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Background: Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting. Aim: To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH. Methods: Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification. Results: Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers. Conclusion: PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.
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OBJECTIVE: To explore the potential associations between high-density lipoprotein (HDL) levels and inflammasome components in the context of systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted. A group of 50 patients with SLE and 50 healthy controls matched by sex and similar age ranges were enrolled. Serum HDL cholesterol (HDL-C) and C reactive protein (CRP) levels were quantified. Serum cytokine levels, including IL-1ß and IL-6, were determined by ELISA. The gene expression of inflammasome-related genes in peripheral blood mononuclear cells was measured by quantitative real-time PCR. RESULTS: HDL-C levels were lower in the patients with SLE (p<0.05), and on segregation according to disease activity, those with active SLE had the lowest HDL-C levels. Patients with SLE presented higher concentrations of the serum inflammatory cytokines IL-1ß and IL-6 (p<0.0001) but similar levels of CRP to those in controls. A similar scenario was observed for the gene expression of inflammasome components, where all the evaluated markers were significantly upregulated in the SLE population. These results revealed significant negative correlations between HDL levels and disease activity, serum IL-6 and IL-1ß levels and the mRNA expression of NLRP3, IL-1ß and IL-18. In addition, significant positive correlations were found between disease activity and serum IL-1ß and between disease activity and the mRNA expression of IL-18, and interestingly, significant positive correlations were also observed between active SLE and serum IL-1ß and the mRNA expression of NLRP3. CONCLUSION: Our results suggest that HDL is essential for SLE beyond atherosclerosis and is related to inflammation regulation, possibly mediated by inflammasome immunomodulation.
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Proteína C-Reativa , Inflamassomos , Interleucina-1beta , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/sangue , Feminino , Masculino , Estudos Transversais , Adulto , Inflamassomos/imunologia , Pessoa de Meia-Idade , Interleucina-1beta/sangue , Proteína C-Reativa/análise , Lipoproteínas HDL/sangue , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Estudos de Casos e Controles , Interleucina-6/sangue , HDL-Colesterol/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Citocinas/sangueRESUMO
OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.
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Acroleína , Aterosclerose , Histona Desacetilase 1 , Isoflavonas , Estresse Oxidativo , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Histona Desacetilase 1/metabolismo , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Acroleína/farmacologia , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Western Blotting , Aorta/efeitos dos fármacos , Aorta/patologiaRESUMO
Atherosclerosis (AS) has become the leading cause of cardiovascular disease worldwide. Our previous study had observed that Nippostrongylus brasiliensis (Nb) infection or its derived products could inhibit AS development by inducing an anti-inflammatory response. We performed a metabolic analysis to screen Nb-derived metabolites with anti-inflammation activity and evaluated the AS-prevention effect. We observed that the metabolite uridine had higher expression levels in mice infected with the Nb and ES (excretory-secretory) products and could be selected as a key metabolite. ES and uridine interventions could reduce the pro-inflammatory responses and increase the anti-inflammatory responses in vitro and in vivo. The apolipoprotein E gene knockout (ApoE-/-) mice were fed with a high-fat diet for the AS modeling. Following the in vivo intervention, ES products or uridine significantly reduced serum and liver lipid levels, alleviated the formation of atherosclerosis, and reduced the pro-inflammatory responses in serum or plaques, while the anti-inflammatory responses showed opposite trends. After blocking with 5-HD (5-hydroxydecanoate sodium) in vitro, the mRNA levels of M2 markers were significantly reduced. When blocked with 5-HD in vivo, the degree of atherosclerosis was worsened, the pro-inflammatory responses were increased compared to the uridine group, while the anti-inflammatory responses decreased accordingly. Uridine, a key metabolite from Nippostrongylus brasiliensis, showed anti-inflammatory and anti-atherosclerotic effects in vitro and in vivo, which depend on the activation of the mitochondrial ATP-sensitive potassium channel.
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Anti-Inflamatórios , Aterosclerose , Nippostrongylus , Uridina , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Apolipoproteínas E/genética , Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Aterosclerose/genética , Modelos Animais de Doenças , Canais KATP/metabolismo , Canais KATP/genética , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Uridina/farmacologiaRESUMO
Fundamento: la aterosclerosis es una enfermedad de origen multifactorial que se agrava a consecuencia de un medio ambiente adverso y de estilos de vida no saludables. Las evidencias confirman su inicio desde las etapas más tempranas de la vida. Objetivo: describir la presencia de lesiones ateroscleróticas tempranas en las aortas de fetos y neonatos fallecidos hijos de madres hipertensas. Método: se realizó un estudio descriptivo de tipo transversal que incluyó a los fetos mayores de 22 semanas y neonatos fallecidos hijos de madres hipertensas, a quienes se les realizó autopsia en el departamento de anatomía patológica, del Hospital Universitario Ginecobstétrico Eusebio Hernández Pérez, en el período comprendido entre enero del 2021 hasta diciembre 2022, con un total de 18. Se recogieron los siguientes datos en las historias clínicas: sexo del fallecido, edad gestacional en el momento del parto, peso postparto, edad materna y antecedentes de hipertensión arterial (crónica o gestacional). Se analizaron las 18 aortas (torácicas y abdominales) de los fallecidos seleccionados. Resultados: del total de fallecidos estudiados el 70,6 % presentó lesiones ateroscleróticas tempranas, caracterizadas por engrosamiento de la íntima a modo de cojinete, presencia de linfocitos en la íntima o en la pared arterial cercana a ella y/o macrófagos. En algunos casos se observó una de estas variantes histológicas y en otros la combinación de dos o tres. Conclusiones: las lesiones ateroscleróticas tempranas están presentes en las aortas de la mayoría de los fetos y neonatos estudiados, con predominio en las que presentaban hipertensión gestacional.
Foundation: atherosclerosis is a disease of multifactorial origin that is aggravated as a result of an adverse environment and unhealthy lifestyles. Evidence confirms its onset from the earliest stages of life. Objective: to describe the presence of early atherosclerotic lesions in the aortas of deceased fetuses and neonates born to hypertensive mothers. Method: a descriptive cross-sectional study was carried out that included fetuses older than 22 weeks and deceased neonates born to hypertensive mothers, who underwent autopsy in the pathological anatomy department of the Eusebio Hernández Pérez Gynecobstetric University Hospital, in the period between January 2021 and December 2022, with a total of 18. The following data were collected in the medical records: sex of the deceased, gestational age at the time of delivery, postpartum weight, maternal age, and history of arterial hypertension (chronic or gestational). The 18 aortas (thoracic and abdominal) of the selected deceased were analyzed. Results: of the total number of deceased studied, 70.6 % presented early atherosclerotic lesions, characterized by thickening of the intima as a cushion, presence of lymphocytes in the intima or in the arterial wall close to it and/or macrophages. In some cases, one of these histological variants was observed and in others a combination of two or three. Conclusions: early atherosclerotic lesions are present in the aortas of the majority of the fetuses and neonates studied, with a predominance in those with gestational hypertension.
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Resumo Fundamento Alcançar as metas nutricionais estabelecidas pelas sociedades científicas é um desafio constante e nem sempre alcançado. Objetivo Investigar a adequação alimentar de indivíduos com doença cardiovascular (DCV), participantes do Programa Alimentar Brasileiro Cardioprotetor residentes da região Nordeste do Brasil, segundo as recomendações da Sociedade Brasileira de Cardiologia (SBC). Métodos Análise transversal com dados do estudo de implementação da Dieta Cardioprotetora Brasileira (DICA BR) que avaliou indivíduos com DCV, atendidos em centros especializados em saúde cardiovascular em oito estados do Nordeste. O consumo alimentar foi obtido por recordatório alimentar de 24 horas e a adequação da dieta seguiu as recomendações da SBC. Foram considerados significantes valores de p < 0,05. Resultados Foram estudados 647 pacientes, com média (desvio padrão) de idade de 63,1 (9,4) anos, sendo 50,2% do sexo feminino. Na avaliação da ingestão alimentar, observou-se baixa adequação de carboidratos (52,3%), proteínas (70,9%), lipídios (38,8%) e fibras (22,4%). Observou-se que a maioria das mulheres consumia dieta hipoproteica (59,2%) e idosos tinham maior inadequação no consumo de carboidratos (52,6%). Em relação a ingestão de sódio, os homens apresentaram maior ingestão (72,9%), enquanto os idosos apresentaram redução de 13%. Além disso, foi demonstrado que os homens ingeriam mais fibras (28,1%) e indivíduos com maior escolaridade tinham um consumo elevado de ácidos graxos saturados (70,5%). Conclusões A maioria dos indivíduos não alcançou as metas dietoterápicas preconizadas para prevenção cardiovascular secundária. Os achados do presente estudo reforçam a necessidade de implementação de estratégias estruturadas, a fim de estimular hábitos alimentares saudáveis nesses indivíduos.
Abstract Background Achieving nutritional goals established by scientific societies is a constant challenge and not always achieved. Objective To investigate the dietary adequacy of individuals with cardiovascular disease (CVD), participants in the Cardioprotective Brazilian Food Program residing in the Northeast region of Brazil, according to the recommendations of the Brazilian Society of Cardiology (SBC). Methods Cross-sectional analysis with data from the study implementing the Brazilian Cardioprotective Diet (DICA BR), which evaluated individuals with CVD treated in specialized cardiovascular health centers in eight states in the Northeast region. Food consumption was obtained by 24-hour dietary records and dietary adequacy followed SBC recommendations. Values of p < 0.05 were considered significant. Results 647 patients were studied, with a mean (standard deviation) age of 63.1 (9.4) years, 50.2% of whom were female. When evaluating food intake, a low adequacy of carbohydrates (52.3%), proteins (70.9%), lipids (38.8%), and fiber (22.4%) was observed. It was observed that the majority of women consumed a low-protein diet (59.2%) and the elderly had a greater inadequacy in carbohydrate consumption (52.6%). Regarding sodium intake, men had a higher intake (72.9%), while the elderly showed a 13% reduction. Furthermore, it was shown that men ate more fiber (28.1%) and individuals with higher education had a high consumption of saturated fatty acids (70.5%). Conclusions Most individuals did not achieve the recommended dietary therapy goals for secondary cardiovascular prevention. The findings of the present study reinforce the need to implement structured strategies to encourage healthy eating habits in these individuals.
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LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.
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Doenças Cardiovasculares , Receptores Depuradores Classe E , Humanos , Receptores Depuradores Classe E/metabolismo , Receptores Depuradores Classe E/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Animais , Lipoproteínas LDL/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologiaRESUMO
PURPOSE OF REVIEW: To update information about the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis. This review emphasizes the potential mechanisms linking MASLD with atherosclerosis and the possible causal relationships between these conditions. RECENT FINDINGS: An increased risk of cardiovascular disease is related to MASLD. Several molecular, cellular, and metabolic mechanisms have been described to explain the development of atherothrombosis in MASLD patients. These include atherogenic dyslipidemia, low-grade vascular inflammation, endothelial dysfunction, foam cell formation, proliferation of vascular smooth muscle cells, insulin resistance, gut microbiota dysbiosis, activation of renin-angiotensin and sympathetic nervous systems, hypercoagulability, and decreased fibrinolysis. Also, there is recent evidence suggesting an association between genetically driven liver fat and coronary heart disease mediated by the causal effect of apoB-containing lipoproteins. Several meta-analyses and systematic reviews have reported a strong association between MASLD and cardiovascular outcomes. MASLD is an important and independent risk factor for atherosclerosis development. Multiple mechanisms may be involved in this association. Further research is required to establish a causal association between MASLD and atherosclerosis.
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Aterosclerose , Humanos , Aterosclerose/etiologia , Aterosclerose/complicações , Fígado Gorduroso/complicações , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Fatores de Risco , Resistência à InsulinaRESUMO
BACKGROUND: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. OBJECTIVE: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. MATERIAL AND METHODS: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chi-square test, or Fisher's exact test were used. RESULTS: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR- 0.22. CONCLUSION: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.
ANTECEDENTES: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. OBJETIVO: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. MATERIAL Y MÉTODOS: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. RESULTADOS: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. CONCLUSIÓN: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.
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Endotélio Vascular , Termografia , Humanos , Termografia/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Transversais , Endotélio Vascular/fisiopatologia , Adulto , Idoso , Fatores de Risco de Doenças Cardíacas , Sensibilidade e Especificidade , Raios Infravermelhos , Artéria Braquial/fisiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Vasodilatação/fisiologia , Valor Preditivo dos TestesRESUMO
Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation. Here, we showed that PDIA1 mRNA and protein levels were upregulated (average 5-fold) in the intima and media/adventitia following partial carotid ligation (PCL). Our search identified that miR-204-5p and miR-211-5p (miR-204/211), two broadly conserved miRNAs, share PDIA1 as a potential target. MiR-204/211 was downregulated in vascular layers following PCL. In isolated endothelial cells, gain-of-function experiments of miR-204 with miR mimic decreased PDIA1 mRNA while having negligible effects on markers of endothelial activation/stress response. Similar effects were observed in vascular smooth muscle cells (VSMCs). Furthermore, PDIA1 downregulation by miR-204 decreased levels of the VSMC contractile differentiation markers. In addition, PDIA1 overexpression prevented VSMC dedifferentiation by miR-204. Collectively, we report a new mechanism for PDIA1 regulation through miR-204 and identify its relevance in a model of vascular disease playing a role in VSMC differentiation. This mechanism may be regulated in distinct stages of atherosclerosis and provide a potential therapeutic target.
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Accelerated atherosclerosis has been identified as a complication of multiple autoimmune diseases, among which Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis stands out. We describe the case of a 60-year-old patient with a history of hypertension, diabetes mellitus, and chronic kidney disease of unknown etiology, who presented two acute coronary syndromes with only a six-month difference. Rapid progression of coronary involvement was evidenced, along with increased markers of inflammatory response, usual interstitial pneumonia on tomography, and positive anti-myeloperoxidase antibodies (anti-MPO), leading to the diagnosis of microscopic polyangiitis (MPA). In these cases, timely diagnostic suspicion is crucial, as early treatment significantly impacts the course and prognosis of the disease.
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Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175â mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).
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INTRODUCTION: Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD). AIM: To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD. METHODS: We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries. RESULTS: Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF. CONCLUSIONS: We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA.
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Doenças das Artérias Carótidas , Artéria Femoral , Hospitais Comunitários , Doença Arterial Periférica , Placa Aterosclerótica , Humanos , Masculino , Feminino , Artéria Femoral/diagnóstico por imagem , Prevalência , Pessoa de Meia-Idade , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Estudos Prospectivos , Adulto , Placa Aterosclerótica/epidemiologia , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico , Medição de Risco , Valor Preditivo dos Testes , Idoso , Doenças Assintomáticas , Fatores Sexuais , Fatores Etários , Fatores de Risco , Ultrassonografia , Distribuição por Idade , Estudos TransversaisRESUMO
Introducción: Se reconoce la asociación entre los factores de riesgo aterogénico y las alteraciones microvasculares de la retina, pero no hay consenso sobre si estas afectaciones en la retina preceden o son una respuesta fisiopatológica a dichos factores. Objetivo: Determinar si la presencia de los factores de riesgo aterogénico predice las alteraciones vasculares retinianas, a través del fondo de ojo y la retinografía. Métodos: Estudio trasversal en 55 sujetos mayores de 19 años de edad, de cualquier sexo, sin opacidades en los medios transparentes del ojo. Se estudiaron las variables edad, sexo, dislipidemia, hábito de fumar, consumo de alcohol, hipertensión arterial, diabetes mellitus tipo 2, presión arterial sistólica y diastólica, índice de masa corporal, colesterol, glicemia, triglicéridos, creatinina, lipoproteínas de alta densidad, urea, eritrosedimentación y conteo leucocitario. Resultados: El 65,45 % presentó alteraciones en el fondo de ojo: aumento del brillo arteriolar (53,03 %) y disminución del calibre arteriolar generalizado (52,24 %). La retinografía mostró daño en el 58,18 %: rectificación de los cruces arteriovenosos (65,71 %), tortuosidad venosa (28,21 %) y cruces arteriovenosos con aplastamiento (85,71 %). El aumento del colesterol sérico (p= 0,003) se asoció con la presión arterial sistólica (p= 0,037) en el fondo de ojo, y con el antecedente de hipertensión arterial (p= 0,023) en la retinografía. Conclusiones: El colesterol sérico, las cifras elevadas de tensión arterial sistólica y antecedentes de hipertensión arterial son los factores de riesgo que mejor predicen el daño vascular retinal.
Introduction: The association between atherogenic risk factors and retinal microvascular alterations is recognized, but there is no consensus on whether these retinal disorders precede or are a pathophysiological response to these factors. Objective: To determine if the presence of atherogenic risk factors predicts retinal vascular alterations, through fundus examination and retinography. Methods: Cross-sectional study in 55 subjects over 19 years of age, of either sex, without opacities in the transparent media of the eye. The variables studied were age, sex, dyslipidemia, smoking habit, alcohol consumption, arterial hypertension, type 2 diabetes mellitus, systolic and diastolic blood pressure, body mass index, cholesterol, glycemia, triglycerides, creatinine, high-density lipoproteins, urea, erythrocyte sedimentation rate and leukocyte count. Results: 65.45% presented alterations in the fundus of the eye: increased arteriolar brightness (53.03%) and decreased generalized arteriolar caliber (52.24%). Retinography showed damage in 58.18%: rectification of arteriovenous crossings (65.71%), venous tortuosity (28.21%), and arteriovenous crossings with crushing (85.71%). The increase in serum cholesterol (p= 0.003) was associated with systolic blood pressure (p= 0.037) in the fundus, and with a history of arterial hypertension (p= 0.023) in retinography. Conclusions: Serum cholesterol, high systolic blood pressure and a history of hypertension are the risk factors that best predict retinal vascular damage.
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Cardiovascular diseases (CVDs) remain a global health challenge and are the leading cause of deaths worldwide. Proteomics has emerged as a valuable tool for unraveling the complex molecular mechanisms underlying CVDs, offering insights into biomarker discovery, drug targets, and personalized medicine. This review explores key breakthroughs in proteomic applications related to CVDs, mainly coronary artery disease (CAD), ischemic heart diseases such as myocardial infarction (MI), and cardiomyopathies. Notable findings include potential biomarkers, therapeutic targets, and insights into disease pathogenesis. The review highlights the importance of proteomics in advancing our understanding of CVDs and shaping future therapeutic approaches.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Doenças Cardiovasculares/patologia , Proteômica , Medicina de PrecisãoRESUMO
Oxidative modification of low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are important factors determining cardiovascular risk. This study investigated the antioxidant mechanisms and potential protective effect of a hydroethanolic extract of yerba mate (Ilex paraguaiensis; EHEM) on the inâ vitro oxidation of LDL and HDL. EHEM was found to possess ferric reducing power, DPPH free radical scavenging capacity, metal chelating activity, and NO radical scavenging activity. In addition, EHEM reduced the lipoperoxidation induced by α,α'-Azodiisobutyramidine dihydrochloride (AAPH) in HDL and LDL at all tested concentrations. In this study, we demonstrate the antioxidant properties of yerba mate and its phytochemical compounds. These properties may effectively prevent the inâ vitro oxidation of LDL and HDL molecules, a phenomenon linked to the pathogenesis of atherosclerosis.
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Antioxidantes , Ilex paraguariensis , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ilex paraguariensis/química , Oxirredução , LipoproteínasRESUMO
Background: Cardiovascular responses to psychological stressors have been separately associated with preclinical atherosclerosis and hemodynamic brain activity patterns across different studies and cohorts; however, what has not been established is whether cardiovascular stress responses reliably link indicators of stressor-evoked brain activity and preclinical atherosclerosis that have been measured in the same individuals. Accordingly, the present study used cross-validation and predictive modeling to test for the first time whether stressor-evoked systolic blood pressure (SBP) responses statistically mediated the association between concurrently measured brain activity and a vascular marker of preclinical atherosclerosis in the carotid arteries. Methods: 624 midlife adults (aged 28-56 years, 54.97% female) from two different cohorts underwent two information-conflict fMRI tasks, with concurrent SBP measures collected. Carotid artery intima-media thickness (CA-IMT) was measured by ultrasonography. A mediation framework that included harmonization, cross-validation, and penalized principal component regression was then employed, while significant areas in possible direct and indirect effects were identified through bootstrapping. Sensitivity analysis further tested the robustness of findings after accounting for prevailing levels of cardiovascular disease risk and brain imaging data quality control. Results: Task-averaged patterns of hemodynamic brain responses exhibited a generalizable association with CA-IMT, which was mediated by an area-under-the-curve measure of aggregate SBP reactivity. Importantly, this effect held in sensitivity analyses. Implicated brain areas in this mediation included the ventromedial prefrontal cortex, anterior cingulate cortex, insula and amygdala. Conclusions: These novel findings support a link between stressor-evoked brain activity and preclinical atherosclerosis accounted for by individual differences in corresponding levels of stressor-evoked cardiovascular reactivity.
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Resumen Antecedentes: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. Objetivo: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. Material y métodos: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. Resultados: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. Conclusión: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.
Abstract Background: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. Objective: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. Material and methods: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase <11 % at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11 % post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitneys U-test, chi-square test, or Fishers exact test were used. Results: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation (FMV): 2.5 %. The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85 % sensitivity, 70 % specificity, positive and negative predictive values of 78 and 77 %, area under the curve of 0.796, LR+ 2.82, LR- 0.22. Conclusions: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.
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BACKGROUND AND AIMS: Interleukin-6 (IL-6) is an acute-phase protein that plays an important role in the inflammatory response, vascular inflammation, and atherosclerosis process. The study aimed to establish whether IL-6 gene polymorphisms and IL-6 concentrations are associated with premature coronary artery disease (pCAD) and cardiovascular risk factors. METHODS: The IL-6 concentrations and the rs2069827, rs1800796, and rs1800795 IL-6 polymorphisms were determined in 1150 pCAD patients and 1083 healthy controls (coronary artery calcium equal to zero determined by tomography). RESULTS: The IL-6 polymorphisms studied were not associated with pCAD, but they were associated with cardiovascular risk factors in patients and controls. In controls, under the dominant model, the rs1800795 C allele and the rs2069827 T allele were associated with a low risk of central obesity (OR = 0.401, p = 0.017 and OR = 0.577, p = 0.031, respectively), hypoalphalipoproteinemia (OR = 0.581, p = 0.027 and OR = 0.700, p = 0.014, respectively) and hypertriglyceridemia (OR = 0.575, p = 0.030 and OR = 0.728, p = 0.033, respectively). In pCAD, the rs1800795 C allele was associated with an increased risk of hypoalphalipoproteinemia (OR = 1.370, padditive = 0.025) and increased C-reactive protein (CRP) concentrations (OR = 1.491, padditive = 0.007). pCAD patients had significantly higher serum IL-6 concentrations compared to controls (p = 0.002). In the total population, individuals carrying the rs1800795 GC + CC genotypes had higher levels of IL-6 than carriers of the GG genotype (p = 0.025). In control individuals carrying the C allele (CG + CC), an inverse correlation was observed between IL-6 and HDL-cholesterol levels (p = 0.003). CONCLUSIONS: In summary, the IL-6 polymorphisms were not associated with pCAD, however, they were associated with cardiovascular risk factors in pCAD patients and healthy controls. Individuals carrying the rs1800795 GC + CC genotypes had higher levels of IL-6 than carriers of the GG genotype.