BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.

1st Department of Cardiology Interventional Electrocardiology and Hypertension Jagiellonian University Medical College Kraków Poland

Biomedical Science Group Faculty of Medicine University of Leuven Belgium

Center for Molecular and Vascular Biology KU Leuven Department of Cardiovascular Sciences University of Leuven Belgium

Centre for Environmental Sciences Hasselt University Belgium

Centro de Nefrología and Departamento de Fisiopatología Hospital de Clínicas Universidad de la República Montevideo Uruguay

Department of Cardiology Shanghai General Hospital China

Department of Cardiology the 1st Affiliated Hospital of Sun Yat Sen University Guangzhou China

Department of Cardiovascular Medicine Shanghai Key Laboratory of Hypertension Shanghai Institute of Hypertension State Key Laboratory of Medical Genomics National Research Centre for Translational Medicine Ruijin Hospital Shanghai Jiaotong University School of Medicine China

Department of Chronic Disease Prevention Finnish Institute for Health and Welfare Turku Finland

Department of Internal Medicine Faculty of Clinical Sciences College of Health Sciences University of Abuja Nigeria

Department of Medicine Turku University Hospital and University of Turku Finland

Department of Medicine University of Padova Italy

Faculty of Medicine Charles University Pilsen Czech Republic

Hypertension Unit Department of Hypertension and Diabetology Medical University of Gdańsk Poland

Non Profit Research Association Alliance for the Promotion of Preventive Medicine Belgium

Research Unit Environment and Health Department of Public Health and Primary Care University of Leuven Belgium

School of Physiology University of the Witwatersrand Johannesburg South Africa

Servicio de Clínica Médica Sección Hipertensión Arterial Hospital Italiano de Buenos Aires Argentina

The Steno Diabetes Center Copenhagen Herlev and Center for Health Capital Region of Denmark Copenhagen

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