Early Vascular Aging (EVA). New Directions in Cardiovascular Protection. Edition No. 2

Table of Contents

Section 1 Introduction

1. Historical Aspects and Biology of Aging

PETER M. NILSSON

1. The 9 paradigm shifts in cardiovascular aging research

PIERRE BOUTOUYRIE AND PEDRO GUIMARAES CUNHA

1. Vascular Aging and CV Disease

PEDRO GUIMARAES CUNHA AND MICHAEL H. OLSEN

Section 02 Lifecourse approach and population based studies

1. Aging Population: Challenges and Opportunities in a Life Course Perspective

ANGELO SCUTERI AND PETER M. NILSSON

1. Population-Based Studies: Milestones on the Epidemiological Timeline

ERNST RIETZSCHEL AND MARC L. DE BUYZERE

Lifetime Perspective of Vascular Aging

1. a. Lessons from the Amsterdam Growth and Health Longitudinal Study

ISABEL FERREIRA, ROEL J. VAN DE LAAR, FRANK C.T. VAN DER HEIDE, AND COEN D.A. STEHOUWER

1. b. Cardiovascular Aging: Perspectives from Longitudinal Studies of Aging

MAJD ALGHATRIF AND EDWARD G. LAKATTA

1. c. Lessons from the Cardiovascular Risk in Young Finns Study

COSTAN G. MAGNUSSEN, SUVI P. ROVIO, KATJA PAHKALA, AND OLLI T. RAITAKARI

1. Early Vascular Aging in the Young

ELAINE M. URBINA, PETER M. NILSSON, AND CARMEL M. MCENIERY

1. Ethnicity and Arterial Function

J. KENNEDY CRUICKSHANK AND NADIA BENNETT

Section 03 Molecular, Cellular and Mechanist Contributions to Vascular Aging

1. Cellular and Molecular Determinants of Arterial Aging

PATRICK LACOLLEY, PASCAL CHALLANDE, VERONIQUE REGNAULT, EDWARD G. LAKATTA, AND MINGYI WANG

1. Platelet/Leukocyte-Vessel Wall Interactions

and Early Aging
VERONIQUE REGNAULT, JEREMY LAGRANGE, R?UMEYZA BASCETIN AND PATRICK LACOLLEY

1. Age-Induced Endothelial Dysfunction and Intima-Media Thickening

MICHAELA KOZAKOVA AND ARNO SCHMIDT-TRUKSASS

1. Diabetes, Prediabetes, Metabolic Syndrome, and Large Artery Vascular Ageing

COEN D.A. STEHOUWER, FRANK C.T. VAN DER HEIDE, MICHAELA KOZAKOVA, AND CARLO PALOMBO

1. The Cross-Talk Between the Macro- and the Microcirculation

STEPHANE LAURENT, DAMIANO RIZZONI,AND ENRICO AGABITI-ROSEI

1. Changes in Peripheral Blood Pressure with Normal and Accelerated Aging

S. FRANKLIN AND MICHAEL HECHT OLSEN

1. Changes in Arterial Stiffness with Normal and Accelerated Aging

ROSA MARIA BRUNO AND PIERRE BOUTOUYRIE

1. Changes in Central Hemodynamics, Wave Reflection, and Heart_Vessel Coupling with Normal and Accelerated Aging

THOMAS WEBER AND PATRICK SEGERS

1. Arterial Stiffness and Blood Pressure Variability

GIANFRANCO PARATI, JUAN EUGENIO OCHOA,GIUSEPPE SCHILLACI, AND PAOLO SALVI

1. Chronic Inflammation in Atherosclerosis and Arteriosclerosis

JAN ISABEL GONCALVESA, LUCA ZANOLI, JAN NILSSON, AND ANDREAS EDSFELDT

1. Nonhemodynamic Components of EVA: Polycystic Ovary Syndrome (PCOS)

IRENE LAMBRINOUDAKI and ELENA ARMENI

1. Microbiota, Diet, Oral Health and Vascular Aging

DAVIDE AGNOLETTI, FEDERICA PIANI, SILVIA TURRONI, AND MADELEINE JOHANSSON

Section 04 Biomarkers, risk prediction and phenotypes of vascular aging

1. Traditional Versus New Models of Risk Prediction

THOMAS BASTHOLM OLESEN AND MICHAEL HECHT OLSEN

1. Estimated Arterial Stiffness

JULIE VISHRAM-NIELSEN, DIMITRIOS TERENTES-PRINTZIOS, MICHAEL HECHT OLSEN, AND CHARALAMBOS VLACHOPOULOS

1. Vascular Aging Biomarkers: Methodological Measurement Consensus and Reference Values

PIERRE BOUTOUYRIE

1. Imaging Biomarkers: Carotid Intima-Media Thickness and Aortic Stiffness as Predictors of Cardiovascular Disease

CHARALAMBOS VLACHOPOULOS, GEORGIOS GEORGIOPOULOS, GEORGIOS MAVRAGANIS, KIMON STAMATELOPOULOS, AND COSTAS TSIOUFIS

1. Imaging Biomarkers: Flow-Mediated Dilation as Predictor of Cardiovascular Disease

ROSA MARIA BRUNO, SMRITI BADHWAR, ELISABETTA BIANCHINI, AND LORENZO GHIADONI

1. Genetic Markers in Prediction of Cardiovascular Disease

MARTIN W. MCBRIDE, DELYTH GRAHAM, SIMON FISHER, CARA TRIVETT, AND MANSHI ZHOU

1. Phenotypes of Vascular Aging Vascular Chronobiologic asynchrony

PEDRO GUIMARA ES CUNHA, PETER M. NILSSON, PIERRE BOUTOUYRIE, MICHAEL HECHT OLSEN, AND STEPHANE LAURENT

Section 05 Vascular aging, organ damage and late stage disease

1. Early and Late Stages of Chronic Kidney Disease in Relation to Arterial Changes

AGNE-LAUCYTE-CIBULSKIENE AND MIKAEL GOTTS?ATER

1. Arterial Aging, Blood Pressure, and Brain Damage

ANGELO SCUTERI, STEPHANIE DEBETTE, AND ALBERTO AVOLIO

1. Clinical Implications of Ventricular-Arterial Coupling and the Role of Therapeutic Interventions

IGNATIOS IKONOMIDIS, GEORGE PAVLIDIS, AND DIMITRIOS VLASTOS

1. Systemic Ventricular-Arterial Coupling and Heart Disease

JULIO A. CHIRINOS

Section 06 Translating research into clinical practice, with precision cardiovascular medicine: Implications of vascular aging

1. Vascular Aging and Clinical Trials

PIERRE BOUTOUYRIE AND ROSA MARIA BRUNO

1. a. PART I Treatment of Abnormalities in Lipid Metabolism and EVA

VASILIOS KOTSIS

1. b. Part II: Early Vascular Aging and Obesity Treatment

JENS JORDAN

1. c. Part III: Treatment with antidiabetes drugs-Effects on blood pressure and central hemodynamics

PETER M. NILSSON

1. d. Part IV: Arterial Stiffness as Treatment Target: The SPARTE Study

STEPHANE LAURENT

1. Lifestyle Intervention: What Works?

PANAGIOTIS XAPLANTERIS AND CHARALAMBOS VLACHOPOULOS

1. Targeting Blood Pressure Lowering and the Sympathetic Nervous System

DAGMARA HERING AND KRZYSZTOF NARKIEWICZ

1. Targeting Central Blood Pressure Through the Macro- and Microcirculation Cross-Talk STEPHANE LAURENT, ROSA MARIA BRUNO, CLAUDIA AGABITI-ROSEI, CAROLINA DE CIUCEIS, AND DAMIANO RIZZONI

Cardiovascular Aging in Clinical Guidelines

1. a. Cardiovascular Prevention Strategies in a Life Course Perspective

PETER M. NILSSON

1. b. Cardiovascular Prevention Strategies in Patients With Comorbidities (Metabolic, Chronic Inflammation, Immunomodulation, Cancer, and Treatment-Induced Arterial Changes)

ANTONIOS ARGYRIS AND ATHANASE D. PROTOGEROU

1. c. Cardiovascular Risk Prediction

THOMAS BASTHOLM OLESEN AND MICHAEL HECHT OLSEN

1. d. Target Organ Damage

MARIA LORENZA MUIESAN AND CLAUDIA AGABITI ROSEI

1. e. Therapeutic Implications of Early Vascular Aging

PIERRE BOUTOUYRIE, ROSA MARIA BRUNO, AND STEPHANE LAURENT

1. New Drugs Under Development for Cardiovascular Prevention

STEPHANE LAURENT AND ULRIKE M. STECKELINGS

1. Specific Pathways to Prevent Early Vascular Aging

TINE DE BACKER, PIERRE BOUTOUYRIE, AND L VAN BORTEL

1. Immunization, Vaccines, and Immunomodulation

Section 07 Global Mapping of Vascular Aging Research

1. a. European Research Centres

The ARTERY Society. The Association for Research Into Arterial Structure and Physiology
THOMAS WEBER, CARMEL M. MCENIERY, ST_EPHANE LAURENT, AND JOHN COCKCROFT
Clinical Pharmacology Unit-Hopital Europeen Georges Pompidou-APHP (Paris, France)
PIERRE BOUTOUYRIE
Lund University, Department of Clinical Sciences, Malmo, Sweden
PETER M. NILSSON AND ISABEL GONCALVES
Arterial Aging From Bedside to Bench ...and Back
ANGELO SCUTERI
The Maastricht study, The Netherlands: A population-based cohort study with oversampling of participants with type 2 diabetes
COEN D.A. STEHOUWER
Erasmus MC University Medical Center, Rotterdam, The Netherlands
FRANCESCO MATTACE RASO
Acute and Chronic Cardiovascular Deficiency, Nancy, France 000
PATRICK LACOLLEY
Cardiology Department, Klinikum Wels-Grieskirchen, Wels, Austria
THOMAS WEBER
Department of Sport, Exercise and Health at University of Basel, Division of Sport and Exercise Medicine, Basel
ARNO SCHMIDT-TRUCKSASS
Biophysical Models for Medical Applications (BioMMedA), Ghent, Belgium
PATRICK SEGERS
Medical University of Gdansk, Poland
KRZYSZTOF NARKIEWICZ
Department of Geriatrics and Stroke Medicine, Brighton, UK
C. RAJKUMAR
Centre for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Hospital Senhora da Oliveira/Minho University, Guimaraes, Portugal
JORGE COTTER AND PEDRO GUIMARAES CUNHA
Preventive Cardiology and Echocardiography Laboratory
IGNATIOS IKONOMIDIS
Institute of Preventive Pediatrics, Technical University of Munich, Munich, Germany
RENATE OBERHOFFER-FRITZ
Hypertension and Vascular Risk Unit, Internal Medicine Department, Hospital Clinic of Barcelona, Spain
CRISTINA SIERRA AND MIGUEL CAMAFORT
Unitat d’Hipertensio Arterial i Risc Vascular, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain
ANNA OLIVERAS AND SUSANA VA ZQUEZ
Nephrology, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
LUCA ZANOLI
CARDIO HEALTH-LAB: Cardiovascular Pathophysiology and Circulatory Health Laboratory
RAFFAELE DE CATERINA AND CARLO PALOMBO
Italian National Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa Italy
FABIO ANASTASIO RECCHIA AND ELISABETTA BIANCHINI
Cardiovascular Internal Medicine, University of Bologna, Bologna, Italy
CLAUDIO BORGHI
Carvascare Research Group, Cuenca, Spain
IVAN CAVERO-REDONDO
Early Vascular Aging General Practitioner Research Centre, Budapest, Hungary
JANOS NEMCSIK
Cardiovascular Center, University Hospital Ghent, Belgium
TINE DE BACKER
Primary Care Research Unit of Salamanca (APISAL), Salamanca, Spain
LUIS GARCIA ORTIZ
ASKLEPIOS Study, Ghent, Belgium
ERNST RIETZSCHEL AND PATRICK SEGERS
Hypertension Excellence Center, Brescia, Italy
MARIA LORENZA MUIESAN AND ANNA PAINI
Laboratory of Vascular Biology, Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
MARIA LORENZA MUIESAN AND CAROLINA DE CIUCEIS
Department of Clinical and Experimental Medicine, University of Pisa, Italy
STEFANO TADDEI AND LORENZO GHIADONI
The Unit for Vascular Investigations, Vilnius University Santaros Klinikos, Lithuania
LIGITA RYLISKYTE AND JOLITA BADARIENE
Cardiovascular Prevention and Research Unit, Clinic and Laboratory of Pathophysiology, Department of Medicine, School of Health Sciences, National andKapodistrianUniversity of Athens
ATHANASE D. PROTOGEROU
SDCO-Steno Diabetes Center Odense, Odense, Denmark
KURT H�JLUND
Research Centre in Physical Activity, Health and Leisure (CIAFEL)
LUCIMERE BOHN, JORGE MOTA, AND JOSE OLIVEIRA
Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany
JENS JORDAN
Research Centre of Applied and Preventive Medicine/Centre for Population Health Research, Turku, Finland
OLLI T. RAITAKARI
Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
SILVIA TURRONI
Menopause Unit, 2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece
IRENE LAMBRINOUDAKI
Hypertension and Vascular Risk Unit, Internal Medicine Service, University Hospital of Sagunto, Sagunto (Valencia), Spain
ENRIQUE RODILLA
Population Science and Experimental Medicine, Institute of Cardiovascular Science, University College London, United Kingdom
ALUN HUGHES
Centre for Cardiovascular Health and Aging, Cardiff, United Kingdom
BARRY J. MCDONNELL
Peripheral Vessels Unit, First Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration Hospital, Athens, Greece
CHARALAMBOS VLACHOPOULOS

1. b. Asia/Australia Research Centers

Vascular Research Section, Department of Cardiology, Tokyo Medical University, Tokyo, Japan
HIROFUMI TOMIYAMA
Jichi Medical University Center of Excellence in Community Medicine Cardiovascular Research and Development (JCARD), Tochigi, Japan
KAZUOMI KARIO
Blood Pressure and Arterial Function (BPAF) Laboratory, Macquarie Medical School, Macquarie University, Sydney, Australia
MARK BUTLIN
Menzies Institute for Medical Research, Hobart, Australia
RACHEL EMMA CLIMIE
Menzies Institute for Medical Research, Hobart, Australia
JAMES SHARMAN
Miyagi University of Education Medical Center, and Tohoku University Graduate School of Medicine, Sendai, Japan
JUNICHIRO HASHIMOTO

52. c. North American Research Centers

History of North American Artery Society

Preventive Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
ELAINE M. URBINA
Iowa Translational Vascular Physiology Lab, Department of Health and Human Physiology, University of Iowa, Iowa City, United States
GARY L. PIERCE
Chirinos Lab at the University of Pennsylvania
JULIO A. CHIRINOS, KATHERINE GREENE, AND HANNAH MAYNARD
Integrative Human Physiology Laboratory, University of Massachusetts Boston, Boston, MA, United States
TRACY BAYNARD AND BO FERNHALL
Aging and Vascular Physiology Lab, Eugene, OR, United States
ASHLEY WALKER
UNC Cardiometabolic Lab, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
LEE STONER
Integrative Physiology Laboratory, University of Illinois at Chicago, United States
ROBERT W. MOTL

53. d. Latin American Research Centers

ARTERY LATAM Society: Brief Historical Summary
EDUARDO C.D. BARBOSA, PEDRO FORCADA, AND LUIS MARIA PUPI
Clinic of Hypertension and Associated Metabolic Diseases-CHAMA, Rio de Janeiro, Brazil
MARIO FRITSCH NEVES
Hypertension Unity-Instituto do Coracao do HCFMUSP, Sao Paulo, Brazil
LUIZ APARECIDO BORTOLOTTO
Hypertension Unit. Cardiology Department, Medicine School, Federal University of Goias, Brazil
WEIMAR KUNZ SEBBA BARROSO
Research Group on Hypertension, Arterial Stiffness and Vascular Aging (GPHARV), Maringa, Brazil
ROGERIO TOSHIRO PASSOS OKAWA, JAQUELINE LYRIO BERMUDES OKAWA, AND WENDELL ARTHUR LOPES
Vascular Research Center and Its Risk Factors Vascor, Salvador, Bahia, Brazil
LUCELIA BATISTA NEVES CUNHA MAGALHAES
Laboratory of Vascular Dynamics and Non-Invasive Hemodynamics. Hosp. Sao Francisco-Santa Casa de Porto Alegre-Brazil
EDUARDO COSTA DUARTE BARBOSA
Cardiometabolic Center Dr. Luis Maria Pupi, Ciudad Autonoma de Buenos Aires, Argentina
LUIS MARIA PUPI, FABIANA CALABRIA, AND PABLO MARIA PUPI
CardioArenales: Noninvasive Vascular Laboratory
PEDRO FORCADA, HORACIO ALMADA, AND RICARDO GARCIA
Centro de Hipertension Arterial y Biomecanica Vascular
FABIANA CALABRIA AND PABLO G. PIZZALA
SICOR Clinical and Research Center, Medellin, Colombia
DAGNOVAR ARISTIZABAL
Metabolism and Biomechanics in Systemic Vasculopathy
JAVIER OSVALDO SARY
Arterial Stiffness Laboratory
ERNESTO CARDONA MUNOZ AND CARLOS RAMOS BECERRA
University Hospital, Fundacion Favaloro, Arterial Hypertension, Metabolic Unit
RAMIRO SANCHEZ AND AGUSTI´N RAMIREZ
Ricardo Gutierrez Children´s Hospital, Buenos Aires, Argentina
SARDELLA ANGELA
Masira Research Institute, Medical School, Universidad de Santander (UDES), Bucaramanga, Colombia
PATRICIO LOPEZ-JARAMILLO

54. e. Network for Research in Vascular Aging
CHRISTOPHER CLEMENS MAYER, JORDI ALASTRUEY, ROSA MARIA BRUNO, RACHEL EMMA CLIMIE, ANDREA GUALA, BERNHARD HAMETNER, IOANA MOZOS, CHLOE PARK, GIACOMO PUCCI, DIMITRIOS TERENTES-PRINTZIOS, AND ELISABETTA BIANCHINI

Authors

Pedro Guimar�es Cunha Visiting Professor at the School of Medicine, University of Minho, Portugal.

Prof. Pedro Guimar�es Cunha is a Consultant in Internal Medicine and a European Hypertension Specialist (by the European Society of Hypertension). He works as a Professor and Researcher of Minho Medical School and the Life and Health Sciences Research Institute, Minho University. He coordinates the Outpatient Clinic and Research of the Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Hospital Senhora da Oliveira - Guimar�es / Minho University (an ESH Excellence Center in Hypertension). He has served as President of the Working Group Hypertension and Brain - European Society of Hypertension (2018-2022) and is currently the Secretary General of the Executive Committee of the Artery Society. His main focus is clinical research in vascular aging, large arteries, cardiovascular risk, hypertension, cardiometabolic and cardiovascular disease.

Pierre Boutouyrie Full Professor of Pharmacology and Cardiology, University Paris Descartes Sorbonne, Paris, France.

Pierre Boutouyrie is full professor of Pharmacology at Universit� de Paris Cit�, head of Pharmacology department and cardiologist at H�pital Europ�en Georges Pompidou, Assistance Publique H�pitaux de Paris, and researcher at Institut National de Sant� et recherche m�dicale INSERM, PARCC. His main topics are care and research in hypertension, research on arterial remodeling and stiffness. He has published over 340 articles and has over 20,000 quotations.

Michael Hecht Olsen Professor, University of Southern Denmark and Odense University Hospital, Odense C, Denmark.

Michael Hecht Olsen is a professor in Hypertension and Cardiovascular Prevention at the Department for Regional Health Research, University of Southern Denmark, and senior consultant in cardiology at Department of Medicine 1, Holbaek Hospital, Denmark.

Both clinically and in research, he works with hypertension, obesity, diabetes and cardiovascular risk stratification using measurements of subclinical cardiovascular damage (e.g., pulse wave analysis, ultrasound of the carotid arteries and echocardiography) and new biomarkers for deep phenotyping trying to develop individualized treatment. He has published over 200 publications (Web of Science H-index 47).

Peter M Nilsson Senior Professor, Cardiovascular Research, consultant, Department of Clinical Sciences, Lund University, Sweden.

Peter M. Nilsson is Senior Professor/expert in Clinical Cardiovascular Research at Lund University, Department of Clinical Sciences, Sk�ne University Hospital, Malm�, Sweden. For many years he has been developing the concept of EVA with numerous colleagues and the prevention of cardiovascular disease and type 2 diabetes.

Stephane Laurent Emeritus Professor of Pharmacology at Universit� de Paris Cit�, France.

Stepane Laurent's research interests are hypertension pathophysiology and management, pharmacology of antihypertensive drugs, arterial stiffness and vascular ageing. He has served as President of the European Society of Hypertension (ESH) (2007-2009) and President of the ARTERY Society (2010-2012), and is the author of over 500 referenced articles and 20 chapters in books.