National Leadership in Cardiovascular Disease
Prof. Kausik Ray
National Cardiovascular Disease Theme Lead
The NIHR ARCs have eight national priority areas of applied health and care research that benefit from £13.125 million NIHR funding over three years to deliver ‘real world’ impact. NIHR ARC Northwest London is the national lead for Cardiovascular Disease.
Annually, cardiovascular disease (CVD) accounts for 18 million deaths globally. We led the 2022 World Heart Federation Cholesterol Roadmap, outlining the role of management of cholesterol throughout the life-course to mitigate this. Our work on inherited cholesterol disorders identified how to identify these in childhood and adolescence. We identified several gaps in cholesterol management across Europe and England which directly informed the NHS England Cholesterol Care Pathway 2022/23 as well as directly providing the evidence for the new 2023 cholesterol Quality and Outcomes Framework (QOF) indicators for cholesterol through greater use of combination therapies. Our industry collaborations have helped develop novel therapies for patients.
Improving the detection and management of lipid disorders in England and Globally
The process leading to CVD is called atherosclerosis, resulting from the retention of mostly low density lipoproteins containing cholesterol (LDL-C) in the blood vessel wall with cumulative effects over the lifespan; a process accelerated by inherited genetic vulnerability or risk factors, meaning most cases of CVD occur among individuals without extreme cholesterol elevations; hence assessing global risk rather than focusing solely on hypercholesterolaemia is essential, with the aim of implementing appropriate cholesterol lowering to match levels of risk throughout the life-course.
Our findings of unmet need across Europe, show that cholesterol targets are unmet in 80% of high/very high-risk patients and our modelling data shows this will only be achieved through use of combination therapies. This has fed into the NHS Cholesterol pathway guidance and impacted QOF Cholesterol targets.
Familial hypercholesterolaemia (FH) is a genetic condition occurring in 1:311 individuals leading to 32-fold elevation in LDL-C levels from birth, resulting in premature atherosclerotic CVD with <10% of the estimated 25 million cases being identified presenting a major opportunity for public health in England and elsewhere. We demonstrated that cases are diagnosed on average at age 44 with 1:5 having CVD yet only 2% were identified as children. Our latest findings show using LDL-C or genetics, children with FH who have yet to develop CVD can be clearly identified, paving the way for universal screening strategies. This has led to the Prague Declaration advocating for paediatric screening for lipid disorders such as FH in Europe.
Impact on Global Policies
This work has had an impact on national and global policies on the management of lipid disorders. Data from research studies was used to inform the new NHS new Quality and Outcomes Framework (QOF) lipid indicator in the 2023 GP contract.
Globally, the work fed into the World Heart Federation (WHF) Cholesterol Roadmap that aims to reduce the burden of preventable disease from lipid disorders. Further research has been funded in this area by industrial partners - Sanofi (£5M) and Novartis (£3.8M) - to test in England whether a decision support tool which provides detailed estimates of cardiovascular benefits results in optimisation of lipid lowering strategies early.
As part of a technical meeting of the Slovenian presidency of the council of EU 2021, NIHR ARC NWL presented on the importance of FH screening in childhood with findings from the children cohort to advocate for an action plan in Europe.
Why does this matter?
CVD remains a leading cause of death in England. Most people who develop CVD do not have extreme elevations in risk factors such as cholesterol. Hence, early risk assessment is needed.
Contemporary guidelines not only recommend identifying those with genetic causes of elevated cholesterol but also better managing risk itself through more intensive treatment of lipids and other risk factors such as high blood pressure to improve health outcomes for patients and reduce the burden of CVD on the NHS. Despite several lipid lowering therapies being available, many patients remain inadequately treated with both physicians and patients underestimating the value of further cholesterol lowering, i.e., the higher the risk the greater the benefit from cholesterol lowering. Hence, improved awareness, detection and management of lipid disorders and control of lipid has great potential for health gain; as shown in the recent decision by NICE to expand eligibility for drug treatment of lipid disorders. Moreover, with poor implementation of evidence-based therapies, there is a pressing national and global need to develop and evaluate care pathways that better implement novel therapies for the management of lipid disorders.
Unmet Need in England
We undertook a multinational observational study, titled the SANTORINI study looking at treatment gaps in the implementation of LDL cholesterol control among high and very high-risk patients in Europe.
The SANTORINI study demonstrates the unmet need and why it is vital to rethink approaches to manage cholesterol levels in high and very-high risk CV patients, specifically ensuring that these patients receive the most appropriate lipid-lowering therapies, in accordance with best practice, to help them achieve their target LDL-C goals. This study was adopted by the NIHR and showed England was the worst in Europe for use of combination therapy.
Next Steps
Working on progress made we will continue collaboration with NHS England, NICE, the NHS Accelerated Access Collaborative, NHS commissioners such as Integrated Care Boards, and public and patient groups.
If you're interested in more information or getting involved in our future work on Cardiovascular Disease, please get in touch with Professor Ray.