Abstract
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.
Highlights
Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies
Among other parameters known to be associated with increased mortality in COVID-19 patients, estimated pulse wave velocity (ePWV) was higher in deceased patients (Table 1)
The novel findings of this study are that: ePWV, a readily available estimate of arterial stiffness, is increased in patients hospitalized with COVID-19 versus matched non-COVID-19 controls and provides incremental predictive value for 28-day all-cause mortality beyond established risk factors of adverse outcome for the disease, clustering of comorbidities as assessed by the Charlson comorbidity index and a well-validated mortality score in COVID-1913. ePWV was superior to other risk factors derived from blood pressure (BP) measurement previously shown to be associated with mortality such as increased pulse pressure and low SBP12
Summary
Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. By randomly splitting our cohort of patients with COVID-19 (n = 737) into training (80%) and test (20%) sets and replicating our results into 1,000 bootstrapped samples, ePWV significantly improved all classification measures for 28-day death beyond a clinical model with established predictors of adverse prognosis in this d isease[4] (Table 2).
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