Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus. / Resumen ejecutivo: actualización en el tratamiento dietético de la prediabetes y la diabetes mellitus tipo 2.

Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity, and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis, the Spanish Diabetes Society, and the Spanish Society of Internal Medicine.

Diffractive lenses recorded in absorbent photopolymers.

Photopolymers can be appealing materials for diffractive optical elements fabrication. In this paper, we present the recording of diffractive lenses in PVA/AA (Polyvinyl alcohol acrylamide) based photopolymers using a liquid crystal device as a master. In addition, we study the viability of using a diffusion model to simulate the lens formation in the material and to study the influence of the different parameters that govern the diffractive formation in photopolymers. Once we control the influence of each parameter, we can fit an optimum recording schedule to record each different diffractive optical element with the optimum focalization power.

Development and validation of a questionnaire to evaluate lifestyle-related behaviors in elementary school children.

BACKGROUND: The SI! Program promotes cardiovascular health through a multilevel school-based intervention on four lifestyle-related components: diet, physical activity, understanding the body and heart, and management of emotions. We report here the development and validation of the KAH (knowledge, attitudes and habits)-questionnaire adapted for elementary school children (6-7 years old) as a tool for the forthcoming evaluation of the SI! Program, where the KAH scoring will be the primary outcome. The efficacy of such an intervention will be based on the improvements in children's KAH towards a healthy lifestyle. METHODS: The questionnaire validation process started with a pool of items proposed by the pedagogical team who developed the SI! Program for elementary school. The questionnaire was finalized by decreasing the number of items from 155 to 48 using expert panels and statistical tests on the responses from 384 children (ages 6-7). A team of specialized psychologists administered the questionnaire at schools providing standard directions for the final administration. The internal consistency was assessed using Cronbach's α coefficients. Reliability was measured through the split-half method, and problematic items were detected applying the item response theory. Analysis of variance and Tukey's test of additivity were used for multiple comparisons. RESULTS: The final KAH-questionnaire for elementary school children should be administered to children individually by trained staff. The 48 items-questionnaire is divided evenly between the 4 components of the intervention, with an overall Cronbach's α = 0.791 (α = 0.526 for diet, α = 0.537 for physical activity, α = 0.523 for human body and heart, and α = 0.537 for management of emotions). CONCLUSIONS: The KAH-questionnaire is a reliable instrument to assess the efficacy of the SI! Program on instilling healthy lifestyle-related behaviors in elementary school children.

Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

Genetics of population exchange along the historical Portuguese-Spanish border.

The present analysis compares the distribution of surnames by means of spatial autocorrelation analysis in the Spain-Portugal border region. The Spanish National Institute of Statistics provides a database of surnames of residents in the western Spanish provinces of Zamora, Salamanca, Cáceres, Badajoz and Huelva. The Spanish and Portuguese patterns of surname distribution were established according to various geographic axes. The results obtained show a low diversity of surnames in this region - especially in the centre - which can be explained by the absence of any major geographic barriers, with the exception of the mountain ranges between hydrographic basins, and by the presence of traditional roads that have existed since Roman times. The latter have resulted in a constant migratory flow over short-median distances, which, as can be deduced from the surnames, fits two north/south territorial axes running parallel to the border between Spain and Portugal. The distribution patterns of Portuguese and Spanish surnames differ with regard to their frequencies in the five provinces studied, which can be attributed to their respective historical, economic and social conditions. It is concluded that the border delimiting these two countries has affected the migratory flow, thereby conditioning the demographic and genetic structure of the western Spanish regions.

Factors determining the variation in birth weight in Spain (1980-2010).

BACKGROUND: Low weight and premature deliveries arouse clinical interest concerning the survival of newborns. The determinants of birth weight among Spanish natives and immigrants may differ. Research which considers maternal origin and associated factors such as age and parity is important. AIM: This study analyses and models the influence of the rapid and intense arrival of immigrants in Spain on birth weight variation. METHOD: Data on deliveries from the Spanish National Institute for Statistics (n = 9 443 882) are analysed regarding low birth weight, premature births and other variables. The inter-relation among these variables was interpreted by means of logistic regression models. RESULTS AND CONCLUSIONS: The birth weight has decreased since 1980 in Spain, but has slightly recovered in recent years. Meanwhile the percentage of foreign maternities increased to 17.3% in 2010. Logistic regression models assess the different influence of variables known to determine low birth weight (weeks of gestation, sex, etc.) and other maternal characteristics (age at delivery, professional activity, etc.). The progressively greater contribution of foreign women to total births in Spain and their differential numerical input to the various risk groups have slowed the pattern of reduction in the mean weight of newborns in this country.

Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus. / Resumen ejecutivo: actualización en el tratamiento dietético de la prediabetes y la diabetes mellitus tipo 2.

Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity, and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis, the Spanish Diabetes Society, and the Spanish Society of Internal Medicine.

Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus.

Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity; and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis (SEA, for its initials in Spanish), the Spanish Diabetes Society (SED, for its initials in Spanish), and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).

Have the Government's prescription algorithm and the 2013 American College of Cardiology/American Heart Association guidelines for managing dyslipidaemia influenced the management of dyslipidaemia? The MEJORALO-CV Project. / ¿Han influido el algoritmo de prescripción de la Administración y las guías de manejo de la dislipemia de la ACC/AHA 2013 en el manejo de la dislipemia? Proyecto MEJORA-LO CV.

OBJECTIVE: To determine the management of dyslipidaemia in primary care after the publication of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines and Valencian government's algorithm. METHOD: We conducted a cross-sectional descriptive study that employed a survey of primary care physicians of the Community of Valencia between January and October 2016. RESULTS: A total of 199 physicians (mean age, 48.9±11.0 years; experience, 21.3±11.1 years) participated in the survey. The most followed guidelines were those of the European Society of Cardiology (37.5% of respondents) and Valencian government (23.4% of respondents). Some 6.3% of the respondents followed the 2013 ACC/AHA guidelines, and 88.0% established objectives based on LDL cholesterol and cardiovascular risk. The choice of lipid-lowering drug was based on its LDL cholesterol lowering capacity (28.6% of respondents), on the Valencian government's algorithm (23.4%) and on the drug's safety (20.4%). Statins, ezetimibe and fibrates were the preferred hypolipemiant agents, and their combination (51% of respondents) and dosage increases (35%) were the strategies employed for poor control. Lipid profile and transaminase and creatine kinase levels were measured every 6 (59.5%, 52.3% and 54.3% of respondents, respectively) or 12 months (25.1%, 29.2% and 30.3%, respectively). Forty-one percent of the respondents were aware of the controversy surrounding the 2013 ACC/AHA guidelines. Although 60% of the respondents acknowledged its relevance, only 21% changed their daily practices accordingly. CONCLUSIONS: The Valencian government's algorithm had a greater impact than the 2013 ACC/AHA guidelines in primary care in Valencia. Areas for improvement included the low use of validated guidelines and risk tables and the streamlining of laboratory test periodicity.

Retrospective cohort study of clinical characteristics of 2199 hospitalised patients with COVID-19 in New York City.

OBJECTIVE: The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive. DESIGN: Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive. SETTING: All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system. PARTICIPANTS: Participants over the age of 18 years were included. PRIMARY OUTCOMES: We investigated in-hospital mortality during the study period. RESULTS: A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 µg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 µg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL. CONCLUSIONS: In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged.

[Cardiovascular disease and chronic kidney disease: from treatment to promoting health]. / Enfermedades cardiovasculares y nefropatía crónica: del tratamiento al fomento de la salud.

Chronic kidney disease is associated with poor cardiovascular outcomes and should be screened for in all patients with cardiovascular disease or risk factors such as hypertension and diabetes mellitus using estimate of glomerular filtration rate and a random urine albumin-to creatinine ratio. Strategies to identify and prevent chronic kidney disease must be part of a comprehensive program of disease prevention, that include evaluation of tobacco use, diet and exercise patterns, body mass index, blood pressure, lipid profile, blood glucose and patient-appropriate cancer screening. The global increase in patients with chronic kidney disease is threatening to reach epidemic proportions over the next decade, and few countries will be able to meet the economic challenges posed. A change in global approach from treatment of renal failure to aggressive primary and secondary prevention is essential. We propose that the United Nations Millennium Developments Goals for 2000-2015 should be expanded to include combatting infectious diseases as well as chronic diseases such as cardiovascular disease, diabetes, renal disease and cancer, using an integrated approach.

Ovariectomy increases vascular calcification via the OPG/RANKL cytokine signalling pathway.

BACKGROUND: Observational studies suggest a strong relationship between menopause and vascular calcification. Receptor activator of nuclear factor-kappaBeta ligand (RANKL) and osteoprotegerin (OPG) are critical regulators of bone remodelling and modulate vascular calcification. We assessed the hypothesis that ovariectomy increases vascular calcification via the OPG/RANKL axis. MATERIALS AND METHODS: Age-matched sexually mature rabbits were randomized to ovariectomy (OVX, n = 12) or sham procedure (SHAM, n = 12). One month post-procedure, atherosclerosis was induced by 15 months 0.2%-cholesterol diet and endothelial balloon denudations (at months 1 and 3). Aortic atherosclerosis was assessed in vivo by magnetic resonance imaging (MRI) at months 9 and 15. At sacrifice, aortas were harvested for ex vivo microcomputed tomography (microCT) and molecular analysis of the vascular tissue. RESULTS: Vascular calcification density and calcific particle number were significantly greater in OVX than SHAM (8.4 +/- 2.8 vs. 1.9 +/- 0.6 mg cm(-3), P = 0.042, and 94 +/- 26 vs. 33 +/- 7 particles cm(-3), P = 0.046, respectively). Calcification morphology, as assessed by the arc angle subtended by the largest calcific particle, showed no difference between groups (OVX 33 +/- 7 degrees vs. SHAM 33 +/- 5 degrees , P = 0.99). By Western blot analysis, OVX increased the vascular OPG:RANKL ratio by 66%, P = 0.029, primarily by decreasing RANKL (P = 0.019). At month 9, MRI demonstrated no difference in atheroma volume between OVX and SHAM, and no significant change was seen by the end of the study. CONCLUSIONS: In contrast to bone, vascular OPG:RANKL ratio increased in response to ovariectomy with a corresponding fourfold increase in arterial calcification. This diametrical organ-specific response may explain the comorbid association of osteoporosis with calcifying atherosclerosis in post-menopausal women.

The effect of tissue-segmented attenuation maps on PET quantification with a special focus on large arteries. / Efecto de la segmentación por tejidos en los mapas de atenuación sobre la cuantificación PET con especial hincapié en grandes arterias.

OBJECTIVES: Accuracy on quantitative PET image analysis relies on the correct application of attenuation correction which is one of the major challenges for PET/MRI that remains to be solved. The purpose of this study is to evaluate the effect of MRI-based attenuation maps and the use of flexible coils on the quantitative accuracy of PET images with a special focus on large arteries. MATERIALS AND METHODS: PET/CT data from eight oncologic patients was used. PET data was reconstructed using attenuation maps with different level of detail emulating several approaches available on current PET/MRI scanners. PET images obtained with CT-based and MRI-based attenuation maps were compared to evaluate the quantitative biases obtained. The quantitative effect produced by flexible MRI receiver coils on the attenuation maps was also studied. RESULTS: The use of simpler attenuation maps produced increased biases between PET data reconstructed with CT-based and MRI-based attenuation maps for fat, non-fat soft-tissues and bone. Biases in lung were very high due to the large heterogeneity and inter-patient variability of the lung. The quantification on large arteries had small deviations except for the case when flexible coils were used. The TBR provided smaller biases in all cases as it cancelled out the similar deviations obtained for arteries and reference veins. CONCLUSIONS: Simplified attenuation maps used on PET/MRI significantly increase the quantitative variability of PET images especially on lungs and bones. The quantification of PET images acquired with PET/MRI scanners applied to studies of atherosclerosis has small deviations, especially when the TBR is considered.

Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit.

The effects of homologous plasma HDL and VHDL fractions on established atherosclerotic lesions were studied in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a 0.5% cholesterol-rich diet for 60 d (group 1). Another group of animals were maintained on the same diet for 90 d (group 2). A third group was also fed the same diet for 90 d but received 50 mg HDL-VHDL protein per wk (isolated from normolipemic rabbit plasma) during the last 30 d (group 3). Aortic atherosclerotic involvement at the completion of the study was 34 +/- 4% in group 1, 38.8 +/- 5% in group 2, and 17.8 +/- 4% in group 3 (P less than 0.005). Aortic lipid deposition was also significantly reduced in group 3 compared with group 1 (studied at only 60 d) and group 2. This is the first in vivo, prospective evidence of the antiatherogenic effect of HDL-VHDL against preexisting atherosclerosis. Our results showed that HDL plasma fractions were able to induce regression of established aortic fatty streaks and lipid deposits. Our results suggest that it may be possible not only to inhibit progression but even to reduce established atherosclerotic lesions by HDL administration.

Normalization of platelet reactivity in clopidogrel-treated subjects.

BACKGROUND: Aspirin (ASA) + clopidogrel are commonly used in acute coronary syndrome (ACS), but persistent antiplatelet effects may complicate surgery. METHODS AND RESULTS: To study the possibility of normalizing platelet reactivity after ASA + clopidogrel treatment, 11 healthy subjects received a 325-mg ASA + clopidogrel loading dose (300 or 600 mg dependent on study arm), followed by 81 mg of ASA + 75 mg of clopidogrel daily for 2 days. Platelet reactivity was assessed by light transmittance aggregometry (LTA) [challenged by adenosine diphosphate (ADP), arachidonic acid (AA), collagen, and thrombin receptor activating peptide (TRAP)] and flow cytometry for platelet activation by GPIIb/IIIa receptor exposure pretreatment, 4 and 72 h postload. To normalize platelet reactivity, increasing amounts of pooled platelets from five untreated volunteers [volunteers (V)-platelet-rich plasma (PRP)] were added ex vivo to the subject's PRP (S-PRP). At both 4 and 72 h, 40% and 50% V-PRP were needed to overcome platelet disaggregation in the 300 or 600 mg arms, respectively, after ADP challenge; an additional 10% V-PRP fully normalized aggregation. Recovery of function was linear with each incremental increase of V-PRP. ADP-induced GPIIb/IIIa activation showed the same pattern as LTA (r = 0.74). Forty percent V-PRP was required to normalize platelet function to AA, collagen, and TRAP. CONCLUSION: Our results suggest that the pre-operative transfusion of 10 platelet concentrate units (the equivalent of 40% V-PRP) after a 300-mg clopidogrel loading or 12.5 units (50% V-PRP) after a 600 mg loading may adequately reverse clopidogrel-induced platelet disaggregation to facilitate postoperative hemostasis. An additional 2.5 units fully normalized platelet function. The potential clinical implications of our observations could include shorter hospitalizations and reduced bleeding complications. But these observations should be fully explored in an in vivo clinical setting with clopidogrel-treated patients before and after surgery.

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.

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.

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.

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.

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.