Anglo-Scandinavian Cardiac Outcomes Trial

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Objective for processing

This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. Imperial College London requires access to NHS England data for the purpose of the following research project: The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. Anglo-Scandinavian Cardiac Outcomes Trial The lawful basis for Imperial College London to process this data under GDPR is Article 6(1)(e) - Task in the public interest, and Article 9(2)(j) - Scientific or historical research in accordance with Article 89(1). The following is a summary of the aims of the research project provided on behalf of Imperial College London: The purpose of this application is to extend the linkage of participants in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) to all death, HES and mental health records. The ASCOT trial was a large trial comparing the health of participants randomly allocated to a statin (atorvastatin) or placebo, and to one of two blood pressure lowering drugs (amlodipine+/- perindopril or atenolol +/- bendrofluazide). The trial followed up participants for 5-years within the trial, and chiefly concentrated on measuring cardiovascular events, such as myocardial infarction and stroke. The trial was designed in 1995, and recruited participants between 1998 and 2000. The ASCOT trial was a large trial comparing the health of participants randomly allocated to a statin (atorvastatin) or placebo, and to one of two blood pressure lowering drugs (amlodopine+/- perindopril or atenelol +/- bendrofluazide). The trial followed up participants for 5-years within the trial, and concentrated on measuring cardiovascular events, such as myocardial infarction and stroke. ASCOT trial investigators evaluated the effects of the randomised treatments on long term measures of cardiovascular disease, renal endpoints and dementia. ASCOT was a large 2x2 factorial trial based in general practice in the UK, Ireland and Nordic countries. 19,342 patients with hypertension (i.e. SBP>160mmHg if untreated, or >140mmHg if treated, or DBP>100mmHg if untreated or >90mmHg if treated) and who had with >3 risk factors for cardiovascular disease, and no history of coronary heart disease (though some with a history of stroke) were eligible for the ASCOT-Blood Pressure-Lowering Arm (BPLA). Participants were randomized between 2 blood pressure lowering strategies: amlodipine with or without perindopril (amlodipine based) or atenolol with or without bendroflumethiazide (atenolol based). 10306 participants with fasting cholesterol of >6.5 mmol/L untreated with a cholesterol lowering agent were randomized to atorvastatin 10mg or placebo to ASCOT-Lipid-Lowering Arm (LLA). Atorvastatin led to a significant reduction in the hazard of the primary endpoint, fatal CHD and non-fatal MI (hazard ratio [HR], 0.64 [95% CI, 0.50-0.83). Although the amlodipine regime did not lead to a reduction in hazards of the primary endpoint, it was association with a reduction in fatal and non-fatal stroke (0.77 [0.66-0.89]) and all-cause mortality (0.89 [0.81-0.99 The trial was designed in 1995, and recruited participants between 1998 and 2000. At the time the trial was designed the relationship between blood pressure and dementia, and cholesterol and dementia was not well defined, and dementia was not a public health priority. Dementia is an insidious process that takes many years to develop. Data that is held within trial follow-up and mortality records contains very little information on the occurrence of dementia, and it is believed that by linking to HES and mental health records that ASCOT will be able to contribute to the understanding of the effect of blood pressure or cholesterol lowering on dementia. The aim of the study are to : The ASCOT trial investigators would therefore now like to evaluate the effects of the randomised treatments on dementia and other measures of long term health. 1. Determine whether participants randomised to atorvastatin have a lower long term risk of dementia, stroke diabetes and other vascular events compared to patients randomised to placebo ASCOT was a large 2x2 factorial trial based in general practice in the UK, Ireland and Nordic countries. 19,342 patients with hypertension (i.e. SBP≥160mmHg if untreated, or ≥140mmHg if treated, or DBP≥100mmHg if untreated or ≥90mmHg if treated) and who had with ≥3 risk factors for cardiovascular disease, and no history of coronary heart disease (though some with a history of stroke) were eligible for the ASCOT-Blood Pressure–Lowering Arm (BPLA). Participants were randomized between 2 blood pressure lowering strategies: amlodipine with or without perindopril (amlodipine based) or atenolol with or without bendroflumethiazide (atenolol based). 10306 participants with fasting cholesterol of ≤6.5 mmol/L untreated with a cholesterol lowering agent were randomized to atorvastatin 10mg or placebo to ASCOT-Lipid–Lowering Arm (LLA). 2. Determine whether participants randomised to an amlodipine-based regime have a lower risk of dementia, stroke, diabetes and other vascular events than patients randomised to an atenolol-based regime. Atorvastatin led to a significant reduction in the hazard of the primary endpoint, fatal CHD and non-fatal MI (hazard ratio [HR], 0.64 [95% CI, 0.50–0.83). Although the amlodipine regime did not lead to a reduction in hazards of the primary endpoint, it was association with a reduction in fatal and non-fatal stroke (0.77 [0.66-0.89]) and all-cause mortality (0.89 [0.81-0.99]). 3.Carry out further analyses of the databases to determine the phenotypic characterisation of subjects with high blood pressure variability Large observational studies have demonstrated associations between higher blood pressure and higher cholesterol in mid-life and a higher risk of dementia. However, there is little support from randomised trials or Mendelian randomisation studies for a strategy of lowering midlife blood pressure, or prescribing statins to prevent dementia. Therefore more data is needed in order to support public health interventions to prevent dementia. 4.To provide further information on the effects of drugs on blood pressure variability Therefore Imperial need access to records which measure the incidence of dementia. Dementia records are found in records of HES, emergency department admission and mental health records, and therefore Imperial will need to access all of these record types. 5.To investigate the role of biomarkers on blood pressure variability Dementia is an insidious condition, and probably develops over many years. Very long term trials may not be feasible, would be extremely expensive, and would take many years before they could have an impact on public health. In order to lengthen the follow up period of existing trials, Imperial propose to follow up UK participants in ASCOT by using information in the electronic health records of the English, Scottish, and Welsh national health systems and to measure the development of dementia over the very long term. 6.To investigate the role of blood pressure variability on the progression of renal disease The study therefore aims to determine whether: 7. To complete analyses on the long term effects of lipid lowering with atorvastatin on cardiovascular disease 1. Participants randomised to atorvastatin have a lower long term risk of dementia, stroke diabetes and other vascular events compared to patients randomised to placebo ICL published the results of the long term 20 year follow up on cardiovascular endpoints and dementia. One of the most important findings was that visit-to-visit systolic blood pressure variability was an independent predictor of several cardiovascular endpoints including coronary disease and stroke and also dementia, and that a treatment strategy involving the calcium channel blocker amlodipine not only reduced blood pressure variability but also lowered cardiovascular events by a mechanism involving reduced blood pressure variability. 2. Participants randomised to an amlodipine-based regime have a lower risk of dementia, stroke, diabetes and other vascular events than patients randomised to an atenolol-based regime. The following NHS England Data are currently held: The overall aims of ASCOT, are to determine the effect of higher LDL cholesterol and higher blood pressure on human health, remains the same as when it was founded. - Hospital Episode Statistics: Linkage to mortality for participant in the UK was begun as part of the initial ASCOT study, though Imperial are now requesting more detailed information on hospitalisations for other reasons (including mental health) in order to detect whether the treatments studies in the trial had any impact on the long term incidence of long term conditions including myocardial infarction, stroke, dementia or diabetes. Section 251 approval has been sought and obtained to cover the cohort linkage. Admitted Patient Care The aim of this study is to determine the effect of different regimes of lowering blood pressure and LDL-cholesterol on the long term health. Therefore significant years of follow-up are useful because: Accident & Emergency Long term health conditions are often under-recorded in each individual hospitalisation. It is necessary to try to ascertain these in multiple hospitalisations over the course of a participant’s life from the time of randomisation into the trial. Therefore, in the first instance, many years of follow-up increase the chance of ascertaining these illnesses. Outpatients Conditions such as dementia and diabetes may take many years to develop, sometimes 10 or 20 years. Therefore, in the second instance, many years of follow-up allow time for these conditions to develop, particularly diseases associated with ageing." - Mental Health and Learning Disablilities Data Sets (MHLDDS) - Mental Health Service Data Sets(MHSDS) - Mental Health Minimum Data Sets (MHMDS) The level of data will be identifiable. The Data will be minimised as follows - Limited to a cohort size of 7305 participants Imperial College London is the research sponsor and the controller as the organization responsible for ensuring that the Data will only be processed for the purpose described above. The lawful basis for Imperial College London to process this data under GDPR is 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 The lawful basis for processing special category data under the UK GDPR is: 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 funding is provided by Imperial College London. Data will be accessed by substantive employees of Imperial College London and Individuals holding an honorary contract under the supervision of a substantive employee of Imperial College London for the purposes described in this DSA only. Imperial College London must maintain records in a single location that cover the following details of each individual given access under an honorary contract: o Their substantive employer; o Their role in respect of the purpose for the processing specified in the DSA; o The start date and end date of the duration in which the Data will be accessed by the individual under an honorary contract; o The necessity for the Data to be accessed by the person(s) holding an honorary contract, instead of a substantive employee of an organisation named as controller or a processor in this DSA; o Confirmation that an appropriate contract is in place which follows the relevant guidance and is countersigned by the substantive employer of the honorary contract holder.

Processing activities

This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. Imperial College London transfered data to NHS England. The data consisted of identifying detail NHS Number, Name, Family Name, Date of Birth, Postcode, Gender and a unique person ID) for the cohort to be linked with NHS England data. The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. NHS England provided the relevant records from the list of datasets above to Imperial College London . The Data contained no direct identifying data items but contained a unique person ID which can be used to link the Data with other record level data already held by the recipient such as randomised allocation and in-trial events data NHS England already hold the identifiers from participants in the ASCOT trial, from their previous consent to mortality linkage. NHS Englandwill use these identifiers to further link participants to other aspects of the EHR. Also, each individual is currently identified by an ASCOT trial number. The Data will not be transferred to any other location. The ASCOT trial investigators do not hold identifiers for each individual, but do hold trial numbers. The Data will be stored on servers at Imperial College London Data received by Imperial will include ASCOT trial ID, age at recruitment and age at death or event, outcomes of relevance, and data from: HES admitted patient care, HES outpatients, A&E, mental health, date and cause of death. In addition Imperial are requesting data from a UK-wide dementia audit, that Imperial have previously been informed is linkable. The Data will be accessed onsite at the premises of Imperial College London. The ASCOT trial investigators will then use the trial ID to link data received from NHS England to other non-identifiable data held by the ASCOT team (for example randomised allocation, in-trial events. etc.) The Data will be accessed by authorised personnel via remote access. The ASCOT trial investigators will receive and link these datasets in a IG toolkit environment. For Imperial's purposes, this data is not identifiable, and investigators will then export the dataset with trial ID and age (to nearest year only) and age at death for analysis. This dataset will be available to bona fide researchers who approach the ASCOT team chief investigator. 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 long term effect of blood pressure and LDL cholesterol lowering treatments is of great interest. In order to power studies of these questions adequately, meta-analysis of study data may be needed. If such meta-analyses are performed, Imperial will share either ASCOT level summary estimates, or where appropriate anonymised individual level data with approved collaborators. For remote access: Because the long term follow-up of clinical trials is a matter of great interest, and the utility of clinical trial data many years after collection has often been proved to be greater than at the time of approvals (ASCOT has a number of good examples), Imperial would propose to keep an anonymised dataset indefinitely for the following reasons:. - 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; 1. Long term data retention is necessary to allow tabular data sharing which is now a requirement for publishing in high impact journals. Any tabulations would be aggregated with small number suppressed in line with the HES analysis guide - Access controls granting users the minimum level of access required are in place; 2. The study may wish to request further data depending on the results of this study. - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; For data from the Mental Health (MHSDS, MHLDDS, MHMDS) data sets, the following disclosure control rules must be applied: - Multifactor authentication (MFA) is required for remote access; • National-level figures only may be presented unrounded, without small number suppression - Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access; • Suppress all numbers between 0 and 5 - 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. • Round all other numbers to the nearest 5 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). • Percentages can be calculated based on unrounded values, but need to be rounded to the nearest integer in any outputs The Data will not leave England and Wales at any time. • 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 5. Access is restricted to employees or agents of Imperial College London who have authorisation from the ASCOT team chief Investigator. University of Edinburgh will not have access to any record level data." All personnel accessing the Data have been appropriately trained in data protection and confidentiality. The Data will be linked with the ASCOT database containing additional information on the participants who participated in the long-term follow-up. There will be no requirement and no attempt to reidentify individuals when using the Data. Researchers from Imperial College London will process the Data for the purposes described above.

Expected output

This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. ASCOT expect the following outputs: The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. 1. To obtain further detailed phenotypic characteristics of individuals with raised blood pressure variability who are at high cardiovascular risk and at high risk of dementia "ASCOT expect the following outputs: 2. To provide new information on the association of blood biomarkers with cardiovascular disease and dementia 1. An analysis of the effect of each drugs on dementia, hospitalisation, and cardiovascular outcomes in the very long term 3. To provide new data on the association of blood pressure variability and deterioration of renal function 2. An analysis to determine whether the effects of the drugs on long term outcomes is affected by their baseline characteristics. These outputs will be submitted for presentation at national and international conferences and submitted for publication. All outputs are publicised on the ASCOT website. When these outputs are available and submitted for publication, ASCOT will provide them to funders and other relevant boards. All outputs are publicised on the ASCOT website. Once data has been received by the ASCOT study team, they expect the initial analyses to take 18 months to 2 years. All outputs that will be published will be aggregated with small numbers suppressed in line with the HES analysis guide. All outputs will be that will be published will be aggregated with small numbers suppressed in line with the HES analysis guide. The study aim to present the findings of the work at the European Stroke Conference, Alzheimer’s Research UK and European Stroke Organisation Conference within 12 – 24 months. The study have extensive contacts with the Alzheimer’s Society, the Stroke Association and the British Heart Foundation, which they will use to communicate to patient groups, and as a conduit to policy makers such as NICE and other national guideline bodies. The ASCOT trial investigators will publish these outputs in major clinical journals (e.g. Lancet, BMJ, Stroke etc.) and present them in international meetings by study end, target 2019-2020 . it is anticipated these would contribute to national guidelines on reducing cardiovascular risk. Imperial will present outputs at international academic conferences (European Stroke Organisation Conference etc.), as well as at national meeting for people with dementia."

Expected measurable benefits

This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. Previous analyses of ASCOT outcome data have influenced national and international guidelines on bllod pressure and lipid management The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. Outcomes from the electronic data received from NHS England and PH Scotland have identified blood pressure variability to be a major independent cause of cardiovascular disease and dementia. Long term follow up of the UK cohort of the ASCOT population has shown that, 11 years after randomisation and approximately 8 years after trial closure, there was a significant reduction in all-cause mortality in subjects initially randomised to atorvastatin, suggesting a legacy effect of statins which persists many years after treatment (Sever PS et al, Eur Heart J 2011). Analysis of mortality data a further four years after trial closure showed further persistence of the legacy effect of atorvastatin on all-cause mortality (data presented at British Hypertension Society 2016.). Recent reviews incorporating our findings have highlighted the need to incorporate blood pressure variability in national and international guidelines for cardiovascular disease prevention and identify blood pressure variability as a new paradigm in the management of individuals with high blood pressure However, no such legacy benefits were apparent for the blood pressure lowering arm of the study. In order to strengthen the information on the legacy benefits of statins, and to ascertain whether such benefits exist for blood pressure lowering, It is proposed to extend the analysis to include all fatal and non-fatal events, such as dementia, diabetes, and fatal and non-fatal vascular events. It is believed that the results of this research will be of benefit to patients considering the long term benefits and harms of vascular secondary preventative medication, for example those in mid-life who are considering taking a statin or blood pressure lowering medication. Determining precisely the roles of higher blood pressure and LDL-cholesterol for dementia prevention is a priority for public health. If the control of vascular risk in mid-life or effective treatment of pre-symptomatic cerebral vascular disease could be shown to prevent or delay dementia, this would have considerable implications for the global burden of vascular-mediated dementia and for public policy. It would expand the number of people eligible for intervention at a younger age; and identify new methods to target interventions (currently targeted based on absolute risk of heart attack and stroke, not dementia). The cost-savings estimated from risk factor control (£60 million saved for every year’s delay in dementia in the 1% of the population with vascular risk factors) have been estimated solely from observational data (nice.org.uk/Guidance/NG16). Data from this analysis might substantially modify these estimates, giving commissioners better evidence to weigh the benefits of different interventions. If, on the other hand, a causal role for vascular risk factors or pre-symptomatic cerebral vascular disease cannot be demonstrated, this would lead to a radical shift in both research and public health priorities.""

Benefits reported

The data obtained from the incorporation of electronic data on the cause hospitalisations and causes of death for the ASCOT flagged patients has shown the long term benefits in the use of statins certain blood pressure treatment strategies and lipid lowering in the prevention of cardio-vascular cardiovascular disease. This has been influential in the debate around statin use, and UK guidelines. [5 paragraphs unchanged]

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

Objective for processing

[2 paragraphs unchanged] "The The lawful basis for Imperial College London to process this data under GDPR [10 words unchanged] Article 9(2)(j) - Scientific or historical research in accordance with Article 89(1). [17 paragraphs unchanged]

Processing activities

[2 paragraphs unchanged] "NHS NHS England already hold the identifiers from participants in the ASCOT trial, from [20 words unchanged] EHR. Also, each individual is currently identified by an ASCOT trial number. [15 paragraphs unchanged]

Expected measurable benefits

[2 paragraphs unchanged] "Long Long term follow up of the UK cohort of the ASCOT population has [65 words unchanged] of atorvastatin on all-cause mortality (data presented at British Hypertension Society 2016.). [5 paragraphs unchanged]

Benefits reported

[2 paragraphs unchanged] The study presented the findings of the work on dementia at the European Stroke Conference, Alzheimer’s Research UK and European Stroke Organisation Conference . The work on blood pressure variability has been presented at the British and Irish Hypertension Society, the International Society of Hypertension and the American Heart Association hypertension meeting [2 paragraphs unchanged] The additional linkage to records of hospitalisation from NHS England have already [9 words unchanged] and blood pressure variability on long term stroke outcomes and dementia .Stroke. 2021;52:3088-3096. 2021;52:3088-3096.New publications include European Heart Journal. 2024;45:1159 and several manuscripts in preparation

Unchanged: Expected output.

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

Objective for processing

The lawful basis for Imperial College London to process this data under GDPR is Article 6(1)(e) - Task in the public interest, and Article 9(2)(j) - Scientific or historical research in accordance with Article 89(1). This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. "The lawful basis for Imperial College London to process this data under GDPR is Article 6(1)(e) - Task in the public interest, and Article 9(2)(j) - Scientific or historical research in accordance with Article 89(1). [16 paragraphs unchanged] Conditions such as dementia and diabetes may take many years to develop, [13 words unchanged] follow-up allow time for these conditions to develop, particularly diseases associated with ageing. ageing."

Processing activities

NHS Digital already hold the identifiers from participants in the ASCOT trial, from their previous consent to mortality linkage. NHS Digital will use these identifiers to further link participants to other aspects of the EHR. Also, each individual is currently identified by an ASCOT trial number. This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. "NHS England already hold the identifiers from participants in the ASCOT trial, from their previous consent to mortality linkage. NHS Englandwill use these identifiers to further link participants to other aspects of the EHR. Also, each individual is currently identified by an ASCOT trial number. [2 paragraphs unchanged] The ASCOT trial investigators will then use the trial ID to link data received from NHS Digital England to other non-identifiable data held by the ASCOT team (for example randomised allocation, in-trial events. etc.) [11 paragraphs unchanged] University of Edinburgh will not have access to any record level data. data." 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).

Expected output

ASCOT expect the following outputs: This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. "ASCOT expect the following outputs: [6 paragraphs unchanged] Imperial will present outputs at international academic conferences (European Stroke Organisation Conference etc.), as well as at national meeting for people with dementia. dementia." We are seeking an extension as we have to receive HES data from NHS Digital.

Expected measurable benefits

Long term follow up of the UK cohort of the ASCOT population has shown that, 11 years after randomisation and approximately 8 years after trial closure, there was a significant reduction in all-cause mortality in subjects initially randomised to atorvastatin, suggesting a legacy effect of statins which persists many years after treatment (Sever PS et al, Eur Heart J 2011). Analysis of mortality data a further four years after trial closure showed further persistence of the legacy effect of atorvastatin on all-cause mortality (data presented at British Hypertension Society 2016.). This Data Sharing Agreement (DSA) permits continued retention of the data only. The DSA does not permit any other processing of the data. The detail below was provided in the previous version of the DSA and serves as a background to the Agreement. "Long term follow up of the UK cohort of the ASCOT population has shown that, 11 years after randomisation and approximately 8 years after trial closure, there was a significant reduction in all-cause mortality in subjects initially randomised to atorvastatin, suggesting a legacy effect of statins which persists many years after treatment (Sever PS et al, Eur Heart J 2011). Analysis of mortality data a further four years after trial closure showed further persistence of the legacy effect of atorvastatin on all-cause mortality (data presented at British Hypertension Society 2016.). [4 paragraphs unchanged] It would expand the number of people eligible for intervention at a [97 words unchanged] would lead to a radical shift in both research and public health priorities. priorities.""

Benefits reported

[1 paragraph unchanged] Cholesterol and blood pressure trials have led to major changes in NICE [61 words unchanged] was one of the first trials to use a high intensity statin. The published data has contributed to a new paradigm in cardiovascular risk assessment using blood pressure variability (QRISK3). The study presented the findings of the work on dementia at the European Stroke Conference, Alzheimer’s Research UK and European Stroke Organisation Conference . The incorporation of blood pressure variability as cardiovascular risk factor into the new risk factor model QRISK 3 was largely influenced by data from ASCOT. More recent guidelines for management of hypertension ( European Society of Cardiology/ European Society of Hypertension Guidelines for the management of arterial hypertension 2018) have also incorporated blood pressure variability as an important determinant of risk [1 paragraph unchanged] No benefits from the additional linkage have been achieved, as no data has been received for hospitalisation from NHS Digital. The additional linkage to records of hospitalisation from NHS England have already demonstrated the importance of specific blood pressure lowering strategies and blood pressure variability on long term stroke outcomes and dementia .Stroke. 2021;52:3088-3096.