Low-density Lipoprotein Cholesterol Research Articles

Familial hypercholesterolemia: Current limitations and future breakthroughs

Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations, presenting with xanthomas, corneal arch, and severe cardiovascular diseases. Early identification, diagnosis, and treatment are crucial to prevent severe complications like acute myocardial infarction. Statins are the primary treatment, supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, though their effectiveness can be limited in severe cases. Over 90% of FH cases remain undiagnosed, and current treatments are often inadequate, underscoring the need for improved diagnostic and management systems. Future strategies include advancements in gene testing, precision medicine, and novel drugs, along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats. Lifestyle modifications, including health education, dietary control, and regular exercise, are essential for managing FH and preventing related diseases. Research into FH-related gene mutations, especially LDLR , is critical for accurate diagnosis and effective treatment.

Prevalence of hypercholesterolemia in the elderly and very elderly members of the Polish population: results of a national cross‑sectional representative survey.

Lipid disorders are the most common cardiovascular risk factor among the adult population in Poland. However, epidemiological data on the ever‑growing group of older adults remain insufficient. Our aim was to describe and analyze the epidemiology of lipid disorders among Polish seniors. A random sample of 4101 participants (2136 men; 1965 women) aged 65 to 104 years, evenly distributed across age subgroups (65-69, 70-74, 75-79, 80-84, 85-89, and ≥90 years), was included in the cross‑sectional, national PolSenior survey. Anthropometric measurements, blood pressure values, and blood samples for lipid profile testing were obtained. Hypercholesterolemia was present in 62.4% of Polish seniors (56.1% of men; 66.3% of women). The highest mean (95% CI) total cholesterol (TC) levels were observed in those aged 65-69 years: 206 (201-210.9) mg/dl in men and 220.6 (215.6-225.6) mg/dl in women. Women had higher TC levels than men across all age groups. Mean (95% CI) low‑density lipoprotein cholesterol (LDL‑C) levels followed a similar trend: in women, they decreased from 131.6 (127.2-136.1) mg/dl in the age group of 65-69 years to 120.1 (115.2-125) mg/dl in those aged 90 years or above. In men, LDL-C values declined from 121.6 (117.3-125.9) mg/dl to 106.5 (102.5-110.5) mg/dl over the same age span. LDL‑C concentrations were higher in women across all age categories. In the elderly Polish population, mean serum TC and LDL‑C concentrations are consistently higher in women than in men. The findings emphasize the significance of lipid disorders as a cardiovascular risk factor in older adults in Poland.

Effect of Statins on the Prognosis After Thoracic Endovascular Aortic Repair for Patients With Acute Type B Aortic Dissection.

To analyze the clinical efficacy of long-term statin therapy following thoracic endovascular aortic repair (TEVAR) in patients with acute type B aortic dissection (ATBAD). We retrospectively analyzed data from 645 patients treated between January 2005 and June 2022, dividing them into Statin Group (n=330) and Non-statin Group (n=315) based on whether they received long-term postoperative statin therapy. Patients were further categorized based on median admission low-density lipoprotein cholesterol (LDL-C) levels into High and Low LDL-C Groups to assess the effect of statins on the prognosis of ATBAD patients after TEVAR. The cohort had an average age of 53.44±11.42 years old, and 81.71% were male. Statin therapy significantly reduced occurrences of all-cause death (3.03% vs 8.57%, p=0.002) and aorta-related death (0.91% vs 3.81%, p=0.015), particularly in patients with high admission LDL-C levels. In addition, patients with statin therapy had a lower incidence of aorta-related adverse events (ARAE) (4.24% vs 11.11%, p=0.001). Kaplan-Meier analysis indicated statins reduced 5-year cumulative incidence rates of all-cause death and ARAE (all Log-rank p<0.05). These trends were sustained after adjustment. Multivariate Cox analysis confirmed that statin therapy was associated with reduced risks of all-cause and aorta-related deaths, as well as ARAE. Long-term statin therapy appears to decrease the risk of all-cause and aorta-related death in ATBAD patients after TEVAR, particularly patients with high admission LDL-C levels. Patients with lower LDL-C levels at admission have a reduction of aorta-related death in the follow-up period. Statin therapy also was associated with a lower incidence of ARAE in follow-up. These findings suggest that statins might be crucial in improving long-term outcomes in this patient population. Long-term statin therapy administered to patients with acute type B aortic dissection (ATBAD) following thoracic endovascular aortic repair (TEVAR) demonstrates a substantial reduction in both all-cause and aorta-related mortality. Notably, this therapeutic benefit is most evident in patients presenting with elevated low-density lipoprotein cholesterol (LDL-C) levels at admission. Furthermore, statin therapy is associated with a decreased incidence of aorta-related adverse events during follow-up. These findings underscore the pivotal role of statin therapy in enhancing long-term clinical outcomes for ATBAD patients undergoing TEVAR, thereby contributing to improved patient care and prognosis.

Global and Regional Burden of Ischemic Stroke Disease from 1990 to 2021: An Age-Period-Cohort Analysis.

Ischemic stroke is a significant global public health issue that impacts health burdens across various regions. This study analyzed data from the Global Burden of Disease Study 2021 to assess the incidence, mortality, and disability-adjusted life years (DALYs) associated with ischemic stroke worldwide and across different Socio-demographic Index (SDI) regions. Using joinpoint regression and age-period-cohort (APC) models, we examined trends in disease burden and made projections for 2022 to 2035. As of 2021, approximately 7,804,449 (95% UI, 6,719,760-8,943,692) individuals were affected by ischemic stroke, resulting in 3,591,499 (95% UI, 3,213,281-3,888,327) deaths and 70,357,912 (95% UI, 64,329,576-76,007,063) DALYs. These numbers represent increases of 88.0%, 55.0%, and 52.4% since 1990. Despite these increases, age-standardized incidence, mortality, and DALYs rates are declining, with annual percentage change rates (AAPC) of - 0.578%, - 0.927%, and - 14.372%, consistent across all SDI regions. The global rates of IS are influenced by age, period, and cohort, showing increased rates with age but declining over time, particularly in high SDI regions. Major risk factors include hypertension, environmental pollution, and low-density lipoprotein cholesterol (LDL-C). Projections indicate that by 2035, incidence, mortality, and DALYs will rise among those aged 45 and above, while decreasing for those under 35. This highlights the urgent need for preventive and therapeutic strategies targeting ischemic stroke, particularly for individuals over 45, while addressing the impact of major risk factors in high-burden regions.

Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner

BackgroundPulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.MethodsA high-throughput screening based on high-throughput sequencing was conducted in HepG2 cells to construct gene expression profiles for several hundred TCMs. In vivo evaluation of the efficacy of PC was performed using rats with hypercholesterolemia. Transcriptome analysis was carried out on PC-treated rat livers and HepG2 cells to investigate the mechanism of action of PC in vitro. The findings were further validated using RT-qPCR and western blot techniques.ResultsPC was identified as similar to Rhizoma Coptidis based on signature genes related to metabolism. Administration of PC via gavage in rats with hypercholesterolemia for 11 weeks resulted in substantially reduced serum total cholesterol and low-density lipoprotein (LDL) cholesterol and ameliorated fatty liver. Transcriptome analysis revealed that PC regulated various pathways associated with lipid metabolism. The LDL receptor (LDLR), a key player in cholesterol metabolism, was upregulated by PC both in vivo and in vitro. It was discovered that PC achieved this upregulation by activating extracellular regulated protein kinase (ERK) signaling in HepG2 cells. To uncover the major bioactive components responsible for the anti- hypercholesterolemia effect of PC, two major saponins, named Pulsatilla saponin D (PCD) and PC anemoside B4 (PCB4), were assessed. PCD, but not PCB4, was identified as the active ingredient responsible for the upregulation of LDLR by PC.ConclusionThese findings demonstrated that PC acts as an antihypercholesterolemic agent by upregulating LDLR in an ERK-dependent manner and holds potential in the treatment of hypercholesterolemia.

Lipid-Lowering Therapy Use When Indicated and Subsequent Ischemic Stroke Severity.

Elevated low-density lipoprotein cholesterol is a risk factor for atherosclerotic cardiovascular disease, including acute ischemic stroke (AIS), due to large- and small-vessel disease. Cholesterol management guidelines recommend lipid-lowering therapy (LLT) to prevent atherosclerotic cardiovascular disease events. This study assessed use of LLT at the time of AIS according to guideline recommendations and determined the association of prestroke LLT use with stroke severity. We conducted a retrospective study of patients hospitalized with AIS from 2015 to 2020 at a large academic comprehensive stroke center. Patients with AIS secondary to either small-vessel disease or large-artery atherosclerosis recorded in the institutional Get With The Guidelines-Stroke registry and with a prestroke indication for LLT were included. Using propensity score subclassification, adjusted logistic regression models were built to explore the associations between LLT use before AIS when indicated and presenting National Institutes of Health Stroke Scale score >4. There were 384 patients with AIS who met guideline-recommended criteria for prestroke LLT (median age 70 years, 57% men), of whom only 207 patients (54%) were prescribed LLT before AIS. Not being prescribed LLT when indicated was associated with a significantly higher likelihood of a presenting with National Institutes of Health Stroke Scale score >4, even when adjusted for specific stroke cause (odds ratio, 1.13 [95% CI, 1.03-1.20]; P=0.006). LLT is underused in patients who present with atherosclerosis-related AIS. Lack of prestroke LLT use was associated with more severe stroke symptoms upon presentation. These findings emphasize the need to prescribe LLT when indicated, because its use may mitigate poststroke disability.

Predictive value of nutritional status and serological indicators in elderly patients with mild cognitive impairment

BACKGROUND Mild cognitive impairment (MCI) in elderly individuals is a transitional stage between normal cognition and dementia. Understanding the risk factors for MCI and identifying those at high risk are extremely important for the elderly population. AIM To analyze the risk factors for MCI in the elderly population and construct a clinical prediction model. METHODS Total 295 elderly individuals presenting with memory loss diagnosed at Wuxi People's Hospital between March 2021 and March 2024 were included. Comprehensive demographic, clinical, and serological data were collected for analysis. Participants were categorized into either an MCI group or a normal group based on their performance on the Montreal Cognitive Assessment Scale. An elaborate clinical predictive model was developed to predict the likelihood of MCI in stroke patients; its accuracy was evaluated using area under curve values and calibration curves. RESULTS The results of the study showed that old age, hypertension, diabetes, hyperlipidemia, smoking, high-salt diet, high-cholesterol diet, decreased red blood count, increased neutrophil lymphocyte ratio and increased low-density lipoprotein cholesterol were risk factors for the onset of MCI, with A high vitamin diet and elevated high-density lipoprotein cholesterol being protective factors. In addition, the prediction model constructed in this study exhibits good degrees of differentiation and calibration. CONCLUSION The risk factors for MCI are diverse. Early identification of individuals at high risk of MCI can better intervene and improve their quality of life of MCI patients.

Comprehensive Mendelian randomization analysis of low-density lipoprotein cholesterol and multiple cancers

PurposeThe aim of this study was to investigate the causal relationship between low-density lipoprotein cholesterol (LDL-C) and five cancers (breast, cervical, thyroid, prostate and colorectal) using the Mendelian Randomization (MR) method, with a view to revealing the potential role of LDL-C in the development of these cancers.MethodsWe used gene variant data and disease data from the Genome-Wide Association Study (GWAS) database to assess the causal relationship between LDL-C and each cancer by Mendelian randomisation analysis methods such as inverse variance weighting and MR-Egger. Specifically, we selected Proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), genes associated with LDL-C levels, as instrumental variables, extracted the corresponding single nucleotide polymorphism (SNP) data and analysed the associations of these SNPs with five cancers.In addition, sensitivity analyses and heterogeneity tests were performed to ensure the reliability of the results.ResultsThe analyses showed that when using HMGCR gene, LDL-C were significantly and positively associated with breast (OR:1.200, 95% CI:1.082–1.329, p = 0.001), prostate (OR:1.198, 95% CI:1.050–1.366, p = 0.007), and thyroid cancers (OR:8.291, 95% CI:3.189- 21.555, p = 0.00001) were significantly positively correlated, whereas they were significantly negatively correlated with colorectal cancer (OR:0.641, 95% CI:0.442–0.928, p = 0.019); the results for cervical cancer were not significant (p = 0.050). When using the PCSK9 gene, LDL-C levels were significantly and positively associated with breast (OR:1.107, 95%:CI 1.031–1.187, p = 0.005) and prostate (OR:1.219, 95%:CI 1.101–1.349, p = 0.0001) cancers, but not with cervical (p = 0.294), thyroid cancer (p = 0.759) and colorectal cancer ( p = 0.572).ConclusionAnalyses using both the HMGCR and PCSK9 genes have shown that LDL-C may be a potential risk factor for breast and prostate cancer, while analyses of the HMGCR gene have also suggested that LDL-C may increase the risk of thyroid cancer and decrease the risk of colorectal cancer.

Relationship of adiponectin, leptin and reproductive endocrine hormones with insulin resistance in polycystic ovary syndrome patients with normal BMI

Objective This study aimed to analyze the correlation of adiponectin (APN) and leptin (LEP), reproductive endocrine hormones with insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI). Methods Totally 160 PCOS patients were categorized into the Normal BMI (BMI: 18.5–25 kg/m2, n = 62) and High BMI (BMI > 25 kg/m2, n = 98) groups. Glucose indicators [fasting plasma glucose, fasting insulin and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)], lipid indicators [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)], adipokines [APN and LEP] and reproductive endocrine hormones [luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), total testosterone (TT), dehy-droepiandrosterone sulfate (DHEAS) and estradiol (E2)] were collected, and their correlations were analyzed. The relationship of HOMA-IR with APN, LEP and reproductive endocrine hormones was subjected to multiple linear regression analysis. Results Correlation analysis revealed positive correlations of HOMA-IR with TC, TG, LDL-C, LEP, PRL, DHEAS and TT and negative correlations with HDL-C, APN, LH, FSH and E2 in PCOS patients with normal BMI. Multiple linear regression analysis showed that LH, FSH and E2 negatively affected HOMA-IR, while PRL positively affected HOMA-IR. Conclusion There were strong correlations of HOMA-IR in PCOS patients with normal BMI with APN, LEP, and reproductive endocrine hormones. Besides, LH, FSH, E2 and PRL expression had an important effect on IR in normal BMI PCOS patients, which provided a theoretical basis for the exploration of pathogenic mechanisms in normal BMI PCOS patients.

Identify unmet needs in diabetes care in Shandong, China: a secondary analysis of a cross-sectional study using cascade of care framework

BackgroundThe continuum management of diabetes remains under-evaluated in China. This study aimed to estimate the proportions of diabetes adults at each stage of the cascade of care framework in Shandong, China.MethodsWe conducted a secondary analysis using the 2018 China Adult Chronic Disease and Nutrition Surveillance (CACDNS) data in Shandong. This nationwide cross-sectional survey was conducted between September and November 2018, investigating the major chronic diseases among Chinese adults through interviews, physical examinations, and laboratory tests. We employed the cascade model to examine the proportion of diabetes adults, including both type 1 and type 2, from diabetes screening, diagnosis, pharmaceutical and non-pharmaceutical treatments, to single and comprehensive management targets, and quantified the attrition between each stage. Diabetes screening was defined as participants reported to have ever received a blood glucose test. Diabetes diagnosis was defined as: 1) fasting plasma glucose (FPG) ≥ 126 mg/dL, or 2) 2-h oral glucose tolerance test (2 h-OGTT) ≥ 200 mg/dL, or 3) hemoglobin A1c (HbA1c) ≥ 6.5%, or 4) self-reported diabetes. Diabetes management targets included: 1) single glycemic target of personalized HbA1c level, 2) comprehensive ABC targets of personalized HbA1c level, blood pressure (BP) < 140/80 mm Hg, and low-density lipoprotein cholesterol (LDL-c) level < 2.6 mmol/L, 3) lifestyle target of not currently smoking. The estimated proportion was calculated through self-reported diabetes status and FPG, 2h-OGTT and HbA1c. The number of diabetes cases in Shandong was extrapolated using the 2018 provincial census data for adults aged 18 years and above (N = 80.6 million). The cascade of diabetes care was further examined by age, sex, and Basic Public Health Service (BPHS) enrollment.ResultsThis secondary analysis included 8,462 individuals (47.8% males, median age: 49.0), among whom 12.4% had diabetes (self-reported: 4.2%, newly diagnosed: 8.2%) and 41.1% had prediabetes. In 2018, an estimated 9.2 million adults in Shandong had diabetes, with 6.4 million (69.6%) receiving diabetes screening but 6.2 million (67.7%) remaining unaware of their conditions. Among self-reported diabetes adults, 2.7 million (86.4%) and 2.8 million (89.6%) received pharmaceutical and non-pharmaceutical treatment, respectively. Of those with treatments, 1.2 million (58.2%) met personalized glycemic target. A rapid decline, however, was observed in BP (31.1%) and LDL-c (39.3%) control among diabetes patients with multimorbidity (≥ 2 diseases). Ultimately, 0.1 million self-reported diabetes adults (3.8%) achieved the ABC targets. BPHS Enrollment slightly improved comprehensive management with ABC targets.ConclusionsA significant unmet need exists for diabetes adults from screening to management, particularly the comprehensive management of glycemia, BP and LDL-c levels among those with multimorbidity. Tailored strategies and appropriate allocation of healthcare resource is needed to addressing gaps in care continuum and reduce long-term disease burden.

Adult-based genetic risk scores for insulin resistance associate with cardiometabolic traits in children and adolescents.

Insulin resistance (IR) is a key factor in the development of cardiometabolic diseases. While genetic risk scores (GRSs) for IR have been developed and validated in adult population, it is unclear if they can be used for risk assessment in youth. Our objective was to investigate whether adult-derived genetic risk scores (GRSs) for insulin resistance (IR) associate with cardiometabolic traits in children and adolescents. We studied a group of children and adolescents with obesity (n= 1,680) and a group without obesity (n=1,804). We constructed three GRSs based on fasting (IR-GRS27), oral glucose tolerance test (IR-GRS8), and IR-related phenotypes (IR-GRS51) from previous genome-wide association studies. Using an additive genetic model, we calculated weighted GRSs and analysed their associations with cardiometabolic traits using linear and logistic regression models. The IR-GRS27 was associated with higher serum concentrations of fasting insulin, C-peptide, triglyceride (TG), gamma-glutamyl transferase and alanine aminotransferase (ALT), and homeostatic model assessment of insulin resistance. The IR-GRS27 was furthermore associated with higher prevalence of IR and ALT. IR-GRS51 was associated with higher TG and lower high-density lipoprotein cholesterol, while IR-GRS8 associated with lower total cholesterol, low-density lipoprotein cholesterol, and increased ALT. IR-GRS27 and IR-GRS8 were additionally associated with higher prevalence of IR and steatotic liver disease respectively. Adult-derived GRSs for IR are significantly associated with cardiometabolic traits in children and adolescents. If validated in independent study samples, our findings suggest the contribution of adult-based GRSs in assessing IR-related cardiometabolic risk in youth.

Association of remnant cholesterol with insulin resistance and type 2 diabetes: mediation analyses from NHANES 1999–2020

BackgroundPrevious studies have established a correlation between elevated levels of remnant cholesterol (RC) and the occurrence of type 2 diabetes mellitus (T2D) as well as insulin resistance (IR); however, the precise nature of these associations remains incompletely elucidated. This study aimed to evaluate the relationships between RC and IR, as well as RC and T2D, and to determine the extent to which IR mediated the relationship between RC and T2D.MethodsThis was an observational study that utilized cross-sectional methods to examine the general population in the National Health and Nutrition Examination Survey (NHANES) 1999–2020. The participants were divided into 4 groups according to the RC quartiles. The outcome was the prevalence of IR and T2D. Survey-weighted binary logistic regression analysis was used to analyze the associations, and the restricted cubic spline (RCS) curve was used to further analyze the nonlinear relationship. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance, and the areas under the curves (AUC) of RC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were compared using the DeLong test. The mediating effect of IR on the relationship between RC and T2D was evaluated through mediation analysis.ResultsA total of 23,755 participants (46.02 ± 18.48 years, 48.8% male) were included in our study. Higher RC levels were significantly associated with increased prevalence of both IR and T2D. After adjusting for potential confounders, logistic regression analysis showed that higher RC quartiles were associated with the increased prevalence of IR [Quartile 4 vs. Quartile 1: odds ratio (OR) (95% confidence interval, CI): 1.65 (1.41–1.94), p < 0.001] and T2D [Quartile 4 vs. Quartile 1: OR (95% CI): 1.24 (1.03–1.50), p = 0.024]. RCS analysis revealed two distinct nonlinear relationships: one between RC levels and the prevalence of IR (nonlinear p < 0.001), and another between RC levels and the prevalence of T2D (nonlinear p < 0.001). ROC curve analysis demonstrated that RC had the highest discriminative ability, significantly outperforming LDL-C, HDL-C, and TG in predicting both IR and T2D risk (all P < 0.001 by DeLong test). Mediation analysis revealed that IR significantly mediated the relationship between RC and T2D, with approximately 54.1% of the effect of RC on T2D being indirect through IR.ConclusionsHigher RC level was associated with increased prevalence of IR and T2D. IR mediated 54.1% of the association between RC and T2D, suggesting that managing IR could be crucial in reducing the risk of T2D in individuals with elevated RC levels.

Daily steps, cardiorespiratory fitness, and remnant cholesterol in schoolchildren: mediation effects for cardiovascular prevention.

To analyse the associations between daily steps, cardiorespiratory fitness (CRF), and remnant cholesterol in schoolchildren and to investigate whether the association between daily steps and remnant cholesterol is mediated by CRF. This cross-sectional study involved 394 schoolchildren (aged 9-12 years, 53.0% girls) from Cuenca, Spain. Daily steps were measured using the Xiaomi MI Band 3, CRF was assessed using the 20-m shuttle run test, and remnant cholesterol was calculated from total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. Mean differences in CRF and remnant cholesterol by daily steps and CRF categories were tested using analysis of covariance. Mediation analysis models examined whether CRF mediates the association between daily steps and remnant cholesterol. Children taking 12,000 and 9000 steps/day had higher CRF (p < 0.001) and lower remnant cholesterol (p = 0.034), respectively. Those with CRF > 47.59 kg/ml/min had lower remnant cholesterol (p = 0.009). CRF mediated the association between 1000 steps/day and remnant cholesterol (indirect effect = -0.027 (-0.055,-0.007)). Both daily steps and CRF are associated with remnant cholesterol. Promoting an increase in daily steps may be a practical and promising strategy to increase CRF and, given its mediating role, to improve remnant cholesterol to prevent cardiometabolic risk in schoolchildren. What's known: Remnant cholesterol is a critical indicator of cardiovascular disease risk in the early atherosclerosis. What's new: In schoolchildren, increased daily physical activity is significantly associated with higher cardiorespiratory fitness and lower remnant cholesterol, especially walking >9000 steps/day and >12,000 steps/day, respectively. What's relevant: Encouraging schoolchildren to take more daily steps may be a promising strategy to increase cardiorespiratory fitness and, given its mediating role, to improve remnant cholesterol to prevent cardiometabolic risk.

Dyslipidemia and metabolic syndrome in childhood-onset systemic lupus erythematosus: is it time to screen?

BackgroundChildhood-onset systemic lupus erythematosus (cSLE) is associated with significant morbidity and mortality. Dyslipidemia and metabolic syndrome are recognized risk factors for premature atherosclerosis. This study aimed to determine the prevalence of dyslipidemia and metabolic syndrome, and to explore the relationships between lipid profiles, anthropometry, and disease status in cSLE.MethodsThis cross-sectional study was conducted at a university-based tertiary referral center from April 2023-March 2024. Patients aged 10–19 years with cSLE diagnosed before 18 years and at least 1 year follow-up were enrolled, excluding those with other autoimmune disorders, chronic kidney disease, infections, receiving lipid lowering drugs prior, and pregnancy. Demographic data, metabolic laboratory tests, disease status, dietary intake, anthropometry, and body composition via bioelectric impedance analysis were evaluated. The prevalence of dyslipidemia and metabolic syndrome were documented. Variables were compared between patients with and without dyslipidemia. Correlations between lipid profiles, metabolic laboratory variables, and SLE disease-related variables were explored.ResultsA total of 132 cSLE patients (94.7% female, mean age 11.6 ± 2.6 years) were included. Dyslipidemia was present in 48.5%, hypertriglyceridemia being the most common (28.8%); metabolic syndrome and hyperuricemia were present in 3.8% and 20.5%, respectively. Patients with dyslipidemia were significantly younger at cSLE diagnosis, had higher percentage of hypertension and active features of organ involvement, lower percentage of Lupus Low Disease Activity State, more use of mycophenolate mofetil and antihypertensive medications, higher uric acid level, higher waist circumference, body mass index, body mass index z-score, and fat mass (P < 0.05). Triglycerides, low-density lipoprotein cholesterol, and total cholesterol correlated positively with urine protein-to-creatinine ratio (r = 0.472, 0.469, and 0.591, respectively; P < 0.001) and negatively with serum albumin (r = -0.372, -0.506, and − 0.528, respectively; P < 0.001). Total cholesterol and low-density lipoprotein cholesterol correlated positively with cumulative prednisolone equivalent dose (rho = 0.350 and rho = 0.351, respectively, P < 0.001).ConclusionsNearly half of cSLE patients had dyslipidemia, especially those with younger age at diagnosis, higher body mass index, proteinuria, and suboptimal-controlled disease. Metabolic syndrome and hyperuricemia were present. Lipid profile assessment in early adolescents is recommended to identify metabolic comorbidities in cSLE.

Discordance Between Triglycerides, Remnant Cholesterol and Systemic Inflammation in Patients with Schizophrenia

Background/Objectives: Hypertriglyceridaemia and systemic inflammation are prevalent in patients with schizophrenia and contribute to an increased risk of cardiovascular disease. Although elevated triglycerides (TGs) and remnant cholesterol are linked to inflammation in the general population and individuals with metabolic syndrome, whether they are associated in patients with schizophrenia remains unclear. Methods: Fasting levels of TG, cholesterol (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and remnant cholesterol)), and markers of systemic inflammation including high-sensitivity C-reactive protein (hsCRP), leukocyte counts and their differentials (neutrophils, monocytes and lymphocytes) were determined in 147 patients diagnosed with schizophrenia on long-term antipsychotic regimens and compared with 56 age- and sex-matched healthy controls. Apolipoprotein B and glycosylation of acute phase reactant (GlycA) signatures were assessed by NMR. Circulating cytokine levels were measured by a cytokine/chemokine multiplex assay. Results: Patients with schizophrenia had markedly elevated TG and remnant cholesterol relative to controls and had evidence of systemic inflammation with increased circulating hsCRP, GlycA, leukocyte, neutrophil counts and neutrophil-to-lymphocyte ratio (NLR). Unexpectedly TG and remnant cholesterol did not correlate with systemic inflammatory markers in patients with schizophrenia, and differences in inflammatory markers between controls and patients persisted after adjusting for the lipid profile. Interleukin (IL)-10 levels were increased in patients with schizophrenia, suggesting an anti-inflammatory signature. Conclusions: The discordance between TG, remnant cholesterol and systemic inflammation in patients with schizophrenia suggests these are likely independent contributors to cardiovascular risk in this population.

Evaluation of Serum Lipids, Biochemical Parameters, Selected Antioxidant Elements and Oxidative Stress Profiles in Late Pregnant Jennies with Hyperlipemia

Donkeys are particularly at risk of hyperlipemia. Hyperlipemia is a metabolic disease caused by the mobilization of fatty acids from adipose tissue, which often impacts pregnant and lactating jennies (female donkeys) during periods of negative energy balance. This study aimed to evaluate the levels of lipids, biochemical parameters, selected antioxidant elements and oxidative stress parameters in late pregnant jennies affected by hyperlipemia. Compared with the healthy jennies, the hyperlipemic animals exhibited significantly elevated levels of triglycerides (TGs), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (p &lt; 0.05), coupled with reduced levels of high-density lipoprotein cholesterol and albumin (ALB) (p &lt; 0.05). The serum levels of biochemical parameters related to liver function, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (AKP) and cholinesterase (CHE), showed a significant increase in the hyperlipemia group compared to the healthy group (p &lt; 0.05). The serum level of selenium was significantly lower (p &lt; 0.05) and positively correlated with TGs (r = 0.85) and ALB (r = 0.73) in the hyperlipemia group. The hyperlipemic jennies showed diminished serum levels of antioxidant capacity and increased levels of malondialdehyde (MDA). The area under the curve values for T-CHO, ALB, AKP, CHE, total superoxide dismutase, glutathione and MDA were relatively high. Thus, our findings reflect metabolic disorders, liver dysfunction and oxidative stress in late pregnant hyperlipemic jennies, providing a basis for the improvement of clinical diagnostic methods and early prevention and control of hyperlipemia in jennies.

Association of plasma endocan levels with metabolic parameters and predictive value of endocan for the development of complications in patients with type 2 diabetes mellitus: An observational study

The aim of the current research was to investigate the association between plasma endocan levels and metabolic control parameters, as well as to evaluate its predictive value for clinical complications in patients with type 2 diabetes mellitus (DMT2). A total of 100 DMT2 patients participated in this prospective observational study. Plasma endocan levels were significantly elevated in DMT2 patients with HbA1c&gt;7% (1.38±0.33 vs. 0.68±0.23 ng/mL; p&lt;0.0001), compared to patients with HbA1c ≤7%. Patients with plasma endocan concentrations &gt;1.10 ng/mL (median value of 1.10 ng/mL) demonstrated significantly higher levels of metabolic parameters: body mass index (BMI), HbA1c%, fasting glucose level, LDL cholesterol, total cholesterol, triglycerides, along with significantly lower HDL cholesterol levels. Furthermore, patients with plasma endocan levels &gt;1.10 ng/mL were found to have an increased risk for the following complications: retinopathy (RR: 2.7500; 95% CI: 1.2150 to 6.2244; p= 0.0152, nephropathy (RR: 2.0952; 95% CI: 1.2294 to 3.5710; p=0.0065), neuropathy (RR: 1.9945; 95% CI: 1.2025 to 3.3081); p=0.0075 ), angina pectoris (RR: 2.4881; 95% CI 1.0865 to 5.6979; p=0.0311, hypertension (RR: 1.1372; 95% CI 1.0060 to 1.2856; p=0.0398), cardiomyopathy (RR: 2.6190; 95% CI 1.1507 to 5.9612; p=0.0218), myocardial infarction (RR: 9.4286; 95% CI 1.2742 to 69.7697; p=0.0280) and stroke (RR: 4.4638; 95% CI 1.3765 to 14.4758; p=0.0127). Correlation analysis revealed that plasma endocan levels were positively correlated with HbA1c% (r=0.856, p&lt;0.0001), fasting glucose level (r=0.631, p&lt;0.0001), LDL (r=0.347, p=0.0004), cholesterol (r=0.282, p=0.0045) and triglycerides (r=0.366, p=0.0002). Conversely, plasma endocan levels were negatively correlated with HDL cholesterol (r= - 0.429, p&lt;0.0001). In conclusion, higher plasma endocan levels were strongly associated with poor metabolic control in DMT2 patients and exhibited significant predictive value for both microvascular and macrovascular complications.

Linear and non-linear relationships between red blood cell indices and cardiovascular risk factors: findings from the China National Health Survey

IntroductionCardiovascular diseases (CVDs) are a leading cause of mortality worldwide. Red blood cell indices (RBIs) are associated with CVD risk factors (CRFs) and easy to test, making them useful as a screening tool for early identification of individuals at high risk for CVDs.MethodsData from 31,781 participants in the China National Health Survey conducted from 2012 to 2017 were analyzed. Linear and non-linear relationships between RBIs and CRFs (hyperuricemia, diabetes, dyslipidemia) were assessed using restricted cubic splines. Propensity score weighting was used to balance confounders between RBI groups in the multivariable logistic regression models.ResultsHemoglobin concentration, red blood cell count and hematocrit all showed a significant linear dose-response association with all CRFs (p values < 0.001). Higher RBIs levels were associated with increased risk of hyperuricemia, diabetes, high LDL, high triglycerides, and high total cholesterol, but decreased HDL. For example, compared to the lowest quantile of HGB, the highest quantile had a 26% (13-40%) higher risk for hyperuricemia, a 43% (25-63%) higher risk of diabetes, 87% (61%-1.18 fold) higher risk of high LDL, and 68% (52-85%) higher risk of high triglycerides. Non-linear relationships were revealed between RBIs and most CRFs except uric acid and glucose. Sex differences were observed, with stronger associations between RBIs and hyperuricemia in women but stronger links with high LDL in men.ConclusionsElevated RBIs indicated higher risk of multiple CRFs. These findings suggest incorporating RBIs into CVD screening strategies to facilitate early prevention efforts, with consideration of sex differences.

Type 2 diabetes genetic risk and incident diabetes across diabetes risk enhancers.

To evaluate the predictive value of a contemporary type 2 diabetes (T2D) polygenic score (PGS) in detecting incident diabetes across a range of diabetes risk factors. We analysed participants in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial (ClinicalTrials.gov, number NCT0176463), which compared the efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab versus placebo in lowering cardiovascular outcomes in participants with stable atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL (1.8 mmol/L) or higher who were receiving statin therapy. Genetic risk was characterized using a previously validated T2D PGS based on ~1.2 million single-nucleotide polymorphisms. PGS was analysed continuously and categorically as high (top 20% of the PGS) and low to intermediate (lower 80% of the PGS). The effect of evolocumab on incident diabetes in patients without diabetes at baseline was also assessed. HbA1c was measured at baseline and every 24 weeks thereafter, while FPG was measured at baseline, week 12, week 24 and every 24 weeks thereafter. Potential cases of incident diabetes were adjudicated centrally. Hazards ratios (HRs) for incident diabetes were adjusted for baseline characteristics and ancestry. Among 9388 participants, the mean age was 63 ± 9 years and 22.7% were women, with median HbA1c 39 mmol/mol (36 mmol/mol - 41 mmol/mol; 5.7% [5.4%-5.9%]) and mean body mass index (BMI) 28.7 ± 5 kg/m2. Diabetes developed in 690 participants (7.3%) during 2.3 years of median follow-up. T2D PGS predicted incident T2D (HR per 1-SD 1.22, 95% CI 1.14-1.32, p < 0.001). The rates of incident T2D in the high and low to intermediate genetic risk categories were 12.1% versus 6.8%, respectively (HR 1.43 95% CI 1.20-1.70, p < 0.001). Notably, high T2D genetic risk had greater predictive strength among individuals with lower HbA1c (P-int = 0.0499) and lower BMI (P-int = 0.004). The T2D polygenic score serves as an independent predictor of incident diabetes, particularly among individuals with lower distribution of traditional risk factors.

Development and validation of a nomogram for predicting the risk of obstructive coronary artery disease in rheumatoid arthritis patients based on LDL-C, Th17 cells, and IL-17

ObjectiveThis study aims to develop and validate a nomogram model for predicting the risk of obstructive coronary artery disease (CAD) in patients with rheumatoid arthritis (RA), incorporating low-density lipoprotein cholesterol (LDL-C), Th17 cells, and interleukin (IL)-17 levels. The proposed model seeks to enable personalized cardiovascular risk assessment for RA patients, thereby optimizing clinical management strategies.MethodsA total of 120 patients with rheumatoid arthritis (RA) who were treated at the Second Hospital of Shanxi Medical University between January 2019 and September 2023 were enrolled in this study. Based on coronary angiography results, patients were categorized into the RA-obstructive CAD group and the RA-non-obstructive CAD group. Additionally, 53 healthy controls (HC group) were included. Clinical characteristics, laboratory parameters, peripheral blood lymphocyte subsets, and cytokine levels were collected for analysis. Univariate logistic regression was used to identify risk factors associated with RA-obstructive CAD. These variables were further refined using a random forest model for optimal selection. Finally, multivariate logistic regression analysis was performed with the selected variables to develop a nomogram model, which was subsequently validated to assess its performance.ResultsCompared with the RA-non-obstructive CAD group, the RA-obstructive CAD group demonstrated significantly elevated levels of immune cell subsets, such as Th17 cells, and cytokines, including IL-17, IL-2, and IL-4, along with a reduction in Treg cells. (2) In the training cohort, univariate and multivariate logistic regression analyses identified LDL-C (OR = 0.04, P &amp;lt; 0.001), Th17 cells (OR = 0.76, P = 0.005), and IL-17 (OR = 0.75, P = 0.001) as independent risk factors for obstructive CAD in RA patients. Subsequently, a predictive nomogram model for RA-obstructive CAD risk was developed based on these indicators, incorporating LDL-C, Th17 cells, and IL-17.ConclusionThis study developed a predictive nomogram for RA-obstructive CAD by combining traditional risk factors, such as LDL-C, with immune biomarkers Th17 and IL-17. The model demonstrated robust predictive accuracy, enabling more precise risk assessment of CAD in RA patients. It offers clinicians a valuable tool for advancing cardiovascular risk management in RA, underscoring its significant potential for clinical application.