Cardiovascular Disease in Latin American Women Gaps and opportunities

Abstract Cardiovascular disease (CVD) remains the leading cause of death in women. This review will address the known disparities in cardiovascular care concerning diagnosing and treating of heart disease in Latin American (LA) women. Gender-specific differences regarding the incidence, treatment, and outcomes of common cardiovascular pathology are increasingly recognized. Today, we identify that women have cardiovascular risk factors (CRFs), specifying the traditional, emerging, unique, or sex-specific determinants and the social and biological determinants that play a leading role in the prevention of CVD. The purpose of this article is to review the literature on cardiovascular disease in LA women, focusing on ischemic heart disease (IHD), valve disease (VD), heart failure, and cardiac rehabilitation (CR), where disparities continue to affect outcomes. Understanding the unique cardiovascular risk profile and barriers to optimal treatment outcomes in women is imperative to eliminate the current disparities in CVD.

Garlic Extract Reverses Ischemic Heart Disease in Female Rats Exposed to Combined Oral Contraceptive Pills

Abstract Background Garlic is an herbal medicinal plant with several pharmacological properties used for the management of various ailments. However, its potential in the reversal of ischemic heart disease induced by combined oral contraceptive pills is not well reported. Objective This study investigated the cardioprotective potential of aqueous garlic extract against cardiotoxicity induced by oral contraceptive pills. Methods Forty-six rats were used for this study. Six were used to determine the lethal dose (LD50), and 40 rats were divided randomly into 5 groups of 8 rats each. Group A received feed and distilled water. Group B received 0.6 mg/kg of oral contraceptive pills. Group C received 500 mg/kg of garlic extract. Group D received 0.6 mg/kg of oral contraceptive pills + 500 mg/kg garlic extract. Group E received 0.6 mg/kg of oral contraceptive pills + 700 mg/kg garlic extract. The animals were sacrificed, and blood and tissue samples were collected for biochemical and histological analysis. Statistical analysis was done using SPSS, and p values < 0.05 were considered significant. Results The acute toxicity dose of combined oral contraceptive pills was 1.5 mg/kg for albino rats. Combined oral contraceptive pills induced ischemic necrosis as revealed by the photomicrographs, in addition to elevation of serum cardiac troponin-1, lactate dehydrogenase, creatine kinase, and malondialdehyde levels. Treatment with garlic extract demonstrated significant reduction in cardiac troponin-1 (p = 0.000), lactate dehydrogenase (p = 0.002), creatine kinase (p = 0.001), and malondialdehyde (p = 0.001) levels, as well as restoration of the cardiac cytoarchitecture changes caused by the combined oral contraceptive pills. Conclusion This study has demonstrated that aqueous garlic juice can reverse ischemic heart disease, lessen cytoarchitectural alterations of the heart caused by combined oral contraceptive pills, and thus ameliorate cardiac dysfunction.

Research progress of traditional Chinese medicine in regulating Nrf2/HO-1 signaling pathway to interfere with myocardial ischemia-reperfusion injury / 中国药房

Myocardial ischemia-reperfusion injury （MIRI） is a serious complication of revascularization in patients with myocardial infarction. The nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway plays an important role in the pathological process of MIRI. Currently，research has found that traditional Chinese medicine has a good effect on myocardial injury caused by ischemia-reperfusion. Based on the Nrf2/HO-1 signaling pathway，this article summarizes the action mechanism of traditional Chinese medicine formulas and monomers in intervening with MIRI. It is found that traditional Chinese medicine formulas （Yixin formula，Wenyang tongmai formula，Dingxin formula Ⅰ），monomers such as terpenoids （ginkgolides， astragaloside Ⅳ，ginsenosides），phenols （brazilin，hematoxylin A，resveratrol） and quinones （aloe，emodin） can alleviate MIRI by activating the Nrf2/HO-1 signaling pathway，inhibiting oxidative stress and inflammatory reactions，etc.

Effect of Guipitang on ERK1/2 and p38 MAPK in Rats with Myocardial Ischemia / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Individualized surgical treatment strategy for children with anomalous aortic origin of coronary artery / 中国胸心血管外科临床杂志

@#Objective To summarize and explore the individualized surgical treatment strategy and prognosis of anomalous aortic origin of coronary artery (AAOCA). Methods The clinical data of children with AAOCA admitted to Shanghai Children's Medical Center from March 2018 to August 2021 were retrospectively analyzed. Results A total of 17 children were enrolled, including 13 males and 4 females, with a median age of 88 (44, 138) months and a median weight of 25 (18, 29) kg. All patients received operations. The methods of coronary artery management included coronary artery decapitation in 9 patients, coronary artery transplantation in 5 patients and coronary artery perforation in 3 patients. One patient with severe cardiac insufficiency (left ventricular ejection fraction 15%) received mechanical circulatory assistance after the operation for 12 days. No death occurred in the early postoperative period, the average ICU stay time was 4.3±3.0 d, and the total hospital stay was 14.4±6.1 d. All the children received regular anticoagulation therapy for 3 months after discharge. The median follow-up time was 15 (13, 24) months. All patients received regular anticoagulation therapy for 3 months after discharge. No clinical symptoms such as chest pain and syncope occurred again. The cardiac function grade was significantly improved compared with that before operation. Imaging examination showed that the coronary artery blood flow on the operation side was unobstructed, and no restenosis occurred. Conclusion AAOCA is easy to induce myocardial ischemia and even sudden cardiac death. Once diagnosed, operation should be carried out as soon as possible. According to the anatomic characteristics of coronary artery, the early effect of individualized surgery is satisfactory, and the symptoms of the children are significantly improved and the cardiac function recovers well in the mid-term follow-up.

Shuangshen Ningxin Capsules Regulates Mitochondrial Fission and Fusion to Alleviate Myocardial Ischemia-reperfusion Injury in Rats / 中国实验方剂学杂志

ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg-1） and trimetazidine group （5.4 mg·kg-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.

Effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia / 中国药房

OBJECTIVE To investigate the effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia. METHODS H9c2 cells were divided into blank group， model group， quercetin high-dose， medium-dose and low-dose groups （40， 20， 10 μmol/L）， and positive control group （cyclosporine A， 1 μmol/L）. Reactive oxygen species （ROS）， mitochondrial membrane potential （MMP）， openness of mitochondrial permeability transition pore （MPTP）， adenosine triphosphate （ATP）， malondialdehyde （MDA）， lactate dehydrogenase （LDH） and creatine kinase （CK） were observed after cell hypoxia treatment. Rats were randomly assigned into sham operation group， model group， quercetin high-dose， medium-dose and low-dose groups （100， 50， 25 mg/kg）， and positive control group （trimetazidine， 6.3 mg/kg）， with 8 rats in each group. They were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last medication， myocardial ischemia model was induced by the ligation of the left anterior descending branch of the coronary artery. The contents of LDH， MDA， creatine kinase isoenzyme-MB （CK-MB）， superoxide dismutase （SOD）， complex Ⅰ， complex Ⅳ and ATP in serum were all determined. RESULTS Compared with the model group， ROS fluorescence intensity， openness of MPTP， the contents of CK， LDH and MDA were significantly decreased in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of MMP and ATP were all increased significantly （P＜0.01）； the contents of CK-MB， LDH and MDA in serum were all decreased significantly in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of SOD， complex Ⅰ， complex Ⅳ and ATP （except for positive control group） were increased significantly （P＜ 0.05 or P＜0.01）. CONCLUSIONS Quercetin can effectively reduce myocardial hypoxic injury， promote endogenous energy production and improve mitochondrial function after myocardial ischemia.

Dolor tóraco-abdominal: "Si miras el corazón, encontrarás la razón". Serie de casos

La isquemia miocárdica es un fenómeno secundario a la perfusión insuficiente del músculo cardíaco que en algunos casos puede ocurrir de forma aguda llevando a la necrosis celular y constituyendo el infarto agudo al miocardio (IAM). A pesar de que el diagnóstico de IAM es principalmente clínico, en ciertos casos en que no se sospeche de forma activa por presentar síntomas no típicos de isquemia miocárdica, el diagnóstico puede sugerirse por la Tomografía Computarizada (TC), que puede mostrar hallazgos sugerentes de IAM. A continuación, se comunica una serie de 4 casos clínicos con diagnóstico imagenológico incidental de IAM.

Myocardial ischemia is secondary to myocardial under perfusion. It can develop acutely leading to cell necrosis and myocardial infarction (AMI), or have a chronic course. Though the diagnosis of AMI is mainly clinical, in certain cases the symptoms may be atypical and the diagnosis can be suggested by images such as Computed Tomography (CT). Herein we report a series of 4 clinical cases with diagnosis of AMI following incidental CT imaging. There was an abdominal pain in 3 patients and a cervical pain in the remaining one. CT scan showed a hypodense myocardial image. The final diagnosis was confirmed by the appropriate laboratory and angiographic methods.

Recurrent acute coronary syndrome after infliximab infusion in a patient with rheumatoid arthritis: Case report

Case description: A 61-year-old male patient with uncontrolled rheumatoid arthritis presented acute coronary syndrome on three occasions, less than 48 hours after infliximab infusion. Clinical findings: He presented with ST-elevation myocardial infarction on two occasions and non-ST-elevation acute coronary syndrome on one, with the identification of multivessel coronary disease. Treatment and outcome: Coronary intervention was performed with thrombus aspiration, medicated stent implantation, medicated balloon angioplasty, discontinuation of infliximab, and modification and optimization of cardiovascular pharmacological management. Clinical relevance: Patients with rheumatoid arthritis have subclinical cardiovascular disease and increased cardiovascular risk. The evidence regarding the relationship between infliximab and ischemic heart disease is controversial. A wide clinical spectrum of cardiac involvement with infliximab infusion is found in case reports, ranging from stable angina to ST-segment elevation acute coronary syndrome. The pathophysiology is not elucidated, with hypotheses proposing plaque rupture, allergic reactions, and vasoconstriction as possible disease mechanisms. The direct association between infliximab infusion and acute coronary syndrome needs more clinical research to optimize the management and prognosis of patients presenting with this type of complication.

Descripción del caso: Paciente masculino de 61 años con artritis reumatoide no controlada, en manejo con infliximab, quién presentó en tres oportunidades síndrome coronario agudo menos de 48 horas posterior a la aplicación del medicamento. Hallazgos clínicos: Presentó infarto con elevación del ST en dos ocasiones y síndrome coronario agudo sin elevación del ST en una oportunidad, encontrándose enfermedad coronaria multivaso. Tratamiento y resultado: Se realizó intervención coronaria con tromboaspiración, implante de stents medicados y angioplastia con balón medicado, suspensión del infliximab y modificación y optimización de manejo farmacológico cardiovascular. Relevancia clínica: Los pacientes con artritis reumatoide tienen enfermedad cardiovascular subclínica y mayor riesgo cardiovascular. La evidencia respecto a la relación entre infliximab y cardiopatía isquémica es controversial. En reportes de caso se encuentra un amplio espectro clínico de compromiso cardíaco con la infusión de infliximab, que va desde la angina estable hasta el síndrome coronario agudo con elevación del segmento ST. La fisiopatología no está claramente dilucidada, con hipótesis que proponen la ruptura de placa, reacciones alérgicas y la vasoconstricción como posibles mecanismos de enfermedad. La asociación directa entre la infusión de infliximab y el síndrome coronario agudo necesita más investigación clínica con el fin de optimizar el manejo y pronóstico de los pacientes que presentan este tipo de complicaciones.

Estudio de caso: revascularización de paciente con enfoque en el proceso de atención de enfermería / Case study: Patient revascularization with focus on the nursing care process

Introducción: la cardiopatía isquémica fue la primera causa de muerte en México en el año 2020. Su prevalencia aumenta con la edad y es superior en los hombres que en las mujeres; se presenta mayormente en forma de infarto en edades entre 45 y 94 años. Objetivo: describir el caso de un paciente sometido a revascularización aorto-coronaria por cardiopatía isquémica con enfoque del proceso de atención de enfermería (PAE). Metodología: estudio de caso observacional y descriptivo con aplicación del PAE en el perioperatorio de un hombre de 50 años con cardiopatía isquémica crónica, enfermedad multivascular e hipertensión sistémica controlada de 6 años desde que inició, en un hospital público de tercer nivel en Mérida, Yucatán, México. Resultados: se demostró que si se aplica el PAE hay menor riesgo de shock hipovolémico ocasionado por sangrado activo y disminución de riesgo de infección del sitio de herida quirúrgica, evidenciado por el procedimiento quirúrgico extenso. Conclusiones: la metodología del PAE como método científico facilita innovaciones dentro de los cuidados enfermeros, además de las diferentes alternativas en las acciones a seguir para el tratamiento del paciente quirúrgico cardiovascular. También proporciona un método informativo para la atención de cuidados, desarrolla una autonomía para la enfermería y fomenta la consideración como profesional de salud.

Introduction: Ischemic heart disease was the leading cause of death in Mexico in 2020. Its prevalence increases with age and it is higher in men than in women; it is presented mostly as a heart attack between the ages of 45 and 94 years. Objective: To describe the case of a patient undergoing aorto-coronary revascularization for ischemic heart disease with a nursing care process (NCP) approach. Methodology: Observational and descriptive case study with application of NCP in the perioperative period of a 50-year-old man with chronic ischemic heart disease, multivessel disease and controlled systemic hypertension of 6 years since its onset, in a third level public hospital in Merida, Yucatan, Mexico. Results: It was demonstrated that by applying NCP there is a lower risk of hypovolemic shock caused by active bleeding and decreased risk of surgical wound site infection, evidenced by the extensive surgical procedure. Conclusions: The NCP methodology as a scientific method facilitates innovations within nursing care, in addition to the different alternatives in the actions to follow for the treatment of the cardiovascular surgical patient. It also provides an informative method for care, develops autonomy for nursing and promotes consideration as a health professional.

Sevoflurane attenuates myocardial ischemia/reperfusion injury by up-regulating microRNA-99a and down-regulating BRD4

Purpose: It has been explored that sevoflurane (Sevo) is cardioprotective in myocardial ischemia/reperfusion injury (MI/RI) and mediates microRNA (miRNA) expression that control various physiological systems. Enlightened by that, the work was programmed to decode the mechanism of Sevo and miR-99a with the participation of bromodomain-containing protein 4 (BRD4). Methods: MI/RImodel was established on mice. MI/RI modeled mice were exposed to Sevo or injected with miR-99a or BRD4-related vectors to identify their functions in cardiac function, pathological injury, cardiomyocyte apoptosis, inflammation, and oxidative stress in MI/RI mice. MiR-99a and BRD4 expression in myocardial tissues were tested, and their relation was further validated. Results: MiR-99a was down-regulated, and BRD4 was up-regulated in MI/RI mice. Sevo up-regulated miR-99a to inhibit BRD4 expression in myocardial tissues of MI/RI mice. Sevo improved cardiac function, relieved myocardial injury, repressed cardiomyocyte apoptosis, and alleviated inflammation and oxidative stress in mice with MI/RI. MiR-99a restoration further enhanced the positive effects of Sevo on mice with MI/RI. Overexpression of BRD4 reversed up-regulation of miR-99a-induced attenuation of MI/RI in mice. Conclusions: The work delineated that Sevo up-regulates miR-99a to attenuate MI/RI by inhibiting BRD4.

Acompanhamento de Dois Anos de Pacientes com Cardiopatia Isquêmica Crônica em um Centro Especializado no Brasil / Two-Year Follow-Up of Chronic Ischemic Heart Disease Patients in a Specialized Center in Brazil

Resumo Fundamento A incidência de eventos cardiovasculares em pacientes com doença cardíaca isquêmica crônica (DCIC) pode variar significativamente entre os países. Embora populoso, o Brasil é frequentemente sub-representado nos registros internacionais. Objetivos Este estudo teve como objetivo descrever a qualidade do atendimento e a incidência de eventos cardiovasculares em dois anos, além de fatores prognósticos associados em pacientes com DCIC em um centro terciário de saúde pública no Brasil. Métodos Pacientes com DCIC que compareceram para avaliação clínica no Instituto do Coração (São Paulo, Brasil) foram cadastrados e acompanhados por dois anos. O desfecho primário foi um composto de infarto do miocárdio (IM), acidente vascular encefálico ou morte. Um nível de significância de 0,05 foi adotado. Resultados De janeiro de 2016 a dezembro de 2018, 625 participantes foram incluídos no estudo. As características basais mostram que 33,1% eram mulheres, a idade mediana era de 66,1 [59,6 - 71,9], 48,6% tinham diabetes, 83,1% tinham hipertensão, 62,6% tinham IM prévio e 70,4% passaram por algum procedimento de revascularização. Em um acompanhamento mediano de 881 dias, 37 (7,05%) desfechos primários foram observados. Após ajustes, idade, acidente vascular encefálico prévio e colesterol LDL foram independentemente associados ao desfecho primário. Comparando a linha de base com o acompanhamento, os participantes relataram alívio da angina com base na escala da Sociedade Cardiovascular Canadense (SCC) de acordo com as seguintes porcentagens: 65,7% vs. 81,7% eram assintomáticos e 4,2% vs. 2,9% eram SCC 3 ou 4 (p < 0,001). Eles também relataram melhor qualidade na prescrição de medicamentos: 65,8% vs. 73,6% (p < 0,001). No entanto, não houve melhora no colesterol LDL ou no controle da pressão arterial. Conclusão O presente estudo mostra que pacientes com DCIC apresentaram uma incidência de 7,05% do desfecho primário composto em um período de dois anos, sendo a diminuição do colesterol LDL o único fator de risco modificável associado ao prognóstico.

Abstract Background The incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly among countries. Although populous, Brazil is often underrepresented in international records. Objectives This study aimed to describe the quality of care and the two-year incidence of cardiovascular events and associated prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Methods Patients with CIHD who reported for clinical evaluation at Instituto do Coração (São Paulo, Brazil) were registered and followed for two years. The primary endpoint was a composite of myocardial infarction (MI), stroke, or death. A significance level of 0.05 was adopted. Results From January 2016 to December 2018, 625 participants were included in the study. Baseline characteristics show that 33.1% were women, median age 66.1 [59.6 - 71.9], 48.6% had diabetes, 83.1% had hypertension, 62.6% had previous MI, and 70.4% went through some revascularization procedure. At a median follow-up (FU) of 881 days, we noted 37 (7.05%) primary endpoints. After adjustments, age, previous stroke, and LDL-cholesterol were independently associated with the primary endpoint. Comparing baseline versus FU, participants experienced relief of angina based on the Canadian Cardiovascular Society (CCS) scale according to the following percentages: 65.7% vs. 81.7% were asymptomatic and 4.2% vs. 2.9% CCS 3 or 4 (p < 0.001). They also experienced better quality of medication prescription: 65.8% vs. 73.6% (p < 0.001). However, there was no improvement in LDL-cholesterol or blood pressure control. Conclusion This study shows that CIHD patients had a two-year incidence of the primary composite endpoint of 7.05%, and the reduction of LDL-cholesterol was the only modifiable risk factor associated with prognosis.

Indicadores Socioeconômicos e Mortalidade por Doença Isquêmica do Coração e Doença Cerebrovascular no Brasil de 2000 a 2019 / Socioeconomic Indicators and Mortality from Ischemic Heart Disease and Cerebrovascular Disease in Brazil from 2000 to 2019

Resumo Fundamento: Estudos prévios identificaram desigualdade na variação das taxas de mortalidade por doença isquêmica do coração (DIC) e doença cerebrovascular (DCBV) quando comparadas regiões com diferentes níveis de indicadores de desenvolvimento socioeconômico. Objetivo: Analisar a variação das taxas de mortalidade por DIC e DCBV e do desenvolvimento econômico, avaliado pelos índices sociodemográfico (ISD) e de vulnerabilidade social (IVS) no Brasil, em um período de 20 anos. Métodos: Estudo ecológico de séries temporais das taxas de mortalidade bruta e padronizada (método direto com a população brasileira de 2000) por DIC e DCBV por sexo e UF entre 2000 e 2019 comparadas com o ISD e com o IVS. Resultados: Houve melhora do ISD e IVS concomitante a redução da taxa de mortalidade padronizada por faixa etária por DIC e por DCBV no país, entretanto isso ocorreu de modo desigual entre as unidades federativas (UFs). As UFs com melhores indicadores socioeconômicos obtiveram maior redução nas taxas de mortalidade. Discussão: A variação das taxas de mortalidade por DIC e DCBV em comparação com a variação do desenvolvimento socioeconômico são compatíveis com estudos prévios, mas vamos além ao comparar de modo concomitante com o ISD e o IVS. As limitações são o fato de ser um estudo observacional, trabalhar com bancos de dados e estar sujeito ao viés ecológico. Conclusão: Os dados observados levantam a hipótese de que a melhora das condições socioeconômicas é um dos fatores responsáveis pela redução das taxas de mortalidade por DIC e DCBV.

Abstract Background: Previous studies have identified inequalities in the variation of mortality rates from ischemic heart disease (IHD) and cerebrovascular disease (CBVD) when comparing regions with different levels of socioeconomic development indicators. Objective: To analyze the variation in IHD and CBVD mortality rates and economic development, evaluated by the sociodemographic index (SDI) and social vulnerability index (SVI) in Brazil over a period of 20 years. Methods: Ecological study of time series of crude and standardized mortality rates (direct method, based on the Brazilian population in year 2000) from IHD and CBVD by sex and Federative Unit (FU) between 2000 and 2019, compared using the SDI and SVI. Results: There was an improvement in SDI and SVI concomitantly to a reduction in age-standardized mortality rate from IHD and CBVD in the country; however, this occurred unevenly across the FUs. The FUs with the best socioeconomic indicators had the greatest reduction in mortality rates. Discussion: The variations in mortality rates from IHD and CBVD, compared using variations in socioeconomic development, are aligned with those from previous studies, but the present study goes further by including the indicators SDI and SVI in the comparison. The limitations include the observational nature of the study, the use of databases, and the vulnerability to ecological bias. Conclusion: The observed data raise the hypothesis that the improvement in socioeconomic conditions is one of the factors responsible for the reduction in mortality rates from IHD and CBVD.

Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways

Abstract This study aimed to investigate the role and signaling pathways of β3-AR in myocardial ischemia/reperfusion (I/R) injury, which is one of the leading causes of death worldwide. 47 male rats were randomly divided into two main groups to evaluate infarct size and molecular parameters. Rats in both groups were randomly divided into 4 groups. Control (sham), I/R (30 min ischemia/120 min reperfusion), BRL37344 (BRL) (A) (5 µg/kg single-dose pre-treatment (preT) before I/R) and BRL (B) (5 µg/kg/day preT for 10 days before I/R). Infarct size was determined with triphenyltetrazolium chloride staining and analyzed with ImageJ program. The levels of AMPK, SIRT1, mTOR, and p70SK6 responsible for cellular energy and autophagy were evaluated by western blot. Infarct size increased in the I/R group (44.84 ± 1.47%) and reduced in the single-dose and 10-day BRL-treated groups (32.22 ± 1.57%, 29.65 ± 0.55%; respectively). AMPK and SIRT1 levels were decreased by I/R but improved in the treatment groups. While mTOR and p70S6K levels increased in the I/R group, they decreased with BRL preT. BRL preT protects the heart against I/R injury. These beneficial effects are mediated in part by activation of AMPK and SIRT1, inhibition of mTOR and p70S6K, and consequently protected autophagy.

Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade / Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability

Resumo Fundamento O nível socioeconômico tem sido associado à doença isquêmica do coração (DIC). Bairros de alta renda podem expor os indivíduos a um ambiente construído que promova caminhadas para atividades diárias (caminhabilidade). Faltam dados sobre a associação entre renda e DIC em países de renda média. Também é incerto se a caminhabilidade medeia essa associação. Objetivos Investigar se a renda está associada à DIC em um país de renda média e se a caminhabilidade dos bairros medeia a associação entre renda e DIC. Métodos O presente estudo transversal avaliou 44.589 pacientes encaminhados para imagem de perfusão miocárdica (SPECT-MPI). A renda e a caminhabilidade foram derivadas do setor censitário residencial dos participantes. A pontuação quantitativa da caminhabilidade combinou as seguintes 4 variáveis: conectividade viária, densidade residencial, densidade comercial e uso misto do solo. A DIC foi definida pela presença de perfusão miocárdica anormal durante um estudo SPECT-MPI. Utilizamos modelos ajustados com efeitos mistos para avaliar a associação entre nível de renda e DIC e realizamos uma análise de mediação para medir o percentual da associação entre renda e DIC mediada pela caminhabilidade. Consideramos valores de p abaixo de 0,01 como estatisticamente significativos. Resultados Dos 26.415 participantes, aqueles que residiam no setor censitário do tercil de menor renda eram mais fisicamente inativos (79,1% versus 75,8% versus 72,7%) quando comparados aos setores censitários do tercil de maior renda (p < 0,001). A renda foi associada à DIC (odds ratio: 0,91 [intervalo de confiança de 95%: 0,87 a 0,96] para cada aumento de 1000,00 dólares internacionais na renda), para homens e mulheres igualmente (p para interação = 0,47). Os setores censitários com maior renda estiveram associados a uma melhor caminhabilidade (p < 0,001); no entanto, a caminhabilidade não mediou a associação entre renda e DIC (porcentagem mediada = −0,3%). Conclusões A renda foi independentemente associada a maior prevalência de DIC em um país de renda média, independentemente de gênero. Embora a caminhabilidade tenha sido associada à renda do setor censitário, ela não mediou a associação entre renda e DIC.

Abstract Background Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. Objectives To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. Methods This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. Results From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = −0.3%). Conclusions Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.

Resposta Exagerada da Pressão Arterial Sistólica ao Exercício e Isquemia Miocárdica à Ecocardiografia sob Estresse Físico / Exaggerated Systolic Blood Pressure Increase with Exercise and Myocardial Ischemia on Exercise Stress Echocardiography

Resumo Fundamento A associação entre resposta exagerada da pressão arterial sistólica ao exercício (REPASE) e isquemia miocárdica é controversa e pouco estudada em indivíduos com síndrome coronariana crônica estabelecida ou suspeita. Objetivo Verificar a relação entre isquemia miocárdica e REPASE em indivíduos submetidos à ecocardiografia sob estresse físico (EEF). Métodos Trata-se de estudo transversal com 14.367 indivíduos submetidos à EEF, de janeiro de 2000 a janeiro de 2022, divididos em dois grupos: G1 - composto por pacientes cuja pressão sistólica de pico apresentou incremento ≥ 90 mmHg (valor correspondente ao percentil 95 da população estudada) -, e G2 - formado por indivíduos que não apresentaram resposta hipertensiva exagerada. Os grupos foram comparados mediante os testes t de Student e qui-quadrado. Foram considerados significativos os valores de p < 0,05. Realizou-se, também, regressão logística para identificação de fatores de risco independentes para isquemia miocárdica, REPASE, queixa de precordialgia típica prévia ao exame e angina durante o teste. Resultados Dos 14.367 pacientes, 1.500 (10,4%) desenvolveram REPASE e 7.471 (52,0%) eram do sexo feminino. Os percentuais de queixa prévia de precordialgia típica, angina durante o teste e isquemia miocárdica dos pacientes com REPASE foram de 5,8%, 2,4% e 18,1% contra 7,4%, 3,9% e 24,2%, em indivíduos sem REPASE, respectivamente (p = 0,021, p = 0,004, p < 0,001). Na análise multivariada, a REPASE foi associada, independentemente, a uma menor probabilidade de isquemia miocárdica (odds ratio: 0,73; intervalo de confiança de 95%: 0,58 a 0,93; p = 0,009). Conclusão O incremento exagerado da pressão arterial sistólica durante a EEF pode ser um marcador de exclusão de isquemia miocárdica.

Abstract Background The association between exaggerated systolic blood pressure response to exercise (ESBPRE) and myocardial ischemia is controversial and little studied in patients with established or suspected chronic coronary syndrome. Objective To verify the relationship between myocardial ischemia and ESBPRE in patients undergoing exercise stress echocardiography (ESE). Methods This is a cross-sectional study with 14,367 patients undergoing ESE, from January 2000 to January 2022, divided into the following 2 groups: G1, composed of patients whose peak systolic pressure increased ≥ 90 mmHg (value corresponding to the 95th percentile of the study population), and G2, patients who did not demonstrate an exaggerated hypertensive response. The groups were compared using Student's t and chi-square tests. P values < 0.05 were considered significant. Logistic regression was also performed to identify independent risk factors for myocardial ischemia, ESBPRE, complaints of typical chest pain prior to the exam, and angina during the test. Results Of the 14,367 patients, 1,500 (10.4%) developed ESBPRE, and 7,471 (52.0%) were female. The percentages of previous complaints of typical chest pain, angina during the test, and myocardial ischemia in patients with ESBPRE were 5.8%, 2.4% and 18.1%, compared to 7.4%, 3.9%, and 24.2%, in patients without ESBPRE, respectively (p = 0.021,p = 0.004, p < 0.001). In multivariate analysis, ESBPRE was independently associated with a lower probability of myocardial ischemia (odds ratio: 0.73; 95% confidence interval: 0.58 to 0.93; p = 0.009). Conclusion Exaggerated increase in systolic blood pressure during ESE may be a marker for excluding myocardial ischemia.

Trends in mortality from cardiovascular diseases in Chile, 2000-2020 / Tendencias de la mortalidad por enfermedades cardiovasculares en Chile, 2000-2020 / Tendências de mortalidade por doenças cardiovasculares no Chile, 2000-2020

ABSTRACT Objective. To analyze trends in mortality caused by cardiovascular diseases (CVD) in Chile during the period 2000-2020. Methods. Data on age-adjusted mortality rates (AAMR) from CVD per 100 000 population in Chile for 2000-2020 were extracted from the World Health Organization Mortality Database. Joinpoint regression was used to analyze the trends and compute the average annual percent change (AAPC) in Chile. In addition, analyses were conducted by sex and type of CVD. Results. Between 2000 and 2020, the AAMR from CVD decreased in Chile from 159.5 to 94.6 per 100 000 population, with a statistically significant decrease in the AAPC of 2.6% (95% CI [-2.8, -2.4]). No joinpoints were identified. The AAMR from CVD decreased annually by 2.6% (95% CI [-2.8, -2.4]) and 2.8% (95% CI [-3.5, -2.6]) in men and women, respectively. The AAMR from ischemic heart disease reduced annually by 3.6% (95% CI [-4.6, -2.7]) with two joinpoints in 2011 and 2015. In the case of stroke, the mortality rate decreased annually by 3.7% (95% CI [-4.5, -3.0]), with two joinpoints in 2008 and 2011. Conclusions. Cardiovascular disease mortality rates have decreased significantly in Chile, in both sexes, especially in women. This decrease could be explained mainly by a significant reduction in the case fatality in recent decades. These results could be a reference for developing primary prevention and acute management of CVD policies focused on populations with higher mortality.

RESUMEN Objetivo. Analizar las tendencias de la mortalidad por enfermedades cardiovasculares (ECV) en Chile durante el período 2000-2020. Métodos. Los datos sobre la tasa de mortalidad ajustada por la edad (TMAE) por ECV por 100 000 habitantes en Chile durante el período 2000-2020 se extrajeron de la base de datos de mortalidad de la Organización Mundial de la Salud. Se utilizó la regresión de tipo joinpoint (punto de cambio) para analizar las tendencias y calcular el cambio porcentual anual promedio (CPAP) en Chile. Además, se realizaron análisis por sexo y por tipo de ECV. Resultados. Entre el 2000 y el 2020, la TMAE por ECV disminuyó en Chile de 159,5 a 94,6 por 100 000 habitantes, con una disminución del CPAP estadísticamente significativa del 2,6% (IC del 95% [-2,8 a -2,4]). No se detectó ningún punto de cambio (joinpoint). La TMAE por ECV disminuyó anualmente un 2,6% (IC del 95% [-2,8 a -2,4]) en los hombres y un 2,8% (IC del 95% [-3,5 a -2,6]) en las mujeres. La TMAE por cardiopatía isquémica se redujo anualmente en un 3,6 % (IC del 95 % [-4,6 a -2,7]), encontrándose dos puntos de cambio en el 2011 y el 2015. En el caso de los ataques cerebrovasculares, la tasa de mortalidad disminuyó anualmente un 3,7% (IC del 95% [-4,5 a -3,0]), encontrándose dos puntos de cambio en el 2008 y el 2011. Conclusiones. La tasa de mortalidad por ECV ha disminuido significativamente en Chile en ambos sexos, pero en especial en las mujeres. Este descenso podría explicarse principalmente por la reducción significativa de la letalidad observada en las últimas décadas. Estos resultados podrían constituir una referencia para la elaboración de políticas de prevención primaria y manejo de casos agudos de ECV que estén centradas en aquellos grupos poblacionales donde la mortalidad es más alta.

RESUMO Objetivo. Analisar as tendências de mortalidade causada por doenças cardiovasculares (DCV) no Chile no período de 2000 a 2020. Métodos. Taxas de mortalidade por DCV ajustadas por idade no Chile referentes ao período de 2000 a 2020 foram extraídas do Banco de Dados de Mortalidade da Organização Mundial da Saúde. Foi usado um modelo de regressão linear segmentada (joinpoint) para analisar tendências e calcular a variação percentual média anual no Chile. Além disso, foram realizadas análises por sexo e tipo de DCV. Resultados. No Chile, entre 2000 e 2020, a taxa de mortalidade por DCV ajustada por idade caiu de 159,5 para 94,6 por 100 mil habitantes, com uma redução estatisticamente significante da variação percentual média anual de 2,6% (IC de 95% [-2,8; -2,4]). Não foram identificados pontos de inflexão. Anualmente, a taxa de mortalidade por DCV ajustada por idade caiu 2,6% (IC 95% [-2,8; -2,4]) e 2,8% (IC 95% [-3,5; -2,6]) entre homens e mulheres, respectivamente. A taxa de mortalidade por doença cardíaca isquêmica ajustada por idade caiu 3,6% (95% CI [-4,6; -2,7]) por ano, com dois pontos de inflexão (em 2011 e 2015). No caso do acidente vascular cerebral, a taxa de mortalidade diminuiu 3,7% (IC de 95% [-4,5; -3,0]) por ano, com dois pontos de inflexão (em 2008 e 2011). Conclusões. As taxas de mortalidade por doenças cardiovasculares diminuíram significativamente no Chile em ambos os sexos, especialmente nas mulheres. Essa queda pode ser explicada principalmente por uma redução significativa na letalidade observada nas últimas décadas. Esses resultados podem ser uma referência para o desenvolvimento de políticas de prevenção primária e manejo de casos agudos de DCV voltadas para populações com maiores taxas de mortalidade.

Economic fluctuations and educational inequalities in premature ischemic heart disease mortality in Argentina / Variaciones económicas y desigualdades educativas en la mortalidad prematura por enfermedad isquémica en Argentina / Flutuações econômicas e desigualdades educacionais na mortalidade prematura por doença isquêmica na Argentina

Abstract: Although mortality from ischemic heart disease has declined over the past decades in Argentina, ischemic heart disease remains one of the most frequent causes of death. This study aimed to describe the role of individual and contextual factors on premature ischemic heart disease mortality and to analyze how educational differentials in premature ischemic heart disease mortality changed during economic fluctuations in two provinces of Argentina from 1990 to 2018. To test the relationship between individual (age, sex, and educational level) and contextual (urbanization, poverty, and macroeconomic variations) factors, a multilevel Poisson model was estimated. When controlling for the level of poverty at the departmental level, we observed inequalities in premature ischemic heart disease mortality according to the educational level of individuals, affecting population of low educational level. Moreover, economic expansion was related to an increase in ischemic heart disease mortality, however, expansion years were not associated with increasing educational inequalities in ischemic heart disease mortality. At the departmental level, we found no contextual association beween area-related socioeconomic level and the risk of ischemic heart disease mortality. Despite the continuing decline in ischemic heart disease mortality in Argentina, this study highlighted that social inequalities in mortality risk increased over time. Therefore, prevention policies should be more focused on populations of lower socioeconomic status in Argentina.

Resumen: Si bien la mortalidad por cardiopatía isquémica ha disminuido en las últimas décadas en Argentina, la cardiopatía isquémica sigue siendo una de las causas más frecuentes de muerte. Los objetivos de este estudio fueron describir el papel de los factores individuales y contextuales en la mortalidad prematura por cardiopatía isquémica y analizar cómo estos cambiaron las diferencias educativas en la mortalidad prematura por cardiopatía isquémica durante las variaciones económicas en dos provincias de Argentina durante el periodo 1990-2018. Para probar la relación entre los factores individuales (edad, género y nivel de educación) y contextuales (urbanización, pobreza y variaciones macroeconómicas), se estimó un modelo de Poisson multinivel. Controlando el nivel de pobreza en el ámbito departamental, se observaron desigualdades en la mortalidad prematura por cardiopatía isquémica según el nivel de educación de los individuos, lo que afecta a la población con bajo nivel de educación; la expansión económica se relacionó con el aumento de la mortalidad por cardiopatía isquémica; sin embargo, el periodo de expansión no estuvo asociado a aumentos de las desigualdades educativas en la mortalidad por cardiopatía isquémica. En el ámbito departamental no se detectó asociación entre el nivel socioeconómico de la área y el riesgo de mortalidad por cardiopatía isquémica. A pesar de la disminución continua de la mortalidad por cardiopatía isquémica en Argentina, este estudio destaca que las desigualdades sociales con relación al riesgo de mortalidad tuvieron un aumento con el tiempo. Por lo tanto, las políticas de prevención deberán dirigirse más a las poblaciones de menor nivel socioeconómico en Argentina.

Resumo: Embora a mortalidade por doença isquêmica do coração tenha diminuído nas últimas décadas na Argentina, a doença isquêmica do coração continua sendo uma das causas mais frequentes de morte. Os objetivos deste estudo foram descrever o papel de fatores individuais e contextuais na mortalidade prematura por doença isquêmica do coração e analisar como as diferenças educacionais na mortalidade prematura por doença isquêmica do coração mudaram durante as flutuações econômicas em duas províncias da Argentina durante o período 1990-2018. Para testar a relação entre fatores individuais (idade, sexo e escolaridade) e contextuais (urbanização, pobreza e variações macroeconômicas), estimou-se um modelo de Poisson multinível. Controlando o nível de pobreza no nível departamental, observaram-se desigualdades na mortalidade prematura por doença isquêmica do coração de acordo com o nível educacional dos indivíduos, afetando a população de baixa escolaridade; a expansão econômica esteve relacionada ao aumento da mortalidade por doença isquêmica do coração; no entanto, os anos de expansão não foram associados a aumentos nas desigualdades educacionais na mortalidade por doença isquêmica do coração. No nível departamental, não foi detectada uma associação contextual entre nível socioeconômico da área e risco de mortalidade por doença isquêmica do coração. Apesar do contínuo declínio da mortalidade por doença isquêmica do coração na Argentina, este estudo destaca que as desigualdades sociais em relação ao risco de mortalidade aumentaram ao longo do tempo. Portanto, as políticas de prevenção devem ser mais focadas nas populações de menor nível socioeconômico na Argentina.