Systemic inflammatory response index and monocyte-to-high density lipoprotein ratio- new biomarkers remarking the inflammation in primary sarcopenia: The SIMPS study.

OBJECTIVE: To investigate the relationship of sarcopenia with systemic inflammation response index (SIRI), monocyte to high-density lipoprotein ratio (MHR) and platelet parameters in geriatric patients. METHODS: We designed a cross-sectional retrospective study in patients presented to a geriatric outpatient clinic for the first time. The diagnosis of sarcopenia was made in accordance with the EWGSOP2 criteria. SIRI, MHR, mean platelet volume /Platelet count (MPV/Plt), platelet distribution width /Platelet (PDW/Plt), platelet/lymphocyte ratio (PLR) were calculated from fasting blood test results at the time of admission. RESULTS: Among 262 patients, 79 patients (30.1%) with sarcopenia had significantly higher frequencies of delirium, hypothyroidism, chronic kidney disease and probable depression (p=0.010; p=0.018; p=0.034; p<0.001). Malnutrition scores and cognitive impairment scores were significantly lower in sarcopenic group (p<0.001 for both). Patients with sarcopenia had significantly higher MHR, SIRI and C-reactive protein values than patients without sarcopenia (p<0.001; p=0.001 and p=0.006, respectively). No significant difference was found between the groups in terms of MPV/Plt, PDW/Plt, PLR (p=0.605; p=0.920; p=0.510). Area under the curve for MHR was 0.675 (95% CI: 0.604-0.746, p0.99. CONCLUSIONS: The finding of higher MHR and SIRI in geriatric sarcopenia patients supports low-grade chronic inflammation in the pathophysiology of sarcopenia. These non-invasive, cost-effective and simple parameters based on traditional peripheral blood cell counts may be warning signs for sarcopenia in the geriatric population (Tab. 3, Fig. 1, Ref. 25). Text in PDF www.elis.sk Keywords: primary sarcopenia, inflammation, systemic inflammation response index, monocyte/high-density lipoprotein ratio, platelet parameters.

Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes.

High-density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A-I (ApoA-I), is essential to this process, and changes in its sequence significantly alter HDL structure and functions. ApoA-I amyloidogenic variants, associated with a particular hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease. Thus, it is conceivable that reconstituted HDL (rHDL) formulations containing ApoA-I proteins with functional/structural features similar to those of amyloidogenic variants hold potential as a promising therapeutic approach. Here we explored the effect of protein cargo and lipid composition on the function of rHDL containing one of the ApoA-I amyloidogenic variants G26R or L174S by Fourier transformed infrared spectroscopy and neutron reflectometry. Moreover, small-angle x-ray scattering uncovered the structural and functional differences between rHDL particles, which could help to comprehend higher cholesterol efflux activity and apparent lower phospholipid (PL) affinity. Our findings indicate distinct trends in lipid exchange (removal vs. deposition) capacities of various rHDL particles, with the rHDL containing the ApoA-I amyloidogenic variants showing a markedly lower ability to remove lipids from artificial membranes compared to the rHDL containing the native protein. This effect strongly depends on the level of PL unsaturation and on the particles' ultrastructure. The study highlights the importance of the protein cargo, along with lipid composition, in shaping rHDL structure, contributing to our understanding of lipid-protein interactions and their behavior.

Reversion of the Inflammatory Markers in Patients With Chronic Limb-Threatening Ischemia.

BACKGROUND: Peripheral artery disease is characterized by an intense inflammatory process that can be associated with a higher mortality rate, particularly in chronic limb-threatening ischemia (CLTI). This study aims to compare the evolution of inflammatory markers between patients with claudication with those with CLTI at 3, 6, and 12 months. METHODS AND RESULTS: An observational, single-center, and prospective study was conducted. A total of 119 patients with peripheral artery disease (65 with claudication and 54 with CLTI) were observed and inflammatory markers collected at admission and 3, 6, and 12 months. At admission, patients with CLTI, when compared with patients with claudication, had significantly higher serum levels of C-reactive protein and fibrinogen (positive acute-phase proteins) and lower serum level of albumin, total cholesterol, and high-density lipoprotein (negative acute-phase proteins): C-reactive protein (g/dL), 2.90 (25th-75th percentile, 2.90-4.90) versus 6.80 (25th-75th percentile, 2.90-53.26) (P=0.000); fibrinogen (mg/dL), 293.00 (25th-75th percentile, 269.25-349.00) versus 415.50 (25th-75th percentile, 312.00-615.75) (P=0.000); total cholesterol (mg/dL), 161.79±95% [152.74-170.85] versus 146.42%±95% [135.30-157.53] (P=0.034); high-density lipoprotein (mg/dL), 50.00 (25th-75th percentile, 41.00-60.00) versus 37.00 (25th-75th percentile, 30.00-45.50) (P=0.000); albumin (g/dL): 4.00 (25th-75th percentile, 3.70-4.20) versus 3.60 (25th-75th percentile, 3.10-4.00) (P=0.003). The association between CLTI and total cholesterol was lost after adjusting for confounders. Three months after the resolution of the CLTI, there was an increase in the levels of negative acute-phase proteins and a decrease in positive acute-phase proteins. These inflammatory proteins did not register an evolution in patients with claudication. The differences in the inflammatory proteins between groups disappeared at 6 months. CONCLUSIONS: CLTI has an inflammatory environment that can be partially reverted after resolution of the ischemic process, emphasizing the importance of timely intervention.

Associations between sleep duration, sleep disturbance and cardiovascular disease biomarkers among adults in the United States.

BACKGROUND: Sleep problems are associated with abnormal cardiovascular biomarkers and an increased risk of cardiovascular diseases (CVDs). However, studies investigating associations between sleep problems and CVD biomarkers have reported conflicting findings. This study examined the associations between sleep problems and CVD biomarkers in the United States. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) (2007-2018) and analyses were restricted to adults ≥ 20 years (n = 23,749). CVD biomarkers [C-reactive Protein (CRP), low-density lipoproteins, high-density lipoproteins (HDL), triglycerides, insulin, glycosylated hemoglobin (HbA1c), and fasting blood glucose] were categorized as abnormal or normal using standardized cut-off points. Sleep problems were assessed by sleep duration (short [≤ 6 h], long [≥ 9 h], and recommended [> 6 to < 9 h) and self-reported sleep disturbance (yes, no). Multivariable logistic regression models explored the associations between sleep duration, sleep disturbance, and CVD biomarkers adjusting for sociodemographic characteristics and lifestyle behaviors. RESULTS: The mean sleep duration was 7.1 ± 1.5 h and 25.1% of participants reported sleep disturbances. Compared to participants with the recommended sleep duration, those with short sleep duration had higher odds of abnormal levels of HDL (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.05-1.39), CRP (aOR = 3.08, 95% CI = 1.18-8.05), HbA1c (aOR = 1.25, 95% CI = 1.05-1.49), and insulin (aOR = 1.24, 95% CI = 1.03-1.51). Long sleep duration was associated with increased odds of abnormal CRP (aOR = 6.12, 95% CI = 2.19-17.15), HbA1c (aOR = 1.54, 95% CI = 1.09-2.17), and blood glucose levels (aOR = 1.45, 95% CI = 1.07-1.95). Sleep disturbance predicted abnormal triglyceride (aOR = 1.18, 95% CI = 1.01-1.37) and blood glucose levels (aOR = 1.24, 95% CI = 1.04-1.49). CONCLUSION: Short and long sleep durations were positively associated with abnormal CRP, HDL, HbA1c, blood glucose, and insulin levels, while sleep disturbance was associated with abnormal triglyceride and blood glucose levels. Since sleep is a modifiable factor, adopting healthy sleeping habits may create a balanced metabolism and reduce the risk of developing a CVD. Our study may provide insights into the relationship between sleep duration, sleep disturbance, and CVD risk.

Exploring the complex dynamics of BMI, age, and physiological indicators in early adolescents.

BACKGROUND AND OBJECTIVES: To investigate the relationship between body mass index (BMI) and blood biochemical indicators in early adolescence, and to provide ideas for early prevention of diseases and explore possible disease-related predictors. METHODS: 3125 participants aged 10 ∼ 14 years were selected from China from the survey of "China Nutrition and Health Surveillance ( 2016 ∼ 2017 ) ". Employing advanced statistical methods, including generalized linear models, heatmaps, hierarchical clustering, and generalized additive models, the study delved into the associations between BMI and various biochemical indicators. RESULTS: In early adolescence, indicators including systolic pressure, diastolic pressure, weight, height, BMI, hemoglobin, blood uric acid, serum creatinine, albumin, vitamin A presented increasing trends with the increase of age ( P < 0.05 ), whereas LDL-C, vitamin D, and ferritin showed decreasing trends with the increase of age ( P < 0.05 ). The increase in hemoglobin and blood uric acid levels with age was more pronounced in males compared to females ( P < 0.05 ). BMI was positively correlated with blood glucose, hemoglobin, triglyceride, LDL-C, blood uric acid, serum creatinine, ferritin, transferrin receptor, hs-CRP, total protein, vitamin A ( P < 0.05 ). There was a significant BMI × age interaction in the correlation analysis with LDL-C, transferrin receptor, serum creatinine, and hs-CRP ( P < 0.05 ). BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and metabolic syndrome in all age groups ( OR > 1, P < 0.05 ). CONCLUSIONS: High BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and MetS in early adolescents. With the focus on energy intake beginning in early adolescence, the maintenance of a healthy weight warrants greater attention.

Mitochondria-associated membranes contribution to exercise-mediated alleviation of hepatic insulin resistance: Contrasting high-intensity interval training with moderate-intensity continuous training in a high-fat diet mouse model.

OBJECTIVE: Mitochondria-associated membranes (MAMs) serve pivotal functions in hepatic insulin resistance (IR). Our aim was to explore the potential role of MAMs in mitigating hepatic IR through exercise and to compare the effects of different intensities of exercise on hepatic MAMs formation in high-fat diet (HFD) mice. METHODS: Male C57BL/6J mice were fed an HFD and randomly assigned to undergo supervised high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). IR was evaluated using the serum triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), glucose tolerance test (GTT), and insulin tolerance test (ITT). Hepatic steatosis was observed using hematoxylin-eosin (H&E) and oil red O staining. The phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K-AKT-GSK3ß) signaling pathway was assessed to determine hepatic IR. MAMs were evaluated through immunofluorescence (colocalization of voltage-dependent anion-selective channel 1 [VDAC1] and inositol 1,4,5-triphosphate receptor [IP3R]). RESULTS: After 8 weeks on an HFD, there was notable inhibition of the hepatic PI3K/Akt/GSK3ß signaling pathway, accompanied by a marked reduction in hepatic IP3R-VDAC1 colocalization levels. Both 8-week HIIT and MICT significantly enhanced the hepatic PI3K/Akt/GSK3ß signaling and colocalization levels of IP3R-VDAC1 in HFD mice, with MICT exhibiting a stronger effect on hepatic MAMs formation. Furthermore, the colocalization of hepatic IP3R-VDAC1 positively correlated with the expression levels of phosphorylation of protein kinase B (p-AKT) and phosphorylation of glycogen synthase kinase 3 beta (p-GSK3ß), while displaying a negative correlation with serum triglyceride/high-density lipoprotein cholesterol levels. CONCLUSION: The reduction in hepatic MAMs formation induced by HFD correlates with the development of hepatic IR. Both HIIT and MICT effectively bolster hepatic MAMs formation in HFD mice, with MICT demonstrating superior efficacy. Thus, MAMs might wield a pivotal role in exercise-induced alleviation of hepatic IR.

Triglicerydes/high-density lipoprotein ratio as a risk factor of post-Covid-19 sinus tachycardia: A retrospective study.

Inappropriate sinus tachycardia (IST) is one of the manifestations of the post-COVID-19 syndrome (PCS), which pathogenesis remains largely unknown. This study aimed to identify potential risk factors for IST in individuals with PCS. The 1349 patients with PCS were included into the study. Clinical examination, 24H Holter ECG, 24H ambulatory blood pressure monitoring and biochemical tests were performed 12-16 weeks after the COVID-19 in all participants. IST was found in 69 (3.5%) individuals. In the clinical assessment IST patients were characterized by a higher age (p < 0.001) and lower prevalence of the diagnosed hypertension (p = 0.012), compared to remaining patients. Biochemical testing showed higher serum triglycerides (1.66 vs. 1.31 pmol/L, p = 0.007) and higher prevalence of a low high-density lipoprotein (HDL) cholesterol (24.6% vs. 15.2%, p = 0.035) in the IST group. Subsequently, the triglicerydes (TG)/HDL ratio, an indicator of insulin resistance, was significantly higher in the IST individuals (3.2 vs. 2.4, p = 0.005). 24H monitoring revealed a significantly higher minimum diastolic, maximum systolic and mean arterial blood pressure values in the IST group (p < 0.001 for all), suggesting a high prevalence of undiagnosed hypertension. A multivariate analysis confirmed the predictive value TG/HDL ratio >3 (OR 2.67, p < 0.001) as predictors of IST development. A receiver operating characteristic curve analysis of the relationship between the TG/HDL ratio and the IST risk showed that the predictive cut-off point for this parameter was 2.46 (area under the ROC curve = 0.600, p = 0.004). Based on these findings, one can conclude that insulin resistance seems to be a risk factor of IST, a common component of PCS.

Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia / Influence of triglyceride concentration in lipoprotein (a) as a function of dyslipidemia

Introducción Recientemente se ha demostrado una relación inversa entre la concentración en sangre de la lipoproteína(a) (Lp[a]) y los triglicéridos (TG). A mayor tamaño de lipoproteínas de muy baja densidad (VLDL), mayor presencia de VLDL ricas en apoliproteína E (apo E) y en sujetos con genotipo apo E2/E2, Lp(a) más baja. El mecanismo de esta asociación contrapuesta es desconocido. El objetivo de nuestro análisis fue evaluar la correspondencia Lp(a)-TG en los pacientes atendidos en las Unidades de Lípidos incluidos en el registro de la Sociedad Española de Arteriosclerosis (SEA) comparando las diferentes dislipidemias. Pacientes y métodos Se incluyeron 5.275 usuarios de ≥ 18 años registrados antes del 31 de marzo de 2023, con datos de concentración de Lp(a) e información completa del perfil lipídico sin tratamiento. Resultados La media de edad fue de 53,0 ± 14,0 años, con 48% de mujeres. Un total de 9,5% (n = 502) tenían diabetes mellitus (DM) y 1.184 sujetos (22,4%) presentaban obesidad. La mediana de TG fue de 130 mg/dL (rango intercuartílico [IQR] 88,0-210) y de Lp(a) 55,0 nmol/L (IQR 17,9 -156). La concentración de Lp(a) mostró una asociación negativa con la de TG cuando los valores de estos superaban los 300 mg/dL. Los pacientes con TG > 1.000 mg/dL mostraron el menor nivel de Lp(a) 17,9 nmol/L y los usuarios con TG < 300 mg/dL, presentaron una media de Lp(a) de 60,1 nmol/L. En pacientes sin DM ni obesidad, la relación inversa de Lp(a)-TG fue especialmente importante (p < 0,001). La mediana de Lp(a) fue de 58,3 nmol/L en aquellos con TG < 300 mg/dL y 22,0 nmol/L si TG > 1.000 mg/dL. No se encontró asociación entre TG y Lp(a) en sujetos con DM y obesidad, ni en los que contaban con hipercolesterolemia familiar (HF). En los que padecen hiperlipemia combinada multifactorial con TG < 300 mg/dL la Lp(a) fue 64,6 nmol/L, en el rango de 300-399 mg/dL de TG la Lp(a) desciende hasta 38,8 nmol/L y hasta 22,3 nmol/L si TG > 1.000 mg/dL. Conclusiones ... (AU)

Background Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)–TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. Patients and methods Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. Results The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)–TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. Conclusions ... (AU)

The high-density lipoprotein cholesterol (HDL-C)-concentration-dependent association between anti-inflammatory capacity and sepsis: A single-center cross-sectional study.

INTRODUCTION: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters. METHODS AND MATERIALS: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity. RESULTS: ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013). CONCLUSION: ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment.

Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders.

Importance: Biomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent. Objective: To examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders. Design, Setting, and Participants: This population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023. Exposures: Lipid, apolipoprotein, and carbohydrate biomarkers measured in blood. Main Outcomes and Measures: The associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, and year of enrollment to the AMORIS cohort, using incidence density sampling. Population trajectories were used to illustrate the temporal trends in biomarker levels for cases and controls. Results: A total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for all tested disorders. The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the 10 years preceding diagnosis, compared with control participants. Conclusions and Relevance: In this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

SGLT2 inhibition, high-density lipoprotein, and kidney function: a mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibition is recognized for its evident renoprotective benefits in diabetic renal disease. Recent data suggest that SGLT2 inhibition also slows down kidney disease progression and reduces the risk of acute kidney injury, regardless of whether the patient has diabetes or not, but the mechanism behind these observed effects remains elusive. The objective of this study is to utilize a mendelian randomization (MR) methodology to comprehensively examine the influence of metabolites in circulation regarding the impact of SGLT2 inhibition on kidney function. METHODS: We used a MR study to obtain associations between genetic proxies for SGLT2 inhibition and kidney function. We retrieved the most recent and comprehensive summary statistics from genome-wide association studies (GWAS) that have been previously published and involved kidney function parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria. Additionally, we included blood metabolite data from 249 biomarkers in the UK Biobank for a more comprehensive analysis. We performed MR analyses to explore the causal relationships between SGLT2 inhibition and kidney function and two-step MR to discover potential mediating metabolites. RESULTS: The study found that a decrease in HbA1c levels by one standard deviation, which is genetically expected to result in SGLT2 inhibition, was linked to a decreased likelihood of developing type 2 diabetes mellitus (T2DM) (odds ratio [OR] = 0.55 [95% CI 0.35, 0.85], P = 0.007). Meanwhile, SGLT2 inhibition also protects eGFR (ß = 0.05 [95% CI 0.03, 0.08], P = 2.45 × 10- 5) and decreased UACR (-0.18 [95% CI -0.33, -0.02], P = 0.025) and albuminuria (-1.07 [95% CI -1.58, -0.57], P = 3.60 × 10- 5). Furthermore, the study found that of the 249 metabolites present in the blood, only one metabolite, specifically the concentration of small high-density lipoprotein (HDL) particles, was significantly correlated with both SGLT2 inhibition and kidney function. This metabolite was found to play a crucial role in mediating the improvement of renal function through the use of SGLT2 inhibition (ß = 0.01 [95% CI 0.005, 0.018], P = 0.001), with a mediated proportion of 13.33% (95% CI [5.71%, 26.67%], P = 0.020). CONCLUSIONS: The findings of this investigation provide evidence in favor of a genetically anticipated biological linkage between the inhibition of SGLT2, the presence of circulating metabolites, and renal function. The findings demonstrate that the protective effect of SGLT2 inhibition on renal function is mostly mediated by HDL particle concentrations in circulating metabolites. These results offer significant theoretical support for both the preservation of renal function and a better comprehension of the mechanisms underlying SGLT2 inhibition.

Association of a single-nucleotide polymorphism in C12orf43 region with the risk of coronary artery disease.

The genetics of organisms play a vital role in the development of coronary artery disease (CAD), with its heritability estimated at approximately 50-60%. For this purpose, we examined the relationship between CAD risk and C12orf43/rs2258287 polymorphisms in the Pakistani population. In this study based on the genetic approach to dyslipidemia, a total of 200 subjects were included from the southern Punjab. The biochemical analysis of parameters (total cholesterol, triglycerides, blood glucose, high-density lipoprotein, and low-density lipoprotein) was carried out along with molecular analysis using an ARMS-PCR-based assay for single-nucleotide polymorphism (SNP) C12orf43/rs2258287 to identify the genotype. Genotypes showed a substantial correlation with both family history and metabolic markers. The cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides and blood glucose levels were higher while the high-density lipoprotein cholesterol (HDL-C) level was lower significantly (p<0.05) in cases than in controls. Age, pulse rate, diabetes, physical activity, smoking, family history, and dietary habits were also significantly associated (p<0.05) with CAD individuals. The SNP C12orf43/rs2258287 also showed an association with CAD in the population of southern Punjab. Based upon this study, it could be concluded that CAD is characterized by an unfavorable lipid profile in association with SNP C12orf43/rs2258287.

High-Density Lipoprotein Metabolism and Function in Cardiovascular Diseases: What about Aging and Diet Effects?

Cardiovascular diseases (CVDs) have become the leading global cause of mortality, prompting a heightened focus on identifying precise indicators for their assessment and treatment. In this perspective, the plasma levels of HDL have emerged as a pivotal focus, given the demonstrable correlation between plasma levels and cardiovascular events, rendering them a noteworthy biomarker. However, it is crucial to acknowledge that HDLs, while intricate, are not presently a direct therapeutic target, necessitating a more nuanced understanding of their dynamic remodeling throughout their life cycle. HDLs exhibit several anti-atherosclerotic properties that define their functionality. This functionality of HDLs, which is independent of their concentration, may be impaired in certain risk factors for CVD. Moreover, because HDLs are dynamic parameters, in which HDL particles present different atheroprotective properties, it remains difficult to interpret the association between HDL level and CVD risk. Besides the antioxidant and anti-inflammatory activities of HDLs, their capacity to mediate cholesterol efflux, a key metric of HDL functionality, represents the main anti-atherosclerotic property of HDL. In this review, we will discuss the HDL components and HDL structure that may affect their functionality and we will review the mechanism by which HDL mediates cholesterol efflux. We will give a brief examination of the effects of aging and diet on HDL structure and function.

The Impact of Regular Screening and Lifestyle Modification on Cardiovascular Disease Risk Factors in South African Women Living With HIV.

BACKGROUND: The Integration of cardiovascular disease SCreening and prevention in the HIV MAnagement plan for women of reproductive age study set out to determine the effectiveness of screening and lifestyle modification in modifying cardiovascular disease (CVD) risk factors in women living with HIV (WLHIV). METHODS: In this prospective, quasiexperimental, intervention study, WLHIV aged 18-<50 years were enrolled from 2 clinics (intervention [I-arm]) and (control arms [C-arm]) in Umlazi, South Africa, between November 2018 and May 2019. Women in the I-arm received lifestyle modification advice on diet, physical activity, alcohol use, and smoking cessation and underwent annual screening for CVD risk. The CVD risk factors were assessed through standardized questionnaires and clinical and laboratory procedures at baseline and at end of 3 years of follow-up. Prevalence of metabolic syndrome and other CVD indices were compared between arms at end-of-study (EOS). RESULTS: Total of 269 WLHIV (149 I-arm and 120 C-arm) with a mean ± SD age of 36 ± 1 years were included in the EOS analyses after 32 ± 2 months of follow-up. The metabolic syndrome prevalence at EOS was 16.8% (25/149) in the I-arm and 24% (24/120) in the C-arm (risk ratio 0.9; 95% CI: 0.5 to 1.1; P 0.86). Proportion of women with fasting blood glucose >5.6 mmol/L in the I-arm and C-arm were 2.7% (4/149) and 13.3% (16/120) respectively (risk ratio 0.2; 95% CI: 0.069 to 0.646; P < 0.01). High-density lipoprotein improved with the intervention arm from baseline to EOS (95% CI: -0.157 to -0.034; P < 0.05). CONCLUSIONS: Although there was no significant difference in the prevalence of metabolic syndrome between study arms, we observed decreased blood glucose levels in the I-arm compared with the C-arm and improved high-density lipoprotein within the I-arm, following lifestyle modification and regular screening for CVD risk factors in WLHIV.

The high-density lipoprotein binding protein HDLBP is an unusual RNA-binding protein with multiple roles in cancer and disease.

The high-density lipoprotein binding protein (HDLBP) is the human member of an evolutionarily conserved family of RNA-binding proteins, the vigilin protein family. These proteins are characterized by 14 or 15 RNA-interacting KH (heterologous nuclear ribonucleoprotein K homology) domains. While mainly present at the cytoplasmic face of the endoplasmic reticulum, HDLBP and its homologs are also found in the cytosol and nucleus. HDLBP is involved in various processes, including translation, chromosome segregation, cholesterol transport and carcinogenesis. Especially, its association with the latter two has attracted specific interest in the HDLBP's molecular role. In this review, we give an overview of some of the functions of the protein as well as introduce its impact on different kinds of cancer, its connection to lipid metabolism and its role in viral infection. We also aim at addressing the possible use of HDLBP as a drug target or biomarker and discuss its future implications.

ANGPTL3 is a novel HDL component that regulates HDL function.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.

The association between lymphocyte to high-density lipoprotein ratio and depression: Data from NHANES 2015-2018.

INTRODUCTION: The relationship of lymphocyte to high-density lipoprotein ratio (LHR) with depression remains uncertain. We aimed to evaluate the association between LHR and depression in US adults. METHODS: In this cross-sectional study, a total of 4216 participants were enrolled from the National Health and Nutrition Examination Survey (2015-2018). Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Participants were classified as having depression if PHQ-9 scores were ≥10. Multiple logistic regression models were used to explore the relationship between the LHR and depression. RESULTS: Overall, the LHR was significantly associated with depression (per standard deviation increment; adjusted odds ratio (OR), 1.31; 95% confidence interval (CI) [1.14, 1.50]) after adjusted potential variables. Interactions between LHR with metabolic syndrome (MetS) and body mass index (BMI) on the risk of depression were found in stratified analysis (p for interaction < .05). CONCLUSIONS: A higher level of LHR was significantly associated with higher odds of having depression in US adults, and it was strengthened in participants with MetS or BMI ranging from 25 to 30 kg/m2 .

NMR-Based Analysis of Plasma Lipoprotein Subclass and Lipid Composition Demonstrate the Different Dietary Effects in ApoE-Deficient Mice.

Plasma lipid levels are commonly measured using traditional methods such as triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol (CH). However, the use of newer technologies, such as nuclear magnetic resonance (NMR) with post-analysis platforms, has made it easier to assess lipoprotein profiles in research. In this study involving ApoE-deficient mice that were fed high-fat diets, significant changes were observed in TG, CH, free cholesterol (FC), and phospholipid (PL) levels within the LDL fraction. The varied proportions of TG in wild-type mice and CH, FC, and PL in ApoE-/- mice were strikingly different in very low-density lipoproteins (VLDL), LDL, intermediate-density lipoprotein (IDL), and HDL. This comprehensive analysis expands our understanding of lipoprotein subfractions and the impacts of the APOE protein and high-fat diet in mouse models. The new testing method allows for a complete assessment of plasma lipids and their correlation with genetic background and diet in mice.

Monocyte-to-high-density lipoprotein ratio and systemic immune-inflammation index: Potential parameters for the evaluation of disease activity and severity in Graves' ophthalmopathy?

PURPOSE: To assess changes in monocyte-to-high-density lipoprotein (HDL) ratio (MHR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) with Graves' ophthalmopathy (GO) and their possible relation with GO disease activity and severity. METHODS: A total of 20 patients with GO and 24 healthy controls were involved in the study. The thyroid status, MHR (monocyte count/HDL cholesterol level), NLR (neutrophil count/lymphocyte count) and SII [(neutrophil count × platelet count)/lymphocyte count] were compared between the groups. The relation of systemic inflammation parameters with disease activity and severity was evaluated. RESULTS: The mean Clinical Activity Score (CAS) was 0.75 ± 0.78 in the GO group. None of the patients were active. The severity was mild for 14 (70.0%) patients and moderate-to-severe for 6 (30.0%) patients. MHR (17.28 ± 5.56 vs. 13.28 ± 5.08), NLR (2.51 ± 1.09 vs. 1.69 ± 0.53) and SII [600.42 (391.79-837.16) vs. 413.69 (344.26-603.82)] values were significantly increased in GO patients than in the controls (p = 0.017, p = 0.005 and p = 0.036, respectively). CAS was significantly correlated with MHR (r = 0.815, p < 0.001), NLR (r = 0.768, p = 0.017) and SII (r = 0.837, p < 0.001). The severity of GO was associated with increased MHR, NLR and SII (p = 0.019, p = 0.036 and p = 0.008, respectively). ROC analysis demonstrated that MHR, NLR and SII have a good ability to differentiate GO patients from healthy individuals. CONCLUSION: GO patients have higher MHR and SII levels than healthy controls. Higher MHR, NLR and SII values were associated with increasing disease severity and activity, supporting the efficacy of these non-invasive, low-cost markers in determining the course of GO. Future prospective controlled trials are needed to elucidate the relation between inflammatory markers and GO.

The association between long-term exposure to ambient PM2.5 and high-density lipoprotein cholesterol level among chinese middle-aged and older adults.

BACKGROUND: Recently, the impact of PM2.5 on human health has been intensively studied, especially the respiratory system. High-density lipoprotein plays a crucial role in removing excess cholesterol from cells and transporting it to the liver for excretion. However, the effects of ambient PM2.5 on high-density lipoprotein (HDL) level have not been further studied. Our research aims to investigate the potential association between ambient PM2.5 concentrations and high-density lipoprotein (HDL) levels within the middle-aged and older adults in China. METHODS: We employed data from individuals aged 45 years and above who were participants in Wave 3 of the China Health and Retirement Longitudinal Study (CHARLS). The high-quality, high-resolution PM2.5 exposure concentration data for each participant were obtained from the ChinaHighAirPollutants (CHAP) dataset, while the HDL levels were derived from blood samples collected during CHARLS Wave 3. This analysis constitutes a cross-sectional study involving a total of 12,519 participants. To investigate associations, we conducted multivariate linear regression analysis, supplemented by subgroup analysis. RESULTS: In this cross-sectional investigation, we discerned a negative association between prolonged exposure to ambient PM2.5 constituents and high-density lipoprotein (HDL) levels. The observed correlation between ambient PM2.5 and HDL levels suggests that older individuals residing in areas with elevated PM2.5 concentrations exhibit a reduction in HDL levels (Beta: -0.045; 95% CI: -0.056, -0.035; P < 0.001). Upon adjusting for age in Model I, the Beta coefficient remained consistent at -0.046 (95% CI: -0.056, -0.035; p < 0.001). This association persisted even after accounting for various potential confounding factors (Beta = -0.031, 95% CI: -0.041, -0.021, p < 0.001). CONCLUSIONS: Our study reveals a statistically significant negative correlation between sustained exposure to higher concentrations of ambient PM2.5 and high-density lipoprotein (HDL) levels among Chinese middle-aged and older individuals.