Estimated pulse wave velocity improves risk stratification for all-cause mortality in patients with COVID-19
Authors: Stamatelopoulos Kimon , Georgiopoulos Georgios , Baker Kenneth F. , Tiseo Giusy , Delialis Dimitrios , Lazaridis Charalampos , Barbieri Greta , Masi Stefano , Vlachogiannis Nikolaos I. , Sopova Kateryna , Mengozzi Alessandro , Ghiadoni Lorenzo , Schim van der Loeff Ina , Hanrath Aidan T. , Ajdini Bajram , Vlachopoulos Charalambos , Dimopoulos Meletios A. , Duncan Christopher J. A. , Falcone Marco , Stellos Konstantinos ,   the Pisa COVID-19 Research Group, Tiseo Giusy , Barbieri Greta , Masi Stefano , Mengozzi Alessandro , Ghiadoni Lorenzo , Falcone Marco , Monzani Fabio , Menichetti Francesco , Virdis Agostino , Forfori Francesco , Rubia Baldassarri , Pietro Bertini , Giulia Brizzi , Francesco Corradi , Alessandra Della Rocca , Fabio Guarracino , Paolo Malacarne , Marco Monfroni , Chiara Piagnani , Naria Park , Alessandro Celi , Carrozzi Laura , Francesco Cinotti , Santini Massimo , Alessandro Cipriano , Martina Biancalana , Matteo Borselli , Elia Nencini , Stefano Spinelli , Francesca Ruberti , Giovanna Forotti , Maria Sciuto , De Marco Salvatore , Rachele Antognoli , Valeria Calsolario , Simone Paterni , Luciano Colangelo , Chiara Sonato , Valentina Galfo , Uliana Monica ,   Newcastle COVID-19 Research Group, Baker Kenneth F. , van der Loeff Ina Schim , Hanrath Aidan T. , Duncan Christopher J. A. , Tee Su Ann , Capstick Richard , Marchitelli Gabriella , Li Ang , Barr Andrew , Eid Alsafi , Ahmed Sajeel , Bajwa Dalvir , Mohammed Omer 
Published: October 2021

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P < 0.001). Using a machine learning approach, ePWV provided incremental prognostic value and improved reclassification for mortality over the core model including age, sex and comorbidities [AUC (core model + ePWV vs. core model) = 0.864 vs. 0.755]. ePWV provided similar prognostic value when pulse pressure or hs-Troponin were added to the core model or over its components including age and mean blood pressure (p < 0.05 for all). The optimal prognostic ePWV value was 13.0 m/s. ePWV conferred additive discrimination (AUC: 0.817 versus 0.779, P < 0.001) and reclassification value (NRI = 0.381, P < 0.001) over the 4C Mortality score, a validated score for predicting mortality in COVID-19 and the Charlson comorbidity index. We suggest that calculation of ePWV, a readily applicable estimation of arterial stiffness, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 beyond established risk factors and scores.