Challenges and Models in CV Risk Management: Start Early, Invest In - - PowerPoint PPT Presentation

Challenges and Models in CV Risk Management: Start Early, Invest In Your Arteries

Professor John Deanfield - University College London, UK Tuesday 28 August 2018

ESC  Munich 2018

ESC  Munich 2018

Professor John Deanfield: Disclosures

▪ Received CME honoraria and/or consulting fees from Amgen,

Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, Bayer

▪ Member of Study Steering Committees for Novo Nordisk ▪ Research grants from British Heart Foundation, MRC(UK), NIHR, PHE,

MSD, Pfizer, Aegerion, Colgate, Roche

▪ No conflicts of interest for this presentation

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CVD: It’s Not All Over!

Source: CVD Statistics– BHF UK Factsheet – February 2018

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CVD Prevention: Challenge!

Source: Alan Gregg (1890-1957), Rockefeller Foundation

“The human race has had long experience and a fine tradition in surviving adversity; we now face a task for which we have little experience, the task of surviving prosperity”

Source: INTERHEART Lancet 2004

Investing In Your Arteries!

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September 18

20 40 60 Age (yrs)

Genetic Environmental

Foetus 9 RFs accounted for 90% of MI in men and 94% in women Clinical Events Lots of risk in front : lots of lost opportunities behind!

Adolescent Smoking and Drinking and CV Health

▪ 1,266 participants (425 males and 841 females) at age 13, 15 & 17 yrs ▪ Ao PWV at 17 yrs * *

PWV (m/s) Adjusted for gender, SBP, BMI, LDL, SES, CRP

5.0 5.5 6.0 6.5

Low drinking Low smoking

• Int. drinking

Low smoking High drinking Low smoking Low drinking

• Int. smoking
• Int. drinking
• Int. smoking

High drinking

• Int. smoking

Low drinking High smoking

• Int. drinking

High smoking High drinking High smoking p=0.002

Source: Charakida et al, EHJ 2018, in press

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ESC  Munich 2018

Most Of Us Have Arterial Disease!

17 37 60 71 85 10 20 30 40 50 60 70 80 90 100

Incidence of Atherosclerosis (%)

<20 20-29 30-39 40-49 >50

Source: Tuzcu, Circ 2001 103:2075-10

32 Year Old Female Age (years)

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Combined Effect of LDL-C and SBP on CV Events

Source: B. Ference (Plymouth, US), FP 3163

N = 14,368 Major Vascular Events

Arterial disease causing heart attacks and strokes may be largely preventable! Never too Late; Never too Early!!

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How Early Should Prevention Start? “Poor Start in Life”

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Obesity at 2 yrs Predicts Status at 35 yrs...

Source: Ward et al, N Engl J Med 2017;377:2145-53

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CV RFs Drive Multiple Diseases

Source: Twig G et al, NEJM 2016;374:2430-40

Obesity Stress BP Smoking Systemic Inflammation

 Ageing

Diabetes Stroke CVD Cancer Cholesterol Oxidative Stress Dementia A Fib.

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Impact of Periodontitis Treatment on Glucose Control, Vascular and Renal Function in T2DM

Source: D’Aiuto Lancet Diabetes 2018

In UK population ▪ Severe in 5-10% ▪ Mild/mod. in 40%

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A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Cognitive Performance, and Healthspan

Source: Brandhorst Cell Metab 2015; 22: 86–99

Upstream biology that underlies NCDs can be targeted resulting in leveraged gains

Fasting-mimicking diet and markers/risk factors for aging, T2DM, cancer, and CVD

Source: Wei et al., Sci. Transl. Med. 9, eaai8700 (2017)

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CANTOS: Additional Non-CV Clinical Benefits

Source: Ridker PM et al. Lancet 2017, 390:1833-1842

Incident Lung Cancer

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CV RF lowering and Dementia Risk?

What’s Good for the Heart is Good for the Brain!

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CV Risk Factors from Childhood and Later Cognitive Function (Young Finns Study)

Source: Rovio JACC 2017; 69: 2279-2289

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Multi-domain Treatment and Cognitive Decline: FINGER Trial

Source: Ngandu Lancet 2015; 385: 2255-2263

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CVD Prediction and Prevention

Empowerment Communication Knowledge

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JBS3 Lifetime Risk Calculator

Source: Heart March 2014 and www.jbs3risk.com

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PHE National Heart Age Launch 04/09/18

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CVD Prevention: One Size Does Not Fit All!

Can’t give novel, expensive drugs, with uncertain long term safety, to everyone!

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Precision Medicine Approaches

Imaging Biomarkers Genetics

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Genome-wide polygenic scores for common diseases

Source: Khera et al, Nature Genetics online (Aug 2018)

UK Biobank Genome-wide polygenic scores for risk (>3x) for: ▪ Coronary artery disease (8.0%) ▪ Atrial fibrillation (6.1%) ▪ T2DM (3.5%) ▪ IBD (3.2%) ▪ Breast Cancer (1.5%) For coronary artery disease, prevalence is 20x higher than the carrier frequency of rare monogenic mutations conferring comparable risks.

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Sources: Mancio et al, Heart 2018; 0:1-9 Antonopoulos et al, JACC 2018; 71;23:2706-12 (Top R)

CT Inflammation Imaging: Fat Attenuation Index (FAI)

Sources: Mancio et al, Heart 2018; 0:1-9 Antonopoulos et al, JACC 2018; 71;23:2706-12 (Top R)

The Digital Health Opportunities

Assessing CV risk factors with Computer Vision Google Research

Source: Poplin et al, Nature Bio Eng; Vol 2, Mar 2018: 158-64

Title of Paper

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Revolution in the Delivery of Medicine

Early Management / Digital Systems Wellness Illness Ageing

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New Models of CV Risk Management

▪ Lifetime management of CV risk ▪ Engage the medical community, healthcare providers, politicians and public to promote societal change ▪ Better communication, especially with the young - use new risk tools to communicate ‘investment benefits’ (eg JBS3) ▪ New technology and testing to deliver personalised medicine

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Final Thought…

“It should be the function of medicine to have people die young as late as possible”

• Ernest L. Wynder M.D