While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Cardiac Catheterization Laboratory Cardiothoracic and Vascular Department Ospedale Cisanello 56124 Pisa Italy

Cardiology Department Klinikum Wels Grieskirchen Wels Austria

Cardiology Unit Department of Medicine Karolinska University Hospital Solna 171 76 Stockholm Sweden

Clinica Medica Department of Clinical and Experimental Sciences University of Brescia Brescia Italy

Department of Angiology University Hospital Graz 8036 Graz Austria

Department of Cardiology and Angiology 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Cardiology Athens University Medical School Attikon University Hospital Athens Greece

Department of Cardiology Charité Universitätsmedizin Berlin 12203 Berlin Germany

Department of Cardiology Dupuytren University Hospital Limoges France

Department of Cardiology Tokyo Medical University 160 0023 Tokyo Japan

Department of Cardiology University of Ioannina Medical School Ioannina Greece

Department of Cardiology Wales Heart Research Institute Cardiff CF14 4XN United Kingdom

Department of Clinical Biochemistry Royal Free Hospital Campus University College London Medical School University College London London NW3 2QG United Kingdom

Department of Medicine and Hypertension Institute Brunner Institute for Cardiovascular Research Sackler Faculty of Medicine Tel Aviv University The E Wolfson Medical Center Holon 58100 Israel

Department of Medicine Cardiology Cheil General Hospital Dankook University College of Medicine Seoul 100 380 Republic of Korea

Department of Medicine Perelman School of Medicine University of Pennsylvania Pennsylvania Philadelphia United States

Department of Pharmacology and INSERM U970 Assistance Publique Hôpitaux de Paris Université Paris Descartes Paris 75015 France

Department of Sport Exercise and Health Division Sports and Exercise Medicine University of Basel 4052 Basel Switzerland

Department of Vascular Surgery Rigshospitalet University of Copenhagen Denmark

Division of Vascular Medicine Ospedale San Giovanni 6500 Bellinzona Switzerland

Heymans Institute of Pharmacology Ghent University 9000 Ghent Belgium

Hypertension Unit and Cardiovascular Research Laboratory 1st Department of Internal and Propedeutic Medicine Laiko General Hospital National and Kapodistrian University of Athens Greece

Peripheral Vessels Unit 1st Department of Cardiology Athens University Medical School Hippokration Hospital Athens Greece

Service de Pharmacologie and INSERM U 970 Université Paris Descartes Assistance Publique Hôpitaux de Paris Hôpital Européen Georges Pompidou 75015 Paris France

St Vincent's Clinic University of New South Wales Victor Chang Cardiac Research Institute Sydney Australia

Unit of Internal Medicine Department of Medicine University of Perugia and Terni University Hospital Terni Italy

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