Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real / Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis

Resumo Fundamento: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. Objetivos: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. Métodos: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. Resultados: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. Conclusões: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.

Abstract Background: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. Objectives: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. Methods: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. Results: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. Conclusions: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

The impact of diabetes and subclinical hypothyroidism association with coronary artery calcium: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: We aimed to analyze the association of diabetes and subclinical hypothyroidism with subclinical atherosclerosis measured by coronary artery calcium (CAC) in the baseline of the ELSA-Brasil study. Materials and methods: CAC was measured using a 64-detector computed tomographic scanner. The association of CAC > 0 was presented as an odds ratio (OR) and 95% confidence intervals (95%CI) in logistic models and as β (95%CI) in linear models after multivariable adjustment for confounders. Results: We analyzed 3,809 participants (mean-age (SD) 50.5 (8.8); 51.7% women). In the main analysis, we did not find an association of diabetes and subclinical hypothyroidism with CAC. However, in stratified analysis according to age strata, we found no significative interaction terms, an important heterogeneity between the groups, with the younger age strata showing an association of the group with both diseases and CAC > 0 (OR 7.16; 95%CI, 1.14; 44.89) with a wide but significative 95%CI, suggesting that the smaller number of participants in the younger group may influence the results. Our findings also showed an association of CAC > 0 and log (CAC+1) with diabetes in logistic (OR, 1.31; 95%CI, 1.05-1.63) and linear models (β, 0.24, 0.16, 0.40), respectively. Diabetes was independently associated with CAC > 0 in linear models. Discussion: In conclusion, our results showed a great heterogeneity in stratified analysis based on age in the younger age strata. Although we found no significant interaction factors, the smaller sample size for the analysis may influence the negative findings.

Electrocardiographic Findings Among Asymptomatic Adults With Haemophilia

Abstract Background: People with haemophilia (PwH) are living longer. Therefore, they can develop atherosclerotic cardiovascular disease (ASCVD). Electrocardiogram (ECG) alterations may be a sign of initial ASCVD before the occurrence of symptoms. Objective: To describe the prevalence of resting ECG alterations among PwH adults asymptomatic for ASCVD. Methods: PwH aged ≥ 30 years without previous ASCVD events were considered for the analysis. Resting ECG traces were analysed according to international reference values and the Brazilian Longitudinal Adult Health Study (ELSA-Brasil) results for asymptomatic Brazilian men. Based on the established normal values and using the QT index, we further described the altered ECGs as minor or major changes, according to the Minnesota Code. Differences between prevalences were evaluated by Pearson's χ2 test. Differences between medians were evaluated by the Mann-Whitney U test. A p-value < 0.05 was accepted as statistically significant. Results: A total of 64 PwH were included in the study. Median age was 44 years (interquartile range 35-52). Most patients had haemophilia A (81%) and 47% were severe. The prevalence of obesity, systemic arterial hypertension (SAH), diabetes mellitus (DM), and dyslipidaemia were 16%, 56%, 14%, and 72%, respectively. All the PwH had sinus rhythm, except for one, who had an implanted pacemaker due to idiopathic third-degree atrioventricular block. Altered ECGs were found in 25% and 30% of PwH, according to established criteria and ELSA-Brasil criteria, respectively. Major changes were found in eight (13%) PwH according to the Minnesota Code, including two ECGs with ischaemia-like wall inactivity. Conclusions: The prevalence of altered ECG varied from 25% to 30% among asymptomatic PwH.

Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2 / 中国结合医学杂志

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.

Exploration of Spectrum-effect Relationship of Zhuriheng Dropping Pills Against Macrophage Foaming Based on UPLC-Q-Exactive Orbitrap MS / 中国实验方剂学杂志

ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

Mechanism of Zhishi Xiebai Guizhitang in Treating AS Based on Regulation of Cholesterol Metabolism in Foam Cells by TRPA1 / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg-1） and simvastatin group （0.002 g·kg-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Predictive Value of Serum Albumin Levels for Coronary Artery Calcification in Patients with Early Chronic Kidney Disease / 中山大学学报(医学科学版)

ObjectiveTo explore the correlation between serum albumin levels and coronary artery calcification （CAC） in patients with early-stage chronic kidney disease （CKD）， as well as the value of serum albumin levels in predicting the incidence and severity of CAC. MethodsThe study included 391 early-stage CKD patients who underwent coronary computed tomography angiography （CTA） at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2019 and December 2022. Demographic and biochemistry data， as well as the coronary CTA results， were collected. Based on the coronary artery calcification score （CACS）， all patients were divided into non-CAC group （CACS=0， n=184） and CAC group （CACS>0， n=207）. All patients were further divided into 3 groups based on the serum albumin levels： group A （serum albumin levels<35 g/L， n=30）， group B （35 g/L≤ serum albumin levels< 40 g/L， n=198） and group C （serum albumin levels≥ 40 g/L， n=163）. Univariate and multivariate binary logistic regression analyses were conducted to investigate the association between serum albumin levels and CAC in early-stage CKD patients. Differences in CAC among groups were analyzed by using post-hoc multiple comparisons and ordinal logistic regression model analysis. ResultsPatients with CAC had significantly lower serum albumin levels than those without CAC （P<0.05）. There was a negative correlation between serum albumin levels and CACS in early-stage CKD patients （P<0.01）， as serum albumin decreased in levels， CAC increased in severity. ConclusionsOur study shows that early-stage CKD patients with lower serum albumin levels have a higher incidence of CAC. Low serum albumin level is an independent risk factor for CAC progression.

Mechanism of Ruanmai decoction in treating atherosclerosis based on YWHAZ/p38MAPK/CASP3 signaling pathway / 中国药理学通报

Aim To explore the mechanism of action of Ruanmai decoction in treating atherosclerosis through network pharmacology. Methods The chemical components and targets of Ruanmai decoction were queried using TCMSP. Relevant targets for atherosclerosis were retrieved from DrugBank, GeneCards, OMIM, and TTD databases. The " Drug-Active Ingredient-Target" PPI network was constructed using Cyto-scape software. GO and KEGG enrichment analysis were performed using the David database. Molecular docking verification of key components with core targets was conducted using the Seesar software. Atherosclerosis mouse models were established by feeding ApoE mice with a high-fat diet, and Ruanmai decoction granules were administered orally. Aortic pathological sections were stained, blood lipids were measured, and immunofluorescence was used to detect Mac2 and YWHAZ protein expression. Western blot was used to detect p-p38MAPK and C-CASP3 protein expression. Results Ruanmai decoction screened a total of 72 active drug components corresponding to 168 target genes for the treatment of atherosclerosis. The targets were primarily enriched in biological processes related to lip-id metabolism, inflammation and immunity, oxidative stress, vascular endothelial function, cell proliferation and apoptosis, glycolysis, and ubiquitination. Signaling pathways such as МАРК, TNF, PDK-Akt, and IL-17 were also involved. Animal experiments verified that RMJ could regulate the p38MAPK signaling pathway by down-regulating key targets YWHAZ, p-p38MAPK, and C-CASP3, thereby reducing AS inflammation and inflammation-induced apoptosis. Conclusions Ruanmai decoction can inhibit the expression of YWHAZ and activate the p38MAPK signaling pathway, potentially improving vascular inflammation, lipid metabolism, oxidative stress, and other pathological processes by regulating the МАРК, TNF, PDK-Akt, and IL-17 signaling pathways, thus preventing and treating atherosclerosis.

Mechanism of Shenshuai Xiezhuo Decoction in Intervention of Chronic Kidney Disease Combined with Atherosclerosis Based on Regulation of PI3K/Akt/mTOR Signaling Pathway by miRNA126 / 中国实验方剂学杂志

ObjectiveExploring the role of microRNA126 （miRNA126） in chronic kidney disease combined with atherosclerosis （CKD AS） by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group， model group， losartan group， and low， medium， and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low， medium， and high dose groups （6.0， 12.0， 24.0 g·kg-1·d-1） of Shenshuai Xiezhuo decoction and the losartan group （20 mg·kg-1·d-1） were gavaged， and the corresponding intervention was carried out for eight weeks. Then， the rats were killed， and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats： blood creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） and Masson staining of aortic tissue and pathological observation under a light microscope were carried out， and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA levels of miRNA126， PI3K， Akt， and mTOR in rats， and Western blot was used to determine the protein expression levels of phosphorylated （p）-PI3K， PI3K， p-Akt， Akt， p -mTOR， mTOR， benzyl chloride 1 （Beclin-1）， and microtubule-associated protein light chain 3Ⅱ/Ⅰ （LC3Ⅱ/LC3Ⅰ）. ResultCompared with the sham operation group， the serum SCr， BUN， TC， TG， and LDL-C in the model group were significantly increased （P<0.01）. Compared with the model group， the SCr， BUN， TC， TG， and LDL-C were decreased in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction （P<0.05）. Compared with the sham operation group， thickening plaques， infiltration of mononuclear macrophages， a small number of foam cells， disordered arrangement of smooth muscle fibers in the tunica media， and increased collagen fibers were observed in the model group， and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group， the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group， the expression of miRNA126 in the aortic tissue of the model group was significantly decreased （P<0.01）， and the mRNA expressions of PI3K， Akt， and mTOR were significantly increased （P<0.01）. Compared with the model group， the expression of miRNA126 in the aortic tissue of rats in high， medium， and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased （P<0.01）， while the mRNA expressions of PI3K， Akt， and mTOR were significantly decreased （P<0.01）. Compared with the sham operation group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the model group were significantly increased （P<0.01）， while the protein levels of Beclin-1， LC3Ⅰ， and LC3Ⅱ were significantly decreased （P<0.01）. Compared with the model group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction were decreased （P<0.05）， while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased （P<0.05）. ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats， and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126， restores the autophagy of aortic endothelial cells， protects the damage of CKD vessels， reduces the formation of As plaques， and slows the development of cardiovascular complications.

Scutellariae Radix-Coptidis Rhizoma Treats Atherosclerosis via NLRP3 Inflammasome-mediated Pyroptosis of Macrophages / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma （SRCR） on atherosclerosis （AS） in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasomes. MethodApoE-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model， atorvastatin （5 mg·kg-1）， and low-， medium-， and high-dose （1.95， 3.9， 7.8 g·kg-1， respectively） SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration， hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 （EMR1）/NLRP3 and EMR1/gasdermin D （GSDMD）. The serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1， cleaved Caspase-1， GSDMD， N-terminus of GSDMD （GSDMD-NT）， pro-IL-1β， IL-1β， and IL-18 were determined by Western blot， and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed obvious plaques， elevated serum levels of TG， TC， LDL-C， IL-1β， and IL-18 （P<0.01）， lowered serum level of HDL-C （P<0.01）， and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques （P<0.01）. Compared with the model group， SRCR， especially at the medium and high doses， alleviated the plaque pathology， reduced the lipid content in plaques （P<0.05， P<0.01）， recovered the serum lipid levels （P<0.05）， reduced the macrophage recruitment （P<0.01）， activation of NLRP3 inflammasomes， and pyroptosis in aortic root plaques （P<0.05）， lowered the serum IL-1β and IL-18 levels （P<0.01）， and down-regulated the protein levels of NLRP3， ASC， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-NT， pro-IL-1β， IL-1β， and IL-18 （P<0.05） and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 in the aortic tissue （P<0.05）. ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.

Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Regulation by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Atherosclerosis （AS） is a chronic inflammatory pathological process in which lipid and/or fibrous substances are deposited in the intima of arteries， and it is one of the pathological bases of many cardiovascular and cerebrovascular diseases. Endoplasmic reticulum stress （ERS） is a protective mechanism of cell adaptation. Moderate ERS can reduce abnormal protein aggregation and increase the degradation of misfolded proteins to repair and stabilize the internal environment， while excessive ERS can cause unfolded protein reaction， activate inflammation， oxidative stress， apoptosis， autophagy， and other downstream pathways， and lead to cell damage， or even apoptosis. A large number of studies have shown that ERS mediates a variety of pathological processes related to AS， affects endothelial cells， smooth muscle cells， macrophages， endothelial progenitor cells， and other cell components closely related to its occurrence and development， influences the progress of AS by regulating cell function， and promotes the formation of AS plaque， the transformation of stable plaque to unstable plaque， and the rupture of unstable plaque. Regulation of ERS may be a key target for the prevention and treatment of AS， and it is a research hotspot at present. Traditional Chinese medicine （TCM） believes that the origin of AS is the imbalance of Yin and Yang， the disharmony of Zangfu organs， and the abnormal operation of Qi， blood， and body fluid， which leads to the accumulation of phlegm， blood stasis， and other pathological products in the pulse channels， making the blood flow blocked or misfunction and causing the disease， which belongs to the syndrome of deficiency in origin and excess in superficiality. As the pathogenesis of AS is complex， and the symptoms are diverse， TCM has significant advantages in treating AS because of its multiple targets， multiple pathways， stable efficacy， strong individualization， and high safety. This paper systematically elaborated on the role of ERS in the occurrence and development of AS and summarized the mechanism research on the regulation and control of ERS by Chinese herbal monomer， Chinese herbal extract， Chinese herbal compound， and proprietary medicine， so as to provide a theoretical basis for clinical research and drug development in the prevention and treatment of AS.

Association between chlamydia pneumoniae, mycoplasma infection and atherosclerosis / 公共卫生与预防医学

Objective To investigate the infection of Chlamydia pneumoniae and mycoplasma pneumoniae in adults and their association with atherosclerosis,and to provide theoretical guidance for the prevention of such diseases. Methods A case-control study was used to collect 362 patients who were diagnosed with atherosclerosis from January 2019 to December 2021 in Department of Sichuan Bazhong Central Hospital, and 370 cases who were admitted to the hospital during the same period of physical examination without any cardiovascular disease were selected as the control group, and whole blood samples of the two groups of study subjects were collected, and the infection of Chlamydia pneumoniae and mycoplasma pneumoniae was detected by PCR. Results The infection rate of Chlamydia pneumoniae was 35.49%, the infection rate of mycoplasma was 40.37%, and the co-infection rate was 11.37%；The infection rate of Chlamydia pneumoniae in the control group was 12.04%, the infection rate of mycoplasma was 15.83%, and the coinfection rate was 3.14%, and the difference between the two groups was statistically significant ( χ2=10.926, P=0.023). The effects of mycoplasma, chlamydia, and co-infection on atherosclerotic patients have sex differences, mainly manifested as higher infection rates in men; In addition, the effects of mycoplasma, chlamydia, and co-infection on atherosclerosis patients varied by age, mainly in the 55-70 years age group (P<0.05). Multivariate logistic regression results showed that Chlamydia pneumoniae infection was a risk factor for atherosclerosis (OR=1.303, 95%CI: 1.043-1.677) in the whole population, and chlamydia pneumoniae (OR=1.472, 95% CI: 1.037-1.556), mycoplasma (OR=2.003, 95%CI: 1.637-3.842) and co-infection in men (OR=1.937, 95%CI: 1.380-2.184) were risk factors for atherosclerosis, while co-infection in women (OR=1.699, 95%CI: 1.263-1.765) was a risk factor for atherosclerosis. Conclusion Chlamydia pneumoniae and mycoplasma infection are risk factors for atherosclerosis, and their impact on male groups is greater, and more attention needs to be paid to them.

Research progress on overweight/obesity and atherosclerosis / 公共卫生与预防医学

Overweight/obesity has become an increasingly serious global public health problem. Studies have shown that many factors caused by overweight/obesity are involved in the occurrence of atherosclerosis, including adipokines, inflammatory factors and overweight/obesity related metabolic syndrome. This paper reviews the research progress on overweight/obesity and atherosclerosis from the above perspectives, aiming to provide reference for the prevention of overweight/obesity-related atherosclerosis.

El endotelio sano y su disfunción en el riesgo cardiovascular / Healthy Endothelium and its Dysfunction in Cardiovascular Risk

Resumen El endotelio es una monocapa formada por células aplanadas llamadas w, que revisten la parte más interna del corazón, los vasos sanguíneos y los linfáticos. Es considerado un órgano que tiene una función de barrera, pero además se encarga de regular la permeabilidad y tono vascular, hemostasia, inflamación y angiogénesis. Esta revisión se centra sobre todo en las generalidades del endotelio vascular sano y su disfunción. Se analizan los conceptos de activación y disfunción, en donde la activación se considera como un proceso autolimitado, indispensable para la hemostasia y la inflamación. La disfunción endotelial, en cambio, es un proceso patológico, de mayor duración y que se presenta cuando el endotelio ya no puede autorregularse y cambia a un fenotipo proinflamatorio y protrombótico permanente. Esta disfunción es el primer cambio que lleva a la ateroesclerosis y al aumento del riesgo cardiovascular, por esta razón se revisan los principales biomarcadores de disfunción endotelial y riesgo cardiovascular. A medida que se avance en el conocimiento básico del endotelio y su disfunción, será posible diseñar nuevas medidas preventivas o terapéuticas que puedan disminuir dicho riesgo.

Abstract The endothelium is a monolayer of flatten cells named endothelial cells that form the inner layer of the heart, blood, and lymphatic vessels. Its function is not just as a barrier, but it is a regulator of vascular permeability and tone, hemostasis, inflammation, and angiogenesis. This review is about the general aspects of vascular endothelium and endothelial dysfunction that leads to increased vascular risk. Activation and dysfunction are discussed, considering the endothelial activation as a self-limiting process, necessary to promote inflammation and hemostasis. Endothelial dysfunction is a pathological process in which the endothelium loses its ability for self-regulation and acquires a prothrombotic and proinflammation phenotype. Endothelial dysfunction is the initial step for atherosclerosis and increased cardiovascular risk, so the main biomarkers of endothelial dysfunction are reviewed. As basic knowledge about endothelium increases, preventive or therapeutic measures can be designed as treatment or prevention the risk of its dysfunction.

Enfermedad arterial periférica en población trabajadora: factores de riesgo y estilo de vida

Introducción: La Enfermedad Arterial Periférica (EAP) es definida como la oclusión de las arterias de las extremidades, se reconoce como la tercera causa de morbilidad vascular aterosclerótica, después del infarto agudo de miocardio y el accidente cerebrovascular. Aunque las enfermedades cardiovasculares se han relacionado con la ocupación, la información sobre la relación entre el trabajo con la EAP es escasa. Objetivo: Identificar la prevalencia de EAP en población laboralmente activa y su relación con variables sociodemográficas, clínicas y estilo de vida. Metodología: Se realizó un estudio analítico de tipo transversal, en 203 sujetos de 40 años o más, laboralmente activos de Popayán. Tras la firma del consentimiento, se realizó una entrevista, y se registraron las variables sociodemográficas y clínicas. Para el tamizaje de EAP se evaluó el índice tobillo brazo (ITB). Los participantes se clasificaron en categorías basadas en el ITB de la siguiente manera: EAP ≤ 0,90; 0,91 a 0,99 normal; y no compresible > 1,40. Los datos fueron analizados con el programa SPSS versión 26.0, se aplicó la prueba de Kolmogorov-Smirnov como prueba de normalidad, la t Student para evaluar diferencias de medias entre los grupos de estudio y la prueba de Chi-cuadrado. Resultados y discusión: La prevalencia fue del 2,5 % para EAP, siendo el primer estudio reportado para población trabajadora en Colombia. La EAP fue más prevalente en empleados manuales (2,8 %) e ingresos bajos (30 %); además, fueron obesos y fumadores. El riesgo encontrado para edad fue OR 1,5; IC95 % 1,17 a 2,14, género OR 1,2; IC95 % 1,20 a 3,28 y DM2 OR 1,5; IC95 % 1,23 a 6,68. Conclusión: Se estableció por primera vez la prevalencia de EAP (2,5 %) en una población laboralmente activa de Popayán, siendo más prevalente en los individuos con ingresos bajos, expuestos a factores de riesgo cardiovascular y con antecedente familiar de DM2.

Introduction: The Peripheral Arterial Disease (PAD) is defined as the occlusion of the extremities' arteries, and it is known to be the third vascular atherosclerotic cause of death after acute myocardial infarction and brain stroke. Even though cardiovascular diseases had been linked to occupation, information about the relation between PAD and labor activity runs short. Objective: To identify the PAD prevalence in the working population and its relationship with sociodemographic, clinical and lifestyle variables. Methodology: A cross-sectional analytical study was conducted in 203 people of >40 years, actively working in the city of Popayán. After consent signing, interviews were completed to record such variables. PAD testing was evaluated through Ankle-Brachial Index (ABI). Participants were grouped into categories based on ABI as follows: PAD ≤0.90; normal 0.91 to 0.99; and non-compressible >1.40. Collected data was analyzed in SPSS version 26.0, applying Kolmogorov-Smirnov test as the normal; t Student test to evaluate mean differences between study groups and Chi-square. Results and discussion: PAD prevalence was 2.5 % being the very first report done for Colombia's working class. PAD was prevalent for manual-labor employees (2.8 %), low-income people (30 %), adding obesity and smoking to their profile. Age risk found was (OR 1.5; IC 95 % 1.17 to 2.14), by gender (OR 1.2; IC 95 % 1.20 to 3.28); DM2 (OR 1.5; IC 95 % 1.23 to 6.68). Conclusion: It was determined for the first time a prevalence of (2.5 °%) PAD for a population actively working in Popayán, being more frequent with individuals with low income, people exposed to higher cardiovascular risks, and for people with family DM2 records.

Uso de Índices Aterogênicos como Métodos de Avaliação das Doenças Ateroscleróticas Clínicas / Use of Atherogenic Indices as Assessment Methods of Clinical Atherosclerotic Diseases

Resumo Fundamento A busca por métodos clinicamente úteis de avaliação de doenças ateroscleróticas, com boa acurácia, de baixo custo, sem invasividade e de fácil manejo, há anos vem sendo estimulada. Dessa forma, os índices aterogênicos avaliados deste estudo podem se encaixar nesta demanda crescente. Objetivos Avaliar o potencial dos índices aterogênicos como métodos de avaliação de pacientes portadores de aterosclerose clínica. Métodos Estudo transversal de centro único, por meio do qual foram avaliados os índices de Castelli I e II, índice aterogênico plasmático (IAP), índice de combinação de lipoproteínas e a variação do índice de perfusão periférica entre 90 e 120 segundos após um estímulo vasodilatador endotélio-dependente (ΔIPP90-120) na predição de aterosclerose. A significância estatística foi estabelecida em p < 0,05. Resultados A amostra foi composta por 298 indivíduos com idade média de 63,0 ± 16,1 anos, dos quais 57,4% eram mulheres. Comparações pareadas da análise curva ROC dos índices que alcançaram área sob a curva (ASC) > 0,6 mostram que ΔIPP90-120 e IAP foram superiores aos demais índices, sem diferenças observadas entre si (diferença entre ASC = 0,056; IC95% -0,003-0,115). Ademais, tanto a ΔIPP90-120 [odds ratio (OR) 9,58; IC95% 4,71-19,46] quanto o IAP (OR 5,35; IC95% 2,30-12,45) foram preditores independentes de aterosclerose clínica. Conclusões O IAP e ΔIPP90-120 apresentaram melhor acurácia para discriminar aterosclerose clínica. Além disso, foram preditores independentes de aterosclerose clínica, evidenciando uma possibilidade promissora para o desenvolvimento de estratégias preventivas e de controle para doenças cardiovasculares. Tratam-se, portanto, de marcadores adequados para estudos multicêntricos do ponto de vista de praticidade, custo e validade externa.

Abstract Background The search for clinically useful methods to assess atherosclerotic diseases (ASCVD) with good accuracy, low cost, non-invasiveness, and easy handling has been stimulated for years. Thus, the atherogenic indices evaluated in this study may fit this growing demand. Objectives To assess the potential of atherogenic indices to evaluate patients with clinical atherosclerosis. Methods Single-center cross-sectional study, through which the Castelli I and II indices, the atherogenic index of plasma (AIP), the lipoprotein combine index, and the variation in the peripheral perfusion index between 90 and 120 seconds after an endothelium-dependent (ΔPI90-120) vasodilator stimulus were evaluated in the prediction of atherosclerosis. Statistical significance was set at p < 0.05. Results The sample consisted of 298 individuals with an average age of 63.0±16.1 years, of which 57.4% were women. Paired comparisons of the ROC curve analysis of the indices that reached the area under the curve (AUC) > 0.6 show that ΔPI90-120 and AIP were superior to other indices, and no differences were observed between them (difference between AUC = 0.056; 95%CI -0.003-0.115). Furthermore, both the ΔPI90-120 [odds ratio (OR) 9.58; 95%CI 4.71-19.46)] and AIP (OR 5.35; 95%CI 2.30-12.45) were independent predictors of clinical atherosclerosis. Conclusions The AIP and ΔPI90-120 represented better accuracy in discriminating clinical ASCVD. Moreover, they were independent predictors of clinical ASCVD, evidencing a promising possibility for developing preventive and control strategies for cardiovascular diseases. Therefore, they are markers for multicenter studies from the point of view of practicality, low cost, and external validity.

Importance of so called "novel cardiovascular risk factors" in severity of coronary artery calcification; how serious they should be taken: a systematic review and metaanalysis / Importancia de los denominados "factores novedosos de riesgo cardiovascular" en la severidad de la calcificación de las arterias coronarias; qué tan serios deben tomarse: una revisión sistemática y un metaanálisis

Abstract Cardiovascular diseases are among important causes of death. Atherosclerosis is an important etiology for coronary artery diseases in which coronary artery calcification plays a principal role. Recently novel cardiovascular risk factors in coronary calcification are under attention. In this study, we investigated possible association between novel cardiovascular risk factors and coronary calcification. This is a prospectively registered systematic review and meta-analysis in PROSPERO and was performed in accordance with PRISMA guidelines. Medical databases were searched. Primary papers were screened and studies reporting our outcomes of interest were selected for data extraction. Quantitative data syntheses were performed using Comprehensive Meta-analysis Ver.3. In this study, 5252 papers were screened and finally 28 papers including 31241 patients underwent data extraction. Based on our findings, neutrophil/lymphocyte ratio (8 out of 10), red cell distribution width (r = 0.250, p < 0.0001), and interleukin 6 (odds ratio [OR]: 1.101 [95% confidence interval (CI): 1.001-1.210], p = 0.047) were associated with severity of coronary calcification while C-reactive protein (one out of eight) was not associated with coronary calcification. Results of lymphocyte/monocyte ratio (r = -0.120, p < 0.001), platelet/lymphocyte ratio (OR: 1.47 [95% CI: 0.89-2.41, p = 0.124]), and MPV (r = 0.017, p = 0.814 vs. OR: 1.91 [95% CI: 1.28-2.85, p = 0.002]) remained controversial due to few number of included studies or contrary results. We can conclude that neutrophil/lymphocyte ratio, red cell distribution width, and interleukin-6 are significantly associated with coronary calcification and C-reactive protein is not significantly associated with severity of coronary calcification. Our results about mean platelet volume, platelet/lymphocyte ratio, and lymphocyte/monocyte ratio are not reliable and require further investigations.

Resumen Las enfermedades cardiovasculares se encuentran entre las primeras causas de mortalidad. La aterosclerosis es una etiología importante de las enfermedades de las arterias coronarias en la que la calcificación de las arterias coronarias juega un papel principal. Recientemente, se están prestando atención a factores novedosos de riesgo cardiovascular en la calcificación coronaria. En este estudio investigamos la asociación posible entre los factores novedosos de riesgo cardiovascular y la calcificación coronaria. Esta es una revisión sistemática y metaanálisis registrados de forma prospectiva en PROSPERO y se realizó de acuerdo con las pautas de PRISMA. Se realizaron búsquedas en bases de datos médicas. Se examinaron los artículos primarios y se seleccionaron para la extracción de datos los estudios cuyos resultados fueron de nuestro interés. Las síntesis de datos cuantitativos se realizaron utilizando Comprehensive Meta-analysis Ver.3. En este estudio se seleccionaron 5252 artículos y finalmente se extrajeron los datos de 28 artículos que incluían 31241 pacientes. Según nuestros hallazgos, la proporción de neutrófilos/linfocitos (8 de 10), el ancho de distribución de glóbulos rojos (r = 0,250, valor de p < 0.0001) y la interleucina 6 (OR: 1.101 [IC del 95%: 1.001-1.210], valor p = 0.047) se asociaron con la gravedad de la calcificación coronaria, mientras que la proteína C reactiva (1 de 8) no se asoció con la calcificación coronaria. Resultados de la proporción linfocitos/monocitos (r = -0,120, valor p < 0,001), la proporción plaquetas/linfocitos (OR: 1,47 [IC 95%: 0.89-2.41, valor p = 0.124]) y el volumen plaquetario medio (r = 0.017, valor p = 0.814 C. OR: 1.91 [IC 95%: 1.28-2.85, valor p = 0.002]) siguieron siendo polémicos debido al escaso número de estudios incluidos o resultados contrarios. Podemos concluir que la proporción de neutrófilos/linfocitos, el ancho de distribución de los glóbulos rojos y la interleucina 6 se asocian significativamente con la calcificación coronaria y la proteína C reactiva no se asocia significativamente con la gravedad de la calcificación coronaria. Nuestros resultados sobre el volumen plaquetario medio, la proporción de plaquetas/linfocitos y la proporción de linfocitos/monocitos no son confiables y requieren más investigaciones.

Satisfacción de los empleadores con el desempeño de egresados de la maestría "Investigación en aterosclerosis" / Employers' Satisfaction with the Performance of Graduates from a Master's Program about Research in Atherosclerosis

Introducción: Los estudios de empleadores cobran cada vez mayor importancia en el ámbito de la educación superior, a partir de la necesidad institucional de evaluar la pertinencia de sus programas e identificar expectativas de crecimiento, al permitir conocer la existencia de vinculación institucional y desarrollo de sus egresados. Objetivo: Describir la satisfacción de los empleadores con el desempeño de egresados de la décima edición de la maestría investigación en aterosclerosis. Métodos: Se hizo un estudio descriptivo de corte transversal. Se seleccionaron los empleadores de los egresados de la última edición terminada. Se les aplicó una encuesta de forma autoadministrada para explorar la satisfacción con el desempeño de los egresados de la maestría. Resultados: El total de los empleadores manifestaron que la maestría respondía a las necesidades asistenciales, docentes e investigativas del centro en el que laboraba el máster; que este aplicaba creativa y críticamente en su práctica diaria los conocimientos adquiridos en el programa de maestría; y que era capaz de diseñar y dirigir proyectos de investigación. El 94,1 por ciento respondió que, después de graduado de la maestría, el máster tenía la capacidad de diseñar y organizar cursos de superación para solucionar problemas de la institución. El 76,5 por ciento contestó que cumplía las expectativas y el 52,9 por ciento que se sentía satisfecho con el desempeño de los egresados. Conclusiones: Los empleadores manifestaron que los egresados satisfacían el perfil declarado en la maestría. Los egresados cumplieron con las expectativas de sus empleadores y los empleadores se encontraron satisfechos con el desempeño de los egresados(AU)

Introduction: Employer surveys are becoming increasingly important in the field of higher education, from the institutional need to evaluate the relevance of their programs and identify growth expectations, by allowing to know the existence of institutional linkage and the development of its graduates. Objective: To describe the satisfaction of employers with the performance of graduates from the tenth edition of a master's program about research in atherosclerosis. Methods: A descriptive and cross-sectional study was carried out. The employers of the graduates from the last completed edition were selected. A self-administered survey was conducted on them to explore satisfaction with the performance of the graduates from the master's program. Results: The whole number of employers stated that the master's degree responded to the care, teaching and research needs of the center where the master's degree holder worked; that he/she applied the knowledge acquired in the master's program creatively and critically in his/her daily practice; and hat he/she was capable of designing and directing research projects. 94.1 percent responded that, after graduating from the master's program, the master's degree holder had the capacity to design and organize professional improvement courses to solve the institutional problems. 76.5 percent answered that the master's degree met the expectations, while 52.9 percent responded that they were satisfied with the performance of the graduates. Conclusions: Employers stated that the graduates met the profile stated in the master's program. The graduates met the expectations of their employers, who were satisfied with the performance of the graduates(AU)

Cardiovascular risk markers in premature canities

Background: An elevated cardiovascular risk has been demonstrated in middle-aged individuals with onset of hair greying before the age of 30 years. Increased serum levels of pro-inflammatory cytokines, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-?), indicate an ongoing state of chronic inflammation that is correlated with cardiovascular risk but have not been studied earlier in patients with early onset of hair greying. Aim/Objective: To study various cardiovascular risk markers including pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-?) in patients with premature canities. Methods: This was a hospital-based case-control study of 40 patients with premature canities (age between 19 and 25 years; >5 grey hair) and an equal number of age and gender-matched healthy controls. The blood pressure, pulse rate and body mass index were recorded, and investigations including fasting blood sugar, serum insulin, fasting lipid profile, high sensitivity c-reactive protein (hs-CRP), IL-6 and TNF-? were performed. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated for all the participants. Results: The mean blood pressure, fasting blood sugar, serum insulin, hs-CRP and HOMA-IR were all significantly elevated in patients with premature canities and the serum HDL levels were significantly lower. A greater number of patients with premature canities had significantly elevated IL-6 as compared with the controls. Limitations: The sample size was small. A subjective scale was used for grading the severity of premature canities. Trichoscopic evaluation of severity of greying or modified phototrichogram could not be used in this study. Conclusion: Abnormalities in cardiovascular risk markers were found in patients with premature canities. Screening and counselling of patients with premature greying of hair is recommended in order to prevent future cardiovascular disease.