Kimon Stamatelopoulos

Background Accumulating evidence suggests that endothelial dysfunction is implicated in the pathogenesis and severity of coronavirus disease 2019 (COVID‐19). In this context, vascular impairment in COVID‐19 might be associated with clinical manifestations and could refine risk stratification in these patients. Methods This systematic review aims to synthesize current evidence on the frequency and the prognostic value of vascular dysfunction during acute and post‐recovery COVID‐19. After systematically searching the MEDLINE, clinicaltrials.gov and the Cochrane Library from 1 December 2019 until 05 March 2022, we identified 24 eligible studies with laboratory confirmed COVID‐19 and a thorough examination of vascular function. Flow‐mediated dilation (FMD) was assessed in 5 and 12 studies in acute and post‐recovery phase respectively; pulse wave velocity (PWV) was the marker of interest in three studies in the acute and four studies in the post‐recovery phase. Results All studies except for one in the acute and in the post‐recovery phase showed positive association between vascular dysfunction and COVID‐19 infection. Endothelial dysfunction in two studies and increased arterial stiffness in three studies were related to inferior survival in COVID‐19. Discussion Overall, a detrimental effect of COVID‐19 on markers of endothelial function and arterial stiffness that could persist even for months after the resolution of the infection and provide prognostic value was congruent across published studies. Further research is warranted to elucidate clinical implications of this association.

Aims The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established. We aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients. Methods and results We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n = 751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n = 2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology guidelines (clinical ESCrisk). Intima-media thickness excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As primary endpoint of the study was defined the composite of cardiac death, acute myocardial infarction and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort. Results MaxWT > 2.00 mm and avg.maxWT > 1.39 mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (P < 0.05 for net reclassification index, integrated discrimination index and Delta Harrell’s C index). MaxWT < 0.9 mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort. Conclusion Integration of carotid ultrasonography in guidelines-defined risk stratification may identify patients at very high-risk in need for further residual risk reduction or at very low probability for events.