Proteomic Studies of Blood and Vascular Wall in Atherosclerosis. Review

The review is devoted to the analysis of literature data related to the role of proteomic studies in the study of atherosclerotic cardiovascular diseases. Diagnosis of patients with atherosclerotic plaques before clinical manifestations is an arduous task. The review presents the results of research on the new proteomic potential biomarkers of coronary heart disease, coronary atherosclerosis, acute coronary syndrome, myocardial infarction, carotid artery atherosclerosis. Also, the analysis of literature data on proteomic studies of the vascular wall was carried out. To assess the involvement of proteins in the pathological process of atherosclerosis, it is important to investigate the specific relationships between proteins in the arteries, expression and concentration of proteins. The development of proteomic technologies has made it possible to analyse the number of proteins associated with the development of the disease. Analysis of the proteomic profile of the vascular wall in atherosclerosis can help to detect possible diagnostically significant protein structures or potential biomarkers of the disease and develop novel approaches to the diagnosis of atherosclerosis and its complications.

Association between Oral Pathology, Carotid Stenosis, and Oral Bacterial DNA in Cerebral Thrombi of Patients with Stroke

Background and purpose. Risk of acute ischemic stroke has been associated with carotid artery atherosclerosis as well as with periodontal disease. We studied whether oral pathology or carotid atherosclerosis was associated with the presence and quantity of bacterial DNA in their aspirated thrombi. Methods. Thrombus aspirates and control arterial blood were taken from 71 patients (70.4% male; mean age, 67.4 years) with acute ischemic stroke. Tooth pathology was registered using CT scans. Carotid stenosis was estimated with CTA and ultrasonography. The presence of bacterial DNA from aspirated thrombi was determined using quantitative PCR. We also analyzed the presence of these bacterial DNAs in carotid endarterectomies from patients with peripheral arterial disease. Results. Bacterial DNA was found in 59 (83.1%) of the thrombus aspirates (median, 8.6-fold). Oral streptococcal DNA was found in 56 (78.9%) of the thrombus aspirates (median, 5.1-fold). DNA from A. actinomycetemcomitans and P. gingivalis was not found. Most patients suffered from poor oral health and had in median 19.0 teeth left. Paradoxically, patients with better oral health had more oral streptococcal DNA in their thrombus than the group with the worst pathology ( p = 0.028 ). There was a trend (OR 7.122; p = 0.083 ) in the association of ≥50% carotid artery stenosis with more severe dental pathology. Oral streptococcal DNA was detected in 2/6 of carotid endarterectomies. Conclusions. Stroke patients had poor oral health which tended to associate with their carotid artery stenosis. Although oral streptococcal DNA was found in thrombus aspirates and carotid endarterectomy samples, the amount of oral streptococcal DNA in thrombus aspirates was the lowest among those with the most severe oral pathology. These results suggest that the association between poor oral health and acute ischemic stroke is linked to carotid artery atherosclerosis.

The Personality Meta-trait of Stability and Carotid Artery Atherosclerosis

Background: Several personality and affective traits increase risk for atherosclerotic cardiovascular disease. Because many of these traits are correlated, much of their association with disease risk could reflect shared variance, rather than unique contributions of each trait individually. Within the Five Factor Model of personality, we examined a higher-order personality trait of Stability (comprising the shared variance of Agreeableness, Conscientiousness, and inverse Neuroticism) as related to extent of preclinical atherosclerosis and tested whether any such relationship might be explained by correlated variation in cardiometabolic risk factors.Method: Among 798 community volunteers (30-54 yr; 52% women), lower-order traits of Neuroticism, Agreeableness, and Conscientiousness were modeled as latent variables (from self- and two informant ratings) and used to estimate the second-order factor, Stability. Aggregated cardiometabolic risk was similarly modeled from indicators of glycemic control, blood pressure, adiposity, and lipids. Carotid artery atherosclerosis was measured as intima-media thickness (IMT) by duplex ultrasonography.Results: A structural equation model incorporating both direct and indirect effects showed lower Stability associated with greater IMT. This relationship was accounted for by the indirect pathway via cardiometabolic risk, with no residual direct effect of Stability on IMT. Secondary analyses showed that: 1) Neuroticism, Agreeableness, and Conscientiousness were unrelated to IMT independent of their shared variance (i.e., Stability); and 2) Stability predicted variation in IMT significantly when estimated from informant-, but not self-rated, traits.Conclusion: Descriptively distinct, but correlated, personality traits may associate with atherosclerotic burden through their shared, rather than unique, variance, as reflected in the meta-trait of Stability.

The Course of Carotid Plaque Vulnerability Assessed by Advanced Neurosonology

Background: Carotid artery atherosclerosis is a major risk factor for ischemic stroke. This risk is related to plaque vulnerability and is characterized by plaque morphology, intraplaque neovascularization, and cerebral microembolization. Advanced neurosonology can identify vulnerable plaques and aid in preventing subsequent stroke. We aimed to assess the time course of cerebral microembolization and intraplaque neovascularization during 6 months of follow-up and to explore the utility of advanced neurosonology in patients with acute cerebral ischemia.Methods: Fifteen patients with acute cerebral ischemia and carotid artery plaques underwent comprehensive extra- and intracranial ultrasound examinations, including microemboli detection and contrast-enhanced ultrasound. The examinations were repeated after 3 and 6 months.Results: We examined 28 plaques in 15 patients. The ultrasonographic features of plaque vulnerability were frequent in symptomatic and asymptomatic plaques. There were no significant differences in stenosis degree, plaque composition, plaque surface, neovascularization, or cerebral microembolization between symptomatic and asymptomatic plaques, but symptomatic plaques had a higher number of vulnerable features. None of the patients had recurrent clinical stroke or transient ischemic attack during the follow-up period. We observed a decrease in cerebral microembolization at 6 months, but no significant change in intraplaque neovascularization.Conclusions: In patients with acute cerebral ischemia and carotid artery plaques, cerebral microembolization decreased during 6 months of follow-up, indicating plaque stabilization.Clinical Trial Registration:ClinicalTrial.gov, identifier NCT02759653.

Correlation between computed tomography angiography and histology of carotid artery atherosclerosis: Can semi-automated imaging software predict a plaque's composition?

Background Using computed tomography angiography to differentiate between components of carotid atherosclerotic lesions remains largely elusive. This study sought to validate a semi-automated software for computed tomography angiography plaque analysis using histologic comparisons. Materials and Methods A retrospective review was performed of consecutive patients that underwent a carotid endarterectomy, with pre-procedural computed tomography angiography imaging of the cervical arterial vasculature available for review. Images were evaluated using a commercially-available software package, which produced segmented analyses of intraplaque components (e.g. intraplaque hemorrhage, lipid-rich necrotic core, and calcifications). On imaging, each component was assessed in terms of its (1) presence or absence, and (2) both volume and proportion of the total plaque volume (if present). On histological evaluation of carotid endarterectomy specimens, each component was evaluated as an estimated proportion of total plaque volume. Results Of 80 included patients, 30 (37.5%) were female. The average age was 69.7 years (SD = 9.1). Based on imaging, intraplaque hemorrhage was the smallest contributor to plaque composition (1.2% of volumes on average). Statistically significant linear associations were noted between the proportion of intraplaque hemorrhage, lipid-rich necrotic core, and calcifications on histology and the volume of each component on imaging ( p values ranged from 0.0008 to 0.01). Area under curve were poor for intraplaque hemorrhage and lipid-rich necrotic core (0.59 and 0.61, respectively) and acceptable for calcifications (0.73). Conclusion Semi-automated analyses of computed tomography angiography have limited diagnostic accuracy in the detection of intraplaque hemorrhage and lipid-rich necrotic core in carotid artery plaques. However, volumetric imaging measurements of different components corresponded with histologic analysis.

Subclinical Carotid Artery Atherosclerosis and Cognitive Function: A Mini-Review

Carotid artery atherosclerosis, the result of a multitude of vascular risk factors, is a promising marker for use in risk stratification. Recent evidence suggests that carotid artery atherosclerosis affects cognitive function and is an independent risk factor for the development of cognitive impairment. Both atherosclerosis and cognitive impairment develop over a prolonged period (years), and due to the aging population, markers to identify persons at risk are needed. Carotid artery atherosclerosis can easily be visualized using non-invasive ultrasound, potentially enabling early and intensified risk factor management to preserve cognitive function or delay further decline. However, the burden of atherosclerosis and temporal exposure required to pose a risk of cognitive impairment is unclear. This mini-review aims to explore the available evidence on the association between carotid atherosclerosis and cognition, and furthermore identify the remaining gaps in knowledge.