Application of the 2019 ESC/EAS dyslipidemia guidelines to a Mexican population: evaluating treatment targets for secondary prevention in clinical practice

Introduction In 2019 the ESC/EAS published the update on their guidelines for the management of dyslipidemias. For patients with prior myocardial infarction or stroke, they recommend achieving an LDL level <55mg/dL as a primary objective, and a non-HDL level <85mg/dL as a secondary target. Objective To analyze the impact and application that the 2019 ESC/EAS dyslipidemia guideline has on the management of dyslipidemia for secondary prevention. Methods Using data from a nationwide register in Mexico, a retrospective study was performed, including adult patients from 2018–2020 treated for hyperlipidemia and with prior history of stroke, myocardial infarction, or peripheral artery disease, with at least one follow-up visit. Patients were divided into 2 groups according to their LDL target attainment, furthermore, those with an appropriate LDL target were subdivided into 2 groups according to the attainment of the secondary target. Results 590 patients were included, the mean age at the last visit was 67 years, 68% were men. The most frequent cardiovascular event was myocardial infarction (75%). The most frequent comorbidity found was obesity (79%). 60% of the sample was on high-intensity statin treatment and 5% received only life-style modifications. When the LDL target attainment was analyzed, only 124 patients (21%) had an adequate control (group 1). Patients in this group had a lower mean age (66±12 vs 67±10), BMI was higher in this group (29 vs 28), meanwhile, blood pressure measurements were slightly lower (systolic 123 vs 126 mmHg, diastolic 73 vs 75 mmHg). They had, however, a higher frequency of comorbidities, such as T2D (46% vs 39%), hypertension (77% vs 73%) and heart failure (26% vs 23%). There were also differences in the pharmacological treatments: in group 1, 58% of the patients were treated with a high-intensity statin (vs 60% in group 2), 24% were treated with a moderate-intensity statin (vs 35% in group 2) and only 16% received a dual treatment strategy with ezetimibe (vs 13% in group 2). Only 8 patients received a PCSK9 inhibitor, and only one of them had an adequate LDL target. When the secondary target attainment was analyzed for patients in group 1, 85% of them had also an adequate control (subgroup 1). Conclusions The treatment targets from the update on the guidelines, are associated with undertreatment of high-risk patients on secondary prevention. At the current time, less than half of the patients included in this study achieved the optimal target, and only 60% of patients are receiving the appropriate intensity of treatment. There might be different patient-physician related barriers to achieving a good control, one to be considered is the important economic implication of the new pharmacologic options. More studies are required to study the before mentioned barriers and to suggest a proper population-based approach to improve adherence to cardiovascular guidelines for secondary prevention. FUNDunding Acknowledgement Type of funding sources: None.

A clearance period after soluble lead nanoparticle inhalation did not ameliorate the negative effects on target tissues due to decreased immune response

Background: The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. Mice were exposed to Pb(NO3)2 NPs in whole-body inhalation chambers for up to 11 weeks. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs (lung, liver, kidney, spleen, bone and blood). Results: After exposure to Pb(NO3)2 NPs, the lead concentration was the highest in femur at all designated time points with the exception of 3-day inhalation. In contrast to other organs, the ability to clear the lead from the femur was very low. In the lungs, Pb(NO3)2 NP inhalation induced serious structural changes; lung damage was present even after a 5-week clearance period despite the lead being almost completely eliminated from the lung tissue. Furthermore, in secondary target organs (kidney and liver), Pb(NO3)2 NPs induced several morphological defects, with alterations that remained visible after the clearance period even though the tissue lead concentrations decreased to minimal values. The numbers of lung and liver macrophages were significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, was increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines (tumour necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGFβ1], interleukin 6 [IL-6], IL-1α and IL-1β) displayed a tissue-specific response to lead exposure. Conclusions: Taken together, diminished inflammatory response in lung and liver after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by enhanced pathological changes in target organs, even after a 5-week clearance period.

A Clearance Period After Soluble Lead Nanoparticle Inhalation did not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response

Background: The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover possible differences in the effects of lead exposure on individual target organs and to reveal potential variability in the clearance of lead from organs after inhalation of soluble and insoluble lead particles. Mice were exposed to Pb(NO3)2 NPs in whole-body inhalation chambers for up to 11 weeks. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs (lung, liver, kidney, spleen, bone and blood). Results: After exposure to Pb(NO3)2 NPs, the lead concentration was the highest in femur at all designated time points with the exception of 3-day inhalation. In contrast to other organs, the ability to clear the lead from the femur was very low. In the lungs, Pb(NO3)2 NP inhalation induced serious structural changes; lung damage was present even after a 5-week clearance period despite the lead being almost completely eliminated from the lung tissue. Furthermore, in secondary target organs (kidney and liver), Pb(NO3)2 NPs induced several morphological defects, with alterations that remained visible after the clearance period even though the tissue lead concentrations decreased to minimal values. The numbers of lung and liver macrophages were significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, was increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines (tumour necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGFβ1], interleukin 6 [IL-6], IL-1α and IL-1β) displayed a tissue-specific response to lead exposure. Conclusions: Taken together, diminished inflammatory response in lung and liver after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by enhanced pathological changes in target organs, even after a 5-week clearance period that contrasts to the stronger effect observed previously after the clearance of insoluble lead nanoparticles.

Confocal Analysis of the Distribution and Persistence of Sindbis Virus (TaV-GFP) Infection in Midguts of Aedes aegypti Mosquitoes

Biological transmission of arthropod-borne viruses (arboviruses) to vertebrate hosts by hematophagous insects poses a global threat because such arboviruses can result in a range of serious public health infectious diseases. Sindbis virus (SINV), the prototype Alphavirus, was used to track infections in the posterior midgut (PMG) of Aedes aegypti adult mosquitoes. Females were fed viremic blood containing a virus reporter, SINV [Thosea asigna virus-green fluorescent protein (TaV-GFP)], that leaves a fluorescent signal in infected cells. We assessed whole-mount PMGs to identify primary foci, secondary target tissues, distribution, and virus persistence. Following a viremic blood meal, PMGs were dissected and analyzed at various days of post blood-feeding. We report that virus foci indicated by GFP in midgut epithelial cells resulted in a 9.8% PMG infection and a 10.8% dissemination from these infected guts. The number of virus foci ranged from 1 to 3 per individual PMG and was more prevalent in the PMG-middle > PMG-frontal > PMG-caudal regions. SINV TaV-GFP was first observed in the PMG (primary target tissue) at 3 days post blood-feeding, was sequestered in circumscribed foci, replicated in PMG peristaltic muscles (secondary target tissue) following dissemination, and GFP was observed to persist in PMGs for 30 days postinfection.

The Potential of Photon Activation and Neutron Activation Techniques for Fast Soil Characterization

In the frame of a partnership between CEA and VINCI, various measurement techniques are applied to soil analysis and tested in different laboratories located at CEA Saclay (France). This paper deals with two nuclear measurement techniques assessed in this project. More specifically, this paper presents the feasibility study carried out for two non-destructive active methods: photon activation and neutron activation. First, some atomic nuclides are activated either by photons or neutrons. Secondly, gamma-rays of specific energies are emitted by activated nuclides and gamma-ray spectrometry enables to identify these activated nuclides. Calibration of the full measurement system with reference samples would enable to quantify the mass of activated nuclides. Irradiations performed for photon activation measurements were conducted using a linear electron accelerator (linac) as the latter enables to generate high-energy photons by Bremsstrahlung thanks to its conversion target. Furthermore, irradiations performed for neutron activation measurements were also conducted with a linac. Indeed, photons may be converted to neutrons by photonuclear reactions using a secondary target. In the frame of this project, experiments were carried out at the SAPHIR platform (CEA Saclay) with a Linatron-M9 VARIAN linac. The electron energy was either 6 or 9 MeV. For neutron activation measurements, a secondary target made of heavy water has been used as neutron source and a polyethylene cell enabled to thermalize neutrons and increase the number of reactions of interest. In this paper, we present the different experimental setups and the measurement protocols established for this feasibility study. We show experimental results obtained with raw material samples coming from three construction sites.

Development of X-ray fluorescence methods by use of a Mo X-ray tube and their application in the case of biological samples

In the present work two different experimental arrangements, aiming in the X-ray fluorescence analysis of solid and liquid biological samples respectively, were developed and studied both theoretically and experimentally in combination with a Mo anode X-ray tube: The secondary target XRF (STXRF) and the Total Reflection XRF set-up (TXRF). The secondary target XRF irradiation chamber was designed and constructed in our laboratory. Careful choice of the materials combined with the tight geometry used, minimize the presence of interference peaks in the spectrum and offer high intensity of the exciting beam at the sample position. Optimum performance was ensured by means of an extended theoretical and experimental study of various parameters affecting the analytical capabilities of secondary target XRF systems, such as: The choice of secondary target material and the operational conditions of the X-ray tube. The secondary target XRF set-up was applied in the determination of the concentrations of trace elements in a pool blood serum sample. A simple preparation technique, like the freeze-drying process was employed, resulting in detection limits of 15 ng/ml for most metal trace elements and for a 6000 sec measuring time. The accuracy of the whole experimental procedure, examined by internal standardization and by analyzing the reference standard material A-13, was found to be about 4% over the whole atomic number range. For the determination of the mass absorption coefficients, necessary in the quantification step, a modified version of the emission transmission method was employed. Total Reflection X-Ray Fluorescence (TXRF) is a well-established method, mainly applied in the analysis of liquid samples, offering very low detection limits in most of the cases. Direct application of the TXRF method is not so efficient in blood serum analysis, since the high content of the organic matrix increases significantly the background due to Compton scattering. Chemical treatment of the blood serum samples and related preconcentration techniques have been suggested in literature, but they are time consuming and increase the possibility of adding contaminants in the sample. In this work, the applicability of direct TXRF analysis in blood serum samples was examined. The insertion of a Mo filter after the cut-off reflector has been found to improve significantly the peak to background ratio, especially for the elements of interest such as Cu, Zn, Se and Br. The influence of self-absorption phenomena in the quantification procedure was also investigated with respect to the internal standard used and the sample mass analyzed. Precision and accuracy in the analysis was found to be about 4% over the whole atomic number range. Detection limits were in the order of 25ng/ml for most metal trace elements and a measuring time of 3600 sec.