Molecular Pathways of Vulnerable Carotid Plaques at Risk of Ischemic Stroke: A Narrative Review.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of ischemic stroke secondary to large-artery atherosclerosis. In macroscopic evaluation, vulnerable plaques are characterized by one or more of the following features: microcalcification; neovascularization; lipid-rich necrotic cores (LRNCs); intraplaque hemorrhage (IPH); thin fibrous caps; plaque surface ulceration; huge dimensions, suggesting stenosis; and plaque rupture. Recognizing these macroscopic characteristics is crucial for estimating the risk of cerebrovascular events, also in the case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that are scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talk governing plaque inflammation, rupture potential, and thrombogenicity. The current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehensive analysis of the current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional attributes that characterize vulnerable plaques.

The Role of the Cumulative Illness Rating Scale (CIRS) in Estimating the Impact of Comorbidities on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: A Pilot Study of the MACH (Multidimensional Approach for COPD and High Complexity) Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous systemic syndrome that often coexists with multiple comorbidities. In highly complex COPD patients, the role of the Cumulative Illness Rating Scale (CIRS) as a risk predictor of COPD exacerbation is not known. OBJECTIVE: The objective of this study was determine the effectiveness of the CIRS score in detecting the association of comorbidities and disease severity with the risk of acute exacerbations in COPD patients. METHODS: In total, 105 adults with COPD (mean age 72.1 ± 9.0 years) were included in this prospective study. All participants at baseline had at least two moderate exacerbations or one leading to hospitalization. The primary outcome was a composite of moderate or severe COPD exacerbation during the 12 months of follow-up. RESULTS: The CIRS indices (CIRS total score, Severity Index and Comorbidity Index) showed a positive correlation with modified Medical Research Council (mMRC), COPD assessment test (CAT) and a negative correlation with forced expiratory volume in the first second (FEV1), Forced Vital Capacity (FVC), and FEV1/FVC. The three CIRS indices were able to predict the 12-month rate of moderate or severe exacerbation (CIRS Total Score: Hazard Ratio (HR) = 1.12 (95% CI: 1.08-1.21); CIRS Severity Index: HR = 1.21 (95% CI: 1.12-1.31); CIRS Comorbidity Index = 1.58 (95% CI: 1.33-1.89)). CONCLUSIONS: Among patients with COPD, the comorbidity number and severity, as assessed by the CIRS score, influence the risk in moderate-to-severe exacerbations. The CIRS score also correlates with the severity of respiratory symptoms and lung function.