CETP gene polymorphisms and haplotypes are explanatory variables for HDL cholesterol level in sickle cell disease

Variations in lipid profile have been observed in sickle cell disease (SCD) and understanding their relationship with disease severity is crucial. This study aimed to investigate the association of polymorphisms of the CETP gene and laboratory markers of disease severity with lipid profile in a pediatric population with SCD. Biochemical and anthropometric analyses and CETP and alpha-thalassemia genotyping were performed. The study included 133 children and adolescents with sickle cell anemia (SCA) or hemoglobin SC disease (SCC), in steady-state. The SCA and no hydroxyurea (no HU) groups had higher values of ApoB, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) compared to the SCC and HU groups. However, there were no significant differences in ApoA1 and HDL-C levels between the groups based on genotype. Furthermore, the groups with altered levels of ApoA1, HDL-C, and the triglyceride/HDL ratio exhibited lower hemoglobin (Hb) levels and higher white blood cell counts. Hb level was associated to HDL-C levels. Analysis of CETP gene variants showed that the minor alleles of rs3764261 (C>A), rs247616 (C>T), and rs183130 (C>T), as well as the TTA haplotype, are explanatory variables for HDL-C levels. These findings suggested that dyslipidemia in SCD, specifically related to HDL-C levels, may be influenced by individual genetic background. Additionally, further investigation is needed to determine if clinical manifestations are impacted by CETP gene variants.

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

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

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

Interferencia generada por la lipemia en la medición de constituyentes bioquímicos

Introducción. La turbidez por lipemia en las muestras para diagnóstico es una de las principales causas de la aparición de sesgos clínicamente significativos en la medición de magnitudes bioquímicas. Objetivo. Valorar la interferencia por lipemia en la medición de 25 constituyentes bioquímicos en dos analizadores con tecnología de química seca (Vitros 7600®) y química liquida (Atellica® Solution). Métodos. Estudio pre-experimental con pre y posprueba. Se añadieron cantidades crecientes de una emulsión lipídica de nutrición parenteral a siete alícuotas de una mezcla de sueros y se determinó por duplicado la influencia del interferente en 25 constituyentes. Se calculó el porcentaje relativo de desviación de la concentración del constituyente por influencia de la turbidez con respecto a una muestra sin interferente. Se establecieron límites de tolerancia para la interferencia utilizando tres criterios: del distribuidor de reactivos, del error sistemático deseable y del error máximo admisible. Resultados. Los constituyentes que presentaron los mayores sesgos para el analizador de química liquida fueron: fósforo (-84,72%), ALT (+81,25%) y AST (-75,76%), mientras que para la plataforma de química seca los constituyentes: ALT (-79,41%), CK (-28,92%) y lipasa (+24,85%). Se detectó interferencia significativa en diferente número de los constituyentes de acuerdo con el criterio de límite tolerable utilizado. Conclusiones. Los distintos resultados encontrados según la metodología y el analizador utilizado, además de la falta de replicabilidad de los ensayos para la valoración de interferencia por lipemia, origina la necesidad de armonizar los procesos e instaurar límites idénticos de interferencia tolerables entre los laboratorios y proveedores de insumos.

Introduction. Turbidity due to lipemia in diagnostic samples is one of the main causes of the appearance of clinically significant biases in the measurement of biochemical magnitudes. Objective. To assess the interference by lipemia in the measurement of 25 biochemical constituents in two analyzers with dry chemistry technology (Vitros 7600®) and liquid chemistry (Atellica® Solution). Methods. Pre-experimental study with pre and post test. Increasing amounts of a parenteral nutrition lipid emulsion were added to seven aliquots of pooled sera and the influence of the interferent on 25 constituents was determined in duplicate. The relative percentage deviation of the concentration of the constituent due to the influence of turbidity with respect to a sample without interference, was calculated. Tolerance limits for interference were established using three criteria: reagent distributor, desirable systematic error, and maximum permissible error. Results. The constituents that presented the greatest biases for the liquid chemistry analyzer were: Phosphorus (-84.72%), ALT (+81.25%) and AST (-75.76%), while for the dry chemistry platform the constituents, ALT (-79.41%), CK (-28.92%) and lipase (+24.85%). Significant interference was detected in a different number of constituents according to the tolerable limit criteria used. Conclusions. The different results found according to the methodology and the analyzer used, in addition to the lack of replicability of the tests for the evaluation of interference by lipemia, originates the need to harmonize the processes and establish identical limits of tolerable interference between the laboratories and suppliers of inputs.

Association between human peripheral blood lipid levels and inflammatory indicators in patients with primary open angle glaucoma / 中华实验眼科杂志

Objective:To investigate the association between serum lipid levels and inflammatory indicators in patients with primary open angle glaucoma (POAG).Methods:A case-control study was conducted.A total of 86 POAG subjects were collected as a POAG group at Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong from January 2016 to March 2022.Meanwhile, 86 with age-related cataract only, matched at age, sex and body mass index were collected as a control group.The intraocular pressure (IOP) and the mean defect of visual field (MD) were measured by Goldmann tonometer and Humphrey field analyzer, respectively.Human peripheral blood samples collected from subjects for serum lipid levels, including total cholesterol, total triglycerides, high density lipoprotein (HDL), and low density lipoprotein (LDL), were analyzed using an automated hematology analyzer and inflammatory markers including C-reactive protein, white blood cells (WBC), neutrophils, lymphocytes, monocytes, were analyzed using an automated biochemical analyzer.Indicators with statistically significant differences between the two groups were selected as independent variables, and multiple logistic regression analysis was used to determine the risk factors for POAG.Correlations between risk factors and ocular parameters (IOP and MD) were assessed using Pearson correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong (No.EC20210313[2]-P03). Written informed consent was obtained from each patient before any medical examination.Results:The HDL was (1.59±0.42)mmol/L in the POAG group, which was significantly lower than (1.76±0.50)mmol/L in the control group ( t=2.435, P=0.016). The LDL was (3.34±0.66)mmol/L in the POAG group, which was significantly higher than (3.08±0.71)mmol/L in the control group ( t=2.520, P=0.013). The WBC was (6.91±1.60)×10 9/L in the POAG group, which was significantly higher than (6.11±1.29)×10 9/L in the control group ( t=3.619, P<0.001). Multiple logistic regression analysis showed that high serum LDL level ( P=0.039, OR=2.354, 95% CI: 1.105-5.303) and high WBC level ( P=0.044, OR=1.310, 95% CI: 1.007-1.703) were risk factors for POAG.Pearson correlation analysis showed that the serum LDL and WBC levels of POAG patients were moderately positively associated with IOP ( r=0.610, P<0.001; r=0.358, P=0.001). LDL level was moderately negatively associated with MD ( r=-0.496, P<0.001). WBC level was weakly negatively associated with MD ( r=-0.235, P=0.030). Conclusions:The elevated peripheral blood LDL and WBC levels are risk factors for POAG onset.The elevated LDL and WBC levels are positively correlated with IOP and negatively correlated with MD in POAG patients.

Investigação da Relação entre Índice de Triglicerídeos-Glicose e Fluxo Lento Coronariano: Um Estudo Retrospectivo de Caso-Controle / Investigation of the Relationship Between Triglycerides-Glucose İndex and Coronary Slow Flow: A Retrospective Case-Control Study

Resumo Fundamento O fluxo lento coronariano (FLC) refere-se à opacificação retardada dos vasos distais na ausência de estenose da artéria coronária epicárdica. O mecanismo etiopatogênico do FLC ainda não está claro. Objetivos Este estudo investiga a relação entre o FLC e o índice de triglicerídeos-glicose (TyG). Métodos A amostra do estudo consistiu de 118 pacientes com FLC e 105 pacientes com fluxo coronariano normal (FCN). A taxa de fluxo coronariano foi medida por medio do método de contagem de quadros (TFC) Thrombolysis in Myocardial Infarction (TIMI) em todos os pacientes. O índice TyG foi calculado como o logaritmo do valor [triglicerídeos em jejum (mg/dL)×glicose em jejum (mg/dL)]/2. Adotou-se como estatisticamente significativo o nível de significância < 0,05. Resultados O índice TyG, lipoproteína de baixa densidade (LDL), índice de massa corporal (IMC), relação neutrófilo-linfócito (RNL) e valores de TFC, proporção masculina e proporção de fumantes foram maiores, enquanto os níveis de lipoproteína de alta densidade (HDL) foram significativamente menores no grupo FLC em comparação com o grupo FNC (p<0,05). A análise de correlação revelou que o FLC estava significativamente correlacionado com os valores do índice TyG, IMC, RNL e HDL. A mais forte dessas correlações foi entre o FLC e o índice TyG (r= 0,57, p<0,001). Além disso, a análise multivariada revelou que o índice TyG, IMC, razão RNL e sexo masculino foram preditores independentes para FLC (p<0,05). A análise da curva ROC (Receiver Operating Characteristic) indicou que um valor de corte ≥ 9,28 para o índice TyG previu FLC com sensibilidade de 78% e especificidade de 78,1% [Área sob a curva (AUC): 0,868 e 95% intervalo de confiança (IC): 0,823-0,914]. Conclusão Os achados deste estudo revelaram uma relação muito forte entre o FLC e o índice TyG.

Abstract Background Coronary slow flow (CSF) refers to delayed distal vessel opacification in the absence of epicardial coronary artery stenosis. The etiopathogenic mechanism of CSF is still unclear. Objectives This study investigates the relationship between CSF and the triglyceride-glucose (TyG) index. Methods The study sample consisted of 118 CSF patients and 105 patients with normal coronary flow (NCF). The coronary flow rate was measured via the Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) method in all patients. The TyG index was calculated as the logarithm of the [fasting triglyceride (mg/dL)×fasting glucose (mg/dL)]/2 value. A significance level of < 0.05 was adopted as statistically significant. Results The TyG index, low-density lipoprotein (LDL), body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR) and TFC values, male ratio, and the ratio of smokers were higher, whereas high-density lipoprotein (HDL) levels were significantly lower in the CSF group compared to the NCF group (p<0,05). The correlation analysis revealed that CSF was significantly correlated with TyG index, BMI, NLR, and HDL values. The strongest of these correlations was between CSF and TyG index (r= 0.57, p<0.001). Additionally, the multivariate analysis revealed that TyG index, BMI, NLR ratio, and male gender were independent predictors for CSF (p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that a cut-off value of ≥ 9.28 for the TyG index predicted CSF with a sensitivity of 78% and a specificity of 78.1% [Area under the curve (AUC): 0.868 and 95% Confidence Interval (CI): 0.823-0.914]. Conclusion The findings of this study revealed a very strong relationship between CSF and TyG index.

Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais / Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications

Resumo Fundamento Embora os ácidos graxos poli-insaturados ômega-3 e ômega-6 (AGPIs n-3 e n-6) tenham efeitos bem conhecidos sobre os fatores de risco de doenças cardiovasculares (DCV), ainda existe um conhecimento limitado sobre como eles afetam os indicadores de qualidade da LDL. Objetivo Avaliar as associações dos AGPIs n-3 e n-6 de hemácias com o tamanho da partícula da LDL, LDL-c pequena e densa (sdLDL-c) e com LDL eletronegativa [LDL(-)] em adultos com fatores de risco para DCV. Métodos Estudo transversal com 335 homens e mulheres de 30 a 74 anos com, pelo menos, um fator de risco cardiovascular. Foram realizadas análises de parâmetros bioquímicos, como glicose, insulina, HbA1c, proteína C reativa (PCR), perfil lipídico, subfrações de lipoproteínas, partícula eletronegativa de LDL [LDL(-)] e seu autoanticorpo, e os AGPIs n-3 e n- 6 de hemácias. Os testes t independente/teste de Mann-Whitney, ANOVA unidirecional/teste de Kruskal-Wallis e regressões lineares múltiplas foram aplicados. Todos os testes foram bilaterais e um valor de p inferior a 0,05 foi considerado estatisticamente significativo. Resultados A relação n-6/n-3 de hemácias foi associada ao aumento dos níveis de LDL(-) (β = 4,064; IC de 95% = 1,381 - 6,748) e sdLDL-c (β = 1,905; IC de 95% = 0,863 - 2,947), e redução do tamanho das partículas de LDL (β = -1,032; IC de 95% = -1,585 − -0,478). Individualmente, os AGPIs n-6 e n-3 apresentaram associações opostas com esses parâmetros, realçando os efeitos protetores do n-3 e evidenciando os possíveis efeitos adversos do n-6 na qualidade das partículas de LDL. Conclusão O AGPI n-6, presente nas hemácias, foi associado ao aumento do risco cardiometabólico e à aterogenicidade das partículas de LDL, enquanto o AGPI n-3 foi associado a melhores parâmetros cardiometabólicos e à qualidade das partículas de LDL.

Abstract Background While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. Objective To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. Methods Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. Results The RBC n-6/n-3 ratio was associated with increased LDL(-) (β = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (β = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (β = -1.032; 95% CI = -1.585 − -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. Conclusion RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

Is there a difference between aortic and brachial vein blood lipoprotein and total cholesterol levels?

SUMMARY OBJECTIVE: Atherosclerosis is a disease of the arteries that is not practically observed in veins. There are a lot of proposed mechanisms underlying this phenomenon. We aimed to compare the lipoprotein and total cholesterol levels in aortic and venous blood samples. METHODS: A total of 125 patients ≥18 years of age were included in the study. After overnight fasting, we drew blood from the proximal ascending aorta and brachial vein. Serum lipid profiles were compared between these samples. RESULTS: Out of 125 patients, 45 (36%) were females, and 80 (64%) were males. The mean age of the patients was 62 years (24-85 years). Notably, 39 (31%) patients were using statin treatment. Coronary angiography showed that 103 (82%) patients had coronary artery disease. Mean arterial total cholesterol (low-density lipoprotein), high-density lipoprotein, and triglyceride levels were significantly lower than mean venous total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels (187.3±45.3 mg/dL vs. 204.5±52.6 mg/dL, p<0.001; 116.7±41.5 mg/dL vs. 128±45 mg/dL, p<0.001; 40.8±12.9 mg/dL vs. 45.3±13.3 mg/dL, p<0.001; and 142.8±81.5 vs. 161.5±100.3 mg/dL, p<0.001, respectively). CONCLUSION: Aortic lipoprotein and total cholesterol levels are significantly lower than venous lipoprotein and total cholesterol levels in patients presenting to the hospital for coronary angiography.

Value of blood lipid parameters in predicting the progression of HBV-related acute-on-chronic pre-liver failure / 临床肝胆病杂志

Objective To investigate the difference in blood lipid parameters between acute-on-chronic pre-liver failure (pre-ACLF) and acute-on-chronic liver failure (ACLF) and the risk factors for disease progression. Methods A retrospective analysis was performed for the related data of 118 patients with ACLF (ACLF group) and 44 patients with pre-ACLF (pre-ACLF group) who were treated in The General Hospital of Western Theater Command from January 2012 to December 2020, including baseline age, albumin, creatinine, routine blood test results, and blood lipids. The independent samples t -test was used for comparison between normally distributed continuous data; and the Mann-Whitney U test was used for comparison between non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used for multivariate analysis to identify independent predictive factors. The receiver operating characteristic (ROC) curve was used to compare the sensitivity and specificity of related indicators, and Youden index was used to calculate cut-off values. Results Compared with the pre-ACLF group, the ACLF group had significantly lower levels of total cholesterol (TC)[2.02(1.56-2.37) mmol/L vs 3.01(2.57-3.66) mmol/L, Z =5.411, P 0.05). The logistic regression analysis showed that TC (odds ratio [ OR ]=0.003, 95% confidence interval [ CI ]: 0.000-0.068, P < 0.05), LDL ( OR =61.901, 95% CI : 3.354-1142.558, P < 0.05), and WBC ( OR =3.175, 95% CI : 1.097-9.185, P < 0.05) had an independent predictive value, and the ROC analysis showed that the area under the ROC curve of TC was 0.852, the sensitivity of LDL was 0.887, and TC had the best specificity of TC was 0.840. Conclusion There are reductions in blood lipid parameters in the progression from pre-ACLF to ACLF, suggesting that clinicians should pay attention to the changes in lipids in the pre-ACLF stage and adjust the nutritional regimen in a timely manner.

Association between serum high-density lipoprotein subtype 3 cholesterol levels and coronary artery diseases severity and in-stent restenosis / 中华检验医学杂志

Objective:To explore the association between serum high density lipoprotein subtype 3 cholesterol (HDL3-C) levels and the severity and in-stent restenosis of patients with coronary artery disease.Methods:124 patients with coronary artery diseases and 62 healthy controls were included in this clinical case-control retrospective study. Participants were hospitalized from November 2020 to November 2021 at Jinling Hospital, Medical School of Nanjing University were enrolled. Patients with coronary artery disease were as follows: 28 patients with acute coronary syndrome and 96 patients with stable coronary heart disease. Serum HDL3-C levels as well as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were determined. According to the coronary artery angiography results of all patients at the time of admission, Gensini scores were calculated and patients were divided into in-stent restenosis group ( n=22), no in-stent stenosis group ( n=23) and non-stent implantation group ( n=79). The correlation between HDL3-C levels and other parameters was analyzed by Pearson or Spearman correlation analyses. Multivariate Logistic regression analyses were used to determine the impact of HDL3-C on the in-stent restenosis of coronary artery diseases. Results:Compared with controls, serum levels of HDL3-C and HDL-C were significantly decreased in patients with coronary artery diseases (all P<0.05). There was a significantly negative correlation between HDL3-C levels and Gensini scores ( r=-0.201, P=0.043). Among patients with coronary artery disease, serum levels of HDL3C, TC and TG in the in-stent restenosis group were significantly lower than in no in-stent stenosis group as well as than in the non-stent implantation group (all P<0.05). Multivariate Logistic regression analyses showed that after adjusting for age, sex, lipid-lowering drugs and TC, TG, LDLC parameters, HDL3-C ( OR=0.885, 95% CI 0.791-0.990, P=0.033) and HDL-C ( OR=0.018, 95% CI 0.001-0.426, P=0.013) levels were both independently associated with the occurrence of coronary artery disease; only HDL3-C levels (no in-stent stenosis group as the reference: OR=0.833, 95% CI 0.698-0.994, P=0.042; non-stent implantation group as the reference: OR=0.812, 95% CI 0.685-0.963, P=0.017) were independently associated with the presence of in-stent restenosis ( P<0.05). Conclusions:Serum HDL3-C levels are decreased in patients with coronary artery disease, especially in patients with in-stent restenosis. HDL3-C levels are associated with the severity of coronary artery lesions and the presence of in-stent restenosis of coronary arteries.

Clinical significance of blood lipids, lipoproteins, PTX-3, TTF-1, NSE, and CYFRA21-1 levels in patients with advanced gastric cancer / 中国医师杂志

Objective:To investigate the significance of blood lipids [triglyceride (TG), total cholesterol (TC)], lipoproteins [high-density lipoprotein (HDL), low-density lipoprotein (LDL)], and serum levels of pentraxin-3 (PTX-3), thyroid transcription factor-1 (TTF-1), neuron specific enolase (NSE), and human cytokeratin 21-1 fragment (CYFRA21-1) in patients with advanced gastric cancer, and to provide a basis for the early, middle, and late diagnosis and treatment of gastric cancer.Methods:127 gastric cancer patients admitted to 3201 Hospital from January 2019 to January 2022 were selected as the research subjects. They were divided into early stage group ( n=45), mild stage group ( n=43), and late stage group ( n=39) based on their condition. Enzyme linked immunosorbent assay (ELISA) was used to detect blood lipids (TG, TC), PTX-3, TTF-1, NSE, CYFRA21-1, and chemical precipitation method was used to detect lipoprotein metabolism (HDL, LDL) in the three groups of patients. The differences in blood lipids, lipoproteins, PTX-3, TTF-1, NSE, and CYFRA21-1 between three groups of gastric cancer patients and the late stage group of gastric cancer patients before and after surgery were analyzed. Logistic regression analysis was conducted to investigate the correlation between blood lipids (TG, TC), lipoprotein (HDL, LDL), PTX-3, TTF-1, NSE, CYFRA21-1, and gastric cancer incidence. The predictive value of individual and combined detection of the above indicators for gastric cancer was analyzed using the receiver operating characteristic (ROC) curve analysis. Results:The results showed that the TG, TC, and LDL levels in the late stage group were higher than those in the mild stage and early stage groups (all P<0.05), while the HDL levels were lower than those in the mild stage and early stage groups (all P<0.05). The serum levels of PTX-3, TTF-1, NSE, and CYFRA21-1 were higher than those in the mild stage and early stage groups (all P<0.05). The postoperative levels of TG, PTX-3, TTF-1, NSE, CYFRA21-1, TC, and LDL in the late stage group were significantly lower than those before surgery (all P<0.05) and the HDL level was higher than that before surgery ( P<0.05). The levels of TG, TC, HDL, LDL, PTX-3, TTF-1, NSE, and CYFRA21-1 were correlated with the late onset of gastric cancer (all P<0.05). The ROC curve showed that the area under the ROC curve (AUC) of PTX-3, TTF-1, NSE, and CYFRA21-1 combined detection was significantly higher than that of PTX3, TTF1, NSE, and CYFRA211 alone. Among them, PTX-3+ TTF-1+ NSE+ CYFRA21-1 combined detection had the highest AUC, sensitivity, and specificity. Conclusions:Patients with advanced gastric cancer have abnormal levels of blood lipids (TG, TC), lipoprotein (HDL, LDL), and serum PTX-3, TTF-1, NSE, and CYFRA21-1. Effective intervention measures need to be developed based on the above indicators to improve survival rate.

Association of non-high-density lipoprotein cholesterol level with non-alcoholic fatty liver disease in patients with early-onset type 2 diabetes / 中国基层医药

Objective:To investigate the association of non-high-density lipoprotein cholesterol (non-HDL-C) level with non-alcoholic fatty liver disease (NAFLD) in patients with early-onset type 2 diabetes.Methods:The clinical data of 100 patients with early-onset type 2 diabetes who were admitted to Beijing Chaoyang Diabetes Hospital from June 2008 to June 2012 were retrospectively analyzed. These patients were divided into a NAFLD group and a non-NAFLD group, with 50 patients in each group, according to the presence or absence of NAFLD. Clinical data, biochemical indices [blood lipids, blood glucose, liver function, uric acid, high-sensitivity C-reactive protein], and glycosylated hemoglobin were collected. Body mass index and non-HDL-C levels were recorded. The association of non-HDL-C level with NAFLD in patients with early-onset type 2 diabetes was analyzed using logistic regression analysis. The predictive value and optimal cut-off point of non-HDL-C for early-onset T2 diabetes complicated by NAFLD were evaluated using the receiver operating characteristic curve.Results:Body mass index, waist-to-hip ratio, systolic blood pressure, and diastolic blood pressure in the NAFLD group were (28.55 ± 3.47) kg/m 2, (0.94 ± 0.05), (121.00 ± 10.25) mmHg (1 mmHg = 0.133 kPa), and (80.00 ± 8.51) mmHg respectively, which were significantly higher than (23.95 ± 2.87) kg/m 2, (0.90 ± 0.07), (115.20 ± 13.36) mmHg, and (73.70 ± 7.75) mmHg in the non-NAFLD group ( t = -7.23, -3.11, -2.44, -3.87, all P < 0.05). Non-HDL-C, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, uric acid, high-density lipoprotein cholesterol, and glycosylated hemoglobin levels in the NAFLD group were (4.88 ± 3.01) mmol/L, (6.33 ± 3.23) mmol/L, (4.50 ± 6.03) mmol/L, (3.27 ± 1.26) mmol/L, (39.80 ± 23.58) U/L, (27.72 ± 13.83) U/L, (52.96 ± 46.16) U/L, (350.32 ± 102.12) μmol/L, (1.26 ± 0.88) mg/L, and (9.3 ± 2.5)%, respectively, which were significantly higher than (3.35 ± 1.03) mmol/L, (4.81±1.24) mmol/L, (1.87 ± 2.29) mmol/L, (2.70 ± 0.71) mmol/L, (23.76 ± 13.45) U/L, (21.98 ± 10.13) U/L, (35.24 ± 35.41) U/L, (296.04 ± 88.26) μmol/L, (0.22 ± 1.54) mg/L, (8.2 ± 2.7)% in the non-NAFLD group ( t = -3.40, -3.11, -2.88, -2.81, -4.18, -2.36, -2.14, -2.85, -4.12, -2.08, all P < 0.05). Logistic regression analysis showed that the increase in non-HDL-C level was an independent risk factor for T2 diabetes mellitus complicated by NAFLD ( OR = 3.064, 95% CI: 1.604-5.852, P = 0.001). The receiver operating characteristic curve analysis results showed that the optimal cut-off point, sensitivity, and specificity of non-HDL-C level to predict NAFLD were 3.60 mmol/L, 0.700, and 0.620 respectively. Conclusion:An increase in non-HDL-C level is an independent risk factor for NAFLD complicated by early-onset type 2 diabetes When non-HDL-C is > 3.60 mmol/L, NAFLD can be predicted.

Lipoproteínas ricas en triglicéridos y riesgo cardiovascular residual / Triglyceride rich lipoproteins and residual cardiovascular risk / Lipoproteínas ricas em triglicerídeos e risco cardiovascular residual / Reconocimiento a la trayectoria del Prof. Dr. Juan Miguel Castagnino†

Resumen Una vasta evidencia científica de resultados de ensayos clínicos, preclínicos, epidemiológicos y genéticos, mostraron una asociación causal entre el aumento de triglicéridos (TG), lipoproteínas ricas en TG (LRT) y sus remanentes para la enfermedad cardiovascular aterosclerótica (ECA). La acumulación de LRT circulantes puede explicar, en parte, el riesgo cardiovascular residual que se observa en pacientes eficazmente tratados para reducir sus niveles de LDL; sin embargo, persiste el riesgo de ECA. Es imprescindible que en el estudio del perfil lipídico se considere la determinación o estimación de estas lipoproteínas, sumada a la medida de TG plasmáticos. El objetivo de la presente revisión fue actualizar el conocimiento acerca de los niveles incrementados de TG, de LRT y sus remanentes, brindar alternativas para su determinación y comprender los mecanismos que involucran a las LRT en el desarrollo acelerado de la aterosclerosis. La actualización de los diferentes parámetros asociados al aumento de TG y sus valores de corte o límites de decisión clínica según la clasificación del riesgo de ECA para cada paciente, permitirá el rediseño de un informe de resultados que será de gran utilidad para el médico y el paciente con respecto a las conductas preventivas y terapéuticas de la ECA.

Abstract Vast scientific evidence from clinical, preclinical, epidemiological, and genetic trial results show a causal association between increased triglycerides (TG), TG-rich lipoproteins (TRL), and their remnants for atherosclerotic cardiovascular disease (ASCVD). The accumulation of circulating LRT may explain, in part, the residual cardiovascular risk observed in patients successfully treated to reduce their LDL levels, however, the risk of ASCVD still persists. It is essential that in the assessment of the lipid profile, the determination or estimation of these lipoproteins be considered, added to the measurement of plasmatic TG. The objective of this review is to update the knowledge about the increased levels of TG, LRT and their remnants, proprovide alternatives for their determination and understand the mechanisms that involve LRT in the accelerated development of atherosclerosis. Updating the different parameters associated with increased TG and their cut-off values or clinical decision limits according to the ASCVD risk classification for each patient will allow for the redesign of a results report that will be very useful for the physician and the patient regarding the preventive and therapeutic behaviours of the ASCVD.

Resumo Vastas evidências científicas de resultados de ensaios clínicos, pré-clínicos, epidemiológicos e genéticos mostraram uma associação causal entre o aumento de triglicerídeos (TG), lipoproteínas ricas em TG (LRT) e seus remanescentes para doença cardiovascular aterosclerótica (DCA). O acúmulo de LRT circulante pode explicar, em parte, o risco cardiovascular residual observado em pacientes tratados de maneira eficaz para reduzir seus níveis de LDL, no entanto, o risco de DCA persiste. É fundamental que no estudo do perfil lipídico seja considerada a determinação ou estimativa dessas lipoproteínas, somada à dosagem de TG plasmáticos. O objetivo desta revisão foi atualizar o conhecimento sobre os níveis aumentados de TG, LRT e seus remanescentes, fornecer alternativas para sua determinação e compreender os mecanismos que envolvem as LRT no desenvolvimento acelerado da aterosclerose. A atualização dos diferentes parâmetros associados ao aumento de TG, e seus valores de corte ou limites de decisão clínica de acordo com a classificação do risco de DCE para cada paciente, permitirá o redesenho de um relatório de resultados que será muito útil para o médico e o paciente quanto às condutas preventivas e terapêuticas da DCE.

Associação Positiva entre Autoanticorpos contra LDL Oxidada e HDL-C: Um Novo Mecanismo para Cardioproteção de HDL? / Positive Association between Autoantibodies Against Oxidized LDL and HDL-C: A Novel Mechanism for HDL Cardioprotection?

Resumo Fundamento No microambiente da placa aterosclerótica, os fosfolipídios oxidados expressos na superfície de lipoproteína de baixa densidade oxidada (oxLDL) se ligam a receptores scavenger em macrófagos provocando a formação de células espumosas e a progressão da placa. Autoanticorpos contra oxLDL (oxLDL-Ab) interagem com epítopos oxidativos levando à formação de imunocomplexos que são incapazes de interagir com receptores de macrófagos, assim suprimindo a aterogênese. A liberação de oxLDL-Ab pelas células B envolve a resposta da interleucina 5 e Th2, que por sua vez são potencializadas pela HDL. Assim, levantamos a hipótese de que indivíduos com níveis mais altos de HDL-C podem apresentar níveis elevados de oxLDL-Ab. Objetivo Avaliar a relação entre os níveis de HDL-C e oxLDL-Ab. Métodos Indivíduos assintomáticos (n = 193) foram agrupados de acordo com sua concentração de HDL-C para uma das três categorias seguintes: baixa (< 68 mg/dL), intermediária (de 68 a 80 mg/dL) ou alta (> 80 mg/dL). Os valores p < 0,05 foram considerados estatisticamente significativos. Resultados Nossa análise incluiu 193 indivíduos (média etária: 47 anos; masculino: 26,3%). Em comparação com os indivíduos no menor tercil de HDL-C, os mais elevados foram mais velhos (36 versus 53 anos; p = 0,001) e, menos frequentemente, masculinos (42,6% versus 20,9%; p = 0,001). Os valores médios de oxLDL-Ab aumentaram à medida que o grupo HDL-C aumentou (0,31, 0,33 e 0,43 unidades, respectivamente; p = 0,001 para tendência). A regressão linear simples encontrou uma relação significativa e positiva entre a variável independente, HDL-C, e a variável dependente, oxLDL-Ab (R = 0,293; p = 0,009). Essa relação manteve-se significativa (R = 0,30; p = 0,044), após ajuste por covariáveis. Os níveis de apolipoproteína AI também estiveram relacionados a oxLDL-Ab nos modelos de regressão linear simples e ajustada. Conclusões HDL-C e oxLDL-Ab estão independentemente relacionados.

Abstract Background In the atherosclerotic plaque microenvironment, oxidized phospholipids expressed in the oxidized low-density lipoprotein (oxLDL) surface bind to scavenger receptors of macrophages eliciting foam cell formation and plaque progression. Auto-antibodies against oxLDL (oxLDL-Ab) interact with oxidative epitopes leading to the formation of immune complexes that are unable to interact with macrophage receptors, thus abrogating atherogenesis. Release of oxLDL-Ab by B cells involves interleukin 5 and Th2 response, which in turn are potentiated by HDL. Thereby, we hypothesized that individuals with higher levels of HDL-C may plausibly display elevated titers of oxLDL-Ab. Objective To evaluate the relationship between HDL-C and oxLDL-Ab levels. Methods Asymptomatic individuals (n = 193) were grouped according to their HDL-C concentration to one of three categories: low (< 68 mg/dL), intermediate (68 to 80 mg/dL) or high (> 80 mg/dL). P values < 0.05 were considered statistically significant. Results Our analysis included 193 individuals (mean age: 47 years; male: 26.3%). Compared to individuals in the lowest HDL-C tertile, those in the highest tertile were older (36 versus 53 years; p = 0.001) and less frequently male (42.6% versus 20.9%; p = 0.001). Mean values of oxLDL-Ab increased as the HDL-C group escalated (0.31, 0.33 and 0.43 units, respectively; p = 0.001 for trend). Simple linear regression found a significant, positive relationship between the independent variable, HDL-C, and the dependent variable, oxLDL-Ab (R = 0.293; p = 0.009). This relation remained significant (R = 0.30; p = 0.044), after adjustment by covariates. Apolipoprotein AI levels were also related to oxLDL-Ab in both simple and adjusted linear regression models. Conclusion HDL-C and oxLDL-Ab are independently related.

Effect of Shuddha Guggulu on Metabolic Syndrome - A Case Report

Metabolic syndrome is conglomeration of symptoms composed of impaired fasting glucose, abdominal obesity, hypertension and dyslipidemia. It is associated with cardio metabolic risk factors with increased risk of multiple chronic diseases, including cancer and cardiovascular disease because of the increased amount of visceral fat together with a chronic inflammatory state. Metabolic Syndrome is resulted by the causative factors which are Santarpanakaraka in nature leading to Medodushti, which in turn leads to Medoroga. The Santarpana karaka Nidanas include the food articles that are rich in Snigdhamsha, Madhura rasa, Guru and Pichchila gunas. By consuming the food rich in such qualities produces the Rasa dhatu which is excessively composed of the qualities like Ati Snehamsha and Madhuratara Guna which produces excess Medo dhatu and causes Sthoulya. Ama present in the Medodhatu leads to further Medo dushti and manifests Metabolic Syndrome. Shuddha Guggulu is potent Ama pachaka dravya and does Pachana of the circulating Atisnigdha Ama in the form of lipoproteins. And also Guggulu having Lekhaneeya Guna reduces deposition of Medo dhatu and prevents inflammatory process by its anti- inflammatory potential. Aim: To assess the effect of Shuddha Guggulu in Metabolic Syndrome, dyslipidaemia. Methodology: Oral administration of the preparation in the patient. Result: There was marked improvement in signs, symptoms and biochemical parameters after intervention. Conclusion: Shuddha Guggulu is significantly effective in reducing lipid levels and CRP

Relación de riesgo entre dislipidemia y COVID-19 / Risk relationship between dyslipemia and COVID-19

La presencia de dislipidemia en pacientes con la COVID-19 parece agravar el curso clínico de la enfermedad. En esta revisión bibliográfica se describen los principales mecanismos que las vinculan y sus implicaciones en el tratamiento de los pacientes afectados. Para realizar este trabajo se efectuó una búsqueda bibliográfica en bases de datos, tales como Google académico, SciELO, Annual Reviews y PMC. Los descriptores analizados fueron COVID-19, SARS-CoV-2, dislipidemia, LDL-colesterol, HDL-colesterol, triglicéridos, hipercolesterolemia y lipoproteínas VLDL. Se revisaron preferentemente artículos de revistas arbitradas por pares y disponibles a texto completo, publicados en inglés y español. A pesar de las controversias, la dislipidemia es un factor de riesgo de pronóstico desfavorable en afectados con la COVID-19 y el tratamiento para los pacientes con esa condición desfavorable mejora dicho pronóstico.

The presence of dyslipemia in patients with COVID-19 seems to increase the clinical course of the disease. In this literature review the main mechanisms that link them and their implications in the treatment of the affected patients are described. To carry out this work a literature search was made in databases, such as academic Google, SciELO, Annual Reviews and PMC. The analyzed describers were COVID-19, SARS-CoV-2, dyslipemia, LDL-cholesterol, HDL-cholesterol, triglycerides, hypercholesterolemia and VLDL lipoproteins. Articles of magazines arbitrated by pairs and available to complete text, published in English and Spanish were preferably revised. In spite of the controversies, dyslipemia is a risk factor of unfavorable prognosis in patients affected with COVID-19 and the treatment for the patients with that unfavourable condition improve this prognosis.

Comparação das Novas Equações de Martin/Hopkins e Sampson para o Cálculo do Colesterol de Lipoproteína de Baixa Densidade em Pacientes Diabéticos / Comparison of Novel Martin/Hopkins and Sampson Equations for Calculation of Low-Density Lipoprotein Cholesterol in Diabetic Patients

Resumo Fundamentos A determinação precisa do colesterol de lipoproteína de baixa densidade (LDL-C) é importante para se alcançar concentrações de LDL-C recomendadas por diretrizes e para reduzir resultados cardiovasculares adversos em pacientes diabéticos. A equação de Friedewald comumente usada (LDL-Cf) produz resultados imprecisos em pacientes diabéticos devido a dislipidemia diabética associada. Recentemente, duas novas equações - Martin/Hopkins (LDL-CMH) e Sampson (LDL-Cs) - foram desenvolvidas para melhorar a precisão da estimativa de LDL-C, mas os dados são insuficientes para sugerir a superioridade de uma equação sobre a outra. Objetivos O presente estudo comparou a precisão e a utilidade clínica das novas equações de Martin/Hopkins e Sampson em pacientes diabéticos. Método Foram incluídos no estudo quatrocentos e dois (402) pacientes com diabetes. O risco cardiovascular dos pacientes e as metas de LDL-C foram calculadas por diretrizes europeias. As concentrações de LDL-Cmh, LDL-Cs, e LDL-Cf calculadas foram comparadas à concentração de LDL-C direto (LDL-Cd) para testar a concordância entre essas equações e LDL-Cd. Um P valor <0,05 foi aceito como estatisticamente significativo. Resultados A LDL-CMH e a LDL-Cs tiveram concordância melhor com o LDL-Cd em comparação com a LDL-Cf, mas não houve diferenças estatísticas entre as novas equações para concordância com o LDL-Cd (Alfa de Cronbach de 0,955 para ambos, p=1). Da mesma forma, a LDL-CMH e a LDL-Cs tinham um grau semelhante de concordância com o LDL-Cd para determinar se o paciente estava dentro da meta de LDL-C (96,3% para LDL-Cmh e 96,0% para LDL-Cs), que eram ligeiramente melhores que a LDL-Cf (94,6%). Em pacientes com uma concentração de triglicérides >400 mg/dl, a concordância com o LDL-Cd foi ruim, independentemente do método usado. Conclusão As equações de Martin/Hopkins e Sampson mostram uma precisão similar para o cálculo de concentrações de LDL-C nos pacientes com diabetes, e ambas as equações são ligeiramente melhores que a equação de Friedewald.

Abstract Background The accurate determination of low-density lipoprotein cholesterol (LDL-C) is important to reach guideline-recommended LDL-C concentrations and to reduce adverse cardiovascular outcomes in diabetic patients. The commonly used Friedewald equation (LDL-Cf), gives inaccurate results in diabetic patients due to accompanying diabetic dyslipidemia. Recently two new equations - Martin/Hopkins (LDL-Cmh) and Sampson (LDL-Cs) - were developed to improve the accuracy of LDL-C estimation, but data are insufficient to suggest the superiority of one equation over the other one. Objective The present study compared the accuracy and clinical usefulness of novel Martin/Hopkins and Sampson equations in diabetic patients. Methods This study included 402 patients with diabetes. Patients' cardiovascular risk and LDL-C targets were calculated per European guidelines. Calculated LDL-Cmh, LDL-Cs, and LDL-Cf concentrations were compared with direct LDL-C concentration (LDL-Cd) to test agreement between these equations and LDL-Cd. A p-value <0.05 was accepted as statistically significant. Results Both LDL-Cmh and LDL-Cs had a better agreement with LDL-Cd as compared to LDL-Cf, but no statistical differences were found among novel equations for agreement with LDL-Cd (Cronbach's alpha 0.955 for both, p=1). Likewise, LDL-Cmh and LDL-Cs showed a similar degree of agreement with LDL-Cd in determining whether a patient was in a guideline-recommended LDL-C target (96.3% for LDL-Cmh and 96.0% for LDL-Cs), which were marginally better than LDL-Cf (94.6%). In patients with a triglyceride concentration >400 mg/dl, agreement with LDL-Cd was poor, regardless of the method used. Conclusion Martin/Hopkins and Sampson's equations show a similar accuracy for calculating LDL-C concentrations in patients with diabetes, and both equations were marginally better than the Friedewald equation.