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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.
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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.
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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.
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Objective:To explore the clinical value of peripheral remnant lipoproteins (RLP), low density lipoprotein cholesterol particle (LDL-P) and sdLDL particle (sdLDL-P) measurement in the diagnosis of carotid plaque, so as to provide practical basis for the accurate diagnosis of carotid plaque and the control of carotid plaque related cardiovascular and cerebrovascular diseases.Methods:People who underwent carotid plaque ultrasound examination in Xingtai Third Hospital , from January 2020 to June 2021 were selected as the research object. According to the ultrasound results, they were divided into carotid plaque group ( n=146) and control group without carotid plaque ( n=149). The fasting RLP, LDL-P and sdLDL-P of the two groups were measured by vertical auto profile (VAP) centrifugal separation phase, and the fasting TG and LDL-C were detected by routine mixed phase method. The indexes were compared between the two groups and the true positive rate, true negative rate, false positive rate and false negative rate of the diagnosis of carotid plaque were analyzed. The receiver operating characteristic curve of each test index was drawn, and AUC was used to evaluate the clinical diagnostic value of each test index for carotid plaque. Results:The levels of RLP, LDL-P and sdLDL-P in carotid plaque group were significantly higher than those in non-carotid plaque group ([1.07±0.36] mmol/L vs [0.59±0.17] mmol/L,[1 300±370] nmol/L vs [781±215] nmol/L,[435±139] nmol/L vs [156±59] nmol/L, all P<0.01). The true positive rate (78.08% [114/146],81.51% [119/146]) and true negative rate (84.56% [126/149], 86.58%[129/149]) of serum RLP and LDL-P for the diagnosis of carotid plaque were significantly higher than TG (58.90%[86/146], 43.62%[65/149]) and LDL-C (59.59% [87/146], 46.98% [70/149]), and the false positive rate (15.44% [23/149], 13.42% [20/149]) and false negative rate (21.92% [32/146], 18.49% [27/146]) were significantly lower than TG (56.38% [84/149], 41.10% [60/146]) and LDL-C (53.02% [79/149], 40.41% [59/146], all P<0.01). The AUC of the ROC curve of RLP (0.890), LDL-P (0.902) and sdLDL-P (0.973) for the diagnosis of carotid plaque was higher than TG (0.682) and LDL-C (0.712). The AUC of ROC curve of the RLP combined with sdLDL-P (0.977) for the diagnosis of carotid plaque was higher than the RLP and sdLDL-P (all P<0.01). Conclusion:The serum RLP, LDL-P and sdLDL-P can be used as indicators of carotid plaque, and their clinical diagnostic value are superior to TG and LDL-C; the combined diagnostic effect of lipoprotein subclass is better than that of single index alone.
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Objective:To correlate homocysteine (Hcy) and blood lipid levels with neurological function in patients with progressive ischemic stroke.Methods:A total of 400 patients with ischemic stroke who received treatment between June 2018 and June 2020 in Linhai Second People's Hospital were included in this study. Progressive ischemic stroke ( n = 126) and non-progressive ischemic stroke ( n = 274) groups were designated. Hcy level was determined by enzyme-linked immunosorbent assay. High-density lipoprotein cholesterol, triacylglycerol, low-density lipoprotein cholesterol and cholesterol levels were measured using a biochemical analyzer. Hcy and blood lipid levels as well as National Institute Health of Stroke Scale (NIHSS) score were determined in each group. Hcy and blood lipid levels were correlated with NIHSS score. Results:Hcy level in the progressive ischemic stroke group was significantly higher than that in the non-progressive ischemic stroke group [(28.39 ± 4.36) μmol/L vs. (20.17 ± 3.24) μmol/L, t = 18.894, P < 0.05]. Low-density lipoprotein cholesterol , triacylglycerol and TC levels in the progressive ischemic stroke group were (3.29 ± 0.45) mmol/L, (2.08 ± 0.34) mmol/L and (4.82 ± 0.79) mmol/L, respectively, which were significantly higher than those in the non-progressive ischemic stroke group [(2.48 ± 0.37) mmol/L, (1.56 ± 0.29) mmol/L and (4.08 ± 0.43) mmol/L, t = 17.644, 14.859, 9.860, P < 0.05]. High-density lipoprotein cholesterol level in the progressive ischemic stroke group was significantly lower than that in the non-progressive ischemic stroke group [(1.03 ± 0.13) mmol/L vs. (1.19 ± 0.14) mmol/L, t =11.158, P < 0.05]. NIHSS score in the progressive ischemic stroke group was significantly higher than that in the non-progressive ischemic stroke group [(21.72 ± 4.35) points vs. (15.52 ± 2.89) points, t = 14.582, P < 0.05]. Hcy, low-density lipoprotein cholesterol, cholesterol and triacylglycerol levels were linearly and positively correlated with NIHSS score ( r = 0.846, 0.724, 0.718, 0.765, all P < 0.05), while igh-density lipoprotein cholesterol level was linearly and negatively correlated with NIHSS score ( r = -0.710, P < 0.05). Conclusion:In patients with progressive ischemic stroke, Hcy level is increased and blood lipid level is obviously abnormal. Hcy and blood lipid levels are greatly correlated with neurological function.
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Resumo Fundamento O Diabetes Mellitus Tipo 2 (DMT2) é comum nos idosos, que também apresentam um nível elevado de fatores de risco para doenças cardiovasculares (DCVs), tais como dislipidemia. Entretanto, o papel da depressão nos pacientes com DMT2 e sua relação com fatores de risco para DCV são pouco estudados. Objetivo O objetivo do presente estudo foi investigar a relação entre sintomas depressivos (SDs) e fatores de risco cardiovascular conhecidos em idosos comunitários portadores de DMT2. Métodos Trata-se de um estudo transversal, no qual foram incluídos 85 idosos comunitários com DMT2. Os SDs foram avaliados através da Escala de Depressão Geriátrica de Yesavage, em versão reduzida (GDS-15). Os seguintes fatores de risco cardiovascular foram avaliados: pressão arterial sistólica (PAS) e diastólica (PAD), glicose plasmática em jejum (GPJ), perfil lipídico (triglicerídeos séricos (TG), colesterol total sérico (CT), colesterol sérico de lipoproteína de baixa densidade (LDL-C) e colesterol sérico de lipoproteína de baixa densidade (HDL-C)) e índice de massa corporal (IMC). A análise de regressão múltipla de Poisson foi utilizada para avaliar a associação entre os SDs e cada fator de risco cardiovascular ajustado por sexo, idade, tempo em atividades físicas moderadas e status funcional. O nível de significância adotado para a análise foi de 5%. Resultados Dentre todos os fatores de risco analisados, apenas o aumento de LDL-C apresentou uma correlação com níveis elevados de SD (RP=1,005; IC95% 1,002-1,008). Foi observada uma associação significativa entre os níveis de HDL-C (RP=0,99; IC95% 0,98-0,99) e a PAS (RP=1,009; IC95% 1,004-1,014). Conclusão Nos idosos com DMT2, a presença de SD foi associada a níveis de LDL-C, HDL-C e PAS, mesmo após o ajuste por sexo, idade, nível de atividade física e capacidade funcional. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
Abstract Background Type 2 Diabetes Mellitus (T2DM) is common in older adults, who also present a high level of risk factors for cardiovascular disease (CVD), such as dyslipidemia. However, the role of depression in T2DM patients and its relationship with CVD risk factors are understudied. Objective The present study aimed to investigate the relationship between depressive symptoms (DS) and known cardiovascular risk factors in community dwelling older adults with T2DM. Methods This is a cross sectional study, in which 85 community-dwelling older adults with T2DM were assessed. DS was assessed using the Yesavage Geriatric Depression Scale - short version (GDS-15). The following cardiovascular risk factors were evaluated: systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), lipid profile (serum triglycerides - TG, serum total cholesterol - TC, serum low-density lipoprotein cholesterol - LDL-C, and serum high-density lipoprotein cholesterol - HDL-C) and body mass index (BMI). Poisson multiple regression was performed to test the association between DS and each cardiovascular risk factor adjusted by sex, age, time spent in moderate physical activity, and functional status. The significance level adopted for the analysis was 5%. Results Among all the analyzed risk factors, only high levels of LDL-C were related to high DS (PR=1.005, CI 95% 1.002-1.008). A significant association was observed between HDL-C levels (PR=0.99, CI 95% 0.98-0.99) and SBP (PR=1.009, CI 95% 1.004-1.014). Conclusion In older adults with T2DM, the presence of DS was associated with LDL-C, HDL-C levels and SBP, even after adjusting for sex, age, physical activity level and functional capacity. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)
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Humans , Aged , Depression/etiology , Diabetes Mellitus, Type 2/complications , Triglycerides , Cross-Sectional Studies , Risk Factors , Cholesterol, HDL , Cholesterol, LDLABSTRACT
Abstract Although low-density lipoprotein cholesterol is central to the development and progression of atherosclerosis, the role of inflammation in the atherosclerotic process is becoming better understood and appreciated. Chronic inflammatory conditions such as rheumatoid arthritis, lupus, psoriasis, HIV infection, and inflammatory bowel disease have all been shown to be associated with an increased blood levels of inflammatory biomarkers and increased risk of cardiovascular events. Evidence from observational studies suggests that anti-inflammatory therapy decreases this risk in these conditions. Clinical trials of anti-inflammatory drugs in patients with coronary disease have yielded mixed results. Drugs that have failed in recent trials include the P38 MAP kinase inhibitor losmapimod, the phospholipase A2 inhibitors darapladib and varespladib, and methotrexate. Canakinumab, an interleukin-1β inhibitor, reduced cardiovascular events in patients with coronary disease in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS). Canakinumab increased the rate of fatal infections in CANTOS and is very expensive; it is thus unlikely to be widely used for risk reduction in cardiology. On the other hand, colchicine is a safe and inexpensive anti-inflammatory drug. In the Colchicine Cardiovascular Outcomes Trial (COLCOT), where patients within 30 days of a myocardial infarction were randomized to low-dose colchicine or placebo and followed for a median of almost 2 years, colchicine treatment was associated with a 23% reduction (p=0.02) in cardiovascular events. Newer studies with anti-inflammatory drugs have the potential to improve outcomes of patients with atherosclerosis, just as low-density lipoprotein cholesterol-lowering drugs have done over the past two decades.
Subject(s)
Atherosclerosis/complications , Heart Disease Risk Factors , Inflammation , Lipoproteins, LDL/adverse effects , Arthritis, Rheumatoid/complications , Psoriasis/complications , Inflammatory Bowel Diseases/complications , Colchicine/therapeutic use , Chronic Disease , Outcome Assessment, Health Care , Lupus Erythematosus, Systemic/complications , Anti-Inflammatory Agents/therapeutic useABSTRACT
Abstract Background: A sizeable proportion of patients have discordant low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Objectives: We assessed the relationship between discordance of LDL-C and non-HDL-C and coronary artery disease (CAD) severity. Methods: We retrospectively evaluated the data of 574 consecutive patients who underwent coronary angiography. Fasting serum lipid profiles were recorded, SYNTAX and Gensini scores were calculated to establish CAD complexity and severity. We determined the medians for LDL-C and non-HDL-C to examine the discordance between LDL-C and non-HDL-C. Discordance was defined as LDL-C greater than or equal to the median and non-HDL-C less than median; or LDL-C less than median and non-HDL-C greater than or equal to median. A p value < 0.05 was accepted as statistically significant. Results: LDL-C levels were strongly and positively correlated with non-HDL-C levels (r = 0.865, p < 0.001) but 15% of patients had discordance between LDL-C and non-HDL-C. The percentage of patients with a Gensini score of zero or SYNTAX score of zero did not differ between discordant or concordant groups (p = 0.837, p = 0.821, respectively). Mean Gensini and SYNTAX scores, percentage of patients with Gensini score ≥20 and SYNTAX score >22 were not different from group to group (p = 0.635, p = 0.733, p = 0.799, p = 0.891, respectively). Also, there was no statistically significant correlation between LDL-C and Gensini or SYNTAX scores in any of the discordant or concordant groups. Additionally, no correlation was found between non-HDL-C and Gensini or SYNTAX score. Conclusions: While there was discordance between LDL-C and non-HDL-C (15% of patients), there is no difference regarding CAD severity and complexity between discordant and concordant groups.
Resumo Fundamento: Uma proporção considerável de pacientes apresenta níveis discordantes de colesterol de lipoproteína de baixa densidade (LDL) e de não alta densidade (não HDL). Objetivos: Avaliar a relação da discordância entre colesterol LDL e não HDL com a gravidade da doença arterial coronariana (DAC). Métodos: Avaliamos retrospectivamente os dados de 574 pacientes submetidos consecutivamente à angiografia coronariana. Foram registrados os perfis lipídicos séricos em jejum, e depois foram calculados os escores SYNTAX e Gensini para estabelecer a complexidade e a gravidade da DAC. Determinamos as medianas para colesterol LDL e não-HDL para examinar a discordância entre ambos. Discordância foi definida como LDL maior ou igual à mediana e não-HDL menor que mediana; ou LDL menor que a mediana e não-HDL maior ou igual à mediana. Valor de p < 0,05 foi aceito como estatisticamente significante. Resultados: Os níveis de colesterol LDL estiveram forte e positivamente correlacionados com os níveis de colesterol não-HDL (r = 0,865, p < 0,001), mas 15% dos pacientes apresentaram discordância entre LDL e não-HDL. A porcentagem de pacientes com escore Gensini ou SYNTAX zero não diferiu entre os grupos discordantes ou concordantes (p = 0,837, p = 0,821, respectivamente). Escores médios de Gensini e SYNTAX, porcentagem de pacientes com escore Gensini ≥ 20 e SYNTAX > 22 não foram diferentes de grupo para grupo (p = 0,635, p = 0,733, p = 0,799, p = 0,891, respectivamente). Além disso, não houve correlação estatisticamente significativa entre os escores de cholesterol LDL e Gensini ou SYNTAX em nenhum dos grupos discordantes ou concordantes. Também não foi encontrada correlação entre cholesterol não HDL e escore Gensini ou SYNTAX. Conclusões: Embora tenha havido discordância entre colesterol LDL e não-HDL (15% dos pacientes), não há diferença quanto à gravidade e complexidade da DAC entre os grupos discordantes e concordantes.
Subject(s)
Humans , Coronary Artery Disease , Retrospective Studies , Risk Factors , Coronary Angiography , Cholesterol, HDL , Cholesterol, LDLABSTRACT
Objective@#To investigate the effects and underlying mechanisms of aspirin on endoplasmic reticulum stress in podocytes induced by hyperlipemia.@*Methods@#Cultured podocytes were divided into four groups: control group, aspirin (100 μg/ml) group, oxidized low density lipoprotein (ox-LDL, 100 μg/ml) group, aspirin+ox-LDL group. The expression of protein kinase R-1ike endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor-4 (ATF4) and CAAT/enhancer binding protein homologous protein (CHOP) at 6 h, 12 h, 24 h, 48 h were evaluated by real-time PCR. The related proteins of p-PERK and p-eIF2α at 24 h and ATF4 at 12 h were evaluated by Western blotting, respectively.@*Results@#The expressions of PERK, eIF2α peaked at 24 h, while ATF4 and CHOP peaked at 12 h in ox-LDL group and aspirin+ox-LDL group. Compared with control group, the expressions of PERK, eIF2α, ATF4 and CHOP were significantly higher in ox-LDL group at each times (all P<0.05). Compared with ox-LDL group, the expressions of the above indicators were significantly lower in aspirin+ox-LDL group at each times (all P<0.05). At 24 h, compared with control group, the expressions of p-PERK and p-eIF2α were significantly higher in ox-LDL group (both P<0.05). Compared with ox-LDL group, the expressions of p-PERK and p-eIF2α were significantly lower in aspirin+ox-LDL group (both P<0.05). At 12 h, the expression of ATF4 protein in each group was similar to that of mRNA. There were no significant difference in the expressions of all indicators between aspirin group and control group.@*Conclusions@#Hyperlipidemia may cause endoplasmic reticulum stress in podocytes by inducing phosphorylation of PERK and eIF2α, activating ATF4 transcription and inducing high expression of CHOP. Aspirin may partially block the PERK pathway, which may have protective effects for podocytes.
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Objective@#To investigate the effect and mechanism of proprotein convertase subtilisin type 9 (PCSK9) on lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediated oxidized low-density lipoprotein (ox-LDL) uptake by mononuclear macrophage (THP-1) derived macrophages.@*Methods@#THP-1 monocyte was incubated with PMA for 48 hours to induce the differentiation into macrophages. Macrophages were pretreated with human recombinant PCSK9 protein for 1 hour and incubated with ox-LDL for 24 hours to induce foam cells. Oil red O staining was used to observe the accumulation of lipid in the control group (foam cells) and groups treated with different concentrations of recombinant PCSK9 protein, and the intracellular cholesterol content was measured by enzyme method, and mRNA and protein expressions of LOX-1 were detected by real-time PCR and Western blot. The uptake of Dil-labeled oxidized low density lipoprotein (Dil-ox-LDL) was observed by fluorescence microscopy in control group (macrophage), PCSK9 protein treated group and PCSK9 protein plus anti-LOX-1 antibody and IgG antibody treated group. mRNA and protein expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2) were detected in control and PCSK9 protein treated group in the absence and presence of TLR4 inhibitor (TAK-242), NF-κB inhibitor (PDTC). In addition, reactive oxygen species (ROS) production was evaluated in the absence or presence of COX-2 inhibitor (NS-398) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (DPI). The mRNA and protein expression of LOX-1 in the control group (PCSK9 protein pretreated foam cells) and PCSK9 protein group in the absence or presence of TAK-242, PDTC, NS-398 and DPI respectively.@*Results@#(1) The total optical density of intracellular lipid droplets, total cholesterol level, cholesterol ester level and cholesterol ester/total cholesterol ratio as well as expression of LOX-1 were significantly higher in PCSK9 group than those in control group (all P<0.05). (2) The fluorescence intensity of Dil-ox-LDL was significantly higher in PCSK9 group and PCSK9+IgG antibody group than in the control group (all P<0.05). The fluorescence intensity was significantly lower in PCSK9+anti-LOX-1 antibody group than in PCSK9 group and PCSK9+IgG antibody group (all P<0.05). (3) The expressions of TLR4, NF-κB and COX-2 were significantly higher in PCSK9 group than in control group (all P<0.05). The expressions of TLR4, NF-κB and COX-2 were significantly lower in PCSK9+TAK-242 group and PCSK9+PDTC group than in PCSK9 group (all P<0.05). The ROS level was significantly higher in PCSK9 group than in the control group (P<0.05). The ROS levels were significantly lower in PCSK9+NS-398 and PCSK9+DPI groups than in PCSK9 group (all P<0.05). (4) The expressions of LOX-1 mRNA and protein were lower in respective PCSK9 protein plus TAK-242, PDTC, NS-398 or DPI group than in PCSK9 protein alone (all P<0.05).@*Conclusion@#PCSK9 may regulate LOX-1 mediated ox-LDL uptake by the THP-1 derived macrophage via TLR4/NF-κB/COX-2/ROS pathway.
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Objective@#To assess the use of statins and low-density lipoprotein cholesterol (LDL-C) levels at admission in hospitalized patients aged 75 years and older with acute coronary syndrome (ACS) in China.@*Methods@#Data used in this study derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a nationwide registry with 150 tertiary hospitals reporting details of clinical information of ACS patients. This study enrolled patients 75 years and older with ACS in CCC-ACS project from November 2014 to June 2017. Patients were divided into two groups according to the history of atherosclerotic cardiovascular disease (ASCVD). Pre-hospital statin use, LDL-C levels at admission and prescription of statins at discharge were reported.@*Results@#A total of 10 899 patients 75 years and older with ACS were enrolled. The median age was 79 years and 58.7% (6 397 cases) were male. Among patients with history of ASCVD, 33.9% (1 028 cases) of them received statins before hospitalization. Among patients without history of ASCVD, 12.7% (996/7 871) received statins before hospitalization. The mean level of LDL-C was (2.4±0.9) mmol/L and LDL-C was <1.8 mmol/L in 24.7% (747 cases) of patients with history of ASCVD. The mean level of LDL-C was (2.6±0.9) mmol/L and LDL-C was <2.6 mmol/L in 51.7% (4 072 cases) of patients without history of ASCVD. At discharge, 91.2% (9 524/10 488) of patients were prescribed with statins in patients without contraindications for statin.@*Conclusion@#In elderly patients with recurrent ASCVD, there was an inadequate statin use before hospitalization and most patients did not reach the LDL-C target level when they had the recurrent events. In the elderly ACS patients without history of ASCVD, more than half of the patients had an ideal LDL-C level. It seems that ideal LDL-C level for primary prevention of ACS in elderly people needs to be reevaluated with further studies.
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Nonalcoholic fatty liver disease (NAFLD) is the most common risk factor for diabetes mellitus and cerebrovascular and cardiovascular diseases. The prevalence of NAFLD is increasing rapidly with the improvement in living. Microsome triglyceride transfer protein (MTP) is a key enzyme for outward transport of liver lipids, and the increase in MTP promoter methylation is an important factor for liver lipid deposition in NAFLD. Traditional Chinese medicine believes that “spleen Qi transfers essence”, and the lipid transport function of MTP may be one of the manifestations of “spleen Qi transfers essence”. Clinical studies have shown that the spleen-strengthening and dampness-removing principle is of great importance in the treatment of NAFLD. By reviewing related articles, this article points out that the spleen-strengthening and dampness-removing therapy can improve NAFLD by regulating MTP promoter methylation, increasing the level of hepatic MTP, promoting the outflow of liver lipids, and alleviating lipid deposition.
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Nonalcoholic fatty liver disease (NAFLD) is the most common risk factor for diabetes mellitus and cerebrovascular and cardiovascular diseases. The prevalence of NAFLD is increasing rapidly with the improvement in living. Microsome triglyceride transfer protein (MTP) is a key enzyme for outward transport of liver lipids, and the increase in MTP promoter methylation is an important factor for liver lipid deposition in NAFLD. Traditional Chinese medicine believes that “spleen Qi transfers essence”, and the lipid transport function of MTP may be one of the manifestations of “spleen Qi transfers essence”. Clinical studies have shown that the spleen-strengthening and dampness-removing principle is of great importance in the treatment of NAFLD. By reviewing related articles, this article points out that the spleen-strengthening and dampness-removing therapy can improve NAFLD by regulating MTP promoter methylation, increasing the level of hepatic MTP, promoting the outflow of liver lipids, and alleviating lipid deposition.
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Objective To investigate the auxiliary diagnostic value of combined detection serum lipoprotein-associated phospholipase A2 (LP-PLA2) and small and dense low-density lipoprotein (sd-LDL) in atherosclerosis.Methods The subjects were divided into experimental group and control group by random block design from May 2017 to January 2018,in the First Affiliated Yijishan Hospital of Anhui Wannan Medical College.The experimental group selected 125 AS patients with clinical diagnosis and confirmed by angiography,and 55 healthy subjects were chosen as the normal control group at the same time.Serum samples were collected within 24 hours after admission,and the level of LP-PLA2,sdLDL-C,low density lipoprotein cholesterol (LDL-C),triglyceride (TG),total cholesterol (TC) and high-sensitive C reactive protein (hs-CRP) were unified detection.The t test,single factor variance analysis and Mann-Whitney U and multivariate logistic regression analysis were used to analyze the data.Results LP-PLA2,sd-LDL,LDL,TC,TG and hs-CRP of the AS group were all higher than those of the healthy control group (Z=5.279,6.663,6.012,5.863,5.508 and 2.845,respectively,P＜0.05).Logistic regression analysis showed that serum LP-PLA2,sd-LDL and hs-CRP level was an independent risk factor for predicting atherosclerosis (OR=1.008,P=0.003;OR=8.282,P=0.012;OR=1.158,P=0.009).The sensitivity of LP-PLA2,sd-LDL,LDL-C,TC,TG,hs-CRP to AS was detected separately (57.6％,73.6％,85.6％,83.2％,76.8％,80.0％),and the specificity was (89.1％,78.2％,67.3％,69.1％,74.5％,52.7％).The ROC curve showed that the diagnostic efficacy of LP-PLA2 and sd-LDL combined detection was 0.854,higher than sd-LDL,LDL-C,TC,TG,LP-PLA2 and hs-CRP (0.811,0.782,0.775,0.758,0.747 and 0.633,respectively).In addition,the levels of both increased with the aggravation of arteriosclerotic lesion(x2=7.954,P=0.019;x2=11.44,P=0.003).The levels of LP-PLA2 and sd-LDL in patients with AS were not significantly different between different lesions (x2=8.042,P=0.09;x2=5.952,P=0.203).There was no significant difference between serum LP-PLA2 and sd-LDL level and sex,age,smoking,hypertension and diabetes (Z1=0.398,0.719,0.619,0.098 and 1.338 respectively,Z2=0.942,0.027,0.894,0.375,0.783,respectively,both P1 and P2 were＞0.05).Conclusions sd-LDL combined with LP-PLA2 has high sensitivity and specificity in the prediction of AS,which makes up for the deficiency of individual detection;sd-LDL and LP-PLA2 serum level has nothing to do with the lesion and has a positive correlation with the degree of lesions.It is not easily affected by other risk factors and can be used as a risk factor for predicting the occurrence of AS.
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Objective To study the serum ox-LDL level and its influencing factors in elderly female hypertension patients.Methods Two hundred and ninety elderly females were divided into hypertension group(n=96)and hypertension-free group(n=194).Their age and blood routine examination data were recorded.The patients in hypertension group were further divided into≥60years old group(n=47)and＜60years old group(n=49),their clinical characteristics were compared. The influencing factors of ox-LDL were analyzed.Results The age was significantly older,the SBP and DBP,serum FBG,ox-LDL,Lp-PLA2,TC,LDL-C levels,BMI,incidence of DM and CHD were significantly higher in hypertension group than in hypertension-free group(P＜0.05,P＜0.01).The age was significantly older,the SBP,serum FPG,ox-LDL,Lp-PLA2,TC,LDL-C levels and incidence of CHD were significantly higher while the DBP was significantly lower in ≥60 years old group than in＜60years old group(P＜0.05,P＜0.01).Serum ox-LDL level was positively related with age,SBP,DBP,serum FPG,creatinine,TC,LDL-C,Lp-PLA2levels and smoking( P＜0.05,P＜0.01).Multivariate linear regression analysis showed that serum TC,Lp-PLA2,LDL-C levels and DBP were the risk factors for ox-LDL in female hypertension patients(P＜0.05,P＜0.01).Conclusion The serum ox-LDL level is significantly higher in elderly female hypertension patients than in elderly male hypertension patients.Serum TC,Lp-PLA2,LDL-C levels and DBP are the risk factors for ox-LDL in elderly female hypertension patients
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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.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Risk Assessment/methods , Atherosclerosis/blood , Lipid Accumulation Product/physiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Apolipoproteins B/blood , Reference Values , Blood Glucose/analysis , Brazil , Insulin Resistance , Biomarkers/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Sex Factors , Anthropometry , Epidemiologic Methods , Apolipoprotein A-I/blood , Atherosclerosis/ethnology , Fatty Acids, Nonesterified/blood , Lipid Accumulation Product/ethnology , Insulin/bloodABSTRACT
@#Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can reduce the low density lipoprotein cholesterol (LDL-C) level in circulatory system by blocking PCSK9-low density lipoprotein receptor (LDLR) pathway to mediate the degradation of LDLR. At present, PCSK9 inhibitors have become the focus of cardiovascular lipid-lowering therapy. A variety of PCSK9 inhibitors have entered the clinical trial stage. This paper mainly reviews the molecular structure and mechanism of PCSK9, the classification of PCSK9 inhibitors, and recent clinical study of the monoclonal antibodies of PCSK9 inhibitors in order to evaluate the effectiveness and long-term safety of cardiovascular risk reduction.