Dr. Valentín Fuster - Enfermedad subclínica de corazón y cerebro

From Clinical &
Subclinical CVD
to Health Locally &
Worldwide
Round Trip of Motivation /
Funding
MM aa dd rr ii dd ,, O cc tt.. 1177,, 22001144 NNoo
DDiisscclloossuurreess

1. A Transition From Disease to Health 2. Hear t – Brain Integration 3. Imaging / Omics / Regeneration / Style
Complex (5) CAD Valv. – CM
Sub-Clinical (4) Ar terial
Health (3) Political
1970 1990 2000 2010 2015
1990 2000 2010 2015 2020

1. A Transition From Disease to Health 2. Hear t – Brain Integration
3. Imaging / Omics / Regeneration /
Complex (5) CAD Valv. – CM
Sub-Clinical (4) Ar terial
1970 Health 1990 (4) 2000 Political
2010 2015
1990 2000 2010 2015 2020

1). Cardio-Cerebro Vascular Disease –
1
D Butler. Nature. 2011;477:261 (UN. NCD). At Present
R. Beaglehole et. al. Lancet 2008;372:1988 - > 30% Across, 2030

2).Cardio-Cerebro Vascular Disease
HEART
MI 1) Emboli
2)Thrombi
2
3)Hemorrh
BRAIN -
STROKE
Thrombi
Macrovascular, Microvascular, Aging

3). Myocardial Infarction &
Stroke
R Corti, V Fuster EHJ. 2011 (April 19)

4). Risk Factors, Motivation Missing
>1 Risk Factors
1. MI & Stroke
25% in 10 Yrs
75% in 30 Yrs
2. DBD / AD /
Cognitive
3. Aging
c
c
Framingham (2010) 5:
Interheart (2004) 2: Obesity, Sedentary(Diet)

5). Deaths Attributable to Selected
Behavioral
Risk Factors in 2010
M Ezzati et. al. N Engl J Med 2013;369:954
SS Lim et. al. Lancet 2012;380:2224

A Community Call
Population Ageing & Cost
The Lancet NCD Action (G Alleyne et. al.) Lancet. 2013;381:566

PPEESSAA && AAWWHHSS HHRRPP >> 55yy,,
4400--544yy,, NN== 44,,006600 ,, FFUU 00,,33,,66yy NN== 5880088 FFUU 33yy
Omics (Framingham)
Telomeres (S.blot, qPCR, Fresh)
a). Predictive ?
b). Economics ?
c). Imaging & Life Style
Three Approaches
1).

HRP - BioImage Study – Mobile Units
PI: Valentin Fuster, Co-PI: Erling Falk, Peter Muntendam - AHJ 2010;160:49

Plaque Burden (N=5808)
Carotid 3D-US, Coronary Calc ification
H Sillesen, P Muntendam, E Falk, V Fuster et.al JACC Imag. 2012;7:681.

Cross Interaction (n=5808)
Between Carotid Plaque Area &
CAC
IIMMTT vvss FFooccaall:: ++
IIlliioo--FFeemmoorraall:: ++++++
(n = 1480) (n = 1477) (n = 1479) (n = 1478)
Carotid Plaque Area Quartiles
V Fuster, U Baber, R Mehran, E Falk, et al, 2014 (Subm)

Three Year All-Cause MACE Rates (N=216)
by Carotid and Coronary Atherosclerosis
Reclassification: CAC 24% - cPB 18%
V Fuster, U Baber, R Mehran, E Falk, et al, 2014 (Subm)

PPEESSAA && AAWWHHSS HHRRPP >> 55yy,,
4400--544yy,, NN== 44,,006600 ,, FFUU 00,,33,,66 yy NN==5880088 FFUU 33yy
Omics (Framingham)
Telomeres (S.blot, qPCR, Fresh)
a) Predictive ?
b) Economics ?
c) Imaging & Life Style
Three Approaches
2).

Sub-Clinical Atherosclerosis (n=4060)
By Vascular Territory
PESA (L Fernandez-Friera, V Fuster et. al.) 2014 (subm.)

Distribution Of The Systemic Extent
Of Subclinical Atherosclerosis
PESA (L Fernandez-Friera, V Fuster et. al.)
2014 (subm.)

3). Cortical Atrophy (Alzheimer’s),
White Matter & Lacunar Lesions
(DBD)
JC Kovacic, V Fuster et. al. Circulation. 2011;123:1900
MA Lim et. al. Clin Geriatr Med. 2009;25:191.

DBD / Alzheimer’s
White Matter and Lacunar Lesions (?)
Promoting Cardiovascular and
Cerebrovascular Health
V Fuster, S Bansilal. Stroke 2010; 41:1079
Highlight Dementia Risk to Reduce CVD
BM Mearns, V Fuster. Nature Rev Card 2010; 7:237
Cellular Senescence, Aging & Vascular Disease
( Part 2 of a 2-Part Review )
JC Kovacic, EG Nabel, V Fuster Circ 2011; 123: 1900
Complex Coronary Disease, Cerebrovascular
Disease and Degenerative Brain Disease
JC Kovacic, V Fuster et al. Ann. NY. Acad. Sc 2012; 1254: 99

Mendelian vs Complex
Disease
25% >65y – FH Dementia, 20% Dementia
CT Loy et. al. Lancet 2014; 383: 828 (Australia)

DBD/AD - CVRFs, Lacunar Les., < Cognitive
MRI – Perfusion
1.V Novak, I Hajjar. Nat. Rev. Cardiol. 2010;7:686(HMS)
2. HW Querfurth, FM LaFerla. NEJM 2010; 362:329
3. WB White et al.Circ 2011;124:2312 (Farmington,Yale)
4. AHA/ASA, Stroke 2011; 42:2672
5. WHO - Dementia report 2012
6. JB Toledo et al. Brain July 10, 2013 – Autopsy (n=6000)
7. C Russo, RL Sacco et.al. Circ. 2013;128:1105
8. JR Kizer Circ 2013;128:1045
9. CARDIA (K Yaffe et al) Circ. 2014; 129 (In Press)
Ischemia affects 60 to 90% of patients with Alzheimer’s

Early Adult to Midlife
CV Risk Factors & Cognitive Function
Studies have linked midlife and late-life CV risk factors
(CVRFs) to cognitive function, yet little is known about
CVRF exposure in early adulthood and subsequent
cognitive function. In a prospective study of 3381 adults
(age, 18-30 years at baseline) with 25 years of follow-up,
we assessed cognitive function at year 25 (2010-2011)
with the Digit Symbol Substitution Test, Stroop Test, and
Rey Auditory Verbal Learning Test. Cumulative
exposure to CVRFs from early to middle adulthood was
associated with worse cognition in midlife.
CARDIA (K Yaffe, et al.) Circulation 2014; 129 (In Press) – 4 Cities

Early Adult to Midlife
CV Risk Factors and Cognitive
Function
Adjusted For Age, Sex, Race And Education
CARDIA (K Yaffe, et al.) Circ 2014 (In Press) (Birmingham, Chicago, Minneapolis, Oakland)

4). Frailty : The Hallmarks of
Aging
Non-specific
Extreme fatigue, unexplained weight loss, frequent infections.
Falls
So-called hot fall is related to a minor illness that reduces postural
balance below a crucial threshold necessary to maintain gait
integrity. Spontaneous falls occur in more severe frailty.
Delirium
Rapid onset of fluctuating confusion and impaired awareness.
Delirium is related to reduced integrity of brain function and is
independently associated with adverse outcomes.
Fluctuating disability
Fluctuating disability is day-to-day instability.
A Clegg et al., Lancet 2013; 381:752

Aging / Senescence
Oxidative Stress on Telomere
1
2
4
3
B Niemann et. al. JACC 2011; 57: 577.
R Madonna, R De Caterina et. al EHJ 2011;32:1190 (Houston &Chieti, Italy)
JC Kovacic, EG Nabel, V Fuster – Circ. 2011;123:1650

Cell /Molecular Pathways & Aging
CB Newgard et. al. J Clin Invest. 2013;123:946

Oxidative Stress & Environment
Telomere Attrition & Shortening
•Smoking
•Obesity
•Sedentary lifestyle
•Mental stress
•Alcohol abuse
Inhibition Of Telomere Shortening
•Healthy lifestyle
F Fyhrquist et al. Nat Rev Card. 2013; 10:274
3,4). TANSNIP 2015-2020

1) Documents on NCD – No FU – Talkers vs Doers

2). Promoting CV Health Worldwide
3x5 36
2011 June 27 2014
Circ. 2011;123:1671 a. Behavior Risk, b. Lack of Policy NCD,
12 RECOMMENDATIONS: c. No Intersectorial, d. Mixt Health Delivery

3). Science, Health, Education
Powered by / for Three Ages
A
Science / Health
2 . C
Polypll / DBD
B
Focus / Group
“Extended healthy lives” in part due to medical research
generates dramatic returns - Albert & Mary Lasker Found.- 2002

Private Corporations
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Facilities: Imaging, Experimental
Education: Intra & Extramural (15)
SSCCIIEENNCCEE 22000055,, JJuullyy 88,,
SSCCIIEENNCCEE 22000066,, SSeepptt 11,,
LLAANNCCEETT 22000066,, AAuugg 1199,,
CCIIRRCCUULLAATTIIOONN 22000077,, AApprriill
EEUURROOPPEEAANN HHEEAARRTT JJ 22001100;; 3311:: 22006677,,
EEUURROOPPEEAANN HHEEAARRTT JJ 22001133;; 3344:: 11001144,,

A).TECHNOLOGY AND INFRASTRUCTURE
Dpt. of Atherothrombosis and Imaging
PRECLINICAL RESEARCH FACILITIES
CARDIOVASCULAR IMAGING RESEARCH LABORATORY
ANIMAL MODELS

B). Education
22001133
Acércate 88
Cicerone Workshop 111144
Cicerone Program 3355
Postgraduate 2211
Master 88
PD degrees 66
PhD students 5544
Cardio-Image 33
Invesmir 44
Res@CNIC 1155
Pathophysiology Course 8877
CTouorstea oln p Vaasrctuilacri Bpioalongyt s110:0 44445599

“CNIC–Joven” Training Plan
2009, 2010, 2011, 2012, 2013

C). Scientific Advisory Board (Strict)

Childhood Obesity & Opportunity
1. Childhood Obesity: Increases Adult BP & Risk of Stroke
2. Childhood Obesity: Accounts For About 60% of Adult’s
The Finish Study (S Mayor) BMJ) 2012; 344:e3065

Non-Profit Private Foundation
JM Santo Domingo

COLOMBIA – CHILDREN’S PROGRAM
EDUCATIVE GOAL: HEALTHY HABITS FOR CHILDREN BETWEEN 3 & 5 YRS
CHILDREN 3-5 6-8 9-14
GENERAL
PUBLIC

KNOWLEDGE (70), ATTITUDES (20) & HABITS (10)
90
85
80
75
70
65
60
Score (mean)
(p<0.0001)
(p=0.0064)
(p<0.0001)
(p=0.1197) ‡
(p<0.0001)
(p=0.7417)
Intervention
period
p< 0.001
Baseline 6 months 18 months
Teachers Parents Children Control ------
Céspedes J, Briceño G, Farkouh ME, Vedanthan R, Baxter J, Leal M,
Boffetta P, Woodward M, Hunn M, Dennis R, Fuster V.
The American Journal of Medicine 2013; 126, 27-35

36m-change In Children’s KAH Mean Scores*
The Amer J of Med 2013;126:1122
Colombia – 25,000 Children, Spain – 40,000, US……

SPAIN - CHILDREN’S PROGRAM
Cardona, J Cardona July, 2011 uly 2013
Madrid, October 2011- Madrid, October 2013

Top 10 Advances in Hear t Disease and
Stroke
2013 AHA / ASA AHA
Dr V Ruster
newsroom.heart.org. Jan 2,
2014

3). Science, Health, Education
A
Science / Health
2 . C
Polypill / DBD
B
Focus / Group

AMPATH Centers In Kenya
BP Control / Non MD / High
Technology
V Fuster, R Vedanthan, et al NHLBI / Kenya Model

CARDONA INTEGRAL – “FIFTY-FIFTY”
SMOKING 0 11 2 -- -- 2
OVERWEIGHT 0 12 2 -- -- 2
SEDENTARISM 0 13 2 -- -- 2
HYPERTENSION 0 14 2† -- -- 2
TOTAL HABIT SCORE 8
SIX MONTHS
95% of the people have improved
in one or more of the habits or RF.

CNIC-F/S*-FERRER POLYPILL, 2ary PREVENTION.
ASA, Statin, ACE-Inhibitor
FOCUS 1 & 2
Argentina
Brazil
Paraguay
Italy
Spain
FREEDOM
AETNA
EU 2020
Am. H J 2011;162:811
Semin.Thor.Cardiov.Surg 2011;23:24
JACC, 2014-In Press - Approved in 22 Countries
* Fuster-Sanz - Funding: European Community

4).From Families to Communities &
Cities
(a). AHA -THE HARLEM FAMILY APPROACH
(b). CNIC-THE SEVEN COMMUNITIES STUDY
(c). VF/MS-SHE -VILLAGE OF CARDONA
HEALTHY.

4a). Science, Health, Education
A
Science / Health
2 . C
Polypill / DBD
B
Focus / Group

American Hear t AssociationStrategically
Focused Prevention Research Center
Family-Based Approach to the Prevention
of Cardiovascular Disease in a Minority
Community Integrating Systems-Biology
Icahn School of Medicine at Mount
Sinai

O
Start
Children
(3 Groups)
Caregivers
(3 Groups)
Start
PPP
P
PP
Teachers
O
I
I
IO
O
O
O O
O
OOO
O
KAH-BEA
Mol. GenomicsKAH-BEA S-KAH-BEA
1st Yr 2nd Yr 3rd Yr
4th Yr
BEWAT
Point of Care.
3D-US
Mol. Genomics
O
O
IP
II II
IP
Control/Interv.
PPPI
S-BEWAT
Point of Care
BEWAT
Point of Care
3D-US
Mol. Genomics
Intervention.
Intervention
Control
IIIP
P = Pilot 1st Year; S = Sustained; O = No Intervention; I = Intervention
PI = Peer Interv., II = Indiv. Interv.; PPPI = Peer-to-Peer Program Interv;
IIIP = Intensive Individual Intervention Program
KAH-BEA = Knowledge, Attitude, Habit -BMI, Exercise, Alimentation
BEWAT = BP, Exercise, Weight, Alimentation, Tobacco

4b). The Seven Community Study
86
86
69
96
104
127
70
N=552

4c). C A R D O N A A S A MODEL FOR THE
DEVELOPMENT OF HEALTHY VILLAGE / CITY

Dr. Valentín Fuster - Enfermedad subclínica de corazón y cerebro

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