Low-density Lipoprotein Cholesterol Research Articles

Risk of Incident Diabetes Related to Lipoprotein(a), LDL Cholesterol, and Their Changes With Alirocumab: Post Hoc Analyses of the ODYSSEY OUTCOMES Randomized Trial

OBJECTIVE Previous genetic and clinical analyses have associated lower lipoprotein(a) and LDL cholesterol (LDL-C) with greater risk of new-onset type 2 diabetes (NOD). However, PCSK9 inhibitors such as alirocumab lower both lipoprotein(a) and LDL-C without effect on NOD. RESEARCH DESIGN AND METHODS In a post hoc analysis of the ODYSSEY OUTCOMES trial (NCT01663402), we examined the joint prediction of NOD by baseline lipoprotein(a), LDL-C, and insulin (or HOMA–insulin resistance [HOMA-IR]) and their changes with alirocumab treatment. Analyses included 8,107 patients with recent acute coronary syndrome on optimized statin therapy, without diabetes at baseline, assigned to alirocumab or placebo with median follow-up 2.4 years. Splines were estimated from logistic regression models. RESULTS Lower baseline lipoprotein(a) and higher baseline insulin or HOMA-IR independently predicted 782 cases of NOD; baseline LDL-C did not predict NOD. Alirocumab reduced lipoprotein(a) and LDL-C without affecting insulin or NOD risk (odds ratio [OR] vs. placebo 0.998; 95% CI 0.860–1.158). However, in logistic regression, decreased lipoprotein(a) and LDL-C on alirocumab were independent, opposite predictors of NOD. OR for NOD for 25% and 50% lipoprotein(a) reductions on alirocumab were 1.12 (95% CI 1.01–1.23) and 1.24 (1.02–1.52). OR for NOD for 25% and 50% LDL-C reductions on alirocumab were 0.88 (95% CI 0.80–0.97) and 0.77 (0.64–0.94). CONCLUSIONS Baseline lipoprotein(a) was inversely associated with risk of NOD. Alirocumab-induced reductions of lipoprotein(a) and LDL-C were associated with increased and decreased risk of NOD, respectively, without net effect on NOD. Ongoing trials will determine the impact of larger and longer lipoprotein(a) reductions on NOD.

The role of systemic inflammation in remnant cholesterol associated cardiovascular risk: insights from the EPIC-Norfolk study.

Both plasma levels of remnant cholesterol and low-density lipoprotein cholesterol (LDL-C) levels are independent risk factors for atherosclerotic cardiovascular disease. However, only remnant cholesterol has consistently been associated with systemic inflammation. In this study, we aimed to assess the extent to which inflammation mediates the effect of remnant and LDL cholesterol on (non)fatal major adverse cardiovascular events (MACE), comprising of coronary artery disease and ischemic stroke. This prospective study included 16,445 participants without prior atherosclerotic cardiovascular disease from the EPIC-Norfolk study, with a mean age of 58.8±9.1 years, of which 9,357 (56.9%) were women. Every 1 mmol/L higher remnant cholesterol was associated with 29.5% higher high-sensitivity C-reactive protein (hsCRP) levels (95% Confidence Interval (CI): 22.1, 37.4, p<0.001), whereas LDL-C was not significantly associated with hsCRP levels in the fully adjusted model. Additionally, each 1 mmol/L higher remnant cholesterol was associated with a hazard ratio (HR) of 1.31 (95% CI: 1.14, 1.50, p<0.001) for MACE, compared to a HR of 1.21 (95% CI: 1.13, 1.31, p<0.001) for LDL-C. Mediation analysis showed that hsCRP mediated 5.9% (95% CI: 1.2, 10.6%, p<0.001) of the effect of remnant cholesterol on MACE, whereas hsCRP did not mediate the effect of LDL-C. Plasma remnant cholesterol levels are independently associated with systemic inflammation and cardiovascular events. Inflammation, as measured with hsCRP, contributed minorly to the association between remnant cholesterol and MACE. This underscores the need to address both remnant cholesterol and systemic inflammation separately in the clinical management of cardiovascular disease.

Remnant cholesterol and its variability independent of low density lipoprotein cholesterol predict metabolic dysfunction associated steatotic liver disease

This study aimed to determine whether remnant cholesterol (RC) and its variability can predict the onset of metabolic dysfunction-associated steatotic liver disease (MASLD) independently of low-density lipoprotein cholesterol (LDL-C) levels. A longitudinal cohort study involving 43,065 participants who underwent at least two physical examinations was conducted. This study used Cox proportional hazards models to assess the relationships among RC quartile levels (Q1–Q4), visit-to-visit variability, and the risk of MASLD. This variability was quantified using several metrics: standard deviation (SD), logSD, average real variability (ARV), logARV, mean absolute deviation (MAD), and logMAD. Concurrently, this study utilized a combined analysis of RC and LDL-C groups to assess the independent risk of MASLD associated with RC. During a mean visit-to-visit of 3.19 years (SD 2.06 years), 8374 patients (19.45%) developed MASLD. Compared with Q1, Q4 was associated with a significantly greater risk of MASLD (hazard ratio [HR] 1.309, 95% confidence interval [CI] 1.220–1.403, P < 0.001). The fully adjusted Cox model revealed that the HRs of SD, logSD, ARV, logARV, MAD and logMAD were 1.400 (95% CI 1.305–1.502), 1.278 (95% CI 1.188–1.374), 1.152 (95% CI 1.079–1.229), 1.183 (95% CI 1.140–1.227), 1.578 (95% CI 1.433–1.737) and 1.263 (95% CI 1.175–1.358), respectively. In both LDL-C subgroups (≥ 3.4 mmol/L and < 3.4 mmol/L), high baseline RC was associated with elevated MASLD risk (HR 1.208, 95% CI 1.148–1.270, P < 0.001; HR 1.246, 95% CI 1.129–1.374, P < 0.001). RC levels were independently associated with MASLD in healthy individuals, irrespective of LDL-C level. The variability of RC during visit-to-visit periods provides a predictive marker for identifying individuals at heightened risk of MASLD.

A Longitudinal Cohort Assessing the Carotid Intima-Media Thickness Progression and Cardiovascular Risk Factors in a Rural Black South African Community

Background: Diabetes mellitus [DM) is a fast-increasing non-communicable disease in South Africa, with a prevalence of 11.3%. The present study aimed to longitudinally investigate the association of carotid intima-media thickness [CIMT) progression and cardiovascular risk factors in the T2DM and non-DM rural black population of South Africa. Methods: This population-based retrospective cohort study was conducted in the Dikgale Mamabolo Mothiba Surveillance area between 2014 and 2023 by the Africa Wits INDEPTH Partnership for Genomic Research (AWI-Gen). The IBM Statistical Package for the Social Sciences version 27 was used to analyze data. The paired T-test was used to determine the mean differences between baseline and follow-up. Longitudinal estimates of the association of CIMT with CVD risk factors in the T2DM and non-DM groups were analyzed using linear mixed models. Results: The baseline mean age was 51.64 years. There was a significant increase in CIMT (left and mean CIMT), low-density lipoprotein-cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate in the T2DM and non-DM groups. In the T2DM group, there was a strong significant association between age (2.20 mm), LDL-C (4.30 mm), SBP (4.57 mm), and waist/hip ratio (0.24 mm) with CIMT progression. The non-DM group revealed a significant association between LDL-C (0.001 mm), SBP (1.41 mm), and CIMT progression. Conclusion: CIMT was associated with other main CVD-related risk factors (age, LDL-C, LDL-C/HDL-C ratio, TC/HDL-C ratio, waist/hip ratio, and SBP). CIMT progression was more pronounced in the T2DM group than non-DM, suggesting a higher risk of atherosclerosis and cardiovascular complications in T2DM individuals.

Exploring the Therapeutic Potential of Artemisia and Salvia Genera in Cancer, Diabetes, and Cardiovascular Diseases: A Short Review of Clinical Evidence

Metabolic syndrome, a cluster of metabolic disorders comprising dyslipidemia, insulin resistance, elevated blood pressure, and abdominal obesity, is a silent epidemic that may lead to outcomes such as cardiovascular disease, diabetes, and cancer. Due to the increase in the prevalence of these pathologies, the search for better treatments and more efficient drugs is imperative. Species of Artemisia and Salvia genera are excellent examples of noteworthy sources of bioactive products with health applications, their therapeutic properties being well known both in popular medicine and in the scientific community. There are reports of plant extracts or compounds from species belonging to either of these genera, which were able to combat cancer, diabetes, and cardiovascular pathologies. For instance, dihydroartemisinin (analog of artemisin extracted from Artemisia annua L.) can reduce tumor markers p53 and Ki-67 expression levels, leading to a reduction in tumor proliferation. Salvia officinalis L. has antihyperglycemic and lipid profile-improving effects since it decreases total cholesterol, glycosylated hemoglobin, fasting glucose, low-density lipoprotein cholesterol, and triglyceride levels while increasing high-density lipoprotein cholesterol levels. Clinical trials using mixtures (dried powdered plants or extracts) of known medicinal plants are recurrent in published works, in contrast with the scarce clinical trial studies with isolated compounds. Salvia miltiorrhiza Bunge. was by far the most targeted plant in the clinical trials analyzed here. Regarding clinical trials concerning Artemisia, there are more studies aiming to see its effect on diabetes, but the studies about cancer are more advanced. This review aims to give a critical summary of the most interesting and promising results from clinical trials. The abundance of studies with limited statistically significant clinical evidence hinders progress in clinical therapy. This situation demands far greater rigor from the scientific community, researchers, regulatory agencies, editors, and reviewers in conducting and publishing clinical studies.

Donut-shaped [NaP5W30O110]14- polyoxometalate as a promising antidiabetic drug-candidate: putative mechanisms of action.

The aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH4)14[NaP5W30O110] 31H2O (NaP5W30) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20mg/kg/day NaP5W30 for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP5W30 (20mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP5W30 significantly reduced hyperglycemia and glycated haemoglobin A1c (HbA1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP5W30 treatment group compared to the diabetic control group. In contrast, NaP5W30 had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP5W30 effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP5W30 did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP5W30 could be considered a promising antidiabetic drug-candidate that deserves further investigation.

Efficacy of selected scales in the assessment of impaired awareness of hypoglycemia in adults with type 1 diabetes.

Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia. Questionnaires may allow for easy identification of patients with IAH andfacilitate appropriate intervention. This study aims to assess the clinical utility of commonly used questionnaires fordiagnosing IAH, providing practical insight for medical professionals. Additionally, weseek to identify clinical factors associated with IAH in adults with type 1 diabetes (T1D), enhancing understanding of this condition in a real-world context. The study included 252 adults with T1D (135 men) aged 41 years (IQR: 30-52). Awareness ofhypoglycemia using the validated questionnaires [Clarke scale, Gold scale, and Hypoglycemia Awareness Questionnaire (HypoA-Q)], anthropometric data, and metabolic control were evaluated. To estimate the optimal cut-off point for the diagnosis of IAH using HypoA-Q, the Receiver Operating Characteristic (ROC) curve analysis wasused. IAH was diagnosed by at least one abnormal questionnaire score. We found a cut-off point of 9 points for diagnosing IAH on HypoA-Q (sensitivity of79%, specificity of 82%, AUC = 0.898). IAH in any abnormal test was found in 98 patients (39%). In the univariable logistic regression models, the diagnosis of IAH was associated with lifetime episodes of severe hypoglycemia, hypertension, glycated hemoglobin (A1c) value, mean glycemia, standard deviation (SD), total, LDL and non-HDL cholesterol levels, anddaily dose of insulin. The HypoA-Q, with a 9-point cut-off, demonstrated the highest sensitivity fordiagnosing IAH, and may be considered the most valuable screening tool for IAH detection.

Cholestyramine in hemodialysis: a new approach for hyperphosphatemia management.

Hyperphosphatemia is a potentially life altering condition in end-stage renal disease patients who are on regular hemodialysis that can lead to cardiovascular calcification, metabolic bone disease and secondary hyperparathyroidism. Bile acid sequestrants are anion exchange resins bind to bile acids and phosphate in the intestine resulting in preventing intestinal absorption of dietary phosphate, interruption of bile acid homeostasis and reduction in low-density lipoprotein cholesterol levels. Cholestyramine is chosen for study in hemodialysis patients based on the effectiveness and safety of bile acid sequestrants such colestilan and colestipol in the treatment of hyperphosphatemia and hypercholesterolemia in hemodialysis patients. A prospective, interventional, randomized, double blinded, placebo-controlled two arm study was carried out to assess the efficacy of oral cholestyramine on reduction of serum phosphate level in adult hemodialysis patients. 76 eligible patients were randomly assigned to either a drug group or a placebo group for the 2-month study period. The protocol was approved by the institutional review board of the faculty of pharmacy Ain Shams University Ethical committee and has been registered on ClinicalTrials.gov: NCT05577507. Over the 2-month treatment period, patients in cholestyramine group showed a significant decline in serum phosphorus levels versus placebo group (4.6 mg/dl vs. 6.6 mg/dl; p < 0.001) and serum calcium-phosphorus product (40 mg2/dl2 vs. 59.8 mg2/dl2; p < 0.001). Median serum triglyceride and low-density lipoprotein cholesterol levels had decreased significantly versus baseline values in the cholestyramine group. Cholestyramine used with phosphate binders effectively lowers phosphorus levels, improves the lipid profile, and has mild adverse effects.

Ebronucimab: First Approval.

Ebronucimab (®) is a subcutaneous fully human anti-proprotein convertase subtilisin/kexin type9 (PCSK9) monoclonal antibody being developed by Akeso Biopharma for the treatment of dyslipidaemia. In September 2024, ebronucimab was approved in China, in combination with statins or statins and other lipid-lowering therapies, for adult patients with primary hypercholesterolaemia [including heterozygous familial hypercholesterolaemia (HeFH)] and mixed hyperlipidaemia who are unable to achieve the low-density lipoprotein cholesterol target after receiving moderate or higher doses of statins. This article summarizes the milestones in the development of ebronucimab leading to this first approval for primary hypercholesterolaemia, mixed hyperlipidaemia and HeFH.

Adipose tissue-derived microRNA-450a-5p induces type 2 diabetes mellitus by downregulating DUSP10.

Type 2 diabetes mellitus (T2DM) has rapidly increased worldwide, emerging as the fifth leading cause of death. The treatment of T2DM is challenging due to the side effects of oral hypoglycemic drugs and the limited efficacy of long-term insulin therapy, which can lead to insulin resistance (IR). Consequently, there is significant in discovering new drugs that have minimal side effects and a pronounced hypoglycemic effect. In obesity, microRNA levels have been implicated in glucose metabolism disorders and T2DM, although many aspects remain unresolved. Here, we confirmed that visceral adipose tissue and serum microRNA-450a-5p content increased under obesity and T2DM, and it was significantly positively associated with fasting blood glucose, triglycerides, cholesterol, low-density lipoproteins-cholesterol levels of the subjects. In high-fat diet (HFD)-induced obese mice, microRNA-450a-5p expression was increased in the serum, liver, and white adipose tissue. Moreover, the adipose Dicer-knockout mouse model was constructed to identify adipose tissue as the main source of microRNA-450a-5p. microRNA-450a-5p could inactivate the insulin signal pathway by targeting the inhibited Dual Specificity Phosphatase 10 (DUSP10) and inducing IR and glucose metabolism disorders in vitro cultured hepatocytes and adipocytes. Additionally, microRNA-450a-5p was found to regulate DUSP10 expression and insulin signaling activity, influencing glucose tolerance and insulin sensitivity across various models, including normal diet, HFD-induced obese, adipose tissue-specific microRNA-450a-5p-knockout, and db/db mice. Furthermore, gallic acid might play a potential role in inhibiting glucose levels by decreasing microRNA-450a-5p expression. Thus, microRNA-450a-5p emerges as an attractive therapeutic target for addressing obesity, IR, and T2DM.

The diagnostic value of the combined application of blood lipid metabolism markers and interleukin-6 in osteoporosis and osteopenia

BackgroundThis study aimed to analyse the relationship of the blood lipid profile and interleukin-6 (IL-6) with osteoporosis and osteopenia and to explore the predictive value of the combined application of these biomarkers in osteoporosis and osteopenia.MethodsData from 276 patients treated in the orthopaedics department were retrospectively analysed. Their general information was collected, and the relationships among the blood lipid profile, IL-6 with bone turnover markers, and bone mineral density (BMD) were analysed. Patients were categorized based on their T scores for intergroup comparisons. Finally, the diagnostic efficiency of lipid metabolism markers and IL-6 for osteoporosis and osteopenia was assessed using receiver operating characteristic (ROC) curves.Results(1) In both males and females, a negative relationship was observed between BMD and several biomarkers, including total cholesterol (TC), apolipoprotein B (ApoB), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFAs), and IL-6. Additionally, apolipoprotein A1 (ApoA1) was negatively correlated with BMD only in females, and the ApoA1/ApoB ratio was positively correlated with BMD only in males. (2) FFAs and IL-6 were positively correlated with β-CrossLaps peptide in males. However, for females, TC, ApoB, LDL-C, and IL-6 were negatively correlated with 25-hydroxyvitamin D. FFAs, IL-6, and age were negatively correlated with osteocalcin in males and females. (3) According to the T scores for the lumbar spine, the TC, ApoA1, ApoB, HDL-C, LDL-C, FFA, and IL-6 levels in the osteoporosis group and the TC, ApoB, LDL-C, and FFA levels in the osteopenia group were significantly greater than those in the normal bone mass group. Additionally, the osteoporosis group presented substantially higher levels of ApoA1, FFAs, and IL-6 than the osteopenia group. (4) IL-6 was positively correlated with FFAs, while a negative correlation was observed with TC, ApoA1, ApoB, HDL-C, and LDL-C. (5) The ROC curve revealed that the areas under the curve (AUCs) of TC, FFAs, IL-6, ApoA1, and the ApoA1/ApoB ratio for predicting osteoporosis or osteopenia were 0.634, 0.713, 0.670, 0.628, and 0.516, respectively, whereas the AUC of the combination of TC, FFAs, IL-6, and ApoA1 was 0.846, and the AUC of the combination of TC, FFAs, IL-6, and the ApoA1/ApoB ratio was 0.842. In the sex stratification analysis, in males, the AUCs of TC, FFAs, IL-6, and the ApoA1/ApoB ratio for the prediction of osteoporosis or osteopenia were 0.596, 0.688, 0.739, and 0.539, respectively. In contrast, the AUC of the combination of TC, FFAs, IL-6, and the ApoA1/ApoB ratio was 0.838. In females, the AUCs of TC, FFAs, IL-6, ApoA1, and the ApoA1/ApoB ratio for predicting osteoporosis or osteopenia were 0.620, 0.728, 0.653, 0.611, and 0.502, respectively, whereas the AUC of the combination of TC, FFAs, IL-6, and ApoA1 was 0.841, and the AUC of the combination of TC, FFAs, IL-6, and the ApoA1/ApoB ratio was 0.828.ConclusionThe levels of TC, FFAs, IL-6, ApoA1, and ApoB could contribute to changes in bone metabolism, moreover, FFAs could induce an increase in IL-6 further aggravating bone mass loss and leading to osteoporosis. Based on the comparison of the AUC results, the combination of TC, FFAs, and IL-6 with ApoA1 or the ApoA1/ApoB ratio can better predict osteoporosis or osteopenia in patients, and the diagnostic efficiency is significantly better than that of any individual indicator. The regulation of blood lipid levels should become a new target for clinicians to treat osteoporosis and osteopenia.

Familial Hypercholesterolemia: Genetics, Symptoms, Diagnosis and Treatment - A Literature Overview

Familial hypercholesterolemia is a genetic disorder of lipid management, especially LDL-C. It's inherited autosomal dominant in most cases. The illness is characterized by high, low-density lipoprotein cholesterol (LDL-C) levels. According to many researchers, the frequency of prevalence is estimated at 1:200 in the global population. Many studies showed that illness is underdiagnosed and therefore undertreated. There are three known genes coding three different proteins, and changes are in charge of wrong lipid management. These are: LDL-Receptor (LDLR), Apolipoprotein B (ApoB), and Proprotein convertase subtilisin/kexin 9 (PCSK9). People who are affected by mutation have around thirteen times higher risk of coronary artery disease (CAD) and, in order to that, premature death. Identifying sickness includes a physical examination, when we can observe xanthomas, corneal arcus, or xanthomata, and scales that focus on the patient's as well as his family's past. A definite diagnosis can be approved by genetic testing, which shows a causable mutation. The main goal in treatment therapy of familial hypercholesterolemia is to reduce the concentration of LDL-C in serum. First of all, patients should know what to do to reduce LDL-C levels. Education is critical for understanding the problem and creating a successful course. Moreover, it is necessary to quit smoking, increase physical activity, and reduce cholesterol, elevating products from diet such as saturated fats and alcohol. Weight reduction is recommended. In addition, pharmacological treatment must be performed. All individuals have statins implemented. In most cases, one drug isn't enough, so therapy containing ezetimib is common. Novel treatments, including monoclonal antibodies (mAb), antisense oligonucleotides (ASO), and PCSK9- inhibitors nowadays, are used with greater frequency and better results, providing higher efficiency in achieving targets.

Efficacy and safety of PCSK9 inhibitors, potent statins, and their combinations for reducing low-density lipoprotein cholesterol in hyperlipidemia patients: a systematic network meta-analysis

BackgroundThe objective of this study is to assess the relative efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab, evolocumab, and inclisiran, in conjunction with potent statins like atorvastatin and rosuvastatin, in patients presenting with hyperlipidemia or heightened cardiovascular risk attributable to elevated low-density lipoprotein cholesterol (LDL-C).MethodsA systematic search was conducted across databases including PubMed, Embase, and the Cochrane Library to explore lipid-lowering therapies in hyperlipidemia from their inception to 7 November 2023. A network meta-analysis (NMA) was conducted via Stata 17 software, with two authors independently conducting the search, screening, and data abstraction.ResultsA total of 68 clinical studies involving 21,288 patients with hyperlipidemia were incorporated into the NMA. PSCK9 inhibitors and potent statins significantly reduced LDL-C levels from baseline vs. placebo regardless of background therapy. Regarding the efficacy of lipid reduction, four principal medications were evaluated: evolocumab and atorvastatin [mean standard deviation (MD) −3.41, 95% CI −4.81 to −2.00] and evolocumab with rosuvastatin (MD −3.44, 95% CI −5.10 to −1.78) vs. placebo; alirocumab combined with rosuvastatin (MD −2.91, 95% CI −3.95 to −1.88) and alirocumab with atorvastatin (MD −2.90, 95% CI −3.97 to −1.84) vs. placebo. Meanwhile, compared with placebo, evolocumab (MD −1.89, 95% CI −2.27 to −1.50), alirocumab (MD −1.83, 95% CI −2.09 to −1.57), rosuvastatin (MD −1.93, 95% CI −2.30 to −1.56), inclisiran (MD −1.68, 95% CI −2.10 to −1.27), and atorvastatin (MD −1.68, 95% CI −2.04 to −1.31) could also play a role in the treatment of LDL-C reduction. Moreover, the incidence of adverse events (AEs) was similar to that observed in the control group, which included both placebo and potent statin groups, with no significant differences identified in our study (P &amp;gt; 0.05).ConclusionsThe combination of PCSK9 inhibitors with robust statins like rosuvastatin and atorvastatin markedly decreases LDL-C levels in patients with hyperlipidemia when compared to placebo or monotherapy. Notably, the pairing of evolocumab and atorvastatin exhibited exceptional efficacy in this investigation. In the interim, the combination of PCSK9 inhibitors and potent statins demonstrates a notable safety profile when contrasted with the control group.

Comparison of the efficacy and safety of GLP-1 receptor agonists on cardiovascular events and risk factors: A review and network meta-analysis.

This study aims to systematically evaluate and perform a systematic review and network meta-analysis comparing the comprehensive cardiovascular protective effects of various glucagon-like peptide-1 receptor agonists (GLP-1RAs), focusing on cardiovascular events and risk factors. We searched PubMed, Embase, Cochrane Library and Web of Science from inception to December 15, 2024. Included studies were published randomized controlled trials (RCTs) comparing GLP-1RAs to placebo or other GLP-1RAs. Missing data were standardized, and network meta-analysis was performed using Stata 17.0. Study heterogeneity, publication bias and evidence quality were assessed using the Cochrane Risk of Bias tool and Confidence in Network Meta-Analysis (CINeMA). As of December 15, 2024, a total of 18 313 articles were retrieved. Based on the inclusion and exclusion criteria, 156 high-quality studies were included, incorporating 144 782 patients and 14 different GLP-1RAs. The network meta-analysis demonstrated low heterogeneity, ensuring the reliability of the results. Comprehensive analysis revealed the following: Efpeglenatide was the most effective in reducing major adverse cardiovascular events. Oral semaglutide shows more significant advantages in reducing all-cause mortality and cardiovascular mortality. Orforglipron excelled in glycaemic control and weight reduction. SC-Semaglutide showed the greatest efficacy in lowering both systolic blood pressure and diastolic blood pressure, Liraglutide showed the greatest efficacy in lowering total cholesterol, Noiiglutide in triglycerides and Taspoglutide in low-density lipoprotein cholesterol, but no GLP-1RAs in high-density lipoprotein cholesterol. GLP-1RAs did not significantly increase the incidence of adverse events, but Orforglipron and Taspoglutide significantly increased the incidence of gastrointestinal adverse events compared with placebo. This study compared the cardiovascular benefits of different GLP-1RAs, including reductions in cardiovascular events and improvements in multiple cardiovascular risk factors. However, due to limitations in the quantity and quality of the included studies, the conclusions should be interpreted with caution. Future large-scale, high-quality clinical trials are needed to validate these findings and further optimize comprehensive cardiovascular management strategies for patients.

The Impact of Astaxanthin Supplementation on the Lipid Profile

Astaxanthin (AST) is a carotenoid renowned for its strong antioxidant properties and its role as a pigment in various aquatic organisms. Initially isolated from lobster and subsequently characterized in detail, AST has garnered significant interest in recent years within the research, pharmaceutical, cosmetic, and supplement industries. This review aims to synthesize current literature on the impact of astaxanthin supplementation on lipid profiles, specifically focusing on low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Evidence suggests that AST effectively prolongs the oxidation lag time of LDL, thereby mitigating the risk of atherosclerosis and cardiovascular diseases through its antioxidative mechanisms. The effects of AST on HDL-C levels are less consistent, with some studies reporting modest increases while others show no significant changes. Similarly, the influence of AST on triglyceride levels remains inconclusive, with studies presenting mixed outcomes ranging from significant reductions to negligible effects. AST is characterized by a high safety profile and favorable bioavailability, which is influenced by its source and isomeric composition. Despite these promising findings, many existing studies are limited by small sample sizes, heterogeneous participant groups, and varied dosing regimens, which impede the ability to draw definitive conclusions. Consequently, there is a need for larger, well-standardized clinical trials to accurately assess the efficacy and safety of astaxanthin as a therapeutic agent for lipid modulation and the prevention of metabolic disorders. Future research should focus on robust methodological designs and standardized supplementation protocols to clarify AST’s role in managing dyslipidemia and enhancing cardiovascular health.

Low-Density Lipoprotein (LDL) is Associated with Earlier Progression in Synchronous Metastatic Colorectal Cancer Treated without Curative Intent.

Low-density lipoprotein cholesterol (LDL) is associated with the occurrence of colorectal cancer (CRC). This study aims to investigate its prognostic role and associated clinicopathological factors in the metastatic setting. Patients with newly diagnosed synchronous metastatic CRC were included. Patients were grouped according to the serum LDL levels at the diagnosis (≤ 130mg/dL: Normal-LDL, > 130mg/dL: High-LDL). LDL-associated clinicopathological factors, progression-free survival (PFS), and overall survival (OS) were assessed. A total of 90 patients were included. 44.4% (n = 40) was in the normal-LDL and 56.6% (n = 50) in the high-LDL group. Colonic localization of the primary tumor was more frequent in the high-LDL group (90% vs. 67.5%, p = 0.009). The high-LDL group more frequently had local treatments [metastasectomy (26% vs. 2.5%, p = 0.002) and embolization-ablation (38% vs. 17.5%, p = 0.033)]. Despite higher curative intent with local treatments in the high-LDL group, PFS [10.03months (95% Confidence Interval (CI):6.97-14.77) vs 9.63 mo. (95% CI: 7.93-14.00), p = 0.872] and OS [20.87 mo. (95% CI: 14.87-36.47) vs. 17.63 mo. (95% CI: 14.30-43.03), p = 0.925] did not differ from the normal-LDL. Among patients treated without any curative intent, high LDL was associated with significantly worse PFS [4.97 mo. (95% CI: 3.00-7.73) vs. 8.43 mo. (95% CI: 6.10-9.90), p = 0.048]. This study suggests that serum LDL is associated with colonic primary localization in synchronous metastatic CRC. Levels > 130mg/dL at diagnosis may be associated with worse survival and may be further investigated as a biomarker. Larger, multicenter and prospective studies are needed.

Clinical Significance of Serum Omega-3 Fatty Acids on Endothelial Function in Patients with Coronary Artery Disease Under Statin Therapy

Vascular endothelial function plays an important role in the pathogenesis of atherosclerosis. The reduction in low-density lipoprotein cholesterol (LDL-C) is a key therapy for preventing coronary artery disease (CAD), but the role of omega-3 fatty acids as residual risk factors of CAD remains controversial. We studied the correlation between serum omega-3 fatty acid levels and endothelial function in patients with CAD receiving statin therapy and examined the effect of eicosapentaenoic acid (EPA) therapy on endothelial function. Methods: A total of 150 consecutive patients with CAD receiving statin therapy (LDL-C levels &lt; 100 mg/dL) were enrolled. Serum omega-3 fatty acid levels were measured, and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery. Subsequently, 65 patients with impaired FMD (&lt; 6%) and low EPA/arachidonic acid (AA) (&lt; 0.3) were administered EPA, and FMD was reassessed after 3 months. Results: A multivariate linear regression analysis demonstrated that serum docosahexaenoic acid (DHA) and EPA plus DHA levels were independent determinants of %FMD (β = 0.214 and 0.163, p &lt; 0.05, respectively). The EPA therapy significantly improved %FMD (from 3.7 ± 1.0% to 4.1 ± 1.0%, p &lt; 0.05) in patients with low EPA/AA, and especially in patients with low EPA/AA and high triglyceride levels (from 3.4 ± 1.0% to 4.0 ± 1.1%, p &lt; 0.01). Conclusions: Serum omega-3 fatty acid levels were associated with endothelial dysfunction in patients with CAD receiving statin therapy. EPA therapy improves endothelial function in patients with low EPA/AA, especially those with low EPA/AA and high triglycerides.

Baccharis trimera Aqueous Extract Protects Neuronal Mitochondrial Function and Reduces Microglial Lysosome Accumulation Induced by LDL Cholesterol

Baccharis trimera Aqueous Extract Protects Neuronal Mitochondrial Function and Reduces Microglial Lysosome Accumulation Induced by LDL Cholesterol

Purified Monascus Pigments: Biological Activities and Mechanisms of Action.

Monascus pigments having yellow, orange, and red colors are widely studied for their potential beneficial properties. Many different biological activities have been reported regarding Monascus pigments and their derivatives, but the usual method is to test complex extracts from the mycelium of the fungus or from a fungus-fermented substrate. However, this review is mainly concerned with the biological activities of purified Monascus pigments. Both yellow (ankaflavin, monascin) and red (rubropunctamine, monascorubramine) Monascus pigments are proven antioxidants if used in concentrations of 10 μg/mL or higher. Antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi has been observed with all Monascus pigments. However, the best antimicrobials are red Monascus pigments, and their amino acid derivatives (l-cysteine derivatives have MIC 4 μg/mL against Enterococcus faecalis). Yellow monaphilones and orange monaphilols seem to have the highest anti-inflammatory activity (IC50 1.7 μM of monaphilol D) and, together with red Monascus pigment derivatives, have mild antiobesity and antidiabetic activities. Further, monascin and ankaflavin in daily doses of 0.5 and 0.08 mg, respectively, lowered serum blood levels of low-density lipoprotein cholesterol complexes in rats on a high-fat diet. Orange Monascus pigments, rubropunctatin and monaphilols A and C, exhibit cytotoxic and antitumor activities (IC50 8-10 μM).

Efficacy of an avocado-based Mediterranean diet on serum lipids for secondary prevention after ischemic stroke: a randomized phase 2 controlled pilot trial

BackgroundThe impact of a healthy diet on the secondary prevention of ischemic stroke (IS) remains uncertain. Levels of low-density lipoprotein cholesterol (LDL-C) are inversely associated with the risk of IS recurrence. A Mediterranean diet (MeDi), consisting of a preference for fish/poultry, monosaturated fats from olive oil, fruit, vegetables, whole grains, legumes/nuts and limited red meats, animal fats and sweetened beverages, reduces metabolic syndrome, LDL-C levels and stroke risk. Avocados also reduce metabolic syndrome and LDL-C levels but are not part of the traditional MeDi diet. The effects of an avocado-based Mediterranean diet on LDL-C were investigated and compared to those of a low-fat diet in patients with previous IS.MethodsThe Avocado-Based Mediterranean Diet on Serum Lipids for Secondary Prevention after Ischemic Stroke (ADD-SPISE) was a prospective, randomized, open-label, blinded outcome assessment, phase 2, clinical trial. The participants were adults with an IS in the previous month who were randomly assigned at a 1:1 ratio to a MeDi or a low-fat diet for three months. Outcome assessors of laboratory results and data analysts were masked. The primary outcome was the mean difference in LDL-C between groups at 90 days, adjusted by statin use. Safety, feasibility and acceptability (assessed through a 14-item questionnaire administered to all patients who completed the follow-up) were also evaluated.ResultsFrom August 2018 to October 2022, 200 participants were enrolled (97 randomized to the low-fat diet and 103 to the MeDi), with 189 (94.5%) completing the study. There were no significant differences in LDL-C levels between the MeDi group and the low-fat group at 90 days: 66.5 mg/dL (95% confidence interval [CI] 59.6, 73.4) in the MeDi group and 69.9 mg/dL (62.6, 77.2) in the low-fat group at the end of follow-up. The adjusted difference was − 3.4 mg/dL (-13.4, -6.62); P = 0.50. The intervention group showed significant improvements in Mediterranean diet adherence (P < 0.01). Moreover, no significant differences in adverse events were observed between the groups.ConclusionCompared with a low-fat diet, the avocado-based MeDi did not significantly lower LDL-C in IS patients after three months. The intervention was safe, feasible, and well accepted. Larger trials should establish whether longer dietary interventions could yield clinically significant benefits in these patients. The study is registered under ADD-SPISE at www.clinicaltrials.gov. Identifier: NCT03524742.