Elevated Cholesterol Research Articles

Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation.

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, nor were the effects on cell membranes or the wider cell known. Using patient-derived cells we show that cholesterol perturbation is a conserved feature of pathological ATAD3 variants that is accompanied by an expanded lysosome population containing membrane whorls characteristic of lysosomal storage diseases. Lysosomes are also more numerous in Drosophila neural progenitor cells expressing mutant Atad3, which exhibit abundant membrane-bound cholesterol aggregates, many of which co-localize with lysosomes. Using nutrient restriction and cholesterol supplementation, we show that the Drosophila Atad3 mutant displays heightened cholesterol dependence. Collectively, these findings suggest elevated cholesterol enhances tolerance to pathological ATAD3 variants, at a cost of inducing cholesterol aggregation in membranes, which lysosomal clearance only partly mitigates.

Increased low-density lipoprotein cholesterol on a low-carbohydrate diet in adults with normal but not high body weight: A meta-analysis

BackgroundLow-density lipoprotein (LDL) cholesterol change with consumption of a low-carbohydrate diet (LCD) is highly variable. Identifying the source of this heterogeneity could guide clinical decision-making. ObjectivesTo evaluate LDL cholesterol change in randomized controlled trials involving LCDs, with a focus on body mass index (BMI) in kg/m2. MethodsThree electronic indexes (Pubmed, EBSCO, and Scielo) were searched for studies between 1 January, 2003 and 20 December, 2022. Two independent reviewers identified randomized controlled trials involving adults consuming <130 g/d carbohydrate and reporting BMI and LDL cholesterol change or equivalent data. Two investigators extracted relevant data, which were validated by other investigators. Data were analyzed using a random-effects model and contrasted with results of pooled individual participant data. ResultsForty-one trials with 1379 participants and a mean intervention duration of 19.4 wk were included. In a meta-regression accounting for 51.4% of the observed variability on LCDs, mean baseline BMI had a strong inverse association with LDL cholesterol change [β = –2.5 mg/dL/BMI unit, 95% confidence interval (CI): –3.7, –1.4], whereas saturated fat amount was not significantly associated with LDL cholesterol change. For trials with mean baseline BMI <25, LDL cholesterol increased by 41 mg/dL (95% CI: 19.6, 63.3) on the LCD. By contrast, for trials with a mean of BMI 25–<35, LDL cholesterol did not change, and for trials with a mean BMI ≥35, LDL cholesterol decreased by 7 mg/dL (95% CI: –12.1, –1.3). Using individual participant data, the relationship between BMI and LDL cholesterol change was not observed on higher-carbohydrate diets. ConclusionsA substantial increase in LDL cholesterol is likely for individuals with low but not high BMI with consumption of an LCD, findings that may help guide individualized nutritional management of cardiovascular disease risk. As carbohydrate restriction tends to improve other lipid and nonlipid risk factors, the clinical significance of isolated LDL cholesterol elevation in this context warrants investigation.This trial was registered at PROSPERO as CRD42022299278.

Self-reported cardiovascular disease risk factor screening among people living with HIV vs. members of the general population in Botswana: a community-based study.

Morbidity and mortality due to cardiovascular diseases (CVDs) are high and increasing in low- and middle-income countries. People living with HIV (PLWH) are more likely to experience CVD than members of the general population. Therefore, we aimed to assess whether PLWH were more likely to have previously been screened for cardiovascular disease risk factors (CVDRFs) than people without HIV. A population-based, cross-sectional study was conducted among individuals aged 16 to 68 years across 22 communities in Botswana from February to August 2017 as part of a larger community-based cluster randomized HIV treatment-as-prevention trial. Participants were asked if they had been screened for and counselled on cardiovascular disease risk factors (history of hypertension or blood pressure check, blood glucose and cholesterol measurements, weight check and weight control, tobacco smoking and cessation, alcohol use and physical activity) in the preceding 3 years. HIV testing was offered to those with an unknown HIV status. Multiple logistic regression analysis controlling for age and sex was used to assess the relationship between CVDRF screening and HIV status. Of the 3981 participants enrolled, 2547 (64%) were female, and 1196 (30%) were PLWH (93% already on antiretroviral therapy [ART]). PLWH were more likely to report previous screening for diabetes (25% vs. 19%, p < 0.001), elevated cholesterol (17% vs. 12%, p < 0.001) and to have had their weight checked (76% vs. 55%, p < 0.001) than HIV-uninfected participants. PLWH were also more likely to have received counselling on salt intake (42% vs. 33%, p < 0.001), smoking cessation (66% vs. 46%, p < 0.001), weight control (38% vs. 29%, p < 0.001), physical activity (46% vs. 34%, p < 0.001) and alcohol consumption (35% vs. 23%, p < 0.001) than their HIV-uninfected counterparts. Overall, PLWH were more likely to have received screening for and/or counselling on CVDRFs (adjusted odds ratio 1.84, 95% CI: 1.46-2.32, p < 0.001). PLWH were almost two times more likely to have been previously screened for CVDRFs than those without HIV, indicating a need for universal scale-up of integrated management and prevention of CVDs in the HIV-uninfected population.

Investigating the relationship between intracranial atherosclerotic plaque remodelling and diabetes using high-resolution vessel wall imaging.

Intracranial atherosclerosis, a leading cause of stroke, involves arterial plaque formation. This study explores the link between plaque remodelling patterns and diabetes using high-resolution vessel wall imaging (HR-VWI). To investigate the factors of intracranial atherosclerotic remodelling patterns and the relationship between intracranial atherosclerotic remodelling and diabetes mellitus using HR-VWI. Ninety-four patients diagnosed with middle cerebral artery or basilar artery atherosclerosis were enrolled. Their basic clinical data were collected, and HR-VWI was performed. The vascular area at the plaque (VAMLN) and normal reference vessel (VAreference) were delineated and measured using image postprocessing software, and the Remodelling index (RI) was calculated. According to the value of the RI, the patients were divided into a positive remodelling (PR) group, intermediate remodelling (IR) group, negative remodelling (NR) group, PR group and non-PR (N-PR) group. The PR group exhibited a higher prevalence of diabetes and serum cholesterol levels than the IR and NR groups [45.2%, 4.54 (4.16, 5.93) vs 25%, 4.80 ± 1.22 and 16.4%, 4.14 (3.53, 4.75), respectively, P < 0.05]. The diabetes incidence was also significantly greater in the PR group than in the N-PR group (45.2% vs 17.5%, P < 0.05). Furthermore, the PR group displayed elevated serum triglyceride and cholesterol levels compared to the N-PR group [1.64 (1.23, 2.33) and 4.54 (4.16, 5.93) vs 4.54 (4.16, 5.93) and 4.24 (3.53, 4.89), P < 0.05]. Logistic regression analysis revealed diabetes mellitus as an independent influencing factor in plaque-PR [odds ratio (95% confidence interval): 3.718 (1.207-11.454), P < 0.05]. HR-VWI can clearly show the morphology and signal characteristics of intracranial vascular walls and plaques. Intracranial atherosclerotic plaques in diabetic patients are more likely to show PR, suggesting poor plaque stability and a greater risk of stroke.

Ethanolic Stem-Bark Extract of Blighia unijugata Possesses Anti-Hyperglycemic and Anti-Hyperlipidemic Activity in a Streptozotocin-Induced Diabetes Model

Introduction: The global rise in the incidence of diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), and its associated complications have become a public health threat. Besides hyperglycemia, hyperlipidemia has been associated with diabetes due to the defect in insulin secretion and/or action. Medicinal plants are being investigated to discover drug alternatives with better efficacies, lesser adverse effects, and cost-effectiveness. This work investigated the anti-hyperglycemic and anti-hyperlipidemic activity of ethanolic stem bark extract of Blighia unijugata (EBU) in streptozotocin (STZ)-induced diabetic Sprague- Dawley (SD) rats.&#x0D; Method: T2DM was induced in male SD rats by a single intraperitoneal injection of STZ (50 mg/kg in 0.1 M citrate buffer, pH 4.5) and confirmed 72 hours later. EBU (100 and 200 mg/kg) and glibenclamide (5 mg/kg) were administered orally to the diabetic rats (n = 5) for 28 days. The effect of the treatments on fasting blood glucose (FBG), lipid profile, atherogenic predictor indices, and body weight were assessed.&#x0D; Results: EBU treatments significantly reduced (p≤0.001) elevated blood glucose, total cholesterol, triglycerides, and Very Low-Density Lipoprotein cholesterol (VLDL-c, p≤0.001) but increased High-Density Lipoprotein cholesterol (HDL, p≤0.05) compared to the diabetic control. Also, all the atherogenic risk predictor indices were significantly reduced (p≤0.001). In addition, EBU treatment mitigated the significant weight loss (p≤0.01) associated with the diabetic state when compared to the normal control.&#x0D; Conclusion: These findings first report the anti-hyperglycemic, anti-hyperlipidemic, and anti-atherogenic properties of the stem bark of ethanolic extract of Blighia unijugata, and can be further studied and used as an anti-diabetic and anti-hyperlipidemic agent.&#x0D; Keywords: Blighia unijugata; hyperglycemia; atherogenic index; hyperlipidemia; diabetes

Blood Biochemical Reference Intervals of Black Caimans (Melanosuchus niger) and Spectacled Caimans (Caiman crocodilus) in the Brazilian Amazon Region.

Reference intervals for physiologic parameters, crucial for assessing the health status of animals, have been documented for various crocodilian species across the globe. Nonetheless, the establishment of plasma biochemical reference intervals specific to Amazonian crocodilians remains incomplete. In an effort to address this gap, we procured blood samples from 65 black caimans (Melanosuchus niger) and 58 spectacled caimans (Caiman crocodilus) during the period of September-December 2019 within the Anavilhanas National Park in the Brazilian Amazon region We aimed to define reference intervals for 11 key plasma variables measured, namely glucose, triglycerides, total cholesterol, calcium, magnesium, sodium, potassium, albumin, total protein, uric acid, and urea. In general, the determined blood reference intervals aligned closely with those established for other crocodilian species. Some specific measurements, such as total cholesterol, sodium, and magnesium, exhibited distinct variations based on the species. Furthermore, female black caimans showcased elevated cholesterol levels compared with their male counterparts. Within the spectacled caimans, disparities related to sex were evident solely in the case of electrolytes sodium and potassium, with males demonstrating higher levels compared with females. These reference intervals not only provide data for assessing potential fluctuations in the health of wild or captive Amazonian crocodilians but also hold value for veterinary management.

VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disease burden in the world and is highly correlated with chronic elevations of LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce the risk of cardiovascular diseases; however, statins are associated with limited efficacy and poor adherence to treatment, whereas PCSK9 inhibitors are only prescribed to a “high-risk” patient population or those who have failed other therapies. Based on the proven efficacy and safety profile of existing monoclonal antibodies, we have developed a peptide-based vaccine against PCSK9, VXX-401, as an alternative option to treat hypercholesterolemia and prevent ASCVD. VXX-401 is designed to trigger a safe humoral immune response against PCSK9, resulting in the production of endogenous antibodies and a subsequent 30–40% reduction in blood LDL-C. In this article, VXX-401 demonstrates robust immunogenicity and sustained serum LDL-C-lowering effects in nonhuman primates. In addition, antibodies induced by VXX-401 bind to human PCSK9 with high affinity and block the inhibitory effect of PCSK9 on LDL-C uptake in a hepatic cell model. A repeat-dose toxicity study conducted in nonhuman primates under good laboratory practices toxicity indicated a suitable safety and tolerability profile, with injection site reactions being the main findings. As a promising safe and effective LDL-C-lowering therapy, VXX-401 may represent a broadly accessible and convenient option to treat hypercholesterolemia and prevent ASCVD.

An Evaluation of Anti-hyperlipidemic Activity of Ethanolic Extract of Coccinia grandis Leaves in High Fat Induced Rodent Model

In the realm of health research, hyperlipidemia is a condition that has lately become prevalent and is a serious issue. Elevated lipid levels in an individual's body are the primary indicator of hyperlipidemia, a condition defined by increased levels of low-density lipoprotein (LDL), total cholesterol, triglycerides, and high lipoprotein levels. Several pharmacological agents are accessible for the treatment of hyperlipidemia. Nevertheless, human beings throughout the globe also thrive on nature-derived therapeutic items. Coccinia grandis is a noteworthy plant known for its antihyperlipidemic properties among them. In this study, we provided a high-fat diet for the experimental rats to generate hyperlipidemia conditions in this rat model. As per our research methodology, Coccnia grandis was administered to all the rats in the treatment group at three (low, medium and high) distinct dosages. It is eventually revealed that Coccnia grandis may successfully lower (p&lt;0.05) the hyperlipidemic state in both medium and high dosages. Elevated and unusual Triglyceride and Total Cholesterol were observed to be restored following Coccnia grandis medication. However, in the case of HDL and LDL, no substantial drop was detected. A considerable restoration was noted similarly in both instances of SGPT and SGOT. These findings show that our plant has components with antihyperlipidemic action, however the concentrations did not meet the necessary threshold. So, additional investigations are needed to examine the chemical structure and the quantities of the molecule as well as find out about genetic alterations.

Comparison of Two Strategies for Hypercholesterolemia Detection through Point-of-Care Testing.

Childhood dyslipidemia is a common condition that can lead to atherosclerotic cardiovascular disease in adulthood. It is usually multifactorial. Screening for cholesterol disorders in children varies based on risk factors, with some guidelines recommending cascade screening for children with a clear family history of familial hypercholesterolemia, targeted screening for those with specific risk factors, and universal screening. Point-of-care testing (POCT) cholesterol tests offer potential advantages, including ease of use, portability, increased patient access, low cost, fewer medical or laboratory visits, and instant results. This study aimed to evaluate the effect of POCT cholesterol screening on the diagnosis of hypercholesterolemia in children in a family practice setting. We used a POCT cholesterol analyzer to perform two different (universal and targeted) screening approaches for dyslipidemia in children. We used the NCEP guidelines for the classification of the results. We screened 183 children, 105 in the universal screening group and 78 in the targeted screening group. Eight patients in the targeted screening group had elevated cholesterol levels (p = 0.02). All participants received instant feedback and recommendations. Using a targeted screening approach, POCT could be a practical and effective tool for identifying at-risk children with hypercholesterolemia.

Cross-sectional association between blood cholesterol and calcium levels in genetically diverse strains of mice.

Genetically diverse outbred mice allow for the study of genetic variation in the context of high dietary and environmental control. Using a machine learning approach, we investigated clinical and morphometric factors that associate with serum cholesterol levels in 840 genetically unique Diversity Outbred mice of both sexes (n = 417 male and 423 female), and on both acontrol chow (% kcals in diet: protein 22%, carbohydrate 62%, fat 16%,no cholesterol) and high fat high sucrose (%kcals in diet: protein 15%, carbohydrate 41%, fat 45%, 0.05% cholesterol). We find expected elevations of cholesterol in male mice, as well as in mice with elevated serum triglycerides and/or fed a high fat high sucrose diet. The third strongest predictor was serum calcium which correlated with serum cholesterol across both diets and sexes (r = 0.39-0.48) in both Diversity Outbred (P = 3.0 × 10-43 ) and BXD (P = 0.005) mice. This is in-line with several human cohort studies which show associations between calcium and cholesterol, and calcium as an independent predictor of cardiovascular events.

IPSC-Derived Endothelial Cells Reveal LDLR Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia.

Defects in the low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. LDLR deficiency in hepatocytes leads to elevated blood cholesterol levels, which damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully understood. In this study, we obtained and examined endothelial derivatives of induced pluripotent stem cells (iPSCs) generated previously from conditionally healthy donors and compound heterozygous FH patients carrying pathogenic LDLR alleles. In normal iPSC-derived endothelial cells (iPSC-ECs), we detected the LDLR protein predominantly in its mature form, whereas iPSC-ECs from FH patients have reduced levels of mature LDLR and show abolished low-density lipoprotein uptake. RNA-seq of mutant LDLR iPSC-ECs revealed a unique transcriptome profile with downregulated genes related to monocarboxylic acid transport, exocytosis, and cell adhesion, whereas upregulated signaling pathways were involved in cell secretion and leukocyte activation. Overall, these findings suggest that LDLR defects increase the susceptibility of endothelial cells to inflammation and oxidative stress. In combination with elevated extrinsic cholesterol levels, this may result in accelerated endothelial dysfunction, contributing to early progression of atherosclerosis and other cardiovascular pathologies associated with FH.

Effects of elevated remnant cholesterol on outcomes of acute ischemic stroke patients receiving mechanical thrombectomy.

Large cohort studies provided evidence that elevated remnant cholesterol (RC) was an important risk factor for ischemic stroke. However, the association between high RC and clinical outcomes in acute ischemic stroke (AIS) individuals was still undetermined. This retrospective study enrolled 165 AIS patients undergoing mechanical thrombectomy in one tertiary stroke center. We divided patients into two groups based on the median of their RC levels (0.49 mmol/L). The modified Rankin Scale (mRS) was used to evaluate the primary outcome 90 days after the onset of symptoms. The mRS scores ≤ 2 and ≤ 1 at 90 days were deemed as favorable and excellent outcomes, respectively. In the overall AIS patients undergoing mechanical thrombectomy, there was no obvious distinction between the high and low RC group at 90-day favorable outcome (41.0% vs. 47.1%, P = 0.431) or excellent outcome (23.1% vs. 31.0%, P = 0.252). In the subgroup analysis stratified by stroke etiology, non-large artery atherosclerosis (non-LAA) stroke patients yielded with less favorable or excellent prognosis in the high RC group (26.8% vs. 46.8%, adjusted OR = 0.31, 95%CI: 0.11-0.85, P = 0.023; or 12.2% vs. 29.0%, adjusted OR = 0.18, 95%CI: 0.04-0.80, P = 0.024, respectively.). Post hoc power analyses indicated that the power was sufficient for favorable outcome (80.38%) and excellent outcome (88.72%) in non-LAA stroke patients. Additionally, RC can enhance the risk prediction value of a poor outcome (mRS scores 3-6) based on traditional risk indicators (including age, initial NIHSS score, operative duration, and neutrophil-to-lymphocyte ratio) for non-LAA stroke patients (AUC = 0.86, 95%CI: 0.79-0.94, P < 0.001). In AIS patients undergoing mechanical thrombectomy, elevated RC was independently related to poor outcome for non-LAA stroke patients, but not to short-term prognosis of LAA stroke patients.

Prevalence and associated factors of dyslipidemia among university students in Central Thailand: a cross-sectional study

Background: Dyslipidemia is regarded as a significant risk factor for atherosclerotic cardiovascular diseases (ASCVDs). Currently, there is limited data regarding dyslipidemia among Thai university students. Objective: This study aimed to examine the prevalence of dyslipidemia and its related factors among university students in the central region of Thailand. Materials and methods: In this cross-sectional study, a total of 434 students aged 18-25 years at Thammasat University and Kasetsart University were recruited using simple random sampling. Fasting venous blood samples were obtained, and plasma lipid profiles were assessed by an automated analyzer. Dyslipidemia was formally characterized according to the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III) guidelines. Demographic information, dietary behavior, and physical activity were collected using questionnaires. Anthropometric measures were also performed according to a standard protocol. Results: The prevalence of elevated total cholesterol, high-risk HDL-C, elevated LDL-C, and elevated triglycerides was 30.4, 18.2, 20.0, and 11.8%, respectively. The most common adverse lipid parameter was total cholesterol in both genders. Obesity and high fat intake were significantly associated with dyslipidemia (p&lt;0.05). Conclusion: This research revealed a significant occurrence of dyslipidemia, primarily driven by elevated total cholesterol, among university students in Thailand. Obesity and high fat intake are significant risk contributors to dyslipidemia. These findings emphasize the need for awareness, prevention, and management strategies targeting this population.

Clinical Presentation of Ischaemic and Haemorrhagic Stroke and Its Relation to Lipid Profile

Introduction: Stroke is a major health hazard in both developed and developing countries. Dyslipidaemia is one of the important risk factors for stroke. The purpose of the present study was to identify clinical presentations of both ischaemic and haemorrhagic stroke, and to find out correlation between stroke and lipid profile. Methods: The observational study was conducted in the Department of Medicine at Sher-e-Bangla Medical College Hospital, Barishal from April to September 2013 for a period of 6 months. All the stroke patients over 20 years of age of both sexes were selected as study population. After admission at the hospital, history was taken from the patients or the attendants. The clinical presentation was recorded in a pre designed data collection sheet. Fasting lipid profile was measured in every stroke patient. Results: Total 100 stroke patients were enrolled for this study, of them 36 were haemorrhagic and 64 were ischaemic stroke patients. The mean ± SD of age were 63.945 ± 8.84 and 62.26 ± 14.40 in haemorrhagic and ischaemic stroke patients respectively (p&gt;0.05). Among both haemorrhagic and ischaemic stroke patients maximum 61.1% and 60.9% used to have sedentary work. Impaired level of consciousness was more common among the haemorrhagic stroke patients (91.7%) than ischaemic stroke patients (57.8%) group and the association is statistically significant (p=0.001). Limb weakness was the commonest presentation in both haemorrhagic (91.7%) and ischaemic (87.5%) stroke patients. The mean ± SD of total cholesterol was 173.47 ± 61.96 and 178.22 ± 54.79 in haemorrhagic stroke and ischaemic stroke patients respectively (p&lt;0.05). Conclusion: Older age, male sex, sedentary work and dyslipidaemia were susceptible to be affected in stroke. Among lipoproteins, elevated total cholesterols, triglycerides and LDL showed strong correlation with both ischaemic and haemorrhagic strokes. J MEDICINE 2024; 25: 24-28

Effectiveness of peer-led intervention in control of non-communicable diseases in rural areas of Khordha district: study protocol for a cluster randomized controlled trial

BackgroundThe main contributors to death and disability from chronic illnesses in developing nations are elevated blood pressure (hypertension), blood sugar (diabetes mellitus), and blood cholesterol (dyslipidaemia). Even though there are affordable treatments, the treatment gap for these conditions is still significant. Few pilot studies from industrialized nations discuss the value of peer-led interventions for achieving community-level management of blood pressure and blood sugar. This study aims to evaluate the effectiveness of peer-led intervention compared to standard care in achieving control of selected non-communicable diseases (NCDs) in Indian context at 1 year of intervention among people of 30–60 years with hypertension and/or diabetes mellitus and/or dyslipidaemia.MethodsA cluster-randomized controlled trial will be conducted in villages of two rural blocks of the Khordha district of Odisha from August 2023 to December 2024. A total of 720 eligible participants (360 in the intervention group and 360 in the control group) will be recruited and randomized into two study arms. The participants in the intervention arm will receive a peer-led intervention model for 6 months in addition to standard care. The sessions will be based on the six domains of NCDs — self-care, follow-up care, medication, physical activity, diet, limiting substance use, mental health and co-morbidities. The mean reduction in blood pressure, HbA1C, and blood cholesterol in the intervention arm compared to the standard care arm will be the main outcome.DiscussionThe increasing burden of NCDs demands for newer strategies for management. Peer-led interventions have proven to be useful at the international level. Incorporating it in India will have remarkable results in controlling NCDs.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2023/02/050022. Registered on 23 February 2023.

Whether and Why Do We Need a Vaccine Against Atherosclerosis? Can We Expect It Anytime Soon?

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of premature death. Lipid disorders, particularly elevated serum low-density lipoprotein cholesterol (LDL-C), contribute significantly to ASCVD. The risk of developing ASCVD is influenced by the duration of exposure to elevated LDL-C concentrations (cholesterol-years concept). Implementing lipid-lowering treatments based on the principles of "the earlier the better," "the lower the better," and "the longer the better" has been shown to reduce cardiovascular risk and significantly extend lifespan. Despite the availability of numerous lipid-lowering drugs, achieving satisfactory control of lipid disorders remains very challenging. Therefore, there is a need for novel approaches to improve treatment adherence. One promising solution under investigation is the development of an anti-PCSK9 vaccine, which could be administered annually to provide long-term control over LDL-C concentrations. Experimental studies and the sole clinical trial conducted thus far have demonstrated that the anti-PCSK9 vaccine induces a durable immune response associated with lipid-lowering and anti-atherosclerotic effects. Furthermore, it has exhibited good tolerability and a satisfactory safety profile. However, we still need data from phase 2, 3, and cardiovascular outcome trial to confirm its safety and efficacy and add value in the armamentarium of available and perspective lipid-lowering drugs. This article highlights the significance of developing an anti-PCSK9 vaccine and provides an overview of the current knowledge on various anti-PCSK9 vaccines.

[Epidemiological characteristics of cardio-metabolic risk factors in women aged 15-49 years in 4 provinces of China in 2018].

To analyze the prevalence of cardio-metabolic(CM) risk in women aged 15-49 years in 4 provinces of China and the influence of socioeconomic factors on them. A total of 2851 women aged 15-49 years from Community-based Cohort Study on Nervous System Disease in 2018 were selected. Obesity, central obesity, elevated triglyceride(TG), elevated total cholesterol(TC), decreased high-density lipoprotein cholesterol(HDL-C), elevated low-density lipoprotein cholesterol(LDL-C), elevated blood pressure, elevated blood glucose and risk factor aggregation were analyzed. χ~2 test was used for univariate analysis, multinomial Logit model was used to evaluate the relationship between socioeconomic factors and CM risk factors, and Cochran-Armitage trend test was used for trend analysis. The detection rate of CM risk factors in this study from high to low were central obesity(26.76%), overweight(22.41%), pre central obesity(17.47%), decreased HDL-C(15.36%), elevated TG(11.78%), borderline elevated TC(11.40%), borderline elevated TG(11.12%), elevated blood pressure(9.71%) and hypertension(9.12%). The prevalence rates of CM risk factors were different among different age groups, income groups and education levels(P&lt;0.05). In addition to decreased HDL-C, the prevalence of other metabolic risk factors increased with age(P_(trend)&lt;0.05). With the improvement of educational level, the prevalence rates of overweight, obesity, central obesity, central obesity, elevated TG, decreased HDL-C, elevated blood pressure, hypertension, elevated blood pressure and diabetes showed a downward trend(P_(trend)&lt;0.05). Multinomial Logit model showed that the rick of metabolic risk factors in the age group of 40 to 49 years old was higher than that in the younger age group aged 15-29 years, and was more significant in hypertension, elevated blood pressure and elevated blood glucose, which were 8.51 times(95% CI 5.45-13.27), 3.14 times(95%CI 2.20-4.48)and 2.66(95% CI 1.52-4.66)times of the younger age group, respectively. Women with high-income level have a higher risk of borderline elevated TC, elevated TC and borderline elevated LDL-C(OR=1.85, 95% CI 1.44-2.38;OR=2.01, 95% CI 1.25-3.22;OR=2.16, 95% CI 1.61-2.90), but the lower risk of overweight and elevated blood pressure(OR=0.79, 95% CI 0.64-0.98;OR=0.69, 95% CI 0.50-0.94). The risk of obesity, hypertension and diabetes of people with college degree or above was about 50% lower than those with junior high school education or below(OR=0.52, 95% CI 0.35-0.78;OR=0.43, 95% CI 0.27-0.67; OR=0.52, 95% CI 0.28-0.96). Central obesity, overweight, pre central obesity and HDL-C decrease were prominent CM risk factors in women aged 15-49 years in four provinces of China in 2018. The detection rate of CM risk factors is higher in women of high age group or low education level.

Contributing Factors for the Increased Inter-arm Systolic Blood Pressure Difference in Different Age Groups

Abstract OBJECTIVE To explore the contributing factors for the increased inter-arm systolic blood pressure difference (IASBPD) in young, middle-aged, and elderly people. METHODS A total of 51,428 workers in Kailuan who underwent arteriosclerosis detection of extremities during physical examination from 2010 to 2020 were selected as the subjects. The subjects were divided into 3 groups according to the age segment proposed by the World Health Organization: young, middle-aged, and elderly group. Each age group was subsequently divided into 2 groups according to whether the IASBPD was increased: IASBPD 15 mm Hg and IASBPD &amp;gt;15 mm Hg group. The detection rate of IASBPD &amp;gt;15 mm Hg in each age group was calculated, and the contributing factors of IASBPD &amp;gt;15 mm Hg in different age groups were analyzed via multifactor logistic regression model. RESULTS The detection rate of IASBPD &amp;gt;15 mm Hg was 15.65% in all the subjects, and it was 12.90%, 15.28%, and 20.69% in the young, middle-aged, and elderly groups, respectively (χ2 = 343.83, P &amp;lt; 0.01). In all the young, middle-aged, and elderly groups, the risk factors for IASBPD &amp;gt;15 mm Hg included decreased ankle–brachial index (ABI), elevated body mass index (overweight and obesity), male, elevated brachial–ankle pulse wave velocity (baPWV), and hypertension. Furthermore, elevated high sensitive C-reactive protein (hsCRP) was a risk factor for increased IASBPD in young people (odds ratio [OR] = l.02, 95% confidence interval [CI] 1.00–1.04). And elevated low-density lipoprotein cholesterol (LDL-C) was a risk factor (OR = 1.09, 95% CI 1.03–1.15) for increased IASBPD in middle-aged people, and the high level of education was a protective factor (OR = 0.86, 95% CI 0.79–0.94). Diabetes (OR = 1.29, 95% CI 1.16–1.42) and old age (OR = 1.01, 95% CI 1.01–1.02) were risk factors for increased IASBPD in the elderly people, and high level of education (OR = 0.84, 95% CI 0.74–0.95) and elevated high-density lipoprotein cholesterol (HDL-C) (OR = 0.82, 95% CI 0.72–0.93) were protective factors. CONCLUSIONS The detection rate of IASBPD &amp;gt;15 mm Hg increases with the increase of age in the young, middle-aged, and elderly groups. Decreased ABI, elevated overweight obesity, male, elevated baPWV, and hypertension are common risk factors for increases IASBPD in 3 age groups. Furthermore, elevated hsCRP, elevated LDL-C, diabetes mellitus, and old age are risk factors for increased IASBPD in young, middle-aged, and elderly group, respectively.

Efficacy and Safety of Alirocumab and Evolocumab as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors in Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.

Familial hypercholesterolemia (FH) is a prevalent and potentially fatal illness that causes a substantial elevation in low-density lipoprotein cholesterol (LDL-C). The aim of this study was to investigate the effects of monoclonal antibodies alirocumab and evolocumab on LDL-C and other lipid parameters, as well as their safety in familial hypercholesterolemia patients. A comprehensive search was done on PubMed/MEDLINE, EMBASE, Web of Science (WOS/ ISI), Scopus, ClinicalTrials (www. gov), and conferences/ congress research papers. Random effect models were used to calculate mean differences (%) and risk ratios (RRs), and confidence intervals (95%). Ten studies (n=1489 patients) were included in this study. PCSK9 inhibitors decreased the levels of LDL-C by -49.59% (95%CI -55.5%, -43.67%) as compared to placebo. They also didn't alter the Treatment-Emergent Adverse Event (TEAE) and neuronal events by RR 0.92 (0.75, 1.13) and 1.31 (0.66, 2.59), respectively. PCSK9 inhibitors were effective and safe in treating patients with FH. There was high-quality evidence showing that monoclonal antibodies (alirocumab & evolocumab) lower LDL-C (GRADE: high), lipoprotein (a) (GRADE: High), triglycerides (TG) (GRADE: High), total cholesterol (GRADE: High), non-high-density lipoprotein cholesterol (non- HDL-C) (GRADE: Moderate), and apolipoprotein B (GRADE: High), and increase the HDL-C (GRADE: High) as well as apolipoprotein A1 (GRADE: High). Comparing PCSK9 inhibitors against placebo, neither TEAE (GRADE: high) nor neuronal events (GRADE: moderate) were changed.

Maternal and Neonatal Effects of Maternal Oral Exposure to Perfluoro-2-methoxyacetic Acid (PFMOAA) during Pregnancy and Early Lactation in the Sprague-Dawley Rat.

Perfluoro-2-methoxyacetic acid (PFMOAA) is a short-chain perfluoroalkyl ether carboxylic acid that has been detected at high concentrations (∼10 μg/L) in drinking water in eastern North Carolina, USA, and in human serum and breastmilk in China. Despite documented human exposure there are almost no toxicity data available to inform risk assessment of PFMOAA. Here we exposed pregnant Sprague-Dawley rats to a range of PFMOAA doses (10-450 mg/kg/d) via oral gavage from gestation day (GD) 8 to postnatal day (PND) 2 and compared results to those we previously reported for perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX). Newborn pups displayed reduced birthweight (≥30 mg/kg), depleted liver glycogen concentrations (all doses), hypoglycemia (≥125 mg/kg), and numerous significantly altered genes in the liver associated with fatty acid and glucose metabolism similar to gene changes produced by HFPO-DA. Pup survival was significantly reduced at ≥125 mg/kg, and at necropsy on PND2 both maternal and neonatal animals displayed increased liver weights, increased serum aspartate aminotransferase (AST), and reduced serum thyroid hormones at all doses (≥10 mg/kg). Pups also displayed highly elevated serum cholesterol at all doses. PFMOAA concentrations in serum and liver increased with maternal oral dose in both maternal and F1 animals and were similar to those we reported for PFOA but considerably higher than HFPO-DA. We calculated 10% effect levels (ED10 or EC10) and relative potency factors (RPF; PFOA = index chemical) among the three compounds based on maternal oral dose and maternal serum concentration (μM). Reduced pup liver glycogen, increased liver weights and reduced thyroid hormone levels (maternal and pup) were the most sensitive end points modeled. PFMOAA was ∼3-7-fold less potent than PFOA for most end points based on maternal serum RPFs, but slightly more potent for increased maternal and pup liver weights. PFMOAA is a maternal and developmental toxicant in the rat producing a constellation of adverse effects similar to PFOA and HFPO-DA.