New Frontiers Imaging vs Geneticsvfustercourse.com/assets/pdfs/ponencia1.pdfB López-Melgar, V Fuster et. al. Atheroscl. 2016;248:230 –Validated 3D vs 2D/3D B López-Melgar, V Fuster

Molecular (M), Clinical (C) and Population (P)Bases of Cardiovascular Disease and Health

16 and 17 July 2018 / 16 y 17 de julio de 2018Cardona (Barcelona, Spain) – Auditori Valentí Fuster

New FrontiersImaging vs Genetics

MCP BASES OF THE TRANSITION FROM DISEASE TO HEALTH, 2019

1). MCP Bases of Transition from Disease to Health

1. Two Critical Tools – Imaging, Genetics

2. Three Behavioral Ages - Elderly, Mid Life, Children

3. Two Historical Paths – B. Blockers, ACE / ARBs / ARNI

4. Two Historical Paths – Statins / PCSK9i, SGLT2i / GLP1-RA

Cardona, July 15, 2019 No Disclosures

Molecular (M), Clinical (C), Population (P)Bases of Cardiovascular Disease and Health, 2019

2. MCP Bases of Atherothrombotic Disease

5. Challenges of ACS STEMI & NSTEMI

6. Challenges of Stable CAD & Microcirculation

7. Challenges of Acute Stroke & Chronic Carotid Disease

8. Challenges of Thoracic & Abdominal Aortic Diseases




3. MCP of Rhythm, Myocardial & Structural Disorders

9. Atrial Fibrillation 21 Challenges

10. Genetics, Omics & Cardiomyopathies at Full Speed

11. Myocardial Tissue Regeneration in Controversy

12. Structural Valvular Heart Disease in Motion

4. Bases of My Academic (Creative) Future

13. A View of my Professional Life. Where I am Going?


CVD Mortality Trends For Males And Females(United States: 1979–2015)

AHA Councils (EJ Benjamin et. al.) Circulation. 2018;137:e67

T=H+T-H

Impact of Major Advances In Cardiovascular Care On Mortality

TF Lüscher et. al. Eur Heart J 2017;38:3066

US Children / Adolescents With Obesity, 1963 - 2014


Projected Direct Costs Of Total CVD Cost From 2015 To 2035 ($ 600 Billions…..)


Primordial

Secondary

Primary

50/50

From Aging / Disease to Youth / Health

4) 1)

2)

5) IIIP

HRP

CABG -ASA Imaging-MRIPCI- RapamycinFREEDOM

PESA AWHS DEMENTIA

3) LONGEVITY

2005 – 2019, 1975 - 2005

50-100 yrs

25-50 yrs

00-25 yrs

6) SHE (3)

7) HARLEMNY - NIHVILLAGE

4). Environment & Risk Factors

c

c

AV Khera, V Fuster, PM Ridker et al., NEJM 2016; 375:2349

H Sillesen, P V Fuster et.al JACC Imag. 2012;7:681.B López-Melgar, V Fuster et. al. Atheroscl. 2016;248:230 –Validated 3D vs 2D/3D B López-Melgar, V Fuster et. al. J Am Coll Cardiol. 2017;70:301

Subclinical Atherosclerotic Burden–N= 12,000Coronary Calcification 2D/3D-VUS

H Sillesen, P Muntendam, E Falk, V Fuster et.al JACC Imag. 2012;7:681.

Subclinical Atherosclerotic BurdenCoronary Calcification & 2D/3D-VUS

4.1). The PESA Study (N=4184) – 2D/3D VUS Atherosclerosis Assessment (mm3)

PESA (L Fernandez-Friera, V Fuster et.al). Circ 2015;131:2104 (B Lopez-Melgar, V Fuster et. al). J Am Coll Cardiol 2017;70:301

4.2). Change in the Prevalence of AtherosclerosisBy 3 Imaging Modalities, Separately & Combination

2DVUS 3DVUS CACSCombining

ImagingModalities

Progressors 26.4% 21.3% 11.5% 41.5%Non-progressors 73.6% 78.7% 88.5% 58.5%B López-Melgar, J Sanz, V Fuster et al. 2019 (Subm)

Chart1

2DVUS2DVUS

3DVUS3DVUS

CACSCACS

0.5850.415

Non-progressors

Progressors

0.736

0.264

0.787

0.213

0.885

0.115

Sheet1

Non-progressorsProgressors

2DVUS73.6%26.4%

3DVUS78.7%21.3%

CACS88.5%11.5%

58.5%41.5%

To resize chart data range, drag lower right corner of range.

4/3). PET/MRI Protocol For The Assessmentof Multiterritorial Atherosclerosis

L Fernández-Friera, V Fuster, J Sanz et. al. J Am Coll Cardiol. 2019; 73: 1371

Atherosclerosis (MRI) & Inflammation (PET) In Men And Women In PESA

L Fernández-Friera, V Fuster, J Sanz et. al. J Am Coll Cardiol. 2019; 73: 1371

Relationship of Uptake And Plaque Presence With CVRF Burden, Age & Vascular Territory

L Fernández-Friera, V Fuster, J Sanz et. al. J Am Coll Cardiol. 2019 (In Press)

4.4). Coronary Artery Calcium Scores of Zero and the Concept of Negative Risk Factors

MJ Blaha, K Nasir et. al. J Am Coll Cardiol 2019;74:12

Shift in Pre- to Post-Test Risk for CHD andCVD with Each Negative Risk Marker

MB Mortensen, V Fuster, E Falk et. al. J Am Coll Cardiol 2019;74:1

Based on 5805 BioImage participants individuals(age 55-80yrs) with CAC = 0, CAC ≤10, low galectin-3, or no carotid plaque had remarkable low CV risk, calling into question the treat-all approach

Shift in Pre- to Post-Test Risk for CHD andCVD with Each Negative Risk Marker

MB Mortensen, V Fuster, E Falk et. al. J Am Coll Cardiol 2019;74:1

International Radiation Dose Survey - Reduction Of Radiation Exposure In CTA, but Large Inter-site Variability

PROTECTION VI (TJ Stocker, J Hausleiter et. al. Eur Heart J. 2018;39:3715

4.5). Genetics

c

c

AV Khera, V Fuster, PM Ridker et al., NEJM 2016; 375:2349

AV Khera, V Fuster et.al.NEJM 2016;375:2349 >Gen

A Genomic Risk Score for CAD (metaGRS)Greater Association with Future CAD

M Inouye et. al. J Am Coll Cardiol. 2019;72:1883

Macrophages In Cardiovascular Disease

L Honold et. al. Circ Res. 2018;122:113

Arbab-Zadeh, V Fuster. J Am Coll Cardiol 2015;65:846 – MIS. Jaiswal, V Fuster et. al. N Engl J Med 2017;377:111 – Loss TET2 JJ Fuster et al Science 2017; 355: 842 – Circ Res 2018; 122: 523

Temporal Sequence & Functions of Leukocytes in the CAs

M1 M2

TET2

Loss of TET2 in Hematopoietic Cells and Atherosclerosis in a Murine Model

S. Jaiswal et. al. N Engl J Med 2017;377:111JJ Fuster et al Science 2017; 355: 842 – Circ Res 2018; 122: 523

CANTOS Persistent Stem Cell Driven Inflammation In Atherosclerosis

TR Cimato. Eur Heart J. 2017; 38: 433P Libby, V Fuster, P Ridker et. al. 2019 (In Press)

CANAKINUMAB M1 (TET2) Like

M1

ACS – CAD & Arterial PET / FDGBone Marrow and Spleen Imaging

PM Robson, V Fuster, ZA Fayad et al. J. Am. Coll. Card. 2017;10:1103JM Tarkin, JHR Rudd et. al. J. Am. Coll/ Card. 2017;69:1774ML Senders, ZA Fayad, C Perez-Medina et. al. JACC 2018;71:321

S. Jaiswal, V Fuster et. al. N Engl J Med 2017;377:111 - Loss of TET2 JJ Fuster et al. 2018;122:523 - Science 2017; 355: 842 Circ Res - In Murine

Inflammation-targeting PET Radiotracers For Detection of I/R Injury

ML Yap and K Peter. Circ Res. 2019;124:827

Primordial

Secondary

Primary

50/50


4) 1)

2)

5) IIIP

HRP


PESA AWHS DEMENTIA

3) LONGEVITY

2005 – 2019, 1975 - 2005

50-100 yrs

25-50 yrs

00-25 yrs

6) SHE (3)


2). Risk Factors of CV DiseaseWhite Matter & Lacunar Lesions (DBD)

MA Lim et. al. Clin Geriatr Med. 2009;25:191.JC Kovacic, V Fuster et. al. Circulation. 2011;123:1900

Vascular Cognitive Impairmentand Dementia

C Iadecola, M Dichgans et. al. J Am Coll Cardiol 2019;73:3326

Risk Factors for Dementia

C Iadecola, M Dichgans et. al. J Am Coll Cardiol 2019;73:3326

Comparison of ACC / AHA vs ESCDefinitions and Management of Hypertension

G Bakris, G Parati et. al. J Am Coll Cardiol 2019;73:3018

BP Variability and Dementia

FH Messerli, S Bangalore et. al. J Am Coll Cardiol 2019;73:2596

BP Variability and Outcomes


Variability of LDL- Cholesterol and of Blood Pressure


With the notable exception of heart rate, CV risk factors must now be defined by 2 components: the magnitude and duration of sustained risk factor elevation and, equally important, the variability of the same risk factor over time.

Microcirculation, Cognitive, 12 Studies

8.P Scheltens et al Lancet 2016;388:507– RF-Dementia 30%9.C Iadecola et al., Hypert. 2016;68:e67- Hyp. AHA-Cognitive10.YFS (SP Rovio et al), JACC 2017;69:2279-RF Child. Cogn.11. A de Roos et. al. Circ. 2017; 135: 2178- A’sD Phys. Fibrin12.TANSNIP (V Fuster et al) 2018- 2020- 5 Prospective Paths

2/8. Distribution and Prevalence Dementia

MR Azarpazhooh et. al. Alzheimers Dement. 2018;14:148 – 2856 pts/10 StudiesA Nucera et al. J Neurochem. 2017 Dec. 21 – Unrecogniced Cognit. Dysf.

Trans-Atlantic Network to Study STEPWISE Noninvasive Imaging as a Tool for Cardiovascular Prognosis and

Prevention-The Heart to Head StudyTANSNIP-H2H

2/12.

TANSNIP Pathway 1STEP 1:

Neurocognitive battery

Cognitive NormalN=110

Cognitive impairedN=115

Source- MSHADRC & Ctr for Cognitive Health

Memory ClinicGeriatric Clinic

CACS

3-D carotid-Carotid Plaque Volume and

ileo-femoral Ultrasound

CV Risk assessment

PET for amyloid

MRI- functional + Microvasculature

TANSNIP Pathway 2

STEP 1: CACS

Carotid & IF US Volume

PET for amyloid

Continuous Scale N=104

Source- MSHCoronary CT Suites

Neurocognitive Testing

3-D carotid and ileo-femoral US

CT

MRI- functional + Microvasculature

CV Riskassessment

TANSNIP Pathway 3

STEP 1: Neurocognitive

battery

Cognitive Normal

Cognitive impaired

CACS

3DVUS-Carotid Plaque Volume and

ileo-femoral

MRI- functional + Micro/

Macrovasculature

CV Risk Assessment

PET for Amyloid

FAD

N=2750

1

3

2

BBB permeability

AD + Placebo AD + Dabigatran

Brai

n ve

ssel

Brai

n pa

renc

hym

a

Dabigatran Treatment Ameliorates AD Pathogenesis

Endothelial Cell

Erythrocyte FibrinMicroglial CellT-CellAstrocyte Endfeet

Neuron

Oligomer

Aβ PlaquePericyte PlateletAstrocyte

Cortes-Canteli, M.; et al. Alzheimers Dis. J. 2014 -- Neurobiol Aging. 2015. Cortes-Canteli, M., Ibanez B., Fuster V., et al. 2019 (Subm)

4. Alzheimer’s Disese – TgCRND8 Mouse Model

5. Cerebral Hypometabolism & High CV Risk

Identified Regions: L & R Inf temp. g.; R Sup & Mid Temp g. Tem. Pole; L & R Parahipp, Fusiform; R. Lateral Orb g.; L Med Orb g.; R precuneus; L Mid front g., Sup Front g.

Primordial

Secondary

Primary

50/50


4) 1)

2)

5) IIIP

HRP


PESA AWHS DEMENTIA

3) LONGEVITY

2005 – 2019, 1975 - 2005

50-100 yrs

25-50 yrs

00-25 yrs

6) SHE (3)









New Frontiers�Imaging vs Genetics Número de diapositiva 4 Número de diapositiva 6Número de diapositiva 7Número de diapositiva 8Número de diapositiva 9Número de diapositiva 10Número de diapositiva 11Número de diapositiva 12Número de diapositiva 13Número de diapositiva 14Número de diapositiva 15Número de diapositiva 16Número de diapositiva 17Número de diapositiva 18Número de diapositiva 19Número de diapositiva 20Número de diapositiva 21Número de diapositiva 22Número de diapositiva 23Número de diapositiva 24Número de diapositiva 25Número de diapositiva 26Número de diapositiva 27Número de diapositiva 28Número de diapositiva 29Número de diapositiva 30Número de diapositiva 31Número de diapositiva 32Número de diapositiva 33Número de diapositiva 34Número de diapositiva 35Número de diapositiva 36Número de diapositiva 37Número de diapositiva 38Número de diapositiva 39Número de diapositiva 40Número de diapositiva 41Trans-Atlantic Network to Study STEPWISE Noninvasive Imaging as a Tool for Cardiovascular Prognosis and Prevention-The Heart to Head Study�TANSNIP-H2H TANSNIP Pathway 1TANSNIP Pathway 2 TANSNIP Pathway 3Número de diapositiva 46Número de diapositiva 47Número de diapositiva 48

Documents

New Frontiers Imaging vs Geneticsvfustercourse.com/assets/pdfs/ponencia1.pdfB López-Melgar, V Fuster et. al. Atheroscl. 2016;248:230 –Validated 3D vs 2D/3D B López-Melgar, V Fuster