Response to 'Laurberg JM, Olsen AK, Hansen SB, et al. Imaging of vulnerable atherosclerotic plaques with FDG-microPET: no FDG accumulation' [Atherosclerosis 2006].
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Adipose Tissue, Brown↗
Biomedical subjects
V Fuster
Publications and source records attributed to V Fuster.
Neovascularization in human atherosclerosis.
In the absence of disease, microvessels provide vessel wall nutrients to the tunica media, while the intima is fed by oxygen diffusion from the lumen. As disease evolves and the tunica intima thickens, oxygen diffusion is impaired, and microvessels become the major source for nutrients to the vessel wall. Microvessels serve as a port of entry for inflammatory cells, from the systemic circulation to the nascent atherosclerotic lesion. As disease progress, microvessels also play a role in intraplaque hemorrhage, lipid core expansion, and plaque rupture. In addition, microvessels are also involved in stent restenosis, and plaque regression. Therefore, microvessels are a pivotal component of atherosclerosis, and proper patient risk-stratification in the near future may include the detection of increased neovascularization in atherosclerotic lesions. This review divided in two parts summarizes the current understanding of atherosclerosis neovascularization, starting with the normal anatomy and physiology and progressing to more advanced stages of the disease. We will review the structure and function of vasa vasorum in health and disease, the mechanisms responsible for the angiogenic process, the role of the immune system, including inflammation and Toll-like receptors, and the pathology of microvessels in early atherosclerotic plaques. Furthermore, the review addresses the advanced stages of atherosclerosis, summarizing the progressive role for microvessels during disease progression, red blood cell extravasation, lipid core expansion, plaque rupture, healing, repair, restenosis, and disease regression, offering the clinician a state-of-the-art, "bench to bedside" approach to neovascularization in human atherosclerosis.
Animals↗
Calcium scoring and contrast-enhanced CT angiography.
Computed tomography (CT) technology has emerged as the most promising imaging modality for the noninvasive evaluation of the coronary circulation. Of the CT-based approaches, multidetector-row computed tomography (MDCT) and to a lesser extent electron beam computed tomography offer the potential of providing not only data on the spatial extent and burden of coronary calcium content, but also angiographic data, and plaque composition characteristics with the potential for prediction of susceptibility to future cardiovascular events. A number of studies have now confirmed that CT-based assessment of the presence and amount of coronary artery calcium provides incremental prognostic information over traditional risk factors in patients with coronary artery disease and can be employed to refine risk stratification in both asymptomatic and symptomatic subjects. With the advent of several recent advances in CT imaging, it is now possible to provide high resolution (sub-millimeter, isotropic voxels) images of the coronary arteries obtained rapidly with iodinated contrast injected peripherally. MDCT is currently the preferred modality for noninvasive contrast angiography of the coronary arteries by most groups, with a new generation of 64-slice scanners promising to further improve the results of this technique. MDCT-derived angiographic information in conjunction with coronary calcium scoring and plaque characterization has the potential of replacing invasive angiography, as it potentially could provide better global assessment of risk.
Calcinosis↗
Atherosclerosis neovascularization and imaging.
Neovascularization in atherosclerotic plaques is particularly prominent in complicated lesions, and has been recently identified as a marker of plaque vulnerability. This observation has led to a growing interest in the development of imaging techniques with the ability to visualize and quantify the extent of plaque neovascularization. Such feature may play an important role in identifying those lesions more prone to destabilization and rupture, and in the guidance and monitoring of therapeutic interventions. Several modalities have emerged as potential candidates for imaging neovessels in atherosclerotic lesions. They include magnetic resonance imaging, x-ray computed tomography, positron emission tomography, single photon emission computed tomography, ultrasound, or near-infrared optical imaging. These techniques differ in their achievable spatial and temporal resolution, availability, cost, reproducibility, degree of intrusiveness, capability to image atherosclerotic plaques in various vascular territories and ability to discern different plaque components, specifically the presence of neovessels. Molecular imaging, a rapidly evolving multidisciplinary field devoted to the visualization of specific physiopathologic processes at the cellular or molecular level, appears particularly well suited for this purpose because of its ability to target and visualize individual molecules specific to neoangiogenesis. In this manuscript we will review current evidence on the potential application of the various modalities, with a particular emphasis in molecular imaging.
Animals↗
Metabolic syndrome and diabetic atherothrombosis: implications in vascular complications.
Metabolic syndrome is characterized by the clustering of a number of metabolic abnormalities in the presence of underlying insulin resistance with a strong association with diabetes and cardiovascular disease morbidity and mortality. The disorder is defined in different ways, but the pathophysiology is attributable to insulin resistance. An increased release of free fatty acids (FFAs) from adipocytes block insulin signal transduction pathway, induce endothelial dysfunction due to increased reactive oxygen species (ROS) generation and oxidative stress. Dyslipidemia, associated with high levels of triglycerides and low concentrations of high density lipoproteins (HDLs), contributes to a proinflammatory state. Inflammation, the key pathogenic component of atherosclerosis, promotes thrombosis, a process that underlies acute coronary event and stroke. Tissue factor, a potent trigger of the coagulation cascade, is increased in diabetes with poor glycemic control. Therapeutic lifestyle changes (weight loss and physical activity) along with pharmacological interventions are recommended to prevent the complications of metabolic syndrome. In addition to statins, metformin, blood pressure lowering medications, interventions to increase HDLs are other important approaches to decrease the risk of cardiovascular disease. Furthermore, the peroxisome proliferator activated receptor (PPAR)-alpha and gamma agonists are potent anti-inflammatory and anti-atherogenic agents that could both improve insulin sensitivity and the long-term cardiovascular risk. In this review we focus on the molecular and pathophysiological basis of metabolic syndrome, which augments diabetes (insulin resistance) and the contribution of neovascularization in the plaque progression in diabetes, leading to rupture and coronary thrombosis.
Animals↗
Links between inflammation and thrombogenicity in atherosclerosis.
Plaque disruption and subsequent thrombus formation play a critical role in the clinical manifestations of atherothrombosis. Vulnerable lesions are characterized by the existence of core rich in lipid, macrophages and tissue factor (TF). Plaque disruption facilitates the interaction between flowing blood with the inner components (TF) of disrupted atherosclerotic lesions triggering the coagulation cascade. TF, thrombin, platelets, fibrin and inflammatory cells are involved in this process of acute thrombus formation. This pathologic process is significantly accelerated by several "cardiovascular risk factors" such as diabetes, smoking, dyslipemia, etc. We will review on the role of TF, plaque cell apoptosis and blood thrombogenicity acting as a thread of inflammatory and prothrombotic mediators. We will also review the role of activated platelets as source for pro-inflammatory cytokines and enunciation of thrombotic process. Overall, we will try to emphasize the most recent understanding of the concepts involved in the interaction between inflammation and coagulation within the setting of atherothrombotic disease.
Animals↗
Negative impact of depression on outcomes in patients with coronary artery disease: mechanisms, treatment considerations, and future directions.
Depressive symptoms are common in coronary artery disease (CAD) patients, and are associated with increased cardiac risk. Although an important relation exists between depression and CAD prognosis, the underlying pathophysiological mechanisms are poorly understood. Additionally, evidence including the recently published ENRICHD (Enhancing Recovery in Coronary Heart Disease Patients) trial suggests that depression treatments do not lower recurrent cardiac risk. The reason for the observed lack of benefit with depression treatment in CAD patients is unclear. In this review, we discuss the impact of depression in CAD patients, the possible mechanisms involved, the studies that have examined the effects of psychological and antidepressant therapies on recurrent cardiac events, and the direction that future research should take.
Antidepressive Agents↗
Looking for the culprit of coronary in-stent restenosis: debatable role for the fibrinolytic system?
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Coronary Restenosis↗
Real time magnetic resonance guided endomyocardial local delivery.
OBJECTIVE: To investigate the feasibility of targeting various areas of left ventricle myocardium under real time magnetic resonance (MR) imaging with a customised injection catheter equipped with a miniaturised coil. DESIGN: A needle injection catheter with a mounted resonant solenoid circuit (coil) at its tip was designed and constructed. A 1.5 T MR scanner with customised real time sequence combined with in-room scan running capabilities was used. With this system, various myocardial areas within the left ventricle were targeted and injected with a gadolinium-diethylenetriaminepentaacetic acid (DTPA) and Indian ink mixture. RESULTS: Real time sequencing at 10 frames/s allowed clear visualisation of the moving catheter and its transit through the aorta into the ventricle, as well as targeting of all ventricle wall segments without further image enhancement techniques. All injections were visualised by real time MR imaging and verified by gross pathology. CONCLUSION: The tracking device allowed real time in vivo visualisation of catheters in the aorta and left ventricle as well as precise targeting of myocardial areas. The use of this real time catheter tracking may enable precise and adequate delivery of agents for tissue regeneration.
Animals↗
Antithrombotic effects of S 18886, a novel orally active thromboxane A2 receptor antagonist.
Platelet activation and thrombus formation play a critical role in the onset of acute coronary syndromes. Thromboxane A2 (TxA2) is among the different chemical modulators released by activated platelets. TxA2 is considered one of the most powerful agonists for platelet activation. In addition, TxA2 exerts a vasoconstrictor effect by serving as an agonist of the thromboxane receptor (TP) on the vascular smooth muscle cell membranes. The putative effect of TxA2 on thrombosis is demonstrated by the clinical effectiveness of acetylsalicylic acid (ASA) in the prevention of acute coronary syndromes. Among the clinically used antiplatelet agents, clopidogrel has shown to be slightly more effective than ASA in the prevention of atherothrombotic events in patients with peripheral arterial disease, and is one of the most widely used after aspirin. The aims of the study were to study the antithrombotic effects of escalating doses of the TP-receptor antagonist, S 18886 and to compare its effects with those achieved by the administration of ASA (5 mg kg-1 day-1), and clopidogrel (3 mg kg-1 day-1). The study was undertaken at high and low shear rate conditions using the Badimon perfusion chamber in a porcine model. Antithrombotic effects were assessed as changes on platelet and fibrin(ogen) deposition. The doses of 30 and 100 micro g kg-1 day-1 were selected based on a previous platelet aggregation study. S 18886 shows a dose-dependent antithrombotic response. The dose of S-100 develops similar antithrombotic effects to those of clopidogrel and superior to those of aspirin. The antithrombotic effects were statistically significant at both studied shear rate conditions. Therefore, the orally active TP-receptor antagonist, S 18886, appears to be a new and effective agent to prevent atherothrombotic complications.
Animals↗
Catheter based intracoronary brachytherapy leads to increased platelet activation.
BACKGROUND: Vascular brachytherapy (VBT) after percutaneous coronary intervention (PCI) is associated with a higher risk of stent thrombosis than conventional treatment. OBJECTIVE: To investigate in vivo periprocedural platelet activation with and without VBT, and to assess a possible direct effect of radiation on platelet activation. DESIGN: Of 50 patients with stable angina, 23 received VBT after PCI, while 27 had PCI only. The 23 patients who received VBT after PCI were pretreated for one month with aspirin and clopidogrel. Platelet activation was assessed by flow cytometry. RESULTS: The two patient groups did not differ in their platelet activation before the intervention. There was a significant increase in activation immediately after VBT, with 21.2% (interquartile range 13.0% to 37.6%) thrombospondin positive and 54.0% (42.3% to 63.6%) CD 63 positive platelets compared with 12.7% (9.8% to 14.9%) thrombospondin positive and 37.9% (33.2% to 45.2%) CD 63 positive platelets before the intervention (p < 0.001 and p < 0.01, respectively). Patients without VBT had no periprocedural difference in platelet activation immediately after PCI. No increase in platelet activation was found after ex vivo irradiation of blood samples obtained from healthy controls. CONCLUSIONS: Catheter based intracoronary VBT carried out according to current standards is highly thrombogenic. The current antithrombotic treatment with aspirin and clopidogrel is not sufficient to suppress platelet activation during the procedure. From in vitro experiments, it appears that platelet activation during brachytherapy is not caused by irradiation but by the procedure of catheter based VBT.
Angina Pectoris↗
Socioeconomic, demographic, and geographic variables affecting the diverse degrees of consanguineous marriages in Spain.
In a population the inbreeding coefficient alpha is determined by the relative incidence of the various degrees of consanguineous marriages--uncle-niece or aunt-nephew (C12), first cousin (C22), first cousin once removed (C23), second cousin (C33)--which may be related to temporal, geographic, demographic, and economic factors. Using published information from Spain corresponding to urban and rural areas, in this article we seek to establish how each specific relationship behaves with respect to geographic, demographic, and socioeconomic factors, to determine differential urban-rural patterns, and to study whether the diverse types of consanguineous matings relate homogeneously to these factors. For this purpose we performed multiple regressions in which the dependent variables were the different degrees of consanguinity previously selected and the independent variables were geographic, demographic, and economic factors. Our results indicate that the various types of consanguineous marriages in Spain are more conditioned by geographic, demographic, and economic variables than by the inbreeding level alpha (the coefficient of determination was between 0.22 and 0.72; the maximum for alpha was 0.35). A regional pattern exists in Spain and corresponds to close and to remote kinship, which may be mainly related to economic and family factors. Close relationships appear to be more associated with economic variables, whereas second-cousin marriages correspond largely to rural areas of the Spanish Central Plateau.
Catholicism↗
Integration of vascular biology and magnetic resonance imaging in the understanding of atherothrombosis and acute coronary syndromes.
The interaction between the vulnerable atherosclerotic plaque prone to disruption and thrombus formation is the cornerstone of acute coronary syndrome (ACS). Although distinct from one another, the atherosclerotic and thrombotic processes appear to be interdependent, hence the term atherothrombosis. Inflammation is a crucial common pathophysiological mechanism. Overall, the association of plaque vulnerability and ACS has been well documented. Given the multifactorial origin of atherothrombosis the best preventive approach should be aggressive management of all the risk factors. New interventions should be directed toward decreasing vulnerability of the lesions thereby decreasing the risk of ACS.
Animals↗
Molecular imaging for the diagnosis of high-risk plaque.
Despite advances in our understanding of the pathogenesis of atherosclerosis and new therapeutic modalities, the absence of an adequate method for early detection limits the prevention and treatment of the disease. High-resolution magnetic resonance has recently emerged as one of the most promising techniques for the non-invasive study of atherothrombotic disease, as it can characterize plaque composition and monitor progression. This review of plaque imaging focuses on the most recent technique: "molecular imaging", which uses specific contrast agents targeted to plaque components, and may allow for better stratification of "high-risk" plaque and "high-risk" patients.
Arteriosclerosis↗
Thrombin inhibitors in acute coronary artery disease.
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Acute Disease↗
Consanguinity in Spain: socioeconomic, demographic, and geographic influences.
Information on consanguinity in Spain was reanalyzed in order to obtain a more complete picture of consanguinity patterns by considering temporal, geographical, demographic, and economic factors. To obtain data on consanguineous marriages, we reviewed 106 published references. Only populations with homogeneous geographical characteristics, economic activities, transportation facilities, and the like, were considered. Two-way analysis of variance (ANOVA) provided highly significant differences (p < 0.001) for a both for time periods and for urban versus rural patterns, but there was no interaction between the latter two. A regression analysis shows that for rural areas the geographic characteristics, economy, communications, and index of demographic tendency were significant predictors of the inbreeding coefficient. The results obtained indicate that urban and rural patterns differ significantly and that the temporal factor needs to be taken into account before comparing inbreeding coefficients. In urban areas the census size and altitude are included in the regression equation as significant variables, but association was not found between alpha and the index of demographic tendency (population increase or decrease). Instead, the absolute number of inhabitants (census size) was significant. In rural areas geographic characteristics, communications, and index of demographic tendency were significant predictors of the inbreeding coefficient.
Analysis of Variance↗
Interpopulation relationship by isonymy: application to ethnosocial groups and illegitimacy.
The application of the isonymic method to establish interpopulation relationships is made difficult by such factors as: (1) a small population size; (2) the subdivision of the population into ethnosocial groups; and (3) the existence of individuals born extramaritally. The present study analyzes the validity of the isonymy method in populations where such difficulties exist. Lasker's R(ij) relationship coefficients were calculated in base to marital records from six Pocho parishes (Argentina) for the period 1766 to 1840. Three endogamous ethnosocial groups were considered-Spanish, American Indians, "Mestizos"--and a fourth group combining mates of the three previous groups. For each ethnosocial category, and taking into account paternal surnames, maternal surnames (both for legitimate and illegitimate mates), and whole surnames merged, R(i) interparish relationship matrices were obtained. All these matrices were correlated by means of the Mantel test. Maternal surnames of illegitimate mates show a similar pattern to the maternal surnames of legitimate mates and to all surnames of each category. Groups with larger sample size in every parish intercorrelate regardless of ethnosocial category. Results suggest the convenience of maximizing the sample size and using maternal surnames in populations with high illegitimacy.
Anthropology, Cultural↗
ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America.
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Adult↗