Novel approaches and concepts in CV risk screening and management

Kausik Ray, MD

Imperial College London

United Kingdom

Professor Kausik Ray

BSc, MBChB. MD, Mphil, FRCP (Lon), FRCP (Ed), FACC, FESC, FAHA

Professor of Public Health

School of Public Health, Imperial College London, UK

Screening for CVD and FH

Disclosures

• Advisory boards PCSK9 – Sanofi/Regeneron, Amgen, Pfizer, Roche, MSD

• NLI/ SC member for Odyssey –(Sanofi/Regeneron), Roche

• Investigator initiated research grant support (Sanofi/Regeneron/Pfizer/Amgen/MSD)

• CME lectures at Symposia (Sanofi/Regeneron, Amgen, Pfizer, AZ, MSD)

Screening- Who is it for?

General Populations

CVD - leading cause of death worldwide

• Current economic burden in the US of $133 million

• Projected costs more than £1 trillion by 2030 according to AHA1

• Most premature CVD deaths (<75 years) are preventable

1Weintraub WS, Daniels SR, Burke LE, et al. Value of Primordial and Primary Prevention for Cardiovascular Disease: A Policy Statement From the American Heart Association. Circulation. 2011 Aug 23. 124(8):967-990.

• Variable death rates for premature CVD from state to state in USA

• If the lowest death rate is observed in all states, 92,000 deaths are preventable 2

2 www.cdc.gov/media/releases/2014/p0501-preventable-deaths.html

CVD deaths are preventable

Use Epidemiological Data to Target those at Risk

Policy Change

• Translate this information into policy change

• Helps raise public awareness

• Provides a systematic approach

The NHS Health Check

The NHS Health Check

Adults aged 40-74 without a pre-existing condition invited for free health screening

Lifestyle questionnaire, BP, Lipid profile, ECG, BMI and Diabetes risk assessment

Follow up results with personalised advice and support

Estimated to prevent 1600 MI/CVAs, 650 premature deaths and >4,000 new diabetes cases/year3

3 www.nhs.uk/Conditions/nhs-health-check/Pages/NHS-Health-Check.aspx

• Assess CVD risk , Screen for DM, CKD

• Early intervention

• Diet, exercise, salt reduction, smoking cessation

• Where needed BP lowering/ Lipid modification

Where do get the biggest pickup

• High Coverage of Health Checks

• Low Socio Economic Groups

• Ethnic Minorities

• Burden of CV risk factors is high

• Ference BA et al. J Am Coll Cardiol 2012;60:2631–2639; Baigent C et al. Lancet 2005;366:1267–1278

Screen early, treat early, think about lifetime risk

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54.5 % relative risk reductionper 1 mM/L (38.7mg/dl)

LDL-C lowering

22 % relative risk reductionper 1 mM/L (38.7mg/dl)

LDL-C lowering

NICE lipid guidelines: primary prevention

QRISK2 assessment

10-year risk ≥10%

No established CVD

Discuss and support lifestyle changes

Manage other risk factors

Offer atorvastatin20 mg

National Institute for Health and Care Excellence

Lipid modification July 2014 http://www.nice.org.uk/Guidance/CG181

The NHS Health Check

Million Hearts® Project

Million Hearts® Project

Million Hearts® Project

Million Hearts® Project

Launched in 2012 with a goal to prevent 1 million MI/CVA by 2017

Educational campaigns to increase aware of CVD

Standardize and improve delivery of care for hypertension and hypercholesterolemia

Promote smoke-free policies and reduce sodium in food supplies

FH

Familial Hypercholesterolaemia

Estimated millions of individuals worldwide with FH by WHO regions and by income groups

Nordestgaard BG et al. Eur Heart J 2013;34:3478-3490

Estimated % of individuals diagnosedwith FH in different countries/ territories, as a fraction of those theoretically predicted based on a frequency of 1/500 in the general population

Familial Hypercholesterolaemia

Nordestgaard BG et al. Eur Heart J 2013;34:3478-3490

Cumulative LDL-C burden with and without familialhypercholesterolaemia as a function of age of

initiation of statin therapy

CHD, coronary heart disease; CV, cardiovascular; FH, familial hypercholesterolaemia; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Nordestgaard BG, et al. Eur Heart J 2013;34:3478–90

Despite available treatment approaches, a significant percentage of familial hypercholesterolaemia patients

are not at goal

Cross-sectional study was conducted in outpatient lipid clinics of three academic centres and two regional hospitals. Patient records of known HeFH patients were retrieved and data were reviewed on the use of lipid-lowering medication,

plasma lipids and lipoproteins, safety laboratory results, and reasons for not achieving treatment goals.HeFH, heterozygous familial hypercholesterolaemia; LDL-C, low-density lipoprotein cholesterol.

Pijlman AH, et al. Atherosclerosis 2010;209:189–94.

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Attainment ofLDL-C

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LDL-C target (mmol/l)

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0 43 5 6 7 8 9 10

• Only 21% of HeFH patients achieved the LDL-C treatment goal of <2.5 mmol/L

• Of those not at target, 73% did not use maximum statin treatment or combination with ezetimibe

n=1249

Using a modified DLCN criteria

1 in 4 to 1 in 5 infarcts under 50y of age could have FH!

Start Simple

• Early index cases , screen first degree family members

• Apps like FHSCORE based on the Dutch Lipid Network Criteria

• Where you have some evidence of a founder effect, worthwhile to send nurses health care professionals to towns villages where large numbers gather, churches, sporting events, community projects

Treatment

• High intensity statin therapy in adults. Trying to achieve at least a 50% reduction in LDL-C

• BUT

• Think about targets as even a 50% reduction will not normalise risk

• So EAS recommend 2.5mmol/L but for HoFHshould be <1.8mmol/L (Consensus Statement)

• NEED additional LMT- ezetemibe, bile acid absorption inhibitors, PCSK9i

• The burden of FH and its consequences can only be overcome by partnerships between academia, clinicians, patient representatives and policy makers in a coordinated systematic and sustained fashion.

EAS FH Studies Collaboration (FHSC)

Mission:

To empower the medical & global community to seek change in their respective countries ororganizations regarding how FH is detected and managed, with a view to promoting early diagnosis andmore effective treatment of this condition.

Through international collaboration of stakeholders we aim to generate large scale robust data on howFH is detected, managed and the clinical consequences of current practice on outcomes.

To work with all stakeholders including patient’s organizations to ensure that these state-of-the-artinformation are utilized to close gaps in knowledge and/or improve clinical practice for our FH patients.

• International steering committee:

– Prof Kausik K. Ray UK Lead FHSC

– Prof Alberico L. Catapano Italy President EAS

– Dr Handrean Soran UK

– Prof John Kastelein The Netherlands

– Prof G. Kees Hovingh The Netherlands

– Prof Pedro Mata Spain

– Prof Gerald Watts Australia

– Prof Frederick Raal South Africa

– Prof Raul Santos Brazil

Coordinating Centre

EAS FHSC Steering Committee

Coordinating Centre

National Lead investigators

Individual Sites

School of Public Health, ICL

Central point for data collation, cleaning, queries and sharing

Dr. Antonio J. Vallejo-Vaz Lead ScientistDr. Sreenivasa R. Kondapally Seshasai Mrs. Della Cole

• South America an important collaborator

• 4 countries so far

Summary

• Need to think about where the burden of silent disease lies

• Actively go out and look for it’s risk factors in the “latent phase”

• Treat it early and appropriately