Herramientas normativas sobre la compleja realidad ambiental : sus generalidades

p.1-5El presente trabajo tiene como objetivo de sistematizar el proceso de las herramientas jurídicas básicas sobre el medio ambiente ya que, es de fundamental importancia el conocimiento normativo que va a regular las relaciones sociales para que, desde una perspectiva holística se puedan lograr resoluciones integrales. El derecho ambiental es la respuesta normativa a la creciente degradación que sugre el medio en que vivimos. Se integra con una serie de normas de diverso nivel de importancia (leyes, decretos, ordenazas, resoluciones, etc.) y diverso origen (demanadas del estado nacional, de los estados provinciales o de los municipios), que en algunos casos se superponen y en otros se contradicen. Con una visión interdisciplinaria y en la necesidad de tomar cnocimiento del derecho ambiental y poder identificar, cuál sería la normativa aplicable a una determinada organización/actividad, en una primera instancia y a modo de guía se han elaborado una serie de preguantas esenciales que pueden resultar de gran utilidad para que, la gestión ambiental de los profesionales en su hacer se ajuste a derecho

Coronary plaque composition influences biomechanical stress and predicts plaque rupture in a morpho-mechanic OCT analysis

Plaque rupture occurs if stress within coronary lesions exceeds the protection exerted by the fibrous cap overlying the necrotic lipid core. However, very little is known about the biomechanical stress exerting this disrupting force. Employing optical coherence tomography (OCT), we generated plaque models and performed finite-element analysis to simulate stress distributions within the vessel wall in 10 ruptured and 10 non-ruptured lesions. In ruptured lesions, maximal stress within fibrous cap (peak cap stress [PCS]: 174 ± 67 vs. 52 ± 42 kPa, p<0.001) and vessel wall (maximal plaque stress [MPS]: 399 ± 233 vs. 90 ± 95 kPa, p=0.001) were significantly higher compared to non-ruptured plaques. Ruptures arose in the immediate proximity of maximal stress concentrations (angular distances: 21.8 ± 30.3° for PCS vs. 20.7 ± 23.7° for MPS); stress concentrations excellently predicted plaque rupture (area under the curve: 0.940 for PCS, 0.950 for MPS). This prediction of plaque rupture was superior to established vulnerability features such as fibrous cap thickness or macrophage infiltration. In conclusion, OCT-based finite-element analysis effectively assesses plaque biomechanics, which in turn predicts plaque rupture in patients. This highlights the importance of morpho-mechanic analysis assessing the disrupting effects of plaque stress

Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance

Background High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). Methods Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. Results Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness &lt; 65 \u3bcm (odds ratio = 1.32 per each 10 \u3bcmol/L mannose change [95% confidence interval, 1.05\u20131.65]) and was an independent predictor of death (hazard ratio for mannose 65vs &lt; 84.6 \u3bcmol/L: 4.0(95%CI, 1.4\u201311.3), p = 0.006)

Diabetes mellitus Typ 2 und koronare Kalzifizierungen - eine Studie mittels optischer Kohärenztomographie bei Patienten mit stabiler koronarer Herzerkrankung

Patients with type 2 diabetes mellitus (T2DM) present a higher risk for acute coronary syndrome (ACS) compared to patients without T2DM. As most of these ACS are pathophysiologically caused by the rupture of a coronary plaque, in the last years researchers focused on predictors for coronary plaque instability, which may then evolve in plaque rupture. A thinner fibrous cap over the necrotic lipid core is, for instance, an established feature of plaque vulnerability and can be visualized and quantified in vivo through optical coherence tomography (OCT), an intravascular imaging technique. However, it has been recently discussed whether localization, size, shape or extent of coronary calcification play a role in plaque instability. In fact, various imaging studies supported this hypothesis by showing a higher incidence of spotty calcifications in lesions of patients with ACS compared to patients with stable coronary artery disease. However, data regarding differences in localization, size, shape or extent of calcification between patients with and without T2DM are currently lacking. Our hypothesis was that these newly suggested features of plaque vulnerability may add to the well-known vulnerable phenotype of coronary plaques in patients with T2DM.We therefore analyzed through OCT lesions of patients with and without T2DM with stable coronary artery disease. In this group we performed a pre-procedural OCT, where we analyzed the localization, size, shape or extent of coronary calcification in addition to the established parameters of plaque vulnerability. We could show that patients with T2DM present a lower minimal fibrous cap thickness (FCT) as well as a higher percent stenosis compared to patients without T2DM. On the contrary, we could not detect any significant difference in localization, size, shape or extent of intravascular calcification in the two groups. In the light of these data, the role of established features of plaque vulnerability - in particular FCT - could be confirmed as marker of the higher cardiovascular risk of patients with coronary artery disease and T2DM. On the contrary, the localization, size, shape or extent of coronary calcification does not seem to influence the higher risk of diabetic patients compared to patients without T2DM

Quantitative flow ratio (QFR) identifies functional relevance of non-culprit lesions in coronary angiographies of patients with acute myocardial infarction

Introduction!#!In patients with acute myocardial infarction (AMI) and multivessel coronary disease, revascularization of non-culprit lesions guided by proof of ischemia usually requires staged ischemia testing. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in AMI patients is unknown. In this study, we tested the diagnostic value of QFR based on acute angiograms (aQFR) during AMI to assess the hemodynamic relevance of non-culprit lesions.!##!Methods!#!We retrospectively assessed the diagnostic efficiency of aQFR in 280 vessels from 220 patients, comparing it with staged ischemia testing using elective coronary angiography with FFR (n = 47), stress cardiac MRI (n = 200) or SPECT (n = 33).!##!Results!#!aQFR showed a very good diagnostic efficiency (AUC = 0.887, 95% CI 0.832-0.943, p &amp;lt; 0.001) in predicting ischemia of non-culprit lesions, significantly superior to coronary lesion's geometry as assessed by quantitative coronary angiography. The optimal cut-off for aQFR to predict ischemia was 0.80 (sensitivity = 83.7%, specificity = 86.1%). Maintaining a predefined level of 95% sensitivity and specificity, we created a decision model based on aQFR: lesions with aQFR ≤ 0.75 should be treated, lesions with aQFR ≥ 0.92 do not yield any hemodynamic relevance, and lesions in the 'grey zone' (aQFR 0.75-0.92) benefit from further ischemia testings. This model would allow to reduce staged ischemia tests by 46.8% without a relevant loss in diagnostic efficiency.!##!Conclusion!#!Our data demonstrate that aQFR allows an effective assessment of hemodynamic relevance of non-culprit lesions in AMI and may guide interventions of non-culprit coronary lesions

High cardiovascular risk of patients with type 2 diabetes is only partially attributed to angiographic burden of atherosclerosis

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events and present more severe coronary artery disease (CAD). The Gensini and COURAGE scores are established angiographic instruments to assess CAD severity, which may also predict future cardiovascular risk. However, it is unclear if these scores are able to depict the increased risk of patients with T2DM and stable CAD (T2DM-SAP). Methods: We performed quantitative coronary angiography and assessed the Gensini and COURAGE scores in 124 patients with T2DM-SAP. Angiographic data were compared to patients with stable angina without T2DM (Non-DM-SAP, n = 74), and to patients with acute coronary syndrome and T2DM (T2DM-ACS, n = 53). Results: T2DM-SAP patients had similar Gensini and COURAGE-scores compared to Non-DM-SAP-patients (Gensini: 14.44 +/- 27.34 vs 11.49 +/- 26.99, p = 0.465; COURAGE: 3.48 +/- 4.49 vs 3.60 +/- 4.72, p = 0.854). In contrast, T2DM-SAP patients had significantly lower Gensini (14.44 +/- 27.34 vs 30.94 +/- 48.74, p = 0.003) and lower COURAGE (3.48 +/- 4.49 vs 5.30 +/- 4.63, p = 0.016) scores compared to T2DM-ACS-patients. Conclusion: Both the Gensini and the COURAGE score fail to predict the high cardiovascular risk of patients with T2DM-SAP. Therefore, these scores should be used with caution in the assessment of future risk of patients with T2DM. However, among T2DM-ACS patients, both scores are increased, reflecting the high cardiovascular risk in this patient population

Co-localization of plaque macrophages with calcification is associated with a more vulnerable plaque phenotype and a greater calcification burden in coronary target segments as determined by OCT

BACKGROUND:The presence of plaque macrophages and microcalcifications are acknowledged features of plaque vulnerability. Experimental data suggest that microcalcifications promote inflammation and macrophages foster microcalcifications. However, co-localization of plaque macrophages and calcification (ColocCaMa) in coronary segments and its impact on plaque phenotype and lesion vulnerability is unexplored. METHODS:Plaque morphology including ColocCaMa of calcified coronary target segments in patients with stable coronary artery disease (n = 116) was analyzed using optical coherence tomography (OCT) prior to coronary intervention. Therefore we considered macrophages co-localized with calcification if their distance in an OCT frame was <100μm and OCT-defined microcalcifications with a calcium arc <22.5°. RESULTS:ColocCaMa was present in 29/116(25.0%) coronary segments. Calcium burden was greater (calcium volume index:1731±1421°*mm vs. 963±984°*mm, p = 0.002) and calcifications were more superficial (minimal thickness of the fibrous cap overlying the calcification 35±37μm vs. 64±72μm, p = 0.005) in the presence of ColocCaMa. Segments with ColocCaMa demonstrated a higher incidence of newly suggested features of plaque vulnerability, with a 3.5-fold higher number of OCT-defined microcalcifications (0.7±1.0 vs. 0.2±0.6, p = 0.022) and a 6.7-fold higher incidence of plaque inflammation (macrophage volume index:148.7±248.3°*mm vs. 22.2±57.4°*mm, p<0.001). Clinically, intima-media thickness (IMT) in carotid arteries was increased in patients with ColocCaMa (1.02±0.30mm vs. 0.85±0.18, p = 0.021). In a multivariate model, IMT (OR1.76 for 100μm, 95%CI 1.16-2.65, p = 0.007), HDL-cholesterol (OR0.36 for 10mg/dl, 95%CI 0.16-0.84, p = 0.017), calcium volume index (OR1.07 for 100°*mm, 95%CI 1.00-1.14, p = 0.049), macrophage volume index (OR5.77 for 100°*mm, 95%CI 2.04-16.3, p = 0.001) and minimal luminal area (OR3.41, 95%CI 1.49-7.78, p = 0.004) were independent predictors of ColocCaMa. CONCLUSION:Plaque macrophages co-localize with calcifications in coronary target segments and this is associated with high-risk morphological features including microcalcifications and macrophage infiltration as well as with greater calcification burden. Our data may add to the understanding of the relationship between plaque macrophages, vascular calcification and their clinical impact

Quantitative Flow Ratio Is Related to Intraluminal Coronary Stenosis Parameters as Assessed with Optical Coherence Tomography

Background: Quantitative flow ratio (QFR) is a novel method for assessing hemodynamic relevance of a coronary lesion based on angiographic projections without the need of a pressure wire. Various studies demonstrated that QFR consistently related to fractional flow reserve (FFR); however, it is still unclear to what extent QFR reflects intraluminal stenosis parameters. Given that optical coherence tomography (OCT) is currently the gold standard to assess intraluminal stenosis parameters, we investigated the relationship between OCT-derived lesion geometry and QFR. Methods: We determined QFR in 97 lesions from 87 patients who underwent coronary angiography and OCT due to stable angina. QFR was measured with proprietary software and compared with OCT-based assessment of intraluminal stenosis parameters as well as lesion morphology. Results: Mean QFR was 0.79 +/- 0.10. QFR demonstrated a consistent association with FFR (r = 0.834, p < 0.001). Interestingly, QFR was associated with OCT-derived parameters such as minimal lumen area (MLA, r = 0.390, p = 0.015), percent area stenosis (r = 0.412, p < 0.001), minimal lumen diameter (MLD, r = 0.395, p < 0.001), and percent diameter stenosis (r = 0.400, p < 0.001). Both minimal luminal area (ROC = 0.734, optimal cut-off 1.75 mm(2)) and minimal luminal diameter (ROC = 0.714, optimal cut-off 1.59 mm) presented a good diagnostic accuracy in diagnosing hemodynamic relevance (QFR <= 0.80). There was no significant association between QFR and anatomic features of plaque vulnerability. Conclusion: OCT-derived intraluminal stenosis parameters are related to QFR values and predict hemodynamic lesion relevance. The data supports the validity of QFR as 3D-vessel reconstruction method to assess coronary physiology without the need of a pressure wire