Associations between various lipid components and premature myocardial infarction: a cross-sectional study / 中华心血管病杂志

Objective: Hyperlipidemia is closely related to premature acute myocardial infarction (AMI). The present study was performed to explore the correlation between various blood lipid components and the risk of premature AMI. Methods: This is a cross-sectional retrospective study. Consecutive patients with acute ST-segment elevation myocardial infarction (STEMI), who completed coronary angiography from October 1, 2020 to September 30, 2022 in our hospital, were enrolled and divided into premature AMI group (male<55 years old, female<65 years old) and late-onset AMI group. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, lipoprotein (a) (Lp (a)), apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA-1), non-HDL-C/HDL-C and ApoB/ApoA-1 were analyzed. The correlation between the above blood lipid indexes and premature AMI was analyzed and compared by logistic regression, restricted cubic spline and receiver operating characteristic curve (ROC). Results: A total of 1 626 patients with STEMI were enrolled in this study, including 409 patients with premature AMI and 1 217 patients with late-onset AMI. Logistic regression analysis showed that the risk of premature AMI increased significantly with the increase of TG, non-HDL-C/HDL-C, non-HDL-C, ApoB/ApoA-1, TC and ApoB quintiles; while LDL-C, ApoA-1 and Lp (a) had no significant correlation with premature AMI. The restricted cubic spline graph showed that except Lp (a), LDL-C, ApoA-1 and ApoB/ApoA-1, other blood lipid indicators were significantly correlated with premature AMI. The ROC curve showed that TG and non-HDL-C/HDL-C had better predictive value for premature AMI. Inconsistency analysis found that the incidence and risk of premature AMI were the highest in patients with high TG and high non-HDL-C/HDL-C. Conclusion: TG, non-HDL-C/HDL-C and other blood lipid indexes are significantly increased in patients with premature AMI, among which TG is the parameter, most closely related to premature AMI, and future studies are needed to explore the impact of controlling TG on incidence of premature AMI.

Value of glycosylated hemoglobin A1c and apolipoprotein A-1 ratio on predicting outcome of patients with acute coronary syndrome / 中华心血管病杂志

Objective: To investigate the predictive value of glycosylated hemoglobin A1c/apolipoprotein A-1 (HbA1c/ApoA-1) ratio for major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Methods: The present study is a retrospective cohort study. ACS patients who were hospitalized and underwent coronary angiography at Beijing Hospital from March 2017 to March 2019 were enrolled. Baseline information such as sex, age, previous history, Gensini score, HbA1c and ApoA-1 were analyzed. Patients were divided into two groups according to presence or absence of MACEs and the difference on HbA1c/ApoA-1 ratio was compared between the two groups. According to the tertiles of HbA1c/ApoA-1 levels, patients were divided into high (5.87-16.12), medium (4.50-5.83) and low (2.11-4.48) HbA1c/ApoA-1 groups. Cox proportional risk model was used to evaluate the differences in MACEs and all-cause mortality among the three groups. Kaplan-Meier survival analysis was used to compare the differences of MACEs between the various HbA1c/ApoA-1 groups. Results: A total of 366 ACS patients were included in this study. The mean age of the patients was (65.9±10.3) years. There were 59 MACEs and 10 all-cause deaths during the mean of (22.3±4.4) months follow-up. After adjusting for age, systolic blood pressure, history of diabetes and Gensini score, the incidence of MACEs was 2.45 times higher in the high HbA1c/ApoA-1 group than in the low HbA1c/ApoA-1 group (95%CI 1.16-5.18, P=0.019). There was no significant difference in all-cause mortality between the high and low HbA1c/ApoA-1 groups (P=1.000). Kaplan-Meier survival analysis showed that patients in the high HbA1c/ApoA-1 group had the highest risk of MACEs, while patients in the low HbA1c/ApoA-1 group had the lowest risk of MACEs (P<0.01). Spearman rank correlation analysis showed that HbA1/ApoA-1 ratio was positively correlated with Gensini score in ACS patients (r=0.274, P<0.01). Conclusion: High HbA1c/ApoA-1 ratio was an independent risk factor for MACEs in ACS patients. Patients with high HbA1c/ApoA-1 ratio had more severe coronary artery disease lesions. HbA1c/ApoA-1 ratio may be used as a potential risk stratification biomarker for ACS patients, it might be useful for the early identification of high-risk population and for predicting the incidence of MACEs among ACS patients.

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

Increased ApoB/ApoA1 ratio is associated with excess weight, body adiposity, and altered lipid profile in children / A razão ApoB/ApoA1 aumentada está associada ao excesso de peso, de adiposidade corporal e ao perfil lipídico alterado em crianças

Abstract Objective: To investigate ApoB/ApoA1 ratio and its association with cardiovascular risk factors in children. Methods: Cross-sectional study with 258 children aged 8 and 9 years old, enrolled in all urban schools in the city of Viçosa-MG. Anthropometric and body composition assessment, as well as biochemical profile of the children was performed. Socioeconomic variables and sedentary lifestyle were evaluated through a semi-structured questionnaire. Results: Many children had excess weight (35.2%), abdominal adiposity (10.5%), and body fat (15.6%), as well as increased ApoB/ApoA1 ratio (14.7%), total cholesterol (51.8%), and triglycerides (19.8%). Children with excess weight and total and central fat had a higher prevalence of having a higher ApoB/ApoA1 ratio, as well as those with atherogenic lipid profile (increased LDL-c and triglycerides and low HDL-c). A direct association was found between the number of cardiovascular risk factors and the ApoB/ApoA1 ratio (p = 0.001), regardless of age and income. Conclusion: The increased ApoB/ApoA1 ratio was associated with excess weight, body adiposity (total and central), and altered lipid profile in children. Children with a higher number of cardiovascular risk factors had higher ApoB/ApoA1 ratio, in both genders.

Resumo Objetivo: Investigar a razão ApoB/ApoA1 e sua relação com fatores de risco cardiovascular em crianças. Métodos: Estudo transversal com 258 crianças de 8 e 9 anos, matriculadas em todas as escolas urbanas de Viçosa-MG. Foi feita avaliação antropométrica, da composição corporal e bioquímica das crianças. As variáveis socioeconômicas e o sedentarismo foram avaliados por questionário semiestruturado. Resultados: Muitas crianças apresentaram excesso de peso (35,2%), de adiposidade abdominal (10,5%) e de gordura corporal (15,6%), bem como a razão ApoB/ApoA1 (14,7%), colesterol-total (51,8%) e triglicerídeos (19,8%) aumentados. Crianças com excesso de peso e de gordura total e central apresentaram maiores prevalências de maior razão ApoB/ApoA1, bem como as com perfil lipídico aterogênico (LDL-c e triglicerídeos aumentados e baixo HDL-c). Foi encontrada associação direta entre o número de fatores de risco cardiovascular e a razão ApoB/ApoA1 (p = 0,001), independente da idade e renda. Conclusão: A razão ApoB/ApoA1 aumentada esteve associada ao excesso de peso, de adiposidade corporal (total e central) e ao perfil lipídico alterado nas crianças. As crianças com maior número de fatores de risco cardiovascular apresentaram maior razão ApoB/ApoA1, em ambos os sexos.

Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Marcadores de fase aguda en niños y adolescentes obesos con trastornos metabólicos / Acute phase markers in obese children and adolescents with metabolic disorders

Introducción. La obesidad es un problema de salud pública mundial y la enfermedad crónica no transmisible más frecuente. Se asocia con la elevación de proteínas inflamatorias de fase aguda y citocinas proinflamatorias. Objetivo. Evaluar los niveles de proteínas de fase aguda en niños y adolescentes obesos con esteatosis hepática y síndrome agudo metabólico. Metodología. Se incluyeron 45 niños con índice de masa corporal ≥ percentil 95, de edades entre 5,0 y 15,5 años. Se determinaron reactantes de fase aguda: proteína C reactiva, haptoglobina, a-2 macroglobulina y apolipoproteína A-1, y se realizó una ecografía para evaluar la esteatosis hepática. Resultados. Todos los pacientes mostraron una elevación de proteína C reactiva. Los pacientes con síndrome metabólico también tuvieron un incremento en la apolipoproteína A-1 y la haptoglobina. Los pacientes con esteatosis hepática tuvieron un aumento significativo en la a-2 macroglobulina además de la protenína C reactiva.

Introduction. Obesity is a worldwide public health problem and the most common non-communicable chronic disease. It is associated with an increase in inflammatory acute phase proteins and proinflammatory cytokines. Objective. To assess the levels of acute phase proteins in obese children and adolescents with hepatic steatosis and metabolic syndrome. Methodology. Forty-five children with a body mass index ≥ 95th percentile aged 5.0-15.5 years were included. The following acute phase reactants were determined: C-reactive protein, haptoglobin, alpha-2-macroglobulin, and apolipoprotein A-1; besides, an ultrasound was done to assess hepatic steatosis. Results. C-reactive protein levels increased in all patients. Patients with metabolic syndrome also had high levels of apolipoprotein A-1 and haptoglobin. Patients with hepatic steatosis had a significant increase in alpha-2-macroglobulin in addition to high C-reactive protein.

Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects? / O Produto de Acumulação Lipídica está Associado a um Perfil Aterogênico de Lipoproteínas em Indivíduos Brasileiros?

Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.

Resumo Fundamento: O produto de acumulação lipídica (LAP), um instrumento simples e de baixo custo, é um novo biomarcador de acúmulo de gordura central e representa um marcador substituto potencial para o perfil aterogênico de lipoproteínas. No entanto, sua associação com subfrações de lipoproteínas ainda não foi descrita na literatura. Objetivo: Determinar se o LAP pode ser usado como um marcador de tamanho da lipoproteína de baixa densidade (LDL) e de alta densidade (HDL) em indivíduos brasileiros. Métodos: Este estudo transversal incluiu 351 pacientes de ambos os sexos e idade entre 30 e 74 anos. Dados clínicos e sociodemográficos e história familiar de doenças foram avaliados. O tamanho das lipoproteínas, e níveis de colesterol total (CT), lipoproteínas, apolipoproteína AI e B (APO AI/APO B), glicose, ácidos graxos não esterificados (AGNEs) e insulina, e índice de resistência insulínica (HOMA-IR) foram avaliados em amostras de sangue. O LAP foi calculado utilizando-se as fórmulas (circunferência da cintura (cm]-58) × (triglicerídeos[mmol/L]) para mulheres e (circunferência da cintura[cm]-65) × (triglicerídeos [mmol/L]) para homens. Associações entre LAP e parâmetros metabólicos foram testadas por tendência linear (modelo linear generalizado, GLM) antes e após ajustes por fatores de confusão (sexo, idade, tabagismo, uso de estatinas, fibratos e hipoglicemiantes) ao nível de significância de p < 0,05). Resultados: LAP apresentou uma associação positiva com CT, APO B, AGNEs, glicose, insulina, HOMA-IR, e uma associação negativa com HDL-C. Maior acúmulo de gordura central correlacionou-se com maior porcentagem de HDL intermediária e de partículas pequenas de LDL e HDL, e menor porcentagem de HDL grande. O tamanho da LDL também era reduzido em valores de LAP mais elevados. O impacto negativo do LAP foi mantido após ajuste para múltiplas variáveis. Conclusão: o LAP esteve fortemente associado com o perfil aterogênico de subfrações de lipoproteínas, independetemente dos fatores de confusão.

Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b

BACKGROUND/AIMS: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. METHODS: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). RESULTS: Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. CONCLUSIONS: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.

Postprandial Lipid Concentrations and Daytime Biological Variation of Lipids in a Healthy Chinese Population

BACKGROUND: Several latest guidelines and consensus statements from Europe and the United States specify that there is no need for fasting prior to routine lipid tests. However, the latest Chinese guidelines still recommend fasting tests owing to a lack of local evidence. This study aimed to investigate postprandial lipid concentrations and daytime biological variation of lipids in a healthy Chinese population. METHODS: Venous blood samples were collected from 41 ostensibly healthy Chinese volunteers at five time points during the day (06:30, 09:00, 12:00, 15:00, and 18:30). The same batch of reagents was used to determine lipid concentrations. A nested ANOVA was performed to calculate within-subject biological variation (CVI) and between-subject biological variation (CVG). RESULTS: Postprandial concentrations of triglyceride were higher than fasting concentrations, with the maximum change occurring at 12:00 (0.5 hours after lunch, 0.21±0.65 mmol/L difference). The daytime biological variation of triglycerides was relatively high (CVI=25%, CVG=35.9%). The postprandial concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B were mostly lower than the fasting concentrations, and their daytime biological variations were relatively low (CVI=2.4–4.4%, CVG=11.8–18.7%). CONCLUSIONS: As most daytime lipid concentrations changed only slightly, non-fasting samples could be used for routine lipid tests. However, in cases of abnormal postprandial triglyceride concentrations, dietary factors and fasting time should be considered when interpreting the results.

Admission levels of high-density lipoprotein and apolipoprotein A-1 are associated with the neurologic outcome in patients with out-of-hospital cardiac arrest

OBJECTIVE: To investigate whether serum levels of high-density lipoprotein (HDL) and apolipoprotein A-1 (ApoA1), after the return of spontaneous circulation, can predict the neurologic outcome in patients with out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective observational study conducted in a single tertiary hospital intensive care unit. All adult OHCA survivors with admission lipid profiles were enrolled from March 2013 to December 2015. Good neurologic outcome was defined as discharge cerebral performance categories 1 and 2. RESULTS: Among 59 patients enrolled, 13 (22.0%) had a good neurologic outcome. Serum levels of HDL (56.7 vs. 40 mg/dL) and ApoA1 (117 vs. 91.6 mg/dL) were significantly higher in patients with a good outcome. Areas under the HDL and ApoA1 receiver operating curves to predict good outcomes were 0.799 and 0.759, respectively. The proportion of good outcome was significantly higher in patients in higher tertiles of HDL and ApoA1 (test for trend, both P=0.003). HDL (P=0.018) was an independent predictor in the multivariate logistic regression model. CONCLUSION: Admission levels of HDL and ApoA1 are associated with neurologic outcome in patients with OHCA. Prognostic and potential therapeutic values of HDL and ApoA1 merit further evaluation in the post-cardiac arrest state, as in other systemic inflammatory conditions such as sepsis.

Changes in Insulin Sensitivity and Lipid Profile in Renal Transplant Recipients Converted from Cyclosporine or Standard Release Tacrolimus to Once-Daily Prolonged Release Tacrolimus / 대한이식학회지

BACKGROUND: Tacrolimus (Tac) can cause impaired insulin release and dyslipidemia, and may affect the development of post-transplant diabetes mellitus. However, these effects on insulin sensitivity and lipid profile have not been compared in renal transplant recipients receiving traditional twice-daily tacrolimus (TacBID) or cyclosporine and those receiving once-daily prolonged release formulation of tacrolimus (TacOD). METHODS: We conducted an observational prospective study of 15 stable non-diabetic renal transplant recipients to observe the changes in insulin sensitivity and lipid profiles for 1 year at a tertiary hospital. We evaluated the levels of hemoglobin A1c, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, apolipoprotein A1, apolipoprotein B, serum creatinine, fasting plasma glucose, fasting insulin, homeostatic model assessment of β-cell (HOMA-β) and HOMA-insulin resistance index at baseline and at 2 and 4 months. To analyze differences in parameters, we conducted a Wilcoxon rank sum test and general linear model (GLM)-repeated measures analysis of variance (ANOVA) in both groups (cyclosporine to TacOD conversion group/TacBID to TacOD conversion group). RESULTS: At baseline, parameters did not differ between groups. GLM-repeated measures ANOVA revealed no change in insulin sensitivity or lipid profile after conversion at baseline or at 2 and 4 months. There were no complications after conversion from standard TacBID or cyclosporine to TacOD. CONCLUSIONS: There was no change in insulin sensitivity or lipid profile in renal transplant recipients. Any conversion from TacBID to TacOD should be performed in a controlled manner under close surveillance.

Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To screen and identify serum biomarkers for childhood hepatoblastoma (HB).</p><p><b>METHODS</b>The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins.</p><p><b>RESULTS</b>After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group.</p><p><b>CONCLUSIONS</b>Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.</p>

Role of Apo-lipoprotein A1 as cardiac biomarker for severity of coronary atherosclerosis

Objective: Coronary heart disease [CAD] is the most prevalent chronic disease and the main leading cause of death in the world, with more than half a million newly diagnosed CAD patients each year. The development of atherosclerosis involves the interaction of multiple metabolic and cellular processes. Central to this are disorders of lipoprotein metabolism. Apolipoprotein A-I is the major protein component of high-density lipoprotein [HDL] in plasma. Chylomicrons secreted from the intestinal enterocyte also contain Apo A-I, but it is quickly transferred to HDL in the blood stream. The aim of this study is to determine if Apo-A1 can be used as indicator to severity and extent of CAD

Methods: This study was conducted in cardiac catheterisation unit at Al Hussein Medical city from November 2014 to September 2015. It included 76 patients [49 males and 27 females] who presented with signs and symptoms of CAD and have undergone angiography. Control group consisted of 20 healthy subjects [14 males and 6 females] matched for age and BMI. Serum levels of Apo-A1 were measured in both groups. After coronary angiography was done for all patients, the extent and severity of CAD was correlated with serum levels of Apo-A1. The extent of CAD was determined by angiography, according to number of coronary arteries involved and degree of narrowing in coronary artery diameter

Results: The angiographic finding in patient group was normal in 22 patients [28.9%], single vessel involvement in 15 patients [19.7%], two vessels disease in 15 patients [19.7%] and three vessels disease in 18 patients [23.8%]. The left main stem disease [LMD] was found in 6 patients [7.9%]. There was no significant difference in the serum level of Apo-A1 between patient with CAD and control group [P = 0.147]. There was no significant correlation between serum level of Apo-A1 and the extent CAD [r = 0.004, P = 0.975]

Conclusion: There was no significant difference in serum level of Apo-A1 between the patients group and the control group. Also, there was no significant correlation between serum level of Apo-A1 and the extent of CAD

Apolipoproteins as Differentiating and Predictive Markers for Assessing Clinical Outcomes in Patients with Small Cell Lung Cancer

PURPOSE: The present study aimed to investigate the value of apolipoproteins, including ApoA-1, ApoC-III, and ApoE, in patients with small cell lung cancer (SCLC) as potential biomarkers for diagnosis, prognosis, and cancer progression. MATERIALS AND METHODS: Lung samples were collected from 89 patients with SCLC. Nineteen lung samples from non-small cell lung cancer (NSCLC) patients and 12 normal lung tissues were used as controls. Expression profiles of ApoA-1, ApoC-III, and ApoE in different samples were examined using immunohistochemical methods, and the expression levels were correlated with cancer types, treatment, and outcomes using chi-square and Mann-Whitney tests. RESULTS: Expression of ApoA-1 and ApoC-III in SCLC was significantly different, compared with that in NSCLC and normal lung tissues, and was correlated with recurrence of SCLC. Patients undergoing neoadjuvant chemotherapy before surgery showed significantly reduced expression of ApoA-1 and increased expression of ApoC-III and ApoE. Nevertheless, the expression levels of ApoA-1, ApoC-III, and ApoE were not correlated with SCLC staging. CONCLUSION: ApoA-1 and ApoC-III may be used as differentiating and predictive markers for SCLC. ApoA-1, ApoC-III, and ApoE may be used to monitor the efficacy of chemotherapy.

Impaired Antioxidant Ability of HDL and More Oxidized LDL are associated with Male Patients with Atrial Fibrillation

OBJECTIVE: Atrial fibrillation (AF) is a common arrhythmia which is generally more prevalent in the elderly population. However, the new onset of AF is frequently found in young populations. In order to identify putative prognostic biomarkers for detection of young-onset AF, we purified and characterized lipoproteins in terms of oxidative and inflammatory properties. METHODS: Male patients with AF (46±7 years of age, n=19) were recruited. Their serum and individual lipoproteins were analyzed and compared with healthy controls (48±9 years of age, n=17). RESULTS: The patients with AF revealed hypertriglyceridemia, hyperuricemia with mild obesity, elevated levels of CRP, and a normal level of cholesterol. All lipoproteins from patients with AF demonstrated higher levels of TG and advanced glycated end products, and decreased particle size than controls. AF-LDL showed an increased extent of oxidation with increased atherogenic macrophage phagocytosis. AF-HDL showed impaired antioxidant ability and a lower level of apoA-I expression. CONCLUSION: These data suggest that lipoprotein properties are severely modified in young AF patients, which were correlated with increased oxidation and inflammation.

Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1-induced EMT in experimental lung fibrosis and clarify its mechanism of action. METHODS: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. RESULTS: TGF-β1-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1-induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1-induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. CONCLUSION: Our data demonstrate that ApoA1 inhibits TGF-β1-induced EMT in experimental lung fibrosis.

Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Association between peroxisome proliferator-activated receptor and gene-gene interactions with the apolipoprotein A I/apolipoprotein B100 ratio / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARα, β, γ) with apolipoprotein A I/apolipoprotein B100 (ApoA I/ApoB100) ratio and the additional role of a gene-gene interactions among the 10 SNPs.</p><p><b>METHODS</b>Participants were recruited under the framework of the Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province (PMMJS) cohort population survey in the urban community of Jiangsu province of China.A total of 630 subjects were randomly selected and no individual was related.Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806 and rs4684847) were selected from the HapMap database,which covered PPARα, PPARβ and PPARγ. A linear regression model was used to analyze the relations between ten SNPs in the PPARs and ApoA I/ApoB100 ratio level. Mean difference and 95% CI were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction (GMDR).</p><p><b>RESULTS</b>After adjusting for age, gender, smoking status, alcohol consumption, occupational physical activity, high-fat diet as well as low-fiber diet, both rs1800206 and rs3856806 were significantly associated with a decreased level of ApoA I/ApoB100 ratio, mean difference (95% CI) values were -1.19 (-1.88 to -0.50) and -0.77 (-1.40 to -0.14). Whereas rs4253778 was significantly associated with an increased level of ApoA I/ApoB100 ratio, Mean difference (95% CI) values was 0.80 (0.08 to 1.52). GMDR analysis showed a significant gene-gene interaction among rs4253778, rs1800206 of PPARα, rs9794, rs2016520 of PPARβ and rs10865710, rs3856806, rs709158, rs1805192 of PPARγ for eight-dimension models (P = 0.01), in which prediction accuracy was 0.624 and cross-validation consistency was 7/10.</p><p><b>CONCLUSIONS</b>The rs1800206 of PPARα and rs3856806 of PPARγ are significantly associated with a decreased level of ApoA I/ApoB100 ratio while rs4253778 of PPARα is associated with an increased level of ApoA I/ApoB100 ratio. There is a gene-gene interaction between multiple SNPs.</p>

Total cholesterol mediates the effect of ABO blood group on coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To find a potential link among ABO blood group, lipid profiles and coronary artery disease (CAD) and to estimate the effect size of connection using mediation analysis model.</p><p><b>METHODS</b>A total of 898 consecutive patients undergoing coronary angiography were enrolled, and divided into CAD group and non-CAD group according to angiographic findings. According to ABO blood group, patients were divided into O blood group and non-O blood group, as well as A blood group and non-A blood group. Baseline characteristics among various groups were compared and the association of ABO blood group, CAD and lipid profile was explored.</p><p><b>RESULTS</b>Subjects of blood type A had higher concentration of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) compared with that of non-A type (TC: (4.43 ± 1.12) mmol/L vs. (4.18 ± 1.09) mmol/L, LDL-C: (2.79 ± 0.99) mmo/L vs. (2.59 ± 1.01) mmol/L, all P < 0.01). TC and LDL-C were significantly higher while high density lipoprotein cholesterol (HDL-C) and ApoA I levels were significantly lower in CAD group than in non-CAD group (TC: (4.36 ± 1.05) mmol/L vs. (4.13 ± 1.16) mmol/L, LDL-C: (2.61 ± 0.87) mmol/L vs. (2.47 ± 0.94) mmol/L; ApoA I: (1.38 ± 0.29) mmol/L vs. (1.45 ± 0.33) mmol/L; all P < 0.01). After adjustment for traditional cardiovascular risk factors, blood group A and TC remained significantly associated with the risk of CAD (OR = 1.88, 95% CI 1.280-2.774, P < 0.01; OR = 1.03, 95% CI 1.018-1.033, P < 0.01, respectively). Specially, mediation analysis indicated that 10.5% of the effect of A blood group on CAD was mediated by TC levels (P < 0.01).</p><p><b>CONCLUSION</b>Our data indicate that there is an association between ABO blood group, TC levels and risk of CAD. Around 10.5% of the effect of A blood group on CAD is mediated by TC levels.</p>

Diagnostic value of FibroTest for liver fibrosis in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the diagnostic value of FibroTest (FT) for liver fibrosis in patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>One hundred and forty-two patients with CHB were tested for the following five indicators: alpha2-microglobulin (a2-MG), haptoglobin (Hp), gamma-glutarnyl peptidase (GGT), total bilirubin (TBIL), and apolipoprotein A1 (ApoA1). The resultant data, along with the age and sex of the patients, were put into an algorithm to compute the final results of the FT. During the same period of FT, all of the CHB patients underwent liver stiffness measurement by FibroScan (FS) as well as liver biopsy. Considering the liver biopsy as the gold standard, we determined receiver operating characteristic (ROC) curves at different endpoints. Calculation of the area under the ROC curves (AUROC) was performed to evaluate the diagnostic importance of FT, FS towards the treatment of liver fibrosis in patients with CHB.</p><p><b>RESULTS</b>Significant fibrosis (Scheuer score (S) more than or equal to 2) was predicted with an AUROC for FS, FT of 0.827 (0.753-0.900), 0.897 (0.844-0.949). Significant fibrosis (S more than or equal to 3) was predicted with an AUROC for FS, FT of 0.883 (0.818-0.949), 0.968 (0.932-1.00). Significant fibrosis (S=4) was predicted with an AUROC for FS, FT of 0.943 (0.893-0.993), 0.991 (0.973-1.00).</p><p><b>CONCLUSION</b>s FT is a novel tool that can be used to assess the degree of fibrosis in patients with CHB.</p>