BACKGROUND: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.

Almazov Federal Medical Research Centre St Petersburg Russia

Cardiometabolic Centre Dept of Angiology Szent Imre University Teaching Hospital Budapest Hungary

Department of Internal Medicine and Geriatric Cardiology Centre of Postgraduate Medical Education Warsaw Poland

Department of Internal Medicine and Gerontology Jagiellonian University Medical College Kraków Poland

Department of Internal Medicine Hospital Mutua Terrassa University of Barcelona Terrassa Spain

Department of Medical Clinical Pharmacology University of Debrecen Hungary

Department of Medicine Section of Geriatric Medicine University of Verona Italy

Department of Medicine Solna Karolinska Institutet and Department of Cardiology Karolinska University Hospital Stockholm Sweden

Department of Medicine Solna Karolinska Institutet and Department of Cardiology Karolinska University Hospital Stockholm Sweden; Inserm U1116 Nancy France; Université de Lorraine CHRU Nancy University Hospital of Nancy France

Department of Nephrology Hypertension Dialysis and Transplantation University Hospital Centre Zagreb Croatia

Department of Preventive Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Foundation Medical Research Institutes Paris France

FSBI Chazov National Medical Research Centre of Cardiology of the Ministery of Health of the Russian Federation Moscow Russia

Government Institution L T Malaya Therapy Institute of the National Academy of Medical Sciences of Ukraine Kharkov Ukraine

Inserm U1116 Nancy France

Inserm U1116 Nancy France; Université de Lorraine CHRU Nancy University Hospital of Nancy France

Institut Universitari d'Investigació en Atenció Primària Jordi Gol Department of Medical Sciences University of Girona Primary Care Services Biomedical Research Institute Institut Català de la Salut Girona Spain

Institute of Cardiology Centre of Preventive Cardiology Yerevan Armenia

Institute of Cardiology Kiev Ukraine

Medical Faculty University of Belgrade and Cardiovascular Institute Dedinje Belgrade Serbia

P Stradins University Hospital Cardiology Centre Riga Latvia

Paris Descartes University AP HP Diagnosis and Therapeutic Center Hôtel Dieu Paris France

Primary Care Research Unit of Salamanca Department of Biomedical and Diagnostic Sciences University of Salamanca Salamanca Spain

Scientific and Research Institute of Cardiology and Internal Diseases Almaty Kazakhstan

Université de Lorraine CHRU Nancy University Hospital of Nancy France

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