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Challenges and Models in CV Risk Management: Start Early, Invest In Your
Arteries
Professor John Deanfield - University College London, UKTuesday 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
ESC Munich 2018
CVD: It’s Not All Over!
Source: CVD Statistics– BHF UK Factsheet – February 2018
ESC Munich 2018
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!
ESC Munich 2018
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
ESC Munich 2018
ESC Munich 2018
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)
ESC Munich 2018
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
ESC Munich 2018
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%
ESC Munich 2018
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