Proteína C reactiva, aspectos cardiovasculares de una proteína de fase aguda: una actualización para el médico / C-reactive protein, cardiovascular issues of an acute-phase protein: an update for the clinician

Resumen La inflamación es un factor patogénico importante para el desarrollo de la enfermedad cardiovascular aterosclerótica. Actualmente, el biomarcador utilizado con mayor frecuencia que refleja la inflamación sistémica es la proteína C reactiva (PCR), una proteína de fase aguda producida principalmente por los hepatocitos bajo la influencia de la interleucina 6, la interleucina 1 beta y el factor de necrosis tumoral. La evidencia proveniente de estudios epidemiológicos ha demostrado una fuerte asociación entre las concentraciones elevadas de PCR en suero o plasma y la incidencia de un primer evento cardiovascular (incluido infarto agudo de miocardio, accidente vascular cerebral isquémico y muerte cardíaca súbita) en la población general, así como la recurrencia de eventos cardiovasculares adversos en los pacientes con enfermedad establecida. El valor aditivo que la medición de la PCR otorga a los factores de riesgo tradicionales se refleja en novedosas calculadoras de riesgo cardiovascular y en los actuales regímenes de intervención, que ya consideran a la PCR como objetivo terapéutico. Sin embargo, las variaciones en los niveles de PCR, que dependen del sexo, la etnia, el estado hormonal y algunas peculiaridades de los ensayos de medición, deben tenerse en cuenta al decidir implementar la PCR como un biomarcador útil en el estudio y el tratamiento de la enfermedad cardiovascular aterosclerótica. Esta revisión pretende ofrecer una visión actualizada de la importancia de medir la PCR como biomarcador de riesgo cardiovascular más allá de los factores tradicionales que estiman el riesgo de enfermedad aterosclerótica.

Abstract Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

Impact of Resting Heart Rate on All-cause Mortality in Ultra-high Risk Atherosclerotic Cardiovascular Disease Patients / 中国循环杂志

Objectives:To investigate the impact of resting heart rate on the risk of all-cause mortality in ultra-high risk atherosclerotic cardiovascular disease(ASCVD)patients. Methods:A total of 3 645 patients with ultra-high risk ASCVD(as defined in the 2023 Chinese Lipid Management Guidelines)were screened from the 2006 to 2020 Kailuan Study cohort,and after excluding 602 patients with missing resting heart rate,3 043 patients were included in the final analysis.Patients were divided into＜68 beats/min group(n=744),68-74 beats/min group(n=786),75-80 beats/min group(n=760),and≥81 beats/min group(n=753)according to the resting heart rate.Cox proportional regression model was used to estimate the hazard ratios(HRs)and 95%CI for all-cause mortality associated with the different resting heart rate groups and every 10 beats/min increase of resting heart rate.The dose-effect relationship of resting heart rate level and all-cause mortality was assessed by a restricted cubic spline regression model.The Kaplan-Meier method was applied to calculate the cumulative all-cause mortality in different groups,and the differences were compared using log-rank test. Results:The median follow-up time was 5.81(3.46,9.64)years,there were 772(25.37%)all-cause deaths during follow up.After adjusting major confounding factors,the results showed that compared with＜68 beats/min group,the risk of all-cause mortality in 75-80 beats/min group and≥81 beats/min group increased by 24%(HR=1.24,95%CI:1.01-1.52,P=0.047)and 47%(HR=1.47,95%CI:1.20-1.81,P＜0.001),respectively;the risk of all-cause mortality in 68-74 beats/min group was similar(HR=1.06,95%CI:0.86-1.31,P=0.625).In addition,an increase of 10 beats/min in resting heart rate was associated with a 13%increase in the risk of all-cause mortality(HR=1.13,95%CI:1.07-1.19,P＜0.001).In stratified analyses,it was found that for every 10 beats/min increase in resting heart rate,women faced a higher risk of all-cause mortality than men,and patients＜65 years old faced a higher risk of all-cause mortality than patients≥65 years old.The restricted cubic spline analysis also showed that resting heart rate was linearly associated with the risk of all-cause mortality(Poverall＜0.001,Pnon-linear=0.933),and the risk increased significantly with resting heart rate＞70 beats/min. Conclusions:Increased resting heart rate is linearly associated with increased risk of all-cause mortality in patients with ultra-high risk ASCVD.The appropriate intervention cut-off point of resting heart rate for ultra-high risk ASCVD patients may be＞75 beats/min.

The Mechanisms of PCSK9 Inhibitor Reducing Lipoprotein(a) / 生物化学与生物物理进展

Lipoprotein(a) (Lp(a)) is a complex circulating lipoprotein, and increasing evidence has demonstrated its role as a risk factor for atherosclerotic cardiovascular disease and as a possible therapeutic target. Proprotein converting enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor significantly decreases the circulating level of Lp(a) and reduces the risk of cardiovascular events. Based on the research results in recent years, this review will systematically summarize the relevant mechanisms of PCSK9 inhibitor reducing Lp(a) synthesis and promoting its degradation. The mechanisms are influenced by whether statins used in combination and baseline levels of Lp(a). PCSK9 inhibitors decrease Lp(a) levels mainly by reducing Lp(a) synthesis. However, the importance of low-density lipoprotein receptor (LDLR) mediated enhancing Lp(a) degradation gradually increases when the LDL level decreases. Meanwhile, many other receptor pathways may also exist, including very low-density lipoprotein (VLDL) receptor, LDL receptor-related protein 1, CD36, toll-like receptor 2, scavenger receptor B1 and plasminogen receptor. At present, further studies are still needed to explore the mechanisms by which PCSK9 inhibitors reduce Lp(a) level, such as inhibition of Lp(a) synthesis and intracellular assembly, and LDLR-mediated Lp(a) degradation. In addition, whether the reduction of Lp(a) level by PCSK9 inhibitor is related to age, gender and race and whether the dose-effect relationship of reducing Lp(a) is influenced by background lipid level, all of which require in-depth exploration. In short, the cellular and molecular mechanisms underlying the regulation of Lp(a) synthesis and degradation is not completely clear. It is worth carrying out relevant research to provide a theoretical basis for better clinical application of such drugs.

Novel wine in an old bottle:Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases / 药物分析学报

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmaco-logical mechanisms of AG underlying the prevention and treatment of ASCVD have not been corrobo-rated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound('old bottle')as a novel drug('novel wine')for the pre-vention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.

Factors affecting blood lipid control among residents at a high risk of atherosclerotic cardiovascular disease / 预防医学

Objective@#To investigate the proportion of achieving the blood lipid control target and its influencing factors among residents at a high risk of atherosclerotic cardiovascular disease (ASCVD), so as to provide insights into management of blood lipid among residents at a high risk of ASCVD.@*Methods@#Residents at a high risk of ASCVD and at ages of 35 to 70 years were sampled using a multi-stage cluster sampling method from 6 counties (districts) in Shaoxing City from May to July 2021. The residents' demographics, smoking, alcohol consumption and medical history of chronic diseases were collected using questionnaires, the height, weight, waist circumference (WC) and blood pressure were measured, and the total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and fasting blood glucose were detected. The proportion of blood lipids achieving the control target was analyzed, and factors affecting the proportion of blood lipids achieving the control target were identified using a multivariable logistic regression model.@*Results@#A total of 1 695 individuals at a high risk of ASCVD were enrolled, including 940 men (55.46%) and 755 women (44.54%), with a mean age of (62.56±6.08) years. There were 285 participants that achieved the target of blood lipid control (16.81%). Multivariable logistic regression analysis identified gender (male, OR=1.962, 95%CI: 1.396-2.758), age (OR=1.037, 95%CI: 1.013-1.061), WC (OR=0.979, 95%CI: 0.964-0.995), diastolic blood pressure (OR=0.981, 95%CI: 0.967-0.994), smoking (OR=1.485, 95%CI: 1.034-2.133), alcohol consumption (OR=0.684, 95%CI: 0.498-0.941), hypertension (OR=1.428, 95%CI: 1.006-2.207), administration of hypoglycemic drugs (OR=2.326, 95%CI: 1.720-3.144) as factors affecting the achievement of the target for blood lipid control among residents at a high risk of ASCVD. @*Conclusions @#Individuals at a high risk of ASCVD with higher WC, higher diastolic blood pressure and alcohol consumption are less likely to achieve the target for blood lipid control, while male individuals with older age, hypertension and administration of hypogcemic drugs are more likely to achieve the target for blood lipid control.

Development progress and application of proprotein convertase subtilisin/kexin type 9 inhibitors / 中国生物制品学杂志

@#Dyslipidemia is a causal risk factor of atherosclerotic cardiovascular disease(ASCVD),and lipid-lowering therapies play a major role in preventing and managing ASCVD. Proprotein convertase subtilisin/kexin type 9(PCSK9)promotes atherosclerosis by increasing low-density lipoprotein cholesterol(LDL-C)and inflammatory response,while PCSK9 inhibitors can target to reduce PCSK9 levels and have high lipid lowering efficiency. Especially on the basis of statin or ezetimibe treatment,it can also bring more clinical benefits. With the in-depth study,PCSK9 inhibitor has become the research focus in recent years. This paper reviewed the development progress of PCSK9 inhibitors,in order to provide references for the clinical application of this class of drugs.

Inclisiran, ARN interferente pequeño: un nuevo enfoque para el tratamiento del colesterol / Inclisiran, small interfering RNA: a new approach to cholesterol treatment

Resumen: La hiperlipidemia es altamente prevalente y contribuye de forma sustancial a la enfermedad cardiovascular aterosclerótica, que es una de las principales causas de morbilidad y mortalidad en Colombia. La reducción del colesterol LDL (c-LDL) produce una disminución del riesgo de enfermedad cardiovascular aterosclerótica y de eventos cardiovasculares adversos. La terapia dirigida a la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9; su sigla en inglés) ha surgido como una herramienta novedosa para el tratamiento de la hiperlipidemia. Inclisiran es un ARN pequeño de doble hebra, que actúa inhibiendo la transcripción de PCSK-9 en los hepatocitos, lo que conduce a una reducción marcada y sostenida del c-LDL. En contraste con otras terapias hipolipemiantes, como estatinas, ezetimibe y anticuerpos monoclonales (MAbs; su sigla en inglés) e inhibidores de PCSK9, inclisiran propone un régimen de dosificación infrecuente de dos o tres veces al año. Su efecto prolongado representa una ventaja frente al incumplimiento del tratamiento, que es una de las principales causas por las que no se alcanzan los objetivos de c-LDL con la terapia estándar. Esta revisión tiene como objetivo presentar y discutir los datos científicos actuales con relación a la eficacia, tolerabilidad y seguridad del inclisiran en el tratamiento de la hipercolesterolemia.

Abstract: Hyperlipidemia is a highly prevalent condition and contributes substantially to atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Colombia. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies (MAbs) PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice or three times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia.

Factores de riesgo de enfermedad cardiovascular aterosclerótica en pacientes con diagnóstico de artritis reumatoide / Risk factors for atherosclerotic cardiovascular disease in patients diagnosed with rheumatoid arthritis

Introducción: La artritis reumatoide es una enfermedad autoinmune sistémica, aunque afecta fundamentalmente las articulaciones sinoviales. Más allá de las implicaciones para la calidad de vida del paciente, la presencia de la artritis reumatoide se asocia con una reducción de la esperanza de vida entre 5-10 años. La tasa de mortalidad estandarizada asociada a la artritis reumatoide es superior a la encontrada en la población no afectada; y este exceso de mortalidad se atribuye en gran medida a las enfermedades cardiovasculares, de las cuales la enfermedad vascular aterosclerótica es su principal componente. Objetivo: Determinar cómo se comportaron los factores de riesgo de enfermedad cardiovascular aterosclerótica en pacientes con diagnóstico de artritis reumatoide comparado con el grupo control. Métodos: Se realizó un estudio observacional, de tipo caso-control durante el período comprendido entre enero de 2007 y enero de 2017. Se estudiaron 110 pacientes y 220 controles. En ambos grupos se analizó la frecuencia de factores de riesgo de enfermedad cardiovascular aterosclerótica (tabaquismo, hipertensión arterial, diabetes mellitus y dislipidemia), machados por edad y sexo. Resultados: Predominaron los pacientes del sexo femenino. La mediana de edad de los pacientes fue de 41,0 años. El tabaquismo fue más frecuente en los casos (23,6 por ciento vs 11,4 por ciento, p=0,004), así como la hipertensión arterial y la diabetes mellitus. Conclusiones: En el presente estudio los factores de riesgo como el tabaquismo, la diabetes mellitus y la dislipidemia fueron más frecuentes en los pacientes son artritis reumatoide que en el grupo control(AU)

Introduction: Rheumatoid arthritis is a systemic autoimmune disease, although it mainly affects the synovial joints. Beyond the implications for the patient's quality of life, the presence of rheumatoid arthritis is associated with a reduction in life expectancy in 5-10 years. The standardized mortality rate associated with rheumatoid arthritis is higher than that found in the unaffected population; and this excess mortality is largely attributed to cardiovascular diseases, of which atherosclerotic vascular disease is the main component. Objective: To determine how the risk factors for atherosclerotic cardiovascular disease behaved in patients diagnosed with rheumatoid arthritis compared to the control group. Methods: An observational, case-control study was carried out from January 2007 to January 2017. A hundred ten (110) patients and 220 controls were studied. In both groups, the frequency of risk factors for atherosclerotic cardiovascular disease (smoking, high blood pressure, diabetes mellitus, and dyslipidemia) was analyzed, matched by age and sex. Results: Female patients predominated. The median age of the patients was 41.0 years. Smoking was more frequent variable in the cases (23.6percent vs 11.4percent, p=0.004), as well as arterial hypertension and diabetes mellitus. Conclusions: In the present study, risk factors such as smoking, diabetes mellitus and dyslipidemia were more frequent in patients with rheumatoid arthritis than in the control group(AU)

Effectiveness of moderate aerobic exercise on prevention of atherosclerotic cardiovascular diseases in patients with hypercholesterolemia / 预防医学

Objective @#To examine the effect of moderate aerobic exercise on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in patients with hypercholesterolemia, so as to provide insights into ASCVD prevention.@*Methods @#The patients with hypercholesterolemia admitted to the Affiliated Hospital of Hebei University from September 2019 to September 2020 were recruited and randomly assigned into the intervention group and the control group using a random number table. Participants in both groups received routine lipid-lowering therapy and health education, and participants in the intervention group were given additional interventions of moderate aerobic exercise. Serum lipid levels were measured before and after 12 weeks of interventions. The 10-year risk of developing ASCVD was evaluated in both groups following interventions.@*Results @#There were 50 participants with hypercholesterolemia in each of the intervention and control groups. The mean age was ( 38.80±1.42 ) years in the intervention group and ( 37.14±1.23 ) years in the control group, and males were accounted for 46.00% and 40.00%, respectively. The increase in high-density lipoprotein cholesterol ( HDL-C ), the reduction in total cholesterol ( TC ), triglyceride ( TG ), low-density lipoprotein cholesterol ( LDL-C ) and the 10-year risk of ASCVD were all significantly greater in the intervention group than those in the control group before and after the interventions ( P<0.05 ).@*Conclusion @#Moderate aerobic exercise may reduce the 10-year risk of ASCVD through regulating blood lipid levels.

Guía de práctica clínica mexicana para el diagnóstico y tratamiento de las dislipidemias y enfermedad cardiovascular aterosclerótica / Mexican clinical practice guideline for the diagnosis and treatment of dyslipidemias and atherosclerotic cardiovascular disease

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Abstract Background: Cardiovascular diseases are the leading cause of mortality worldwide and Mexico is no exception. The epidemiological data obtained in 1990 showed that cardiovascular diseases represented 19.8% of all causes of death in our country. This figure increased significantly to 25.5% for 2015. Some national surveys suggest that more than 60% of the adult population has at least one risk factor for cardiovascular disease (obesity or overweight, hypertension, smoking, diabetes, dyslipidemias). On the other hand, data from the Pan American Health Organization have linked the process of atherosclerosis as the first cause of premature death, significantly reducing life expectancy, which has enormous social repercussions. Objective: This document constitutes the Clinical Practice Guide (CPG) prepared at the initiative of the Mexican Society of Cardiology in collaboration with the Mexican Society of Nutrition and Endocrinology, AC, National Association of Cardiologists of Mexico, AC, Mexican Association for the Prevention of Atherosclerosis and its Complications, AC, National Normative Committee of General Medicine, AC, National College of Geriatric Medicine, AC, College of Internal Medicine of Mexico, AC, Mexican Society of Angiology and Vascular and Endovenous Surgery, AC, Mexican Institute of Research Nephrological, AC and the Mexican Academy of Neurology, A.C.; with the methodological support of the Ibero-American Agency for the Development and Evaluation of Health Technologies, in order to establish recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. The objective of this document is to provide evidence-based recommendations to help decision makers in the diagnosis and treatment of dyslipidemias in our country. Material and methods: This document complies with international quality standards, such as those described by the Institute of Medicine of the USA, the Institute of Clinical Excellence of Great Britain, the Scottish Intercollegiate Guideline Network and the Guidelines International Network. A multidisciplinary group of clinical experts and methodologists with experience in systematic reviews of the literature and the development of clinical practice guidelines was formed. A scope document was agreed upon, relevant clinical questions were established, the best available evidence critically evaluated in systematic literature reviews was exhaustively identified, and clinical recommendations were developed. The modified Delphi Panel methodology was used to achieve an adequate level of consensus in each of the recommendations contained in this CPG. Results: 23 clinical questions were agreed upon which gave rise to their respective clinical recommendations. Conclusions: We consider that this document contributes to better clinical decision-making and becomes a point of reference for clinicians and patients in the management of dyslipidemias and this contributes to reducing the morbidity and mortality derived from atherosclerotic cardiovascular events in our country.

Enfermedad cardiovascular aterosclerótica según el sexo en personas de edad mediana con diabetes mellitus / Atherosclerotic cardiovascular disease according to sex in middle-aged people with diabetes mellitus

Introducción: El sexo influye en la susceptibilidad de las personas de ambos géneros con relación a la mayoría de las enfermedades comunes, incluidas la diabetes mellitus y la aterosclerosis. Objetivo: Identificar si existen diferencias en la presentación de la enfermedad cardiovascular aterosclerótica entre hombres y mujeres de edad mediana con diabetes mellitus. Métodos: Se realizó un estudio descriptivo de corte transversal en 1449 pacientes con diabetes mellitus en edad mediana (40 a 59 años) que ingresaron en el Centro de Atención al Diabético de Bayamo, Granma, desde el año 2010 al 2019. Se empleó la prueba de Chi Cuadrado para comprobar la relación entre las variables cualitativas, y T de Student para comparar los valores promedio de las variables cuantitativas. Resultados: La proporción de enfermedad cardiovascular aterosclerótica en el sexo masculino fue similar a la del femenino (51,4 por ciento x 48,6 por ciento, p=0.2328). No hubo discrepancias importantes en el porcentaje de la enfermedad, entre ambos sexos, en los diferentes grupos etarios. El riesgo de enfermedad cardiovascular aterosclerótica en los hombres fue mayor que en las mujeres premenopausicas (OR=2,19, IC: 1,4-3,3 p=0,0002), pero inferior respecto a las posmenopáusicas. (OR=1.12, IC: 0.8-1.4, p=0.4129). El análisis multivariado mostró al tiempo de la diabetes >10 años y a la hipertensión arterial como riesgo de enfermedad cardiovascular aterosclerótica en ambos sexos. Asimismo, se evidenció en la edad mayor de 45 años en los hombres (OR=2.5, IC: 1.4-4.6) y la menopausia en las mujeres (OR=1.8, IC: 1.1-3.07). Conclusiones: La frecuencia de la enfermedad cardiovascular aterosclerótica en las personas de edad mediana con diabetes mellitus es similar en ambos sexos. El sexo masculino tiene mayor riesgo de enfermarse que las mujeres premenopausicas, pero menor que las posmenopáusicas. La hipertensión arterial y el tiempo de la diabetes son factores de riesgo comunes para uno y otro sexo(AU)

Introduction: Sex influences the susceptibility of people of both genders to most common diseases, including diabetes mellitus (DM) and atherosclerosis. Objective: Identify if there are differences in the presentation of atherosclerotic cardiovascular disease between middle-aged men and women with diabetes mellitus. Methods: A descriptive cross-sectional study was conducted in 1449 patients with DM in middle age (40 to 59 years) who were admitted to the Diabetic´s Care Center of Bayamo, Granma province, from 2010 to 2019. The Chi-Square test was used to check the relation between the qualitative variables, and the T Student test to compare the average values of the quantitative variables. Results: The proportion of atherosclerotic cardiovascular disease in males was similar to that of females (51.4 percent x 48.6 percent, p=0.2328). There were no major discrepancies in the percentage of atherosclerotic cardiovascular disease, between both sexes, in the different age groups. The risk of atherosclerotic cardiovascular disease in men was higher than in pre-menopausal women (OR=2.19, CI: 1.4-3.3 p=0.0002), but lower than in post-menopausal women. (OR=1.12, CI: 0.8-1.4, p=0.4129). Multivariate analysis showed diabetes >10 years and arterial hypertension as a risk of atherosclerotic cardiovascular disease in both sexes. It was also evidenced in ages over 45 years in men (OR=2.5, CI: 1.4-4.6) and menopause in women (OR=1.8, CI: 1.1-3.07). Conclusions: The frequency of atherosclerotic cardiovascular disease in middle-aged people with diabetes mellitus is similar in both sexes. Males have a higher risk of atherosclerotic cardiovascular disease than pre-menopausal women, but lower than post-menopausal women. High blood pressure and diabetes time are common risk factors for both sexes(AU)

Apolipoproteína B: sus ventajas en el manejo del riesgo cardiovascular aterosclerótico / Apolipoprotein B: its advantages in the assessment of atherosclerotic cardiovascular risk / Apolipoproteína B: suas vantagens no manejo do risco cardiovascular aterosclerótico

Resumen Se analiza la determinación de apolipoproteína B (Apo B) en la evaluación y tratamiento de la enfermedad cardiovascular aterosclerótica (ECVA) con respecto a tres aspectos: a) marcador de riesgo aterogénico; b) ventajas sobre los lípidos; c) utilidad en el laboratorio bioquímico. Apo B participa en la aterogénesis. Habitualmente las partículas lipoproteicas aterogénicas se evalúan por su contenido en colesterol pero su masa por partícula es muy variable. Sin embargo, cada partícula tiene una molécula de Apo B por lo que es un estimador de su número y marcador de riesgo. Apo B desempeña un rol causal y explica mejor que el colesterol LDL (C-LDL) la relación etiológica con la enfermedad, tiene mayor capacidad discriminante que los lípidos, agregación familiar y mejor parámetro para el manejo del tratamiento en presencia de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólico, obesidad y diabetes. Puede determinarse sin ayuno previo con trazabilidad respecto de un patrón de referencia, comparabilidad y armonía de los resultados entre los laboratorios y menor error analítico que el colesterol no-HDL. C-LDL sigue siendo el objetivo primario para la evaluación y tratamiento del riesgo aterogénico. Por consenso se han informado los valores de corte para Apo B según categorías de riesgo de ECVA y se recomendó su uso cuando sea posible determinarla. Apo B es un excelente marcador de riesgo aterogénico, presenta mayor exactitud y precisión que los lípidos y su inclusión en el manejo de casos clínicos específicos contribuye a mejorar la calidad del tratamiento.

Abstract The determination of apolipoprotein B (Apo B) in the evaluation and treatment of atherosclerotic cardiovascular disease (ACVD) is analyzed, referring to three aspects: a) marker of atherogenic risk; b) advantages over lipids; c) utility in the biochemical laboratory. Apo B participates in atherogenesis. Atherogenic lipoprotein particles are usually evaluated for their cholesterol content, but their mass per particle is highly variable. However, each particle has an Apo B molecule so it is an estimator of its number and a marker of risk. Apo B plays a causal role and explains better than LDL cholesterol (LDL-C) the etiological relationship with the disease; it has a greater discriminating capacity than lipids, family aggregation and it is a better parameter for the management of treatment in the presence of LDL-C<70 mg/dL, moderate hypertriglyceridemia, metabolic syndrome, obesity, and diabetes. It can be determined without prior fasting with traceability to a reference standard, comparability and harmony of results between laboratories and lower analytical error than non-HDL cholesterol. LDL-C remains the primary endpoint for the evaluation and treatment of atherogenic risk. By consensus, cut-off values for Apo B have been reported according to ACVD risk categories and its use was recommended when it is possible to determine it. Apo B is an excellent marker of atherogenic risk, it has greater accuracy and precision than lipids and its inclusion in the management of specific clinical cases contributes to improving the quality of treatment.

Resumo A determinação da apolipoproteína B (Apo B) na avaliação e tratamento da doença cardiovascular aterosclerótica (DCVA) é analisada, referindo-se a três aspectos: a) marcador de risco aterogênico; b) vantagens sobre os lipídios; c) utilidade no laboratório bioquímico. Apo B participa da aterogênese. As partículas de lipoproteína aterogênica são geralmente avaliadas quanto ao seu conteúdo de colesterol, mas sua massa por partícula é altamente variável. No entanto, cada partícula possui uma molécula de Apo B, por isso é um estimador de seu número e um marcador de risco. A Apo B tem papel causal e explica melhor que o colesterol LDL (C-LDL) a relação etiológica com a doença, tem maior capacidade discriminante que os lipídios, agregação familiar e melhor parâmetro para o manejo do tratamento na presença de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólica, obesidade e diabetes. Pode ser determinado sem jejum prévio com rastreabilidade a respeito de um padrão de referência, comparabilidade e harmonia de resultados entre laboratórios e menor erro analítico do que o colesterol não-HDL. O C-LDL continua sendo o objetivo primário para a avaliação e tratamento do risco aterogênico. Por consenso, os valores de corte da Apo B foram reportados de acordo com as categorias de risco de DCVA e seu uso foi recomendado quando possível. A Apo B é um excelente marcador de risco aterogênico, possui maior acurácia e precisão que os lipídeos e sua inclusão no manejo de casos clínicos específicos contribui para a melhoria da qualidade do tratamento.

ASCVD indexes in Bama and Shimen area plasma donors, China / 中国输血杂志

【Objective】 To investigate the level of atherosclerotic cardiovascular disease (ASCVD) related indexes in plasma donors from longevity area, and explore its influencing factors. 【Methods】 1 027 plasma donors from longevity hotspot (Bama, Guangxi province) and 1 816 donors from non-longevity region (Shimen, Hunan province) who donated plasma during June to November 2018 were randomly selected. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and fructosamine (FUN) of the two groups were measured and statistically analyzed. 【Results】 Compared with the non-longevity region group, the TG, TC and FUN levels of longevity hotspot group were lower (1.41±0.96 vs 2.31±1.28, 3.89±0.92 vs 4.04±0.82, 176.65±26.60 vs 200.33±34.19; all P<0.05), but HDLC, LDLC, Apo-A1 and Apo-B levels were higher (1.11±0.32 vs 0.96±0.25, 2.53±0.70 vs 2.29±0.56, 1.56±0.28 vs 1.23±0.18, 0.80±0.27 vs 0.72±0.19; all P<0.05). The yield (%) of high TG(12.0 vs 40.01) and FUN(0.58 vs 2.48), low HDLC(24.63 vs 43.90) and Apo-A1(1.66 vs 22.56) were lower in longevity area than those in non-longevity region (all P<0.05), but high LDLC(2.73 vs 0.28) and Apo-B(4.09 vs 0.22) yield(%) were higher in longevity area group ( P<0.05). The levels of TC, HDLC, LDLC, Apo-A1 and Apo-B were significantly different by ages (all P < 0.01), presenting positively correlated with age, significantly by gender and nationality, and slightly by blood type. 【Conclusion】 The ASCVD indexes of plasma donors from Bama were different from those from Shimen. Age, nationality, gender and blood type of donors from Bama all had a certain influence on these indexes levels.

Research Progress on Correlation of Inflammatory Bowel Disease With Risk of Atherosclerotic Cardiovascular Disease / 胃肠病学

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with an increasing incidence in China. Chronic inflammation is considered as an important cause of atherosclerotic cardiovascular disease (ASCVD). IBD is correlated with ASCVD. IBD and ASCVD share common pathophysiological mechanisms in epidemiology, genetics and environmental factors. Many factors related to IBD affect the occurrence and development of ASCVD. This article reviewed the common pathophysiological mechanism of the two diseases and the research progress of related treatment.

Effect and Mechanism of Shenlian Formula in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To analyze active components， its targets and signaling pathways of Shenlian formula based on network pharmacology， and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease （ASCVD）， in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine （TCMSP）， its target proteins were obtained by SymMap and ETCM Databases， and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions （PPI） network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds， 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 （PTGS2）， estrogen receptor 1 （ESR1） and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic， nitric oxide biosynthetic process， response to estradiol， angiogenesis， inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway， phosphatidylinositol-3 kinase （PI3K）/ protein kinase B （Akt） signaling pathway， hypoxia induction factor-1 （HIF-1） signaling pathway and apoptosis. Among them， the regulatory effect of Shenlian formula on apoptosis may act on not only TP53， but also different signaling pathways of apoptosis respectively， thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area， improve the myocardial histopathological changes， and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD， and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.

Associations of plasma lipids, lipoproteins, and cardiovascular outcomes with climatic variations in a large Brazilian population of Campinas, São Paulo state: an eight-year study

In this eight-year retrospective study, we evaluated the associations between climatic variations and the biological rhythms in plasma lipids and lipoproteins in a large population of Campinas, São Paulo state, Brazil, as well as temporal changes of outcomes of cardiovascular hospitalizations. Climatic variables were obtained at the Center for Meteorological and Climatic Research Applied to Agriculture (University of Campinas - Unicamp, Brazil). The plasma lipid databases surveyed were from 27,543 individuals who had their lipid profiles assessed at the state university referral hospital in Campinas (Unicamp). The frequency of hospitalizations was obtained from the Brazilian Public Health database (DATASUS). Temporal statistical analyses were performed using the methods Cosinor or Friedman (ARIMA) and the temporal series were compared by cross-correlation functions. In normolipidemic cases (n=11,892), significantly different rhythmicity was observed in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (C) both higher in winter and lower in summer. Dyslipidemia (n=15,651) increased the number and amplitude of lipid rhythms: LDL-C and HDL-C were higher in winter and lower in summer, and the opposite occurred with triglycerides. The number of hospitalizations showed maximum and minimum frequencies in winter and in summer, respectively. A coincident rhythmicity was observed of lower temperature and humidity rates with higher plasma LDL-C, and their temporal series were inversely cross-correlated. This study shows for the first time that variations of temperature, humidity, and daylight length were strongly associated with LDL-C and HDL-C seasonality, but moderately to lowly associated with rhythmicity of atherosclerotic outcomes. It also indicates unfavorable cardiovascular-related changes during wintertime.

Logro de las metas de colesterol LDL en pacientes con enfermedad coronaria aterosclerótica establecida / Achievement of LDL cholesterol targets in patients with coronary artery disease

Resumen Introducción: Los pacientes con enfermedad aterosclerótica establecida requieren tratamiento con estatinas para reducir la probabilidad de nuevos eventos. Objetivo: Identificar el porcentaje de pacientes con enfermedad coronaria aterosclerótica establecida que logran niveles de cLDL (colesterol LDL) inferiores a 70mg/dl y describir su distribución en tres grupos terapéuticos: estatinas, otros hipolipemiantes y sin tratamiento. Métodos: Estudio observacional descriptivo de corte transversal, en el que se seleccionaron pacientes de tres hospitales de alta complejidad, mayores de 18 años, con enfermedad aterosclerótica diagnosticada a partir del año 2017. El registro del perfil lipídico corresponde al realizado al menos tres meses después del diagnóstico. Resultados: Se incluyeron en total 746 pacientes con enfermedad coronaria aterosclerótica, con un promedio de edad de 65,3±10,9 años y predominio del sexo masculino (75,5%). Del total de los pacientes evaluados se prescribieron un 97,8% de terapia con al menos una estatina, 0,7% de otros hipolipemiantes y 1,5% no presentaron tratamiento. Los pacientes con niveles de cLDL inferior a 70mg/dl corresponden al 56%. Conclusiones: La extensa divulgación de guías de práctica clínica para dislipidemias en adultos en Colombia, y la incorporación de estatinas de alta intensidad, demuestran una mejoría en la proporción del cumplimiento en metas de cLDL para pacientes con enfermedad aterosclerótica establecida. Sin embargo, una alta proporción aún persiste fuera de metas, lo cual constituye una oportunidad de optimización del uso de terapias disponibles y recientemente desarrolladas.

Abstract Introduction: Patients with established atherosclerotic disease require treatment with statins in order to reduce the probability of new events. Objective: To identify the percentage of patients with established atherosclerotic coronary disease that achieve cLDL (LDL - cholesterol) levels less than 70mg/dL, and to describe its distribution in three treatment groups: statins, other lipid lowering drugs, and without treatment. Methods: A cross-sectional, descriptive observational study was conducted on patients diagnosed with atherosclerotic disease from 2017 and over 18-years-old from 3 tertiary hospitals. A record was made of the lipid profile that was performed at least three months after the diagnosis. Results: A total of 746 patients with atherosclerotic coronary disease were included. The mean age was 65.3±10.9 years and the majority (75.5%) were males. Of the total number of patients evaluated, 97.8% were prescribed a therapy with at least one statin, 0.7% with other lipid-lowering drugs, and 1.5% had no treatment. Just over half (56%) of the patients had cLDL levels of less than 70mg/dL. Conclusions: The widespread use of clinical practice guidelines for dyslipidaemias in adults in Colombia, and the incorporation of high-intensity statins, has led to an improvement in the proportion of patients with established atherosclerotic disease achieving cLDL targets. However, a high percentage still does not reach the targets, which suggests a need for an improving of the use of available and recently developed therapies.

Medición directa versus el valor estimado del colesterol de LDL por las ecuaciones de Friedewald, Friedewald modificada y de regresión / Direct measurement versus estimated value of LDL cholesterol by Friedewald, modified Friedewald and regression equations

Diversos estudios evidencian la asociación entre los niveles elevados del colesterol de LDL (cLDL) y el riesgo de desarrollar enfermedad cardiovascular aterosclerótica. Con el objetivo de comparar los valores de cLDL obtenidos mediante la medición directa y los valores estimados por las ecuaciones de Friedewald tradicional, modificada y de regresión, se valoró el cLDL de 4.621 pacientes mediante el ensayo directo en el autoanalizador ADVIA 1800. Dichos resultados se agruparon en los estados de normolipemia, hipercolesterolemia, hiperlipemia mixta e hipertrigliceridemia y se establecieron diferencias de estimación con las mencionadas fórmulas en el total de la muestra y en los niveles de decisión clínica para el cLDL. Las tres fórmulas presentaron correlación significativa con el método directo en la totalidad de la muestra; sin embargo, cuando los niveles de triglicéridos de las muestras superaron los 200 mg/dL, la diferencia entre la fórmula de Friedewald y el método directo resultó -11,94%, y llegó a -19,13% para el nivel de triglicéridos mayor de 400 mg/dL. Por otro lado, las ecuaciones de Friedewald modificada y de regresión se vieron afectadas en menor cuantía por el nivel de triglicéridos. Las fórmulas de regresión y de Friedewald modificada se constituyen como alternativas razonables para estimar el cLDL y presentan buena concordancia con el método directo, incluso en niveles altos de colesterol y triglicéridos.

Several studies show the association between high LDL cholesterol (LDLc) levels and the risk of developing atherosclerotic cardiovascular disease. In order to compare the LDLc values obtained by direct measurement and the values estimated by the traditional, modified and regression Friedewald equations, the LDLc of 4,621 patients was assessed by means of the direct test in the ADVIA 1800 autoanalyzer.These results were grouped into the states of normolipemia, hypercholesterolemia, mixed hyperlipemia and hypertriglyceridemia, establishing differences in estimation with the aforementioned formulas in the total sample and in clinical decision levels for LDLc. The three formulas showed a significant correlation with the direct method in the entire sample; however, when the triglyceride levels of the samples exceeded 200 mg/dL, the difference between Friedewald's formula and the direct method was -11.94% reaching -19,13% for the triglyceride level greater than 400 mg/dL, while the modified Friedewald and regression equations were affected to a lesser extent by the triglyceride level. Regression and modified Friedewald formulas are constituted as reasonable alternatives to estimate LDLc and have good agreement with the direct method, even at high cholesterol and triglyceride levels.

Varios estudos evidenciam a associacao entre niveis elevados do colesterol LDL (cLDL) e o risco de desenvolver doenca cardiovascular aterosclerotica. Visando comparar os valores de cLDL obtidos atraves da medicao direta e os valores estimados pelas equacoes de Friedewald tradicional, modificada e de regressao, o cLDL de 4.621 pacientes foi avaliado por meio do teste direto no analisador automatico ADVIA 1800. Tais resultados foram agrupados nos estados de normolipemia, hipercolesterolemia, hiperlipemia mista e hipertrigliceridemia, estabelecendo-se diferencas na estimativa com as formulas mencionadas no total da amostra e nos niveis de decisao clinica para cLDL. As tres formulas apresentaram correlacao significativa com o metodo direto em toda a amostra, no entanto, quando os niveis de triglicerideos das amostras excederam 200 mg/dL, a diferenca entre a formula de Friedewald e o metodo direto foi de -11,94% atingindo -19,13% para o nivel de triglicerideos superior a 400 mg/dL. Por outra parte, as equacoes de Friedewald modificada e de regressao foram afetadas em menor grau pelo nivel de triglicerideos. As formulas de regressao e de Friedewald modificada se constituem como alternativas razoaveis para estimar o cLDL, e apresentam boa concordancia com o metodo direto, mesmo em niveis elevados de colesterol e triglicerideos.

Dietary and Blood Lipids in Cardiovascular Disease

Blood lipids are essential for life; at the same time, elevated or reduced levels of some of the components of lipid are related to risk of atherosclerotic cardiovascular disease (ASCVD).This article provides a review on dietary and blood lipids with their impact on cardiovascular health. The role of apolipoprotein B (ApoB), Lipoprotein(a) ((Lp(a))and other lipoprotein particles in the development of ASCVD has been reviewed. There are newevidences that ApoB the structural protein of most of the lipoprotein particles (carrier of blood lipids), in addition to low density lipoprotein-cholesterol (LDL-C), plays a central role in the pathogenesis of atherosclerosis with increased risk for ASCVD. Elevated levels of Lp(a) concentrations are associated with an increased risk of ASCVD, but it appears to be a weaker risk factor than ApoB or LDL-C

Monocyte to HDL-Cholesterol ratio as an inflammation marker for ASCVDS / Шинэ санаа Шинэ нээлт

Background@#Monocyte / High Density Lipoprotein Ratio (MHR) has become an inflammation marker of atherosclerotic cardiovascular diseases and is a handy and reliable diagnostic marker at a low cost. @*Objectives@#to suggest MHR as a new inflammation marker for ASCVDs by comparing it with other risk factors of cardiovascular disease and assessing the significance in screening@*Methods@#This study conducted during October to December 2019 is a hospital-based cross sectional study, with a total of 396 clients, all 20 to 64 years old, were selected as subjects of the study using a certain criteria. @*Results@#78.47% of the male subjects and 34.31% of female subjects were diagnosed with dislipidemia, which shows us that males were diagnosed more frequently. The study sample consisted of 274 (72.87%) men and 102 (27.13%) women with mean age of 36.6±8.42 years (range, 20-64 years), 78.47% were male and 34.31% were females. 66.49% of total participants were newly diagnosed with dyslipidemia. An age group of 30 to 40 years old were recorded with the highest cases of dyslipidemia. Monocyte / High Density Lipoprotein Ratio (MHR) were 7.88 and 12.82 in dyslipidemic and non-dyslipidemic subjects, respectively and showed that there is a statistically significant difference(p<0.05). The 10-year ASCVD risk of 113 people aged 40-64 years, which were classified in low risk group (<7.5%) and in high risk group (≥7.5%) were assessed by pooled cohort equation and the results shows that risk percentage were 65.14% and 34.86% and there is statistically significant difference in MHR, which were 10.58±4.80 and 14.07±4. 90 in respective groups.@*Conclusions@#Prevalence of dyslipidemia in preventive screening were high in a group of 20-62 years old and the group of those were estimated high The 10-year ASCVD risk, also had relatively higher MHR. Moreover, there is a positive relation between dyslipidemia and MHR. These results show that it is possible to use MHR as a new inflammation marker in ASCVDs for early detection purpose.