance impairment—and incident HF risk, that persisted despite adjustment for comorbidities, known risk factors for HF and biomarkers of inflammation. Frailty as defined by the Fried frailty index showed a weaker association with HF risk and no associations was observed between a score based on the Gill index and HF. These findings published in OPEN HEART (2021 ) has potential impact on clinical practice. People who are frail should be considered at higher risk of developing HF. Further work might lead to frailty assessment, based on the criteria as describe here, being used as part of HF risk prediction scores. Interventions to prevent or ameliorate frailty might help to reduce the subsequent development of HF. 3. Trajectories of physical activity from midlife to old age with subsequent cardiovascular disease and all-cause mortality. It is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear. A dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive. The findings published in the J Epidemiol Community Health 2020 has important implications for promoting physical activity. Promoting a light sustained level of PA across adulthood may be a feasible intervention target for the most inactive. 4. Oral health and incident frailty Oral health problems, including tooth loss, periodontal disease, and dry mouth, accumulate throughout adult life and worsen with increasing age. The presence of oral health problems was associated with greater risks of being frail and developing frailty in older age (J Am Geriatr Soc. 2018). The identification and management of poor oral health in older people could be important in preventing frailty. 5. Ideal cardiovascular health and prevention of stroke and CVD related outcomes in older men. The European Stroke Organisation and Stroke Alliance for Europe emphasize both risk factor modification and improved stroke risk assessment as means to improve primary prevention in their latest European Stroke Action Plan. As part of the US 2020 strategic impact goal to improve the CVD health by 20%, the American Heart Association (AHA) charted a new strategy for CVD risk assessment and prevention by introducing the concept of ideal Cardiovascular Health (CVH) which comprises 7 metrics, including 4 ideal health behaviours (healthy diet, physical activity, non-smoking, and normal body weight) and 3 risk factors (cholesterol, glucose and blood pressure) commonly referred to as `Life’s simple 7’ . Less is known about its impact on stroke in older ages. We have addressed the impact of maintaining as well as changes in a positive AHA risk profile (`Life’s simple 7’) in older age on risk of stroke. We have shown that CVH is weakly associated with stroke at older ages. The findings published in STROKE (2020) suggests that prevention strategies for older adults should prioritize BP control but also enhance focus beyond traditional risk factors towards better detection and management of wider causes, including atrial fibrillation. We will extend this work to address the impact of life’s simple 7 on other disease endpoints including its impact on heart failure and dementia. 6. Identifying older adults at high risk of developing venous thromboembolism Venous thromboembolism (VTE; deep vein thrombosis and pulmonary embolism) is the third most common cause of cardiovascular death in the UK and other developed countries. Each year, over half a million people die from VTE in the United States and Europe; and 50% of survivors have long-term complications. For the half of VTE episodes which are non-provoked, there is a need to establish further risk predictors, in addition to age, obesity and smoking as assessed by Thrombosis risk score. We examined the associations between haematological and inflammatory variables with future VTE. Our findings suggest that the combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores. Both tests are routinely performed in UK haematology laboratories, to assess bleeding risk and VTE risk. This work is published online in the British Journal Haematology (2022). The study has an established track record of providing high quality evidence about the epidemiology of cardiovascular-related conditions, and improving understanding on how to manage, treat and prevent them (published >600 peer-reviewed research papers). Importantly, these papers have informed evidence-based strategies to reduce the health and social care burden in older populations. The research findings have been published and presented to scientific community at conferences. Some of the research findings have received national and international press attention. Research from this data linkage may provide similar benefits in the long-term of research outputs and producing evidence to influence practice. Some particular examples of evidence generated of relevance to the wider health and social care system are – the importance of oral health and its influence on improving health outcomes in later life; persistent protective effects of physical activity in later life and potential protective effects of vitamin D in reducing the risk of mortality from respiratory disease Research from the BRHS has been used to shape and change many policies on cardiovascular disease prevention, both nationally and internationally. The BRHS provide outputs in the form of peer reviewed publications from the research to directly funding bodies and policy makers (Department of Health, British Heart Foundation, National Institute of Health Research, Medical Research Council, UK Health Forum), clinicians, public health specialists and other health researchers who then use the evidence to develop preventive strategies. The researchers have a track record of research findings informing health policies on a range of issues related to primary and secondary prevention of cardiovascular disease (CVD), management of stroke, angina, arrhythmias, and diabetes and modification of risk factors e.g. lipids, obesity, alcohol use, physical activity, smoking and passive smoking. The Study findings will be cited in reports by a range of influential national and international public sector bodies including the UK House of Commons Health Select Committee, the UK Department of Health, the U.S. Surgeon General (whose reports inform health policies both in USA and other countries around the world) and the World Health Organisation (e.g. their Guidelines for assessment and management of cardiovascular risk). Previous research is also cited in guidelines produced by professional organisations for treatment of specific chronic conditions, e.g. NICE guidelines, American Heart Association guidelines for prevention of stroke and transient ischemic attack, for management of cardiovascular disease, and management of ventricular arrhythmias condition, Australian guidelines for management of cardiovascular disease risk, Joint British Societies management of cardiovascular disease guidelines, Endocrine Society guidelines on hypertriglyceridemia and obesity. Evidence generated from the research has also been used to support local public health programmes, for example, in developing initiatives for primary prevention of CVD and dementia in South East London. The research findings have been published in open-access peer-reviewed scientific journals related to public health. Researchers have drawn on their expertise, established through working with BRHS data to develop independent initiatives for primary prevention of cardiovascular disease (CVD) and dementia in South East London. This was part of work undertaken in 2010. It was through evidence in the form of published peer-reviewed papers from the BRHS which were included as part of evidence for making a case for primary prevention of CVD in the work of the local Primary Care Trusts

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Expected measurable benefits

[3 paragraphs unchanged] The BRHS has a track record of providing high quality evidence to [11 words unchanged] To date (using data received under NIC-148411-Q64H8), the study has published over 500 600 peer reviewed research papers, providing high quality evidence about the epidemiology of [70 words unchanged] which together cause substantial burdens of ill health in UK and globally. [1 paragraph unchanged]

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Datasets: + Emergency Care Data Set (ECDS)

Benefits reported

Yielded Benefits is not a requirement for new applications. This research is on-going, and findings have not yet been published in respect of the HES Data. The immediate benefits are to advance our research capability by enhancing the BRHS cohort with detailed phenotyped disease outcomes from HES linkage. Researchers have undertaken data linkage to the rest of the cohort study. The study has an established track record of providing high quality evidence about the epidemiology of cardiovascular-related conditions, and improving understanding on how to manage, treat and prevent them (published >600 peer reviewed research papers). Importantly, these papers have informed evidence-based strategies to reduce the health and social care burden in older populations. Research from this data linkage may provide similar benefits in the long-term of research outputs and producing evidence to influence practice.

Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits.