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Objectives: This study aims to evaluate the prognostic value of emergency blood test results in patients with acute ischaemic stroke., Methods: We evaluated 592 prospectively patients with neuroimaging-confirmed ischaemic stroke admitted to our stroke unit between 2015 and 2018. We gathered emergency blood test results and calculated the neutrophil-to-lymphocyte ratio and the neutrophil-to-platelet ratio (neutrophils × 1.000/platelets). The association between blood test results and functional prognosis (as measured with the modified Rankin Scale) and such complications as haemorrhagic transformation was evaluated by logistic regression analysis. The additional predictive value of blood test parameters was assessed with receiver operating characteristic curves and the net reclassification index., Results: An neutrophil-to-lymphocyte ratio ≥ 3 at admission was associated with a two-fold increase in the risk of functional dependence at 3 months (OR: 2.24; 95% CI: 1.35-3.71) and haemorrhagic transformation (OR: 2.11; 95% CI: 1.09-4.05), while an neutrophil-to-lymphocyte ratio ≥ 3.86 resulted in an increase of 2.4 times in the risk of mortality at 3 months (OR: 2.41; 95% CI: 1.37-4.26) after adjusting for the traditional predictors of poor outcomes. Patients with neutrophil-to-platelet ratio ≥ 32 presented 3 times more risk of haemorrhagic transformation (OR: 3.17; 95% CI: 1.70-5.92) and mortality at 3 months (OR: 3.07; 95% CI: 1.69-5.57). Adding these laboratory parameters to standard clinical-radiological models significantly improved discrimination and prognostic accuracy., Conclusions: Basic blood test parameters provide important prognostic information for stroke patients and should therefore be analysed in combination with standard clinical and radiological parameters to optimise ischaemic stroke management., (Copyright © 2022 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Smoking is an important cardiovascular risk factor whose underlying mechanism is incompletely understood. However, it has been suggested that alterations in the balance between synthesis and degradation of the extracellular matrix (ECM) may play a role. The aim of this study was to determine whether there is an independent association between smoking and the concentration of circulating metalloproteinases (MMPs) in individuals without cardiovascular disease., Methods: Metabolic parameters, the carotid intima-media thickness (IMT), inflammatory markers (fibrinogen, C-reactive protein and interleukin-6), markers of endothelial damage (e.g., von Willebrand factor), and the concentration of MMP-1, -9 and -10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in 400 asymptomatic individuals with cardiovascular risk factors. Subjects were divided into non-smokers (n=195), smokers (n=118) and former smokers (n=87). In addition, global cardiovascular risk was determined from PROCAM and REGICOR scores., Results: Both MMP-1 and MMP-10 concentrations were significantly higher in smokers than non-smokers (P< .05 and P< .001, respectively), though there was no difference in the levels of MMP-9, TIMP-1, IMT and other inflammatory parameters. There were positive correlations between the MMP-10 concentration and PROCAM and REGICOR scores (P< .001). Multivariate analysis showed that there was still an association between smoking and the MMP-10 concentration after adjustment for age, sex and other cardiovascular risk factors (P< .001). Multiple regression analysis showed that smoking accounted for 28% of the variability in the MMP-10 concentration., Conclusions: There was an independent association between smoking and the MMP-10 concentration in asymptomatic individuals. This relationship between MMP-10 and the ECM may indicate a mechanism through which this MMP contributes to smoking-related atherosclerosis.

Background and Objective: We assessed whether an independent association between inflammatory markers and age-related subclinical atherosclerosis could be found in subjects free from cardiovascular disease., Patients and Method: Metabolic parameters, inflammatory and endothelial markers, such as high-sensitivity C-reactive protein, interleukin-6, fibrinogen and von Willebrand factor, as well as the carotid intima-media thickness were assessed in 890 asymptomatic subjects (mean age: 55 years; range: 20-80 years; 80% men) with cardiovascular risk factors., Results: Subjects in the upper quartile (age 61-80 years) showed a significant increase of traditional risk factors, particularly arterial pressure and glucose levels (p < 0.01) as compared with lower quartiles. We also found a significant increase in the levels on inflammatory and endothelial markers (p < 0.001) and intima-media thickness (p < 0.001) in older adults. In the multivarate analysis, after adjustment for cardiovascular risk factors, intima-media thickness was independently associated with inflammation and endothelial dysfunction in older adults (p < 0.01)., Conclusions: Besides age, systemic inflammation and vascular damage are associated with subclinical atherosclerosis in asymptomatic subjects. The age-related inflammatory profile may predispose to cardiovascular complications.

Defects in the synthesis and breakdown of the extracellular matrix (ECM) are now seen as key processes in the development of atherosclerosis and its thrombotic complications. Correlations have been observed between circulating levels of ECM biomarkers and the clinical manifestations of and risk factors for atherosclerosis. Several matrix metalloproteinases (MMPs), endopeptidases that can degrade the ECM, such as MMP-9 and MMP-10, play important roles in the pathophysiology of atherothrombosis and contribute to the expansion of abdominal aortic aneurysms. Moreover, they may also be useful biomarkers of atherosclerotic risk and serve as predictors of coronary and cerebrovascular disease recurrence. Although at present the effect of tissue inhibitors of MMPs (TIMPs) on cardiovascular disease prognosis is still uncertain, the ECM could be a promising therapeutic target in atherothrombotic disease, and several MMP inhibitors are currently undergoing clinical trials.

The recognition that inflammation is a hallmark of atherosclerotic disease and its complications has led to a series of studies reporting high prevalence of atherosclerosis in chronic inflammatory diseases. Indeed, chronic immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, are associated with proinflammation, accelerated atherosclerosis and increased incidence of cardiovascular disease. Since the susceptibility towards cardiovascular events cannot be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors, potentially important for future prevention and treatment of atherosclerosis associated with chronic inflammatory diseases.

It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Systemic inflammatory markers (C reactive protein, cytokines adhesion molecules) also play a role in this process. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. Recent reports by our group have demonstrated increased monocyte COX-2 activity and the production of prostaglandin E2 in relation to cardiovascular risk factors and subclinical atherosclerosis in asymptomatic subjects. Our findings support the notion that the COX-2/prostaglandin E2 axis may have a role, raising the question as to whether its selective inhibition might be an attractive therapeutic target in atherosclerosis. COX-2 inhibitors, collectively called "coxibs" (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise as anti-inflammatory drugs without the some of the side effects of aspirin or non steroidal antiinflammatory agents. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk, and therefore coxibs should be restricted in atherosclerosis-prone patients.

The formation of a fibrin clot is one of the key events in atherothrombotic vascular diseases, such as myocardial infarction, ischemic stroke and peripheral arterial disease. Fibrin is formed from a circulating precursor, fibrinogen, by the action of thrombin. Both genetic and environmental factors are important determinants of the circulating fibrinogen levels. Epidemiologic studies have demonstrated a role for this hemostatic protein in the prediction of cardiovascular disease. As an acute-phase reactant, fibrinogen is also a marker of inflammation. Likewise, recent studies from our group have shown that increased fibrinogen levels represent a marker of subclinical atherosclerosis, likely to be useful in the identification of asymptomatic subjects at risk for cardiovascular disease.

Arterial thrombosis results from complex gene-gene and gene-environment interactions. While Vichow's triad was traditionally referred to venous thrombosis, the same process has been applied to arterial thrombosis: abnormalities of hemorrheology, abnormal blood constituents and abnormal vessel wall/endothelial dysfunction. Research carried out in the past decade has identified several polymorphisms in genes related to coagulation and fibrinolytic factors, platelet receptors, endothelial dysfunction, homocysteine metabolism, endothelial nitric oxide synthase, abnormal blood flow and oxidative stress. Whereas the individual contribution of each polymorphism to the overall cardiovascular risk seems to be modest, multiple gene-gene and gene-environment interactions appear more relevant in the pathogenesis of arterial thrombosis.

As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion. A number of imaging modalities (vascular ultrasound, MRI, and coronary computed tomography) are used for non-invasive assessment of atherosclerosis; most of them can identify luminal stenosis, wall thickness and plaque volume and composition, and can even characterize the rupture-prone vulnerable plaques. Several classes of drugs, including statins, ACE inhibitors, -blockers, and antithrombotics, are able to reduce the plaque burden and the incidence of cardiovascular events; this may be attibutable, at least in part, to plaque-stabilizing effects and the improvement of endothelial dysfunction.