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

Arteries

Professor John Deanfield - University College London, UKTuesday 28 August 2018

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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

0 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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Most Of Us Have Arterial Disease!

17

37

60

71

85

0

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

DiabetesStroke CVD

Cancer

Cholesterol

Oxidative Stress

DementiaA 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-SystemRegeneration, 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 commondiseases

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 VisionGoogle 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