Relationship Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Lipoprotein (a) and Other Biomarkers.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) primarily affects the adult population and is closely related to obesity. The most severe form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), can progress to liver fibrosis. While lipoprotein(a) (Lp(a)) is known to be associated with cardiovascular disease, its relationship with MASLD remains unclear. This study aims to determine the prevalence of MASLD in ambulatory patients and to explore the association between Lp(a) levels and advanced liver damage. METHODS: This retrospective cross-sectional study included 130 patients older than 18 years seen in a healthcare center in Medellin, Colombia, between April 2023 and May 2024. Sociodemographic, clinical, and specific biomarker data were collected. Patients with cirrhosis, previous liver disease, frequent alcohol consumption, cancer, and other severe conditions were excluded. Continuous variables were analyzed using Student's t-tests or Mann-Whitney tests according to their distribution, and categorical variables were analyzed using contingency tables and chi-square tests. RESULTS: Of the 130 patients, 57.9% (n=73) had MASLD, with a higher prevalence in patients with obesity (80%, n=32). Lp(a) levels were abnormally high in 43.1% (n=31) of patients; however, a weak but significant inverse correlation was found between Lp(a) levels and the Fibrosis-4 (FIB-4) score, which is used to assess the severity of liver fibrosis. Patients with MASLD had significantly lower high-density lipoprotein (HDL) and vitamin D levels, and higher levels of gamma-glutamyl transferase (GGT). CONCLUSIONS: This study highlights the significant prevalence of MASLD in outpatients and its relationship with various biomarkers, including Lp(a), HDL, vitamin D, and GGT. Although the findings suggest a possible utility of Lp(a) as a biomarker in MASLD, longitudinal studies are needed to confirm these associations and clarify their role in liver disease progression. The study's limitations include its cross-sectional nature and potential selection bias, indicating the need for further research to validate these results.

Efficacy Assessment of Five Policosanol Brands and Damage to Vital Organs in Hyperlipidemic Zebrafish by Six-Week Supplementation: Highlighting the Toxicity of Red Yeast Rice and Safety of Cuban Policosanol (Raydel®).

Policosanol is a mixture of long-chain aliphatic alcohols (LCAAs) derived from various plant and insect origins that are marketed by various companies with distinct formulations and brand names. Policosanols offer several beneficial effects to treat dyslipidemia and hypertension; however, a comprehensive functionality comparison of various policosanol brands has yet to be thoroughly explored. In the present study five distinct policosanol brands from different origins and countries, Raydel-policosanol, Australia (PCO1), Solgar-policosanol, USA (PCO2), NutrioneLife-monacosanol, South Korea (PCO3), Mothernest-policosanol, Australia (PCO4), and Peter & John-policosanol, New Zealand (PCO5) were compared via dietary supplementation (1% in diet, final wt/wt) to zebrafish for six weeks to investigate their impact on survivability, blood lipid profile, and functionality of vital organs under the influence of a high-cholesterol diet (HCD, final 4%, wt/wt). The results revealed that policosanol brands (PCO1-PCO5) had a substantial preventive effect against HCD-induced zebrafish body weight elevation and hyperlipidemia by alleviating total cholesterol (TC) and triglycerides (TG) in blood. Other than PCO3, all the brands significantly reduced the HCD's elevated low-density lipoprotein cholesterol (LDL-C). On the contrary, only PCO1 displayed a significant elevation in high-density lipoprotein cholesterol (HDL-C) level against the consumption of HCD. The divergent effect of PCO1-PCO5 against HCD-induced hepatic damage biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), was observed. PCO1, PCO2, and PCO4 efficiently curtailed the AST and ALT levels; however, PCO3 and PCO5 potentially aggravated the HCD's elevated plasma AST and ALT levels. Consistently, the hepatic histology outcome revealed the least effectiveness of PCO3 and PCO5 against HCD-induced liver damage. On the contrary, PCO1 exhibited a substantial hepatoprotective role by curtailing HCD-induced fatty liver changes, cellular senescent, reactive oxygen species (ROS), and interleukin-6 (IL-6) production. Likewise, the histological outcome from the kidney, testis, and ovary revealed the significant curative effect of PCO1 against the HCD-induced adverse effects. PCO2-PCO5 showed diverse and unequal results, with the least effective being PCO3, followed by PCO5 towards HCD-induced kidney, testis, and ovary damage. The multivariate interpretation based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) validated the superiority of PCO1 over other policosanol brands against the clinical manifestation associated with HCD. Conclusively, different brands displayed distinct impacts against HCD-induced adverse effects, signifying the importance of policosanol formulation and the presence of aliphatic alcohols on the functionality of policosanol products.

Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis.

BACKGROUND: Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific HDL subspecies contribute to the increased atherosclerosis associated with T1D, we created mouse models of T1D that exhibit human-like HDL subspecies. We also measured HDL subspecies and their association with incident CVD in a cohort of people with T1D. METHODS: We generated LDL receptor-deficient (Ldlr-/-) mouse models of T1D expressing human APOA1 (apolipoprotein A1). Ldlr-/-APOA1Tg mice exhibited the main human HDL subspecies. We also generated Ldlr-/-APOA1Tg T1D mice expressing CETP (cholesteryl ester transfer protein), which had lower concentrations of large HDL subspecies versus mice not expressing CETP. HDL particle concentrations and sizes and proteins involved in lipoprotein metabolism were measured by calibrated differential ion mobility analysis and targeted mass spectrometry in the mouse models of T1D and in a cohort of individuals with T1D. Endothelial transcytosis was analyzed by total internal reflection fluorescence microscopy. RESULTS: Diabetic Ldlr-/-APOA1Tg mice were severely hyperglycemic and hyperlipidemic and had markedly elevated plasma APOB levels versus nondiabetic littermates but were protected from the proatherogenic effects of diabetes. Diabetic Ldlr-/-APOA1Tg mice expressing CETP lost the atheroprotective effect and had increased lesion necrotic core areas and APOB accumulation, despite having lower plasma APOB levels. The detrimental effects of low concentrations of larger HDL particles in diabetic mice expressing CETP were not explained by reduced cholesterol efflux. Instead, large HDL was more effective than small HDL in preventing endothelial transcytosis of LDL mediated by scavenger receptor class B type 1. Finally, in humans with T1D, increased concentrations of larger HDL particles relative to APOB100 negatively predicted incident CVD independently of HDL-cholesterol levels. CONCLUSIONS: Our results suggest that the balance between APOB lipoproteins and the larger HDL subspecies contributes to atherosclerosis progression and incident CVD in the setting of T1D and that larger HDLs exert atheroprotective effects on endothelial cells rather than by promoting macrophage cholesterol efflux.

Connecting impaired fibrinolysis and dyslipidemia.

A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023. Hemostasis balances the consequences of blood clotting and bleeding. This balance relies on the proper formation of blood clots, as well as the breakdown of blood clots. The primary mechanism that breaks down blood clots is fibrinolysis, where the fibrin net becomes lysed and the blood clot dissolves. Dyslipidemia is a condition where blood lipid and lipoprotein levels are abnormal. Here, we review studies that observed connections between impaired fibrinolysis and dyslipidemia. We also summarize the different correlations between thrombosis and dyslipidemia in different racial and ethnic groups. Finally, we summarize relevant and new findings on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress. More studies are needed to investigate the mechanistic connections between impaired fibrinolysis and dyslipidemia and whether these mechanisms differ in racially and ethnically diverse populations.

Prevalence of Metabolic Syndrome and Its Risk Factors Influence on Microvascular Complications in Patients With Type 1 and Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) long-term macrovascular and microvascular complications pose significant health risks and increase mortality. In DM patients, metabolic syndrome (MetSy) either precedes or coexists with the condition. Central obesity, poor glycemic control, hypertension, elevated triglycerides (TG), and low high-density lipoproteins (HDL-C) are the components of MetSy. The purpose of this study is to investigate related diabetic microvascular complications in type 1 DM (T1DM) by comparing them with type 2 DM (T2DM), determine potential risk factors, and estimate prevalence based on the diagnosis of MetSy. METHODOLOGY: This study included 160 T1DM and 160 T2DM patients, totaling 320 DM patients. It was carried out from April 20, 2022, to September 31, 2023, at the Sheikh Zayed Hospital, Rahim Yar Khan, in the Outdoor Diabetic Clinic and Medicine Department. A unique questionnaire was utilized to gather socio-demographic, general, clinical, and laboratory data for the MetSy criteria set forth by the International Diabetes Federation (IDF). The blood pressure, BMI, and waist circumference (WC) were measured, while venous fasting blood was used to assess biochemical markers such as HDL-C, TG, and fasting blood sugar. The microvascular diabetes complications were identified using abdominal ultrasound, fundus ophthalmoscopy, and routine laboratory tests. We quantified and analyzed these variables individually for T1DM and T2DM patients with or without MetSy and compared them in the presence or absence of diabetes microvascular complications. RESULTS: MetSy prevalence was 25.62% (41, n=160) for T1DM and 60.62% (97, n=160) for T2DM, totaling 43.12%. Among T1DM patients with MetSy, the majority were married males, aged 36-49 years, with a BMI of 26.69±2.20 kg/m2 and a WC of 85.12±4.23, and 67.5% (108) patients had diabetes microvascular complications. Comparatively, in T2DM with MetSy, the majority were married females aged 50-59 years with a BMI of 29.79 ± 4.65 kg/m² and a large WC of 93.43±4.49, and 75% (123) patients had diabetes microvascular complications. Overall, this study noted significant p-values for hypertension, elevated TG, low HDL-c, high WC, obesity, female gender in T2DM, and above 36 years of age in both groups with MetSy. Diabetic retinopathy (DR) at 32.4% (p<0.001) was the most prevalent T1DM microvascular complication, followed by nephropathy (30.6%), neuropathy (DN) at 28.1%, and gastroparesis (DG) at 22.3%. Whereas in T2DM, the prevalence of DN was 36.3% (p<0.001), followed by DKD (29.3%), DG (28.9%), and DR (24.9%). CONCLUSION: Nearly a quarter of T1DM patients had MetSy, with increasing percentages of overweight and obese patients who are more likely to have DR, DKD, or DN. MetSy affects two-thirds of T2DM patients, with married obese females aged 50-59 being more susceptible than males, who are more likely to suffer DN, DKD, or DG. Risk factors that contribute to the MetSy burden in T1DM and T2DM include hypertension, poor glycemic management, low HDL-C, high TG, and a higher BMI or WC. Increasing age, female gender in T2DM, longer diabetes duration, and co-morbid hypertension were independent predictors of microvascular complications. DR, DN, DKD, and gastroparesis are the most prevalent diabetic microvascular sequelae. The clinical management of diabetic patients with healthy lifestyle adaptations, good glycemic control, antihypertensives, and statins will contribute greatly to MetSy prevention.

Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties.

Several studies in animal models and human cohorts have recently suggested that HDLs (high-density lipoproteins) not only modulate innate immune responses but also adaptative immune responses, particularly CD4+ T cells. CD4+ T cells are central effectors and regulators of the adaptive immune system, and any alterations in their homeostasis contribute to the pathogenesis of cardiovascular diseases, autoimmunity, and inflammatory diseases. In this review, we focus on how HDLs and their components affect CD4+ T-cell homeostasis by modulating cholesterol efflux, immune synapsis, proliferation, differentiation, oxidative stress, and apoptosis. While the effects of apoB-containing lipoproteins on T cells have been relatively well established, this review focuses specifically on new connections between HDL and CD4+ T cells. We present a model where HDL may modulate T cells through both direct and indirect mechanisms.

Enhancement of Antioxidant and Anti-Glycation Properties of Beeswax Alcohol in Reconstituted High-Density Lipoprotein: Safeguarding against Carboxymethyllysine Toxicity in Zebrafish.

The antioxidant and anti-inflammatory abilities of beeswax alcohol (BWA) are well reported in animal and human clinical studies, with a significant decrease in malondialdehyde (MDA) in the blood, reduced liver steatosis, and decreased insulin. However, there has been insufficient information to explain BWAs in vitro antioxidant and anti-inflammatory activity owing to its limited solubility in an aqueous buffer system. Herein, three distinct reconstituted high-density lipoproteins (rHDL) were prepared with palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apolipoprotein A-I (apoA-I), and BWA at molar ratios of 95:5:1:0 (rHDL-0), 95:5:1:0.5 (rHDL-0.5), and 95:5:1:1 (rHDL-1) and examined for antioxidant and anti-glycation effects. A rHDL containing BWA, precisely rHDL-1, displayed a remarkable anti-glycation effect against fructose (final 250 mM), induced glycation of HDL, and prevented proteolytic degradation of apoA-I. Also, BWA incorporated rHDL-0.5, and rHDL-1 displayed substantial antioxidant activity by inhibiting cupric ion-mediated low-density lipoprotein (LDL) oxidation. In contrast to rHDL-0, a 20 and 22% enhancement in ferric ion reduction ability (FRA) and paraoxonase (PON) activity was observed in HDL treated with rHDL-1, signifying the effect of BWA on the antioxidant activity enhancement of HDL. rHDL-1 efficiently inhibits Nε-carboxylmethyllysine (CML)-induced reactive oxygen species (ROS) generation and apoptosis in zebrafish embryos, consequently improving embryo survivability and developmental deformities impaired by the CML. The dermal application of rHDL-1 to the CML-impaired cutaneous wound of the adult zebrafish inhibited ROS production and displayed potent wound-healing activity. Conclusively, incorporating BWA in rHDL significantly enhanced the anti-glycation and antioxidant activities in rHDL via more stabilization of apoA-I with a larger particle size. The rHDL containing BWA facilitated the inherent antioxidant ability of HDL to suppress the CML-induced toxicities in zebrafish embryos and ameliorate CML-aggravated chronic wounds in adult zebrafish.

lipoproteínas y colesterol total en adultos con colesterolemia normal y elevada en un policlínico de Lima-Perú 2022: Un estudio correlacional / Lipoproteins and total cholesterol in adults with normal and elevated cholesterolemia in a clinic in Lima-Peru 2022: A correlational study

RESUMEN Objetivo: Evaluar el grado de correlación entre las lipoproteínas de alta densidad, baja densidad, muy baja densidad y el colesterol total en pacientes con colesterolemia normal y alta. Metodología: Estudio observacional, analítico y transversal realizado desde enero a setiembre de 2022 con 207 pacientes mayores de 18 años, divididos en un grupo de colesterol normal y otro con hipercolesterolemia. Se realizó la prueba de correlación de Spearman. Resultados: En normocolesterolémicos, hubo una correlación baja y negativa entre lipoproteínas de alta densidad y las lipoproteínas de baja densidad (-0.263) así como entre lipoproteínas de alta densidad y las de muy baja densidad (-0.220). En hipercolesterolémicos, hubo una correlación baja y positiva entre lipoproteínas de alta densidad con colesterol total (0.344). En ambos grupos, hubo una correlación alta entre colesterol y lipoproteínas de baja densidad y baja y positiva entre colesterol y lipoproteínas de muy baja densidad. Conclusiones: Las lipoproteínas se correlacionan en normocolesterolémicos y las lipoproteínas de alta densidad se correlacionan en hipercolesterolémicos.

ABSTRACT Objective: To evaluate the degree of correlation between high-density, low-density, and very low-density lipoproteins and total cholesterol in patients with normal and high cholesterolemia. Methodology: Observational, analytical and cross-sectional study carried out from January to September 2022 with 207 patients over 18 years of age divided into a group with normal cholesterol and another with hypercholesterolemia. The Spearman correlation test was performed. Results: In normocholesterolemic subjects there was a low and negative correlation between high-density lipoproteins and low-density lipoproteins (-0.263) as well as between high-density lipoproteins and very low-density lipoproteins (-0.220). In hypercholesterolemic patients there was a low and positive correlation between high-density lipoproteins and total cholesterol (0.344). In both groups there was a high correlation between cholesterol and low-density lipoproteins and a low and positive correlation between cholesterol and very low-density lipoproteins. Conclusions: Lipoproteins are correlated in normocholesterolemics and high-density lipoproteins are correlated in hypercholesterolemics.

The benefits of measuring the size and number of lipoprotein particles for cardiovascular risk prediction: A systematic review and meta-analysis / Los beneficios de medir el tamaño y el número de partículas de lipoproteínas para la predicción del riesgo cardiovascular: una revisión sistemática y un metaanálisis

Objective: Cardiovascular risk (CVR) is conventionally calculated by measuring the total cholesterol content of high-density lipoproteins (HDL) and low-density lipoproteins (LDL). The purpose of this systematic review was to assess the CVR associated with LDL and HDL particle size and number as determined by nuclear magnetic resonance (NMR) spectroscopy. Material and methods: A literature search was performed using the electronic databases MEDLINE and Scopus. All cohort and case–control studies published before January 1, 2019 that met the following inclusion criteria were included: HDL-P, LDL-P, HDL-Z and/or LDL-Z measured by NMR spectroscopy; cardiovascular event as an outcome variable; risk of cardiovascular events expressed as odds ratios or hazard ratios; only adult patients. A meta-analysis was performed for each exposure variable (4 for LDL and 5 for HDL) and for each exposure measure (highest versus lowest quartile and 1-standard deviation increment). Results: This review included 24 studies. Number of LDL particles was directly associated with CVR: risk increased by 28% with each standard deviation increment. LDL particle size was inversely and significantly associated with CVR: each standard deviation increment corresponded to an 8% risk reduction. CVR increased by 12% with each standard deviation increase in number of small LDL particles. HD, particle number and size were inversely associated with CVR. Conclusion: Larger particle size provided greater protection, although this relationship was inconsistent between studies. Larger number of LDL particles and smaller LDL particle size are associated with increased CVR. Risk decreases with increasing number and size of HDL particles.(AU)

Objetivo: El riesgo cardiovascular (RCV) se calcula convencionalmente midiendo el contenido de colesterol total de las lipoproteínas de alta densidad (HDL) y las lipoproteínas de baja densidad (LDL). El propósito de esta revisión sistemática fue evaluar el RCV asociado con el tamaño y el número de partículas de LDL y HDL, según lo determinado por espectroscopia de resonancia magnética nuclear (RMN). Material y métodos: Se realizó una búsqueda bibliográfica utilizando las bases de datos electrónicas Medline y Scopus. Se incluyeron todos los estudios de cohortes y de casos y controles publicados antes del 1 de enero de 2019, que cumplieron con los siguientes criterios de inclusión: HDL-P, LDL-P, HDL-Z y/o LDL-Z medidos por espectroscopia de RMN; evento cardiovascular como variable de resultado; riesgo de eventos cardiovasculares expresado como cociente de posibilidades o cociente de riesgos instantáneos; solo pacientes adultos. Se realizó un metaanálisis para cada variable de exposición (cuatro para LDL y cinco para HDL) y para cada medida de exposición (cuartil más alto vs. más bajo e incremento de 1 desviación estándar [DE]). Resultados: Esta revisión incluyó 24 estudios. El número de partículas LDL se asoció directamente con el RCV: el riesgo aumentó 28% con cada incremento de la DE. El tamaño de las partículas de LDL se asoció inversa y significativamente con el RCV: cada incremento de la DE correspondió a una reducción del riesgo de 8%. El RCV aumentó 12% con cada aumento de la DE en el número de partículas pequeñas de LDL. HDL, número y tamaño de partículas se asociaron inversamente con CVR. Conclusión: El tamaño de partícula más grande proporcionó una mayor protección, aunque esta relación fue inconsistente entre los estudios. Un mayor número de partículas de LDL y un tamaño de partícula de LDL más pequeño se asocian con un aumento de la RCV. El riesgo disminuye con el aumento del número y tamaño de las partículas de HDL.(AU)

Consumption of Policosanol (Raydel®) Improves Hepatic, Renal, and Reproductive Functions in Zebrafish: In Vivo Comparison Study among Cuban, Chinese, and American Policosanol.

The current study compared three policosanols from Cuba (sugarcane, Raydel®, policosanol (1), China (rice bran, Shaanxi, policosanol (2), and the USA (sugarcane, Lesstanol®, policosanol (3) in the treatment of dyslipidemia and protection of the liver, ovary, and testis in hypercholesterolemic zebrafish. After twelve weeks of supplementation of each policosanol (PCO, final 0.1% in diet, w/w) with a high cholesterol diet (HCD, final 4%, w/w), the Raydel policosanol (PCO1) group showed the highest survivability, approximately 89%. In contrast, Shaanxi policosanol (PCO2) and Lesstanol policosanol (PCO3) produced 73% and 87% survivability, respectively, while the HCD alone group showed 75% survivability. In the 12th week, the PCO1 group demonstrated the most modest increase in body weight along with significantly lower levels of total cholesterol (TC) and triglycerides (TG) in comparison to the HCD control group. Additionally, the PCO1 group exhibited the highest proportion of high-density lipoprotein (HDL)-cholesterol within TC. Notably, the PCO1 group displayed the lowest level of aspartate aminotransferase and alanine aminotransferase, minimal infiltration of inflammatory cells, reduced interleukin (IL)-6 production in the liver, a notable decline in reactive oxygen species (ROS) generation and mitigated fatty liver changes. HCD supplementation induced impairment of kidney morphology with the greatest extent of ROS production and apoptosis. On the other hand, the PCO 1 group showed a remarkably improved morphology with the least ROS generation and apoptosis. Within the ovarian context, the PCO1 group exhibited the most substantial presence of mature vitellogenic oocytes, accompanied by minimal levels of ROS and apoptosis. Similarly, in the testicular domain, the PCO1 group showcased optimal morphology for spermatogenesis, characterized by the least interstitial area and diminished production of ROS in testicular cells. At week 8, the PCO1 group showed the highest egg-laying ability, with around 244 eggs produced per mating. In contrast, the HCD alone, PCO2, and PCO3 groups showed significantly lower egg-laying ability (49, 59, and 86 eggs, respectively). The embryos from the PCO1 group exhibited the highest survivability with the fastest swimming ability and developmental speed. These results suggest that PCO1 consumption significantly enhanced the reproduction system, egg-laying ability, and embryo survivability. In conclusion, among the three policosanols, Cuban (Raydel®) policosanol had the strongest effect on survivability, improving dyslipidemia, liver protection, kidney, ovary, and testis with a restoration of the cell morphology, and the least ROS production and apoptosis-induced by HCD supplementation.

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.

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.

Lipoprotein particles exhibit distinct mechanical properties.

Lipoproteins (LPs) are micelle-like structures with a similar size to extracellular vesicles (EVs) and are therefore often co-isolated, as intensively discussed within the EV community. LPs from human blood plasma are of particular interest as they are responsible for the deposition of cholesterol ester and other fats in the artery, causing lesions, and eventually atherosclerosis. Plasma lipoproteins can be divided according to their size, density and composition into chylomicrons (CM), very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Here, we use atomic force microscopy for mechanical characterization of LPs. We show that the nanoindentation approach used for EV analysis can also be used to characterize LPs, revealing specific differences between some of the particles. Comparing LPs with each other, LDL exhibit a higher bending modulus as compared to CM and VLDL, which is likely related to differences in cholesterol and apolipoproteins. Furthermore, CM typically collapse on the surface after indentation and HDL exhibit a very low height after surface adhesion both being indications for the presence of LPs in an EV sample. Our analysis provides new systematic insights into the mechanical characteristics of LPs.

Monocytes to high-density lipoprotein cholesterol ratio predicts the early neurological deterioration and outcome in patients with acute anterior circulation ischemic stroke / 国际脑血管病杂志

Objective:To investigate the monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) for the predictive value of early neurological deterioration (END) and poor outcome in patients with acute anterior circulation ischemic stroke (AACIS).Methods:Patients with AACIS admitted to Henan Provincial People's Hospital from January 2021 to January 2022 were included retrospectively. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d of onset increase ≥2 compred with baseline or the increase of motor function score ≥1. The patients were divided into END group and non-END group according to the presence or absence of END. The patients were also divided into good outcome group (0-2 points) and poor outcome group (3-6 points) according to the modified Rankin Scale score 3 months after onset. Multivariate logistic regression analysis was used to determine the independent risk factors for END and poor outcome, and the predictive value of MHR for END and poor outcome was evaluated by receiver operating characteristic (ROC) curve. Results:A total of 522 patients were enrolled, including 338 male (64.8%), aged 61.99±11.39 years old. One hundred and five patients (20.1%) had END, 123 (23.6%) had poor outcome. Multivariate logistic regression analysis showed that baseline NIHSS score (odds ratio [ OR] 1.075, 95% confidence interval [ CI] 1.017-1.137; P=0.010) and MHR (with the lowest quartile as the reference, the third quartile: OR 2.778, 95% CI 1.255-6.151, P=0.012; the fourth quartile: OR 12.645, 95% CI 5.942-26.912; P<0.001) were the independent risk factors for END; the baseline NIHSS score ( OR 1.075, 95% CI 1.021-1.132; P=0.006), END ( OR 2.306, 95% CI 1.010-6.261; P=0.047) and MHR (with the first quartile as reference, the fourth quartile: OR 2.769, 95% CI 1.167-6.569; P=0.021) were the independent risk factors for poor outcomes. ROC curve analysis showed that area under the curve of MHR for predicting END and poor outcome in patients with AACIS were 0.805 (95% CI 0.750-0.860; P<0.001) and 0.747 (95% CI 0.690-0.803; P<0.001) respectively. The best cutoff value was 0.435, the sensitivity was 73.3% and 64.2%, and the specificity was 79.6% and 78.7% respectively. The area under the curve of MHR for predicting END and poor outcome was higher than that of monocyte and HDL-C alone. Conclusion:MHR can be used as a predictor of END and poor outcome in patients with AACIS, and its predictive value is higher than that of monocytes or HDL-C.

The level and clinical value of monocyte/high-density lipoprotein ratio in patients with coronary heart disease / 中国医师杂志

Objective:To investigate the clinical value of serum monocyte/high-density lipoprotein ratio (MHR) level in the diagnosis of coronary heart disease(CHD).Methods:A total of 127 patients who underwent coronary angiography in the cardiology department of the Third Hospital of Changsha were enrolled as subjects. Patients with coronary artery stenosis ≥50% were included in the CHD group ( n=97), and patients with coronary artery stenosis <50% were included in the control group ( n=30). According to the clinical classification of CHD, the patients were divided into stable angina group ( n=31), unstable angina group ( n=35) and acute myocardial infarction group ( n=31). The general clinical data of the selected cases were collected, and the serum MHR, myeloperoxidase (MPO) and high sensitivity C-reactive protein (hs-CRP) were detected. The degree of coronary artery lesions was scored by Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score system, and the number of coronary artery lesions was counted. The relationship between MHR level, MPO, hs-CRP and the degree of coronary artery stenosis in CHD group was analyzed. The MHR level of CHD was divided into three subgroups by triquartile: the differences of SYNTAX score and the number of coronary artery lesions were compared in the low MHR group (≤0.41, n=40), the middle MHR group (0.41<MHR≤0.48, n=30) and the high MHR group (MHR>0.48, n=27). The value of serum MHR in diagnosing CHD was analyzed by receiver operating characteristic (ROC) curve. The risk factors of CHD were analyzed by multivariate logistic regression. Results:(1) The serum MHR level in CHD group was higher than that in non-CHD group ( P<0.001). In different clinical subgroups of CHD: the levels of serum MHR were significantly higher in acute myocardial infarction group than unstable angina group and stable angina group ( P<0.001). (2) There was a positive correlation between serum MHR, MPO level with SYNTAX score in CHD group ( r=0.878, 0.477, 0.285, all P<0.001). (3) The SYNTAX score in high MHR group was higher than those in middle MHR and low MHR group; the SYNTAX score in middle MHR group was higher than that of low MHR group ( P<0.001); There was no significant difference in the number of coronary artery lesions among the three MHR level subgroups ( P>0.05). (4) Multivariate logistic regression analysis showed that LDL-C ( OR=1.107, 95% CI: 0.974-1.259), MHR ( OR=1.873, 95% CI: 1.352-2.496) were independent risk factors for CHD (all P<0.05). (5) ROC curve showed that the area under the curve of MHR in diagnosing CHD was 0.987, and the sensitivity was 82.8%. Conclusions:Serum MHR level is higher in patients with CHD, which is closely related to the severity of coronary artery disease and is an independent risk factor of CHD.

Effect of dyslipidemia on clinical outcome of infertility patients receiving donor eggs / 中华妇产科杂志

Objective:To explore the effect of dyslipidemia on the clinical outcome of intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in infertility patients receiving donor eggs.Methods:A total of 118 patients were selected to receive egg donors and ICSI-ET at the First Affiliated Hospital of Nanjing Medical University between April 2007 and December 2020. According to the levels of triacylglycerol, serum cholesterol, high density lipoprotein (HDL), and low density lipoprotein, they were divided into dyslipidemia group (35 cases) and normal blood lipids group (83 cases). The influence of body mass index (BMI) and age was adjusted by 1∶1 propensity score matching, and the general condition and clinical outcome of the two groups were analyzed retrospectively. Finally, the relationship between lipid composition and clinical outcome was analyzed according to patients′ age and BMI.Results:(1) Comparing the pre-matching dyslipidemia group with the normal blood lipids group, the BMI of the dyslipidemia group was significantly higher than that of the normal blood lipids group [(23.5±2.4) vs (22.4±2.7) kg/m 2], and the embryo implantation rate was significantly lower than that of the normal blood lipids group [13.6% (8/59) vs 27.3% (36/132)], the differences were statistically significant (both P<0.05). (2) There were no significant differences in years of infertility, number of pregnancies, number of abortions, number of transplanted embryos, protocol of endometrial preparation, endometrial thickness on transplantation day and high quality embryo rate between the two groups, through propensity score matching (all P>0.05). The biochemical pregnancy rate [28.6% (10/35)], embryo implantation rate [13.6% (8/59)] and live birth rate [20.0% (7/35)] in dyslipidemia group were significantly lower than those in the normal blood lipids group ( P<0.05). The clinical pregnancy rate was lower than that of the normal blood lipids group ( P>0.05). (3) The results of stratified analysis showed that the level of HDL in the clinically non-pregnant group was significantly lower than that in the pregnant group in patients ≤ 35 years old [(1.5±0.3) vs (1.8±0.5) mmol/L; P<0.05]. In the overweight recipient patients, the level of HDL of the clinically non-pregnant group was lower than that of the pregnant group ( P>0.05). Conclusions:Dyslipidemia significantly reduces the biochemical pregnancy rate, embryo implantation rate and live birth rate in patients with receiving donor eggs. Especially in patients aged ≤35 years old, the reduction of HDL is closely related to adverse pregnancy outcomes.

Correlation of homocysteine and blood lipid levels with neurological function in patients with progressive ischemic stroke / 中国基层医药

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.

Relationship between monocyte/high-density lipoprotein ratio and severity and prognosis of chronic kidney disease / 中华肾脏病杂志

Objective:To investigate the relationship between monocyte/high-density lipoprotein ratio (MHR) and clinical parameters and the prognosis of patients with chronic kidney disease (CKD).Methods:Clinical data were collected of CKD patients who were diagnosed and followed up regularly in Henan Provincial People's Hospital from January 1, 2017 to June 30, 2020. According to the median baseline MHR of the selected patients, they were divided into two groups: low-level MHR group (MHR≤0.347 8) and high-level MHR group (MHR>0.347 8). The patients were regularly followed up for 3-42 months, the renal adverse prognostic events were defined as serum creatinine doubled, estimated glomerular filtration rate (eGFR) reduced to at least 50% of the original, new entry into end-stage renal disease (ESRD), starting renal replacement therapy, death due to renal or cardiovascular events. The Kaplan-Meier method was used to compare the differences in survival rates between the two groups, and Cox regression analysis method was used to explore the influencing factors of renal adverse prognosis in CKD patients. Stratified analysis was used to find special factors that might affect the relationship between MHR and renal adverse prognosis in CKD patients.Results:A total of 405 patients were included in this study. Their age was (49.77±14.82) years old. Body mass index was (25.18±4.22) kg/m 2. Women accounted for 30.62%(124/405). The proportion of patients with smoking, drinking, hypertension and diabetes was 39.51%(160/405), 35.06%(142/405), 73.33%(297/405) and 38.27%(155/405), respectively. Compared with the low-level MHR group ( n=202), the high-level MHR group ( n=203) had more people in late CKD, males, and hypertension (all P<0.01), and body mass index, white blood cells, monocytes, serum creatinine, serum uric acid, serum urea nitrogen, retinol binding protein, cystatin C, blood phosphorus were higher (all P<0.05), while hemoglobin, high density lipoprotein and eGFR were lower (all P<0.05). Spearman rank correlation results show that MHR level was positively correlated with white blood cells, serum creatinine, serum uric acid, serum urea nitrogen, retinol-binding protein, cystatin C, serum phosphorus (all P<0.01), and negatively correlated with hemoglobin and eGFR (both P<0.01). The median follow-up time was 8(4, 16) months. To the end of the follow-up, 113 patients (27.90%) had renal adverse prognostic events. Kaplan-Meier survival analysis results showed that the renal cumulative survival rate of the high-level MHR group was lower than that of the low-level MHR group ( χ2=8.277, P=0.004). Multivariate Cox regression analysis showed that high MHR level was an independent influencing factor for poor renal prognosis in CKD patients ( HR=1.628, 95% CI 1.050-2.523, P=0.029). Stratified analysis showed that, without hypertension, MHR had a more significant effect on the prognosis of the kidneys ( HR=3.414, 95% CI 1.091-10.686, P for interaction=0.001). Conclusions:The level of MHR is related to the severity and poor renal prognosis of CKD, and the high MHR level is an independent predictor for poor renal prognosis in CKD patients.

Assessment of the hemogram parameters in patients with paroxysmal supraventricular tachycardia: a retrospective study

SUMMARY OBJECTIVE: Inflammation has been suggested as a potential mechanism in the pathogenesis of arrhythmia. Hemogram parameters such as monocyte count to high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) have been considered to be markers of inflammation and new cardiovascular risk predictors. This retrospective study aimed to investigate the relationship between MHR, NLR, and MLR in patients with paroxysmal supraventricular tachycardia (PSVT). METHODS: A retrospective study conducted at a university hospital in Bolu, Turkey, between 2017 and 2019. Our study included 196 patients who underwent electrophysiological study (EPS) due to palpitation or documented PSVT on electrocardiography (ECG). Patients having documented atrioventricular nodal re-entrant tachycardia (AVNRT) on ECG or inducible AVNRT on EPS were included in the PSVT group (n=130), and patients with palpitation but without inducible arrhythmia on EPS (n=66) were included in the control group. Routine biochemical and hemogram tests were performed before the EPS procedure. RESULTS: When hemogram parameters were compared, there was no statistically significant difference in MHR values [0.010 (0.001-0.030) vs 0.010 (0.001-0.020) p =0.67]. Additionally, both NLR [2.21(0.74-11.36) vs 1.98(0.72-24.87) p=0.13] and MLR [0.25 (0.03-1.05) vs 0.24(0.07-1.39) p=0.41] were not statistically significant between the two groups. CONCLUSION: There is no significant difference in PSVT patients regarding hemogram parameters including white blood cell subtypes, MLR, NLR, and MHR. Therefore the evaluation of hemogram parameters may not be clinically relevant for PSVT patients.

RESUMO OBJETIVO: A inflamação tem sido sugerida como um mecanismo potencial na patogênese da arritmia. Parâmetros do hemograma, como contagem de monócitos e razão de colesterol lipoproteína de alta densidade (MHP), proporção de neutrófilos / linfócitos (NLP) e proporção de monócitos / linfócitos (MLR), foram considerados marcadores de inflamação e novos preditores de risco cardiovascular. Este estudo retrospectivo teve como objetivo investigar a relação entre MHP, NLP e MLP em pacientes com taquicardia paroxística supraventricular (PSVT). MÉTODOS: Estudo retrospectivo realizado em um hospital universitário em Bolu, Turquia, entre 2017 e 2019. Nosso estudo incluiu 196 pacientes submetidos a estudo eletrofisiológico (EPS) devido a palpitações ou PSVT documentada na eletrocardiografia (ECG). Os pacientes com taquicardia nodal atrioventricular reentrante (AVNRT) no ECG ou AVNRT indutível no EPS foram incluídos no grupo PSVT (n = 130) e os pacientes com palpitações sem arritmia induzível no EPS (n = 66) foram incluídos no grupo controle. Testes bioquímicos e de hemograma de rotina foram realizados antes do procedimento de EPS. RESULTADOS: Quando os parâmetros do hemograma foram comparados, não houve diferença estatisticamente significante nos valores de MHP (0,010 (0,001-0,030) vs 0,010 (0,001-0,020) p = 0,67). Além disso, tanto o NLP (2,21 (0,74-11,36) vs 1,98 (0,72-24,87) p = 0,13) quanto o MLP (0,25 (0,03-1,05) vs 0,24 (0,07-1,39) p = 0,41) não foram estatisticamente significantes entre os dois grupos. CONCLUSÃO: Não há diferença significativa nos pacientes com PSVT em relação aos parâmetros do hemograma, incluindo os subtipos de glóbulos brancos, MHP, NLP e MHP. Portanto, a avaliação dos parâmetros do hemograma pode não ser clinicamente relevante para pacientes com PSVT.