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.

Sugar-Rich Food Intake Is Negatively Associated with Plasma Pentraxin 3 Levels.

Background: Levels of pentraxin 3 (PTX3), an anti-inflammatory cardioprotective protein, increase after weight loss in obese men and aerobic exercise in non-obese adults. However, the effect of nutritional characteristics on PTX3 levels remains unclear. This population-based, cross-sectional study investigated the association between circulating PTX3 levels and food intake in Japanese adults. Methods: We hypothesized that the consumption of high amounts of high-sugar foods would lead to low plasma PTX3 levels, resulting in obesity. This study included 327 participants categorized depending on the consumption of the recommended amount of confectionary and sugar-sweetened beverages (CSSB) into high and low groups. Results: PTX3 levels were significantly lower in the high CSSB group than in the low CSSB group. Biological sex was the strongest effector of PTX3 levels. Moreover, the intake of Tsukudani and CSSB, as well as some metabolic syndrome factors, also affect PTX3 levels. In the groups categorized by sex and age, the determinants of PTX3 levels differed. Body mass index, waist circumference (WC), and high-density lipoprotein cholesterol (HDL-C) were significantly associated with PTX3 levels in women. Tsukudani, HDL-C, heart rate, saturated fatty acids, systolic blood pressure, and CSSB were associated with PTX3 levels in individuals aged >65 years. Conclusion: Our results show that circulating PTX3 levels are affected by sex, sugar-rich foods, and metabolic syndrome characteristics (WC, HDL-C).

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)

HDL anti-inflammatory function is impaired and associated with high SAA1 and low APOA4 levels in aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease with high morbidity and mortality rates. Within 24 hours after aSAH, monocytes are recruited and enter the subarachnoid space, where they mature into macrophages, increasing the inflammatory response and contributing, along with other factors, to delayed neurological dysfunction and poor outcomes. High-density lipoproteins (HDL) are lipid-protein complexes that exert anti-inflammatory effects but under pathological conditions undergo structural alterations that have been associated with loss of functionality. Plasma HDL were isolated from patients with aSAH and analyzed for their anti-inflammatory activity and protein composition. HDL isolated from patients lost the ability to prevent VCAM-1 expression in endothelial cells (HUVEC) and subsequent adhesion of THP-1 monocytes to the endothelium. Proteomic analysis showed that HDL particles from patients had an altered composition compared to those of healthy subjects. We confirmed by western blot that low levels of apolipoprotein A4 (APOA4) and high of serum amyloid A1 (SAA1) in HDL were associated with the lack of anti-inflammatory function observed in aSAH. Our results indicate that the study of HDL in the pathophysiology of aSAH is needed, and functional HDL supplementation could be considered a novel therapeutic approach to the treatment of the inflammatory response after aSAH.

Adsorption of Acylhydroperoxy-Derivatives of Phospholipids from Biomembranes by Blood Plasma Lipoproteins.

It has been established that acylhydroperoxy derivatives of phospholipids from oxidized rat liver mitochondria are captured predominantly by LDL particles but not by HDL during co-incubation with blood plasma lipoproteins, which refutes the previously suggested hypothesis about the involvement of HDL in the reverse transport of oxidized phospholipids and confirms the possibility of different mechanisms of lipohydroperoxide accumulation in LDL during oxidative stress.

HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy.

Epidemiologic studies detected an inverse relationship between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major risk factor for ASCVD and suggesting atheroprotective functions of HDL. However, the role of HDL-C as a mediator of risk for ASCVD has been called into question by the failure of HDL-C-raising drugs to reduce cardiovascular events in clinical trials. Progress in understanding the heterogeneous nature of HDL particles in terms of their protein, lipid, and small RNA composition has contributed to the realization that HDL-C levels do not necessarily reflect HDL function. The most examined atheroprotective function of HDL is reverse cholesterol transport, whereby HDL removes cholesterol from plaque macrophage foam cells and delivers it to the liver for processing and excretion into bile. Indeed, in several studies, HDL has shown inverse associations between HDL cholesterol efflux capacity and ASCVD in humans. Inflammation plays a key role in the pathogenesis of atherosclerosis and vulnerable plaque formation, and a fundamental function of HDL is suppression of inflammatory signaling in macrophages and other cells. Oxidation is also a critical process to ASCVD in promoting atherogenic oxidative modifications of LDL (low-density lipoprotein) and cellular inflammation. HDL and its proteins including apoAI (apolipoprotein AI) and PON1 (paraoxonase 1) prevent cellular oxidative stress and LDL modifications. Importantly, HDL in humans with ASCVD is oxidatively modified rendering HDL dysfunctional and proinflammatory. Modification of HDL with reactive carbonyl species, such as malondialdehyde and isolevuglandins, dramatically impairs the antiatherogenic functions of HDL. Importantly, treatment of murine models of atherosclerosis with scavengers of reactive dicarbonyls improves HDL function and reduces systemic inflammation, atherosclerosis development, and features of plaque instability. Here, we discuss the HDL antiatherogenic functions in relation to oxidative modifications and the potential of reactive dicarbonyl scavengers as a therapeutic approach for ASCVD.

Critical assessment of the metabolic syndrome definitions in the adult general population of the United States - the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Metabolic syndrome (MetS) consists of a cluster of cardiometabolic risk factors and is an important determining factor for cardiovascular diseases (CVDs). We intended to use latent class analysis to classify the study population into several clusters. Methods: The baseline information of 6,814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) aged 45-84 years in 2000-2002 was used. The latent class analysis was conducted to extract different patterns of components. SAS 9.2 and Stata 12 software were used for analysis. Results: The components of MetS tend to accumulate, hence it would be feasible to categorize the population into three classes: [1] Non-Metabolic Syndrome Latent Class (NonMetS-LC), [2] Low Risk Latent Class (LowR-LC), and [3] Metabolic Syndrome Latent Class (MetS-LC). In women, adding high-density lipoprotein (HDL) component to the two-component combinations of NonMetS-LC will transfer the individual to MetS-LC, and it was found in 100% of combinations of MetS-LC. However, in men, blood pressure (BP) played such a similar role, which was found in 97.36% of combinations of MetS-LC. Conclusion: Results showed that clinical value of each MetS component is different by gender. The main component in men was elevated BP; while low HDL and elevated fasting blood sugar (FBS) were in next ranks. However, the main component in women was low HDL; while elevated BP and FBS were in next ranks. Special attention should be paid to BP and HDL components, because these can be useful for clinicians and health policy-makers in diagnosis and screening. In conclusion, this study showed that revisions might be needed for the MetS definitions.

Delineating the impact of pathogenic mutations on the conformational dynamics of HDL's vital protein ApoA1: a combined computational and molecular dynamic simulation approach.

Apolipoprotein A1 (ApoA1), is the important component of high-density lipoproteins (HDL), that has key role in HDL biogenesis, cholesterol trafficking, and reverse cholesterol transport (RCT). Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in ApoA1 have been linked to cardiovascular diseases and amyloidosis as they alter the protein's native structure and function. Therefore in this study, we attempted to understand the molecular pathogenicity profile of nsSNPs of ApoA1 using various computational approaches. We used state-of-the-art computational methods to thoroughly investigate the 295 ApoA1 nsSNPs at sequence and structural levels. Seven nsSNPs (L13R, L84R, L84P, L99P, R173P, L187P, and L238P) out of 295 were classified as the most deleterious and destabilizing. In order to estimate the effect of such destabilizing mutations on the protein conformation, all-atom molecular dynamics simulations (MDS) of ApoA1 wild-type (WT), L99P and R173P for 100 ns, was carried out using GROMACS 5.0.1 package. The MD simulation investigation revealed significant structural alterations in L99P and R173P. In addition, they had changed principal component analysis and electrostatic surface potential, decreased structural compactness, and intramolecular hydrogen bonds, which supported the rationale underpinning ApoA1 dysfunction with such mutations. This work sheds light on ApoA1 dysfunction due to single amino acid alterations, and offers new insight into the molecular basis of ApoA1-related diseases progression.Communicated by Ramaswamy H. Sarma.

Beneficial Effect of Cuban Policosanol on Blood Pressure and Serum Lipoproteins Accompanied with Lowered Glycated Hemoglobin and Enhanced High-Density Lipoprotein Functionalities in a Randomized, Placebo-Controlled, and Double-Blinded Trial with Healthy Japanese.

This study evaluated the efficacy and safety of 20 mg of Cuban policosanol in blood pressure (BP) and lipid/lipoprotein parameters of healthy Japanese subjects via a placebo-controlled, randomized, and double-blinded human trial. After 12 weeks of consumption, the policosanol group showed significantly lower BP, glycated hemoglobin (HbA1c), and blood urea nitrogen (BUN) levels. The policosanol group also showed lower aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) levels at week 12 than those at week 0: A decrease of up to 9% (p < 0.05), 17% (p < 0.05), and 15% (p < 0.05) was observed, respectively. The policosanol group showed significantly higher HDL-C level and HDL-C/TC (%), approximately 9.5% (p < 0.001) and 7.2% (p = 0.003), respectively, than the placebo group and a difference in the point of time and group interaction (p < 0.001). In lipoprotein analysis, the policosanol group showed a decrease in oxidation and glycation extent in VLDL and LDL with an improvement of particle shape and morphology after 12 weeks. HDL from the policosanol group showed in vitro stronger antioxidant and in vivo anti-inflammatory abilities. In conclusion, 12 weeks of Cuban policosanolconsumption in Japanese subjects showed significant improvement in blood pressure, lipid profiles, hepatic functions, and HbA1c with enhancement of HDL functionalities.

Population-representative study reveals cardiovascular and metabolic disease biomarkers associated with misaligned sleep schedules.

STUDY OBJECTIVES: Social jetlag manifests as a difference in sleep timing on workdays and free days. Social jetlag is often associated with shorter, lower-quality sleep, so it is unclear how much the chronic circadian misalignment contributes to observed negative health outcomes. We aimed to (1) investigate associations between social jetlag, chronotype (one of its determinants), and the levels of health markers, (2) describe factors associated with social jetlag, and (3) examine whether working from home can reduce social jetlag. METHODS: Adult respondents participated in a nationally representative longitudinal survey of Czech households (individuals in each wave: n2018/19/20 = 5132/1957/1533), which included Munich ChronoType Questionnaire to evaluate chronotype and social jetlag. A subset provided blood samples (n2019 = 1957) for detection of nine biomarkers and was surveyed in three successive years (social jetlag calculated for n2018/19/20 = 3930/1601/1237). Data were analyzed by nonparametric univariate tests and mixed effects multivariate regression with social jetlag, chronotype, sex, age, body-mass index, and reported diseases as predictors and biomarker levels as outcomes. RESULTS: Higher social jetlag (≥0.65 h) was significantly associated with increased levels of total cholesterol and low-density lipoprotein cholesterol, particularly in participants older than 50 years (Mann-Whitney, men: pCHL = 0.0005, pLDL = 0.0009; women: pCHL = 0.0079, pLDL = 0.0068). Extreme chronotypes were associated with cardiovascular disease risk markers regardless of social jetlag (Kruskal-Wallis, p < 0.0001). Commuting to work and time stress were identified as important contributors to social jetlag. Individual longitudinal data showed that working from home decreased social jetlag and prolonged sleep. CONCLUSIONS: We report significant associations between sleep phase preference, social jetlag, and cardio-metabolic biomarkers.

The benefits of measuring the size and number of lipoprotein particles for cardiovascular risk prediction: A systematic review and meta-analysis.

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.

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 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.

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.