Improving residual risk stratification of cardiovascular events using carotid ultrasonography

This editorial refers to ‘Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients’, by G. Georgiopoulos et al., https://doi.org/10.1093/eurjpc/zwac095. Atherosclerosis is a chronic and progressive disease characterized by lipid accumulation, macrophage infiltration, and excessive fibrous plaques in arterial intima.1 Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death worldwide.2 In western societies, ASCVD accounts for approximately 50% of all-cause mortality. ASCVD has increased the burden of healthcare systems in the United States and in Europe, costing these societies an estimated $363.4 billion and $221.6 billion, respectively.3–5 Risk stratification is crucial in the optimization of treatment strategies for ASCVD patients. Carotid ultrasonography is advantageous in screening ASCVD, given that it is low-cost, non-invasive, and allows for reproducible imaging.6 Additionally, carotid ultrasonography can quantify atherosclerosis by measuring the well-established imaging markers of carotid intima-media thickness (CIMT) and carotid plaque.7 The change in the carotid intima thickness is associated with subclinical atherosclerosis.8,9 Ultrasonographic measurements of intima-media thickness are viewed as highly accurate and are equivalent to histopathological examination .10 Carotid artery plaque is an additional predictive factor for ASCVD.11,12 The presence of carotid plaques or a CIMT value greater than or equal than the 75th percentile are considered abnormal, based on guidelines from the American Society of Echocardiography.13 The measurement of CIMT and identification of carotid plaque are essential in the refinement of ASCVD risk stratification. Georgiopoulos et al.14 analyzed two ASCVD cohort studies, Athens and atherosclerosis risk in communities. CIMT was measured at six carotid locations, and the average value of left and right CIMT was defined as average CIMT. Maximal wall thickness (maxWT) is determined by the maximal wall thickness from CIMT or atherosclerotic plaque and avg.maxWT is the average of maxWT from each of the carotid sites. Georgiopoulos et al.14 observed that MaxWT>2.00 mm, avg.maxWT>1.39 mm, as well as the number of carotid plaques>2 yield incremental prognostic value for ASCVD, in which the Harrell C-index, net reclassification index, and integrated discrimination improvement reach statistical significance. They also found that patients with maxWT<0.9 mm have a low risk of cardiovascular events. Overall, this study found that carotid ultrasonography should be included in guidelines for risk stratification due to its ability to differentiate high-risk patients in need of risk reduction with patients at a low probability for cardiovascular events. Although Georgiopoulos et al.14 included two cohort studies, this study only targeted high risk and very high risk ASCVD patients. Therefore, the findings from this study may not generalize to all populations. This is a retrospective study that used vastly different recruitment timings between the two cohort studies. These factors represent a disadvantage, as it makes the study susceptible to selection bias and poor control over the covariates.15 In the case of this particular study, the analysis of two cohort studies minimizes selection bias. This study did not include cerebrovascular events. The increase of CIMT is associated with elevated risk of ischaemic strokes or cardiovascular events.16 Future studies are needed to identify the prognostic value of carotid ultrasonography in predicting ischaemic strokes. The risk of developing ASCVD over a 10-year period of time is reportedly associated with carotid injury.17 Carotid ultrasonography is one of the best methods in assessing ASCVD events, particularly when compared to coronary calcium scoring.18 Some studies suggest that assessment of carotid arterial plaque is important for cardiovascular risk stratification, because carotid atherosclerosis is highly prevalent in subjects with low Framingham risk scores.19 Additionally, it is recommended by American Society of Echocardiography and European Society of Cardiology Guidelines to include two- and three-dimensional carotid ultrasonography for the assessment and quantification of carotid arterial plaque to provide cardiovascular risk stratification.20 Three-dimensional carotid ultrasonography can detect changes in both plaque texture and total plaque volume.21 The pathobiology of carotid plaque advancement involves thickening of the carotid intima from lipids pooling, followed by necrosis and the development of necrotic cores.22 Carotid plaques are generally defined as areas where the media-adventitia interface to the intima-lumen interface is >1.5 mm in thickness.23 CIMT can represent multiple morphologic processes, whereas carotid plaque is more reflective of atherosclerosis.19, 24 CIMT has a precision of 78% sensitivity and 75% specificity to diagnose atherosclerosis.25 CIMT increases of at least 0.1mm are associated with a 15% increase in myocardial infarction risk.26 CIMT can predict the development of carotid plaques.27 The presence of plaque(s) is associated with an increased risk of cardiovascular events.28 A study showed that addition of CIMT with the presence of plaque improves the Framingham cardiovascular risk score.29 Thus, the ideal method to predict the risk of adverse cardiovascular events is to average the maxWT of several carotid artery segments and include plaque if it is observed. Future large population studies are needed to confirm this. Overall, Georgiopoulos et al. suggested carotid ultrasonography parameters that may be useful in the prediction of cardiovascular events. This study can help to standardize the interpretation of CIMT width and measuring methodology to evaluate cardiovascular risk in clinical contexts. Physicians should consider carotid ultrasonography when evaluating risk stratification for cerebral and cardiovascular events by measuring CIMT and detecting plaque in carotid arteries. E.T. is supported by National Institutes of Heart, Lung and Blood Grants HL121776.