Estimated pulse wave velocity improves risk stratification for all-cause mortality in patients with COVID-19

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.

Associations between estimated and measured carotid-femoral pulse wave velocity in older Black and White adults: the atherosclerosis risk in communities (ARIC) study

“…Greve et al [12] compared ePWV and cfPWV in both the Danish MONItoring of trends and determinants in CArdiovascular disease (MONICA) 10 cohort (n = ~2300 individuals from Copenhagen) and the Paris cohort (n = ~1000 adults with essential hypertension), reporting a moderate correlation between the two measures (r range: 0.52 to 0.67). Hametner et al [29] compared ePWV to invasively measured aortic PWV measured during cardiac catheterization and noted a similar correlation between ePWV and aortic PWV (r = 0.67). Association between ePWV and cfPWV was assessed in a subset from this study, and correlations were reported to be slightly lower (r = 0.54) [29] .…”

“…Hametner et al [29] compared ePWV to invasively measured aortic PWV measured during cardiac catheterization and noted a similar correlation between ePWV and aortic PWV (r = 0.67). Association between ePWV and cfPWV was assessed in a subset from this study, and correlations were reported to be slightly lower (r = 0.54) [29] . Stamatelopoulos et al [30] recently compared ePWV to cfPWV in 934 adults from the Athens Vascular Registry (mean age 60 years) and noted a correlation of r = 0.64.…”

“…Despite the weak associations between ePWV and cfPWV noted herein, ePWV may still hold promise as a measure of vascular aging and CVD risk. ePWV has been shown to predict cardiovascular and cerebrovascular events and all-cause mortality independent of traditional CVD risk factors (including the following adjustment for age and BP) [8][9][10][11][12][13][14]29,[43][44][45] . Recently, ePWV was shown to improve risk stratification for all-cause mortality in hospitalized patients with COVID-19 beyond traditional risk factors and risk scores [30] .…”

Vascular Dysfunction and Its Cardiovascular Consequences During and After COVID-19 Infection: A Narrative Review

“…MDA and thrombomodulin were higher in COVID-19 patients than both hypertensives and controls. Stamatelopoulos et al, 2021 22 55–87 years Case- 1671 Control- 934 Retrospective, longitudinal cohort study ePWV was calculated using age and MBP (derived from cfPWV data) Calculation of ePWV, a readily applicable estimation of arterial stiffness and it may serve as an additional clinical tool to refine risk stratification beyond established risk scores Aydin et al, 2021 23 65.7 ± 10.7 years Case- 65 Control-50 Prospective case control study Systolic and diastolic blood pressure, urea, creatinine, eGFR at admission, serum lipid profile, BMI, CAVI, and ABPI Right and left cardio-ankle vascular index values were increased in COVID-19 patients which was thought to be prognostically significant Judd P et al, 2021 24 ˃18 years Case – 14 Healthy control- 14 ASCVD control cohort - 14 Cross-sectional, observational study FMD, NMD, PWV, AIx, IMT, compounds of arginine and kynurenine metabolism, homocysteine, vWF, EMP, antiendothelial cell antibodies, inflammatory, and immunological parameters, as well as nailfold capillary morphology FMD and NMD (parameters of endothelial dysfunction) and inflammation were altered in post-COVID-19 patients Bruno et al, 2021 [Covid-19 effects on ARTErial StIffness and vascular AgeiNg (CARTESIAN) study] 25 Not mentioned Group 1–3 Patients tested for SARS-CoV-2 requiring 1.hospitalization in intensive care unit 2.hospitalization in medical ward 3.no hospitalization Group 4 Patients tested negative and presenting at Emergency department Case control, longitudinal, multicentric study Mandatory - cf PWV, brachial blood pressure, central blood pressure, carotid ultrasound, brachial FMD, Recommended - cardiac ultrasound, 24 h blood pressure, thoracic aortic calcification “At the time of writing (10 November 2020), 43 centres from 21 countries had expressed interest in participating with a total expected number of >2500 included patients.” Abbreviations : FMD, flow-mediated dilation; NMD, nitroglycerin-mediated dilation; PWV, aortic pulse wave velocity; Aix, augmentation index; cIMT, carotid intima-media-thickness; CVMR, cerebral vasomotor reactivity to hypercapnia; cfPWV, carotid-femoral pulse wave velocity; baPWV, brachial ankle pulse wave; PWA,...…”

“…21 In a retrospective longitudinal cohort study, estimated pulse wave velocity (ePWV) has been calculated using age and mean blood pressure (MBP) [derived from cfPWV data] and the study has concluded that calculation of ePWV, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 besides already established risk factors and scores. 22 A prospective, case-control study reported that right and left cardio-ankle vascular index values (one of the non-invasive surrogate markers of the arterial stiffness) were more in COVID-19 patients and have a prognostically significance. 23 Another cross-sectional, observational study reiterated the previous findings i.e; most of the parameters of endothelial dysfunction (FMD, NMD) and inflammatory vasculopathy were altered in COVID patients.…”