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Background: The prevalence of hypertension among the Tibetan population in Tibet is higher than in other regions of China, and there is a lack of unified epidemiological surveys. This study aims to conduct a standardized epidemiological investigation to assess the current status of hypertension among the Tibetan population, as well as to explore the dose–response relationship between cholesterol (TC), triglyceride glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI), and hypertension in this population. Methods: From June 2020 to July 2023, a total of 5042 Tibetans aged 18 to 80 years from three cities and one region in Tibet were randomly sampled for the study. Logistic regression analysis models combined with restricted cubic splines were used to analyze the relationship between LDL-C, TC, TyG, TyG-BMI index, and HTN in the Tibetan population. Results: (1) The prevalence of HTN in the Tibetan population in Tibet, China, was 32.35%, of which men were slightly higher than women. (2) Age, BMI, fasting blood glucose (FBG), uric acid (UA), TC, triglycerides (TG), LDL-C, homocysteine (Hcy), TyG, and TyG-BMI were higher in HTN populations compared to non-HTN populations (P < 0.05). (3) The risk of HTN was increased in individuals with borderline elevated and elevated LDL-C, borderline elevated TC, the second(Q2), third(Q3), and fourth quartile groups(Q4) of TyG as well as the third(Q3) and fourth quartile groups(Q4) of TyG-BMI. The prevalence risk of HTN gradually increased with elevated levels of LDL-C, TC, TyG, and TyG-BMI (P trend < 0.001). (4) The results of restricted cubic spline analysis showed a nonlinear dose–response relationship between LDL-C, TC, and TyG-BMI and the risk of developing HTN (P < 0.001, P Nonlinear < 0.05), and a linear dose–response relationship between TyG and the risk of developing HTN (P < 0.001, PNonlinear > 0.05). Conclusion: Higher LDL-C, TC, TyG, and TyG-BMI are risk factors for HTN in the Tibetan population of Tibet, China. Effective prevention can be achieved by controlling lipid and glucose indices. [ABSTRACT FROM AUTHOR]

Dihydrotanshinone I (DHT), a lipophilic compound extracted from Salvia miltiorrhiza, has cardiovascular protective effects, but the underlying molecular mechanisms of action have rarely been reported. Based on this, whether DHT affects cholesterol metabolism by regulating LDLR is investigated in this work. The results revealed that DHT can increase LDLR expression and promote LDL uptake by HepG2 cells. Meanwhile, DHT stabilizes LDLR mRNA expression by activating the epidermal growth factor receptor/extracellular signal-regulated kinase 1/2 (EGFR/erk1/2) signaling pathway. In addition, DHT inhibits the expression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) by down-regulating the liver nuclear transcription factor 1 A (HNF1A) and up-regulating the forkhead box O3 (FOXO3). All of these indicate that DHT increases LDLR expression at the post-transcriptional and post-translational levels thereby promoting LDL-C metabolism. The potential mechanism of DHT to improve lipid metabolism has been revealed as a promising drug against AS. [ABSTRACT FROM AUTHOR]

• Advances in single-cell biology have revolutionized the understanding of atherosclerosis, highlighting the interaction between different cell populations and molecular pathways in plaque progression and regression. • The formation and progression of atherosclerotic plaques are driven by LDL cholesterol and chronic exposure to pro-inflammatory stimuli, resulting in endothelial dysfunction and the formation of foam cells. • The concept of "vulnerable plaque" describes plaques prone to rupture, erosion, or calcified nodules, leading to acute coronary syndrome (ACS). Modern imaging techniques like IVUS, NIRS, and OCT are crucial for identifying and assessing these high-risk plaques. • Intensive lipid-lowering therapies, particularly statins and PCSK9 inhibitors, have shown efficacy in reducing plaque volume and stabilizing plaque features, with ongoing research needed to confirm their long-term benefits in reducing cardiovascular events. Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death globally despite advances in preventive therapies. Understanding of the initiation and progression of atherosclerosis, the interplay between lipoproteins, endothelial dysfunction, inflammation, and immune responses is critical to treating this disease. The development of vulnerable coronary plaques prone to thrombosis, can lead to acute coronary syndromes, for these reasons, the potential plaque stabilization and regression through pharmacological interventions, particularly lipid-lowering agents like statins and PCSK9 inhibitors is crucial. The imaging techniques such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) play a key role in assessing plaque composition and guiding interventional therapeutic strategies. Clinical evidence supports the efficacy of intensive lipid-lowering therapy in inducing plaque regression, with studies demonstrating reductions in plaque volume and improvements in plaque morphology assessed by IVUS, OCT and NIRS. While pharmacological interventions show promise in promoting plaque regression and stabilization, their impact on long-term cardiovascular events requires further investigation. Multimodality imaging and comprehensive outcome trials are proposed as essential tools for elucidating the relationship between plaque modification and clinical benefit in coronary atherosclerosis. The stabilization or regression of atherosclerotic plaque might serve as the phenomenon linking the reduction in LDL-C levels to the decrease in cardiovascular events. Overall, this review emphasizes the ongoing efforts to advance our understanding of ASCVD pathophysiology and optimize therapeutic approaches for improving patient outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Dyslipidemia is the most significant risk factor for cardiovascular diseases (CVDs) Secondary dyslipidemia: its treatments and association with atherosclerosis. Glob Health Med, Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies. The current treatment strategies for managing dyslipidemia focus on reducing low-density lipoprotein cholesterol (LDL-C) to minimize the risks of atherosclerosis and myocardial infarction (MI). Homozygous Familial Hypercholesterolemia (HoFH) is an inherited autosomal dominant disease caused by a mutation in the LDL receptor (LDLr), which can lead to extremely high levels of LDL-C The Beneficial Effect of Lomitapide on the Cardiovascular System in LDLr(-/-) Mice with Obesity, The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity. Although statin therapy has been the primary treatment for dyslipidemia, HoFH patients do not respond well to statins, requiring alternative therapies. Microsomal triglyceride transfer protein (MTP) inhibition has emerged as a potential therapeutic target for treating HoFH. MTP is primarily responsible for transferring triglyceride and other lipids into apolipoprotein B (ApoB) during the assembly of very low-density lipoprotein (VLDL) particles in the liver. Lomitapide, an inhibitor of MTP, has been approved for treatingof HoFH adults. Unlike statins, lomitapide does not act on the LDLr to reduce cholesterol. Instead, lomitapide lowers the levels of ApoB-containing proteins, primarily VLDL, eventually decreasing LDL-C levels. Studies have shown that lomitapide can reduce LDL-C levels by more than 50% in patients with HoFH who have failed to respond adequately to other treatments. Lowering LDL-C levels is important for preventing atherosclerosis, reducing cardiovascular risk, improving endothelial function, and promoting overall cardiovascular health, especially for patients with HoFH Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. This review paper focuses on research findings regarding the therapeutic benefits of lomitapide, highlighting its effectiveness in lowering cholesterol levels and reducing the risk of CVDs The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity. [ABSTRACT FROM AUTHOR]

Purpose: Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design. Methods: We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis. Results: In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117--1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106--1.597, P = 0.002). Conclusions: Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C. [ABSTRACT FROM AUTHOR]

Anomalies in lipid metabolism involve multifactorial pathogenesis, among other factors, being associated with an inflammatory state and disturbances in vitamin D status. The literature has focused on the binary relationships between inflammation and dyslipidemia, vitamin D and dyslipidemia, or vitamin D and inflammation. Our study aimed to explore the link between all these three factors: 25-OH vitamin D serum levels, the presence of inflammation assessed through serum C-reactive protein (CRP), and serum lipid profile in 2747 hospitalized patients. Our results showed a positive correlation of HDL-C with 25 (OH) vitamin D and a negative correlation of HDL-C with CRP. This relationship had different patterns in the statistical network analysis. The network analysis patterns are preserved for males and females, except for the relationship between CRP and vitamin D, which is present in male cases and absent in females. The same triangular relationship between all three—CRP, vitamin D, and HDL-C was found with different strengths of partial correlation in obese and non-obese patients. This pattern was similar in patients with and without fatty liver. A shifted pattern was found in the network analysis of hypertensive patients. The CRP was negatively correlated with vitamin D and HDL-C, and vitamin D was positively correlated with HDL-C in non-hypertensive patients. Castelli's Risk indexes I and II were positively associated with CRP, suggesting that increased cardiovascular risk is proportional to an inflammatory state. The triad formed by altered serum lipid levels, inflammation, and vitamin D represents a complex relationship marked by specific dynamics between lipidic fractions such as HDL-C and C-reactive protein and vitamin D. [ABSTRACT FROM AUTHOR]

Hyperlipidemia and obesity represent significant global health challenges associated with heightened risks of angina, atherosclerosis, and stroke due to elevated blood lipid levels. Exploring natural agents as potential therapeutic interventions is promising in addressing these conditions. In this study, the antihyperlipidemic and anti-obesity effects of ethanolic extract from Parmotrema tinctorum were evaluated using an olive oil-induced hyperlipidemic rat model. Rats were divided into distinct treatment groups, including simvastatin, distilled water (control), and two doses of the extract (200 mg/kg and 400 mg/kg). The experiment was conducted over 28 days. Administration of Parmotrema tinctorum extract led to significant reductions in body and liver weight gain. The serum lipid profile exhibited dose-dependent decreases in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). Additionally, there were notable reductions in the atherogenic index and blood glucose levels. The observed effects were attributed to potential anorectic actions mediated through the central nervous system. The extract did not affect gastric emptying and demonstrated inhibition of de novo cholesterol biosynthesis. This study underscores the potential of ethanolic extract from Parmotrema tinctorum as a dual-action therapeutic agent for addressing hyperlipidemia and obesity. The findings highlight its ability to modulate lipid metabolism, suggesting implications for managing cardiovascular and metabolic disorders. Further research is needed to elucidate the underlying mechanisms of its effects and to explore its potential application in clinical settings. [ABSTRACT FROM AUTHOR]

Abstract The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to

The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance "low LDL-c–high LDL-p" group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55–5.00) in the reference of the concordance "low LDL-c–low LDL-p" group. This was followed by the concordance "high LDL-c–high LDL-p" group of 2.56 (1.69–3.85) and the discordance "high LDL-c–low LDL-p" group of 2.40 (1.29–4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS. [ABSTRACT FROM AUTHOR]

Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of >60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of >90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in >51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients. [ABSTRACT FROM AUTHOR]

Objective: The effective administration of lipid-lowering treatment is of utmost importance in mitigating cardiovascular (CV) risk in patients who are undergoing secondary prevention. High-dose statins, ezetimibe, and the relatively newer PCSK9 inhibitors (PCSK9i) have shown effectiveness in achieving low density lipoprotein cholesterol(LDL-C) treatment targets for these patients. However, despite substantial evidence supporting their efficacy, these interventions remain significantly underutilized, primarily due to poor levels of patient adherence. Moreover, there is limited data available on the overall effectiveness of cholesterol-lowering treatment and the proportion of secondary prevention patients who have achieved a well-regulated lipid profile. In light of these factors, the principal aim of this investigation was to evaluate the present status of lipid-lowering medication within this specific group of individuals. Methods: The study was conducted at Mardin Artuklu University, Mardin Training and Research Hospital between April 2021 and March 2023, focusing on patients with a history of secondary prevention of CVD. The study investigated prescribed cholesterol-lowering drugs, factors contributing to statin underuse, and lipid profile disclosure. Results: 872 patients were included. 86.8% received statins, 5.2% ezetimibe, and 3.4% fibrates, while 13.2% received no lipidlowering therapy. 64% of those on statins were on high doses. LDL-C values were assessed in 452 patients, with only 30% below the recommended cutoff of 70 mg/dL. Conclusion: In this investigation involving secondary prevention patients, slightly over half of the participants received highdose statins, while a negligible proportion received ezetimibe treatment. Alarmingly, over two-thirds of the patients demonstrated LDL-C values that deviated significantly from the therapeutic range, indicating a considerable gap between their lipid profiles and the recommendations set forth by clinical guidelines. [ABSTRACT FROM AUTHOR]

• Post hoc study using pooled data from two phase 3 bempedoic acid clinical trials. • Patients with and without heterozygous familial hypercholesterolemia were included. • In both groups, bempedoic acid lowered LDL-C and other lipid parameters vs. placebo. • Bempedoic acid was generally well tolerated in both patient groups. • No new safety findings in patients with heterozygous familial hypercholesterolemia. Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy. To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH. Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety. A total of 217 (bempedoic acid, 146; placebo, 71) patients with HeFH and 2,792 (bempedoic acid, 1,864; placebo, 928) without HeFH were included (mean baseline LDL-C, 172.8 mg/dL and 102.6 mg/dL, respectively). Bempedoic acid significantly lowered LDL-C at week 12 vs. placebo regardless of HeFH status (with HeFH, −21.2%; without HeFH, −18.2% [both P <0.0001]). Bempedoic acid significantly reduced other lipid parameters and high-sensitivity C-reactive protein vs. placebo regardless of HeFH status (all P ≤0.01). Among patients with HeFH treated with bempedoic acid, 32% and 27% achieved LDL-C <100 mg/dL at weeks 12 and 52, respectively. Overall treatment-emergent adverse event incidence was comparable across all four groups (74.7–77.5%). Bempedoic acid significantly lowered LDL-C levels vs. placebo and was generally well tolerated in all patients, with no new safety findings in patients with HeFH, despite more intensive lipid-lowering therapy in patients with vs. without HeFH. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Introduction This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. Methods This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. Results A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51–68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7–4.2) mmol/L (131.5 [IQR 104.4–162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds

Purpose of Review: To discuss the history of cardiovascular outcomes trials of cholesteryl ester transfer protein (CETP) inhibitors and to describe obicetrapib, a next-generation, oral, once-daily, low-dose CETP inhibitor in late-stage development for dyslipidemia and atherosclerotic cardiovascular disease (ASCVD). Recent Findings: Phase 1 and 2 trials have evaluated the safety and lipid/lipoprotein effects of obicetrapib as monotherapy, in conjunction with statins, on top of high-intensity statins (HIS), and with ezetimibe on top of HIS. In ROSE2, 10 mg obicetrapib monotherapy and combined with 10 mg ezetimibe, each on top of HIS, significantly reduced low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total LDL particles, small LDL particles, small, dense LDL-C, and lipoprotein (a), and increased HDL-C. Phase 3 pivotal registration trials including a cardiovascular outcomes trial are underway. Summary: Obicetrapib has an excellent safety and tolerability profile and robustly lowers atherogenic lipoproteins and raises HDL-C. As such, obicetrapib may be a promising agent for the treatment of ASCVD. [ABSTRACT FROM AUTHOR]

Introduction: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. Methods: This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. Results: A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51–68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7–4.2) mmol/L (131.5 [IQR 104.4–162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds < 1.8, < 1.4 and < 1.0 mmol/L (< 70, < 55 and < 40 mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12 months. Conclusion: These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk. [ABSTRACT FROM AUTHOR]

The accumulations of lipid low-density lipoprotein cholesterol (LDL-C) and other chemicals on the artery wall are known as atherosclerosis. Atherosclerosis can constrict the arteries and obstruct the blood flow. Our goal is to debate the model of unsteady pulsatile Cross fluid (blood model) flows through a vertical porous microchannel with multiple stenoses under the influence of thermal radiation and Joule heating. The equations of momentum, energy, and LDL-C concentration have been simplified with the help of mild stenosis approximation. Then they have been solved numerically by using the finite difference method. It is noticed that the blood velocity increases and reaches a steady state in the case of non-pulsating flow, while the blood velocity fluctuates in the case of pulsating flow. Moreover, the value of LDL-C concentration in the case of a chemical reaction is lower than in the absence of a chemical reaction.

Testosterone replacement therapy (TRT) in transgender men (TM) results in side effects such as elevated triglycerides and increased arterial stiffness. Exercise may be useful to ameliorate such effects, but no studies have examined the effects of acute aerobic exercise in TM. This study aimed to investigate the effects of acute aerobic exercise on arterial stiffness in TM. Thirty-six participants were included, comprising 12 TM (duration of TRT: 57.4 ± 30.3 months), 12 males and 12 females. All participants performed acute aerobic exercise on a treadmill at 50% heart rate reserve for 30 min. Arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) was measured before exercise (Pre), 30 min after exercise (Post30), and 60 min after exercise (Post60). Serum sex hormone levels, and serum lipid profile were determined only before exercise. Serum low-density lipoprotein cholesterol (LDL-C) levels before exercise were significantly higher in TM than in males or females (males: p < 0.01; females: p < 0.05). At all points, baPWV in TM was significantly higher than in females (p < 0.05) and significantly lower than in males (p < 0.05). However, when comparing changes in baPWV over time in each group, significant decreases in Post30 and Post60 were seen in males compared to Pre (both p < 0.05), but no significant change after aerobic exercise was seen in TM or females. These results suggest that acute aerobic exercise yield different effects in TM than in males, but is unlikely to reduce arterial stiffness in TM receiving TRT. [ABSTRACT FROM AUTHOR]

Background: Limited reports addressing physicians’ understanding of the various low-density lipoprotein cholesterol (LDL-C) targets/statin intensity required for treating the various dyslipidemia patient populations in Saudi Arabia are available. Therefore, the current study assessed the perceptions and beliefs of practicing clinicians in Saudi Arabia regarding the current practice for management of dyslipidemia and potential perceived barriers to adherence to lipid guidelines encountered in their regular clinical practice. Knowledge of different clinical practices and beliefs could have a positive impact on improving the quality of future care provided by physicians. Methods: A survey questionnaire was designed to assess physicians’ familiarity, usage, and adherence to seven different international guidelines and used to evaluate the management of dyslipidemia, practice of patient treatment, and perceived obstacles to adhering to lipid guidelines related to specific patients, doctors, and practice issues. Results: A total of 467 physicians were recruited for the study: (1) 57.2% were primary care physicians (PCPs) and (2) 42.8% were specialists. About 90.8% of them followed lipid guidelines of which the most common set were based on those by the American College of Cardiology/American Heart Association. The most utilized risk assessment tool was the atherosclerotic cardiovascular disease (ASCVD) risk calculator. About 60% of the physicians set an LDL-C target for their patients based on a combination of patients’ risk factors and lipid profiles. In all, 42.1% of the physicians chose not to change existing therapy among patients with dyslipidemia to attain a non-high-density lipoprotein goal with controlled LDL-C level. Atorvastatin accounted for the greatest percentage of primary and secondary prevention choices (71.9% and 69.6%, respectively). Rosuvastatin was mostly preferred by physicians for patients with familial hypercholesterolemia. About two-thirds of the physicians (77.9%) prescribed statins to diabetic patients aged 40–75 years. Statin intolerance was encountered by 62.9% of the physicians in ≤ 10% of patients by 62.9%. Therapeutic strategies included switching to an alternative statin (40.1%) followed by reducing the statin dose (35.3%). Ezetimibe was prescribed by most physicians (77.9%) as an add-on to statin if the LDL-C target was not achieved. Fibrate was most preferred by physicians (62.7%) for hypertriglyceremia treatment followed by statins (28.7% of the physicians). Sixty-six percent reported not using proprotein convertase subtilisin/kexin type 9 serine protease inhibitors in their clinical practice due to unavailability at their institute (51.8%), high costs (26.3%), and/or lack of knowledge (20.6%). Perceived barriers to guideline adherence identified by physicians were lack of familiarity and knowledge of the guidelines, patient non-adherence, medication costs, and lack of timely follow-up appointments and educational tools. Multiple similarities and differences were observed after comparisons were made between specialists and PCPs in terms of guideline preference, clinical practice, and perceived barriers. Conclusion: Different perceptions and attitudes among physicians in Saudi Arabia were found due to variable recommendations by international lipid guidelines. Perceived barriers that included the patient, physician, and practice were identified by physicians at multiple levels. Multiple challenges and different action gaps were observed when comparing specialists to PCPs. It is recommended that standardized practices be followed by clinicians in Saudi Arabia, and actions to address the outlined barriers are essential for optimizing health outcomes and ASCVD prevention.

Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of >60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of >90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in >51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.

Abstract Background A balanced nutrition is important for children’s physical and cognitive development; yet, remains a challenge in many parts of low- and middle-income countries (LMICs). Early detection of nutritional deficiency and metabolic syndrome in school-aged children is necessary to prevent non-communicable diseases (NCDs) in later life. This study aimed at obtaining baseline data on health, nutritional status, and metabolic markers of NCDs among primary schoolchildren in Côte d’Ivoire. Methods A cross-sectional survey was conducted among 620 children from 8 public primary schools located in the south-central part of Côte d’Ivoire. Underweight and overweight were defined as a body mass index (BMI; kg/m2)

• The very first clinical study that investigated the effects of inclisiran in Chinese patients. • Inclisiran (100 and 300 mg) was generally safe and well-tolerated in Chinese patients. • Similar PK and PD (LDL-C reduction) properties in Chinese patients as those in Caucasian patients. Inclisiran is a novel siRNA therapy that inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9) by targeting the PCSK9 mRNA, consequently, decreases low-density lipoprotein cholesterol (LDL-C). To assess the safety, PK and LDL-C lowering effects of inclisiran in the Chinese patients with elevated LDL-C despite treatment with maximally tolerated LDL-C lowering therapies. Forty Chinese patients with hypercholesterolemia (LDL-C ≥100 mg/dL) who were on maximally tolerated statin were randomized to receive a single dose of either inclisiran sodium 100 or 300mg s.c. injection (each for 15 patients) or placebo (10 patients). Safety, pharmacokinetics and pharmacodynamics (i.e., PCSK9 and LDL-C levels) were evaluated for up to 90 days after the s.c. injection of study drug. Following single subcutaneous injections inclisiran sodium at 100 mg or 300 mg, inclisiran has a relative short elimination half-life (T 1/2 , 6.5 hours). Both plasma PCSK9 and serum LDL-C decreased rapidly and consistently, with the maximal reduction between Day 30 and Day 60; then the decreases of PCSK9 and LDL-C were generally maintained up to 56.4% and 49.6% of 100 mg, 74.9% and 58.3% of 300 mg, respectively, at day 90. All adverse events were mild or moderate in severity, and no discontinuations due to adverse events. There were no serious adverse events being reported. Inclisiran was generally safe and well tolerated. Single dose of both Inclisiran 100 and 300 mg significantly reduced PCSK9 and LDL-C levels in Chinese patients up to Day 90. The greatest reductions were observed with the 300 mg regimen of Inclisiran. ClinicalTrials.gov: NCT04774003 [Display omitted] [ABSTRACT FROM AUTHOR]

PurposeThe objective was to evaluate the influence of low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] on clinical outcomes in patients undergoing coronary artery bypass grafting (CABG).MethodsThis is a secondary analysis of a 5-year follow-up of the DACAB trial (NCT02201771), in which 500 patients who underwent primary isolated CABG were randomized to three-antiplatelet therapy for 1 year after surgery. Of them, 459 patients were recruited in this secondary analysis. Baseline LDL-C and Lp(a) levels were collected, and repeated measurement of LDL-C levels during the follow-up were recorded. Cut-off values for LDL-C were set at 1.8 and 2.6 mmol/L; thus, the patients were stratified into LDL-C

The accumulations of lipid low-density lipoprotein cholesterol (LDL-C) and other chemicals on the artery wall are known as atherosclerosis. Atherosclerosis can constrict the arteries and obstruct the blood flow. Our goal is to debate the model of unsteady pulsatile Cross fluid (blood model) flows through a vertical porous microchannel with multiple stenoses under the influence of thermal radiation and Joule heating. The equations of momentum, energy, and LDL-C concentration have been simplified with the help of mild stenosis approximation. Then they have been solved numerically by using the finite difference method. It is noticed that the blood velocity increases and reaches a steady state in the case of non-pulsating flow, while the blood velocity fluctuates in the case of pulsating flow. Moreover, the value of LDL-C concentration in the case of a chemical reaction is lower than in the absence of a chemical reaction. [ABSTRACT FROM AUTHOR]

According to the latest international and Russian guidelines for the treatment of dyslipidemias, statins are defined as the main group of drugs that significantly reduce the level of low-density lipoprotein cholesterol (LDL-C) effectively prevent atherosclerotic cardiovascular diseases (CVD) and complications and can slow down the progression of atherosclerosis. The principle “the lower LDL-C, the better” is especially relevant in categories of patients with very high and extreme cardiovascular risk, and therefore, in order to achieve target LDL-C values (≤1.4 is optimal ≤1.0) in this category of patients, high-intensity lipid-lowering therapy should be used. Rosuvastatin remains the most effective statin. Its use makes possible to achieve target lipid values at the starting dose of treatment, enhances adherence to treatment, and also reduces the frequency of side effects associated with the use of high doses of other statins. In addition, the proven ability of rosuvastatin to reduce the volume of atherosclerotic plaque, by reducing the level of pro-inflammatory cytokines and C-reactive protein, normalizing endothelial function, antiplatelet action, that is, rosuvastatin, in addition to its powerful lipid-lowering effect, has anti-inflammatory and anti-ischemic effects. Also, rosuvastatin can be successfully used in the presence of comorbidities, including chronic kidney disease and chronic heart failure. Taking into consideration the urgency of the fight against the COVID-19 pandemic (coronavirus Disease 2019), which covered 220 countries, due to the lack of effective etiotropic drugs, the possibility of using statins, including rosuvastatin, for the treatment of comorbid patients with COVID-19, was evaluated.

Objective: Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management. Methods: We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes. Results: Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72-0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258). Conclusions: We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal. [ABSTRACT FROM AUTHOR]

Background: A balanced nutrition is important for children's physical and cognitive development; yet, remains a challenge in many parts of low- and middle-income countries (LMICs). Early detection of nutritional deficiency and metabolic syndrome in school-aged children is necessary to prevent non-communicable diseases (NCDs) in later life. This study aimed at obtaining baseline data on health, nutritional status, and metabolic markers of NCDs among primary schoolchildren in Côte d'Ivoire.Methods: A cross-sectional survey was conducted among 620 children from 8 public primary schools located in the south-central part of Côte d'Ivoire. Underweight and overweight were defined as a body mass index (BMI; kg/m2) < 5th and 85th up to 95th percentile for sex and age, respectively. Dietary diversity of children was calculated based on a 24-hour recall conducted with the primary caretaker according to the guideline of Food and Agriculture Organization. Anaemia, malaria, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and blood glucose levels (HbA1c) were assessed, using capillary blood samples. Logistic models were performed to identify risk factors associated with overweight, HDL-C, LDL-C, and HbA1c.Results: Among the 620 children (330 girls, 290 boys; Mage 8.0 (± 1.7) years), 530 children attended school in a semi-urban and 90 in a rural area. Around 60% of children had a medium dietary diversity score (DDS). Children in peri-urban areas consumed more cereals (80.2% vs. 63.3%, p < 0.05). Most children were normal weight (n = 496), whereas 3.9% of children classified as prediabetic, 5% were underweight, and 15% overweight. LDL-C and HDL-C levels of children were associated with age, high DDS, and moderate anaemia. A significant association was found between prediabetes and malaria infection, as well as medium and high DDS. Overweight was associated with malaria infection and moderate anaemia.Conclusion: Overweight, prediabetes, low HDL-C, malaria, and anaemia are the main concerns of children's health in Taabo. Our findings highlight interactions between infectious diseases, particularly malaria, and NCD risk factors. Monitoring NCD risk and infectious disease comorbidity in LMIC paediatric populations simultaneously is essential to better understand the dual diseases burden and apply early prevention measures. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) affects millions of individuals worldwide, and it is the second most common late-onset neurodegenerative disorder. There is no cure and current treatments only alleviate symptoms. Modifiable risk factors have been explored as possible options for decreasing risk or developing drug targets to treat PD, including low-density lipoprotein cholesterol (LDL-C). There is evidence of sex differences for cholesterol levels as well as for PD risk. Genetic datasets of increasing size are permitting association analyses with increased power, including sex-stratified analyses. These association results empower Mendelian randomization (MR) studies, which, given certain assumptions, test whether there is a causal relationship between the risk factor and the outcome using genetic instruments. Sex-specific causal inference approaches could highlight sex-specific effects thatmay otherwise bemasked by sex-agnostic approaches. We conducted a sex-specific two-sample cis-MR analysis based on genetic variants in LDL-C target encoding genes to assess the impact of lipid-lowering drug targets on PD risk. To complement the cis-MR analysis, we also conducted a sex-specific standard MR analysis (using genome-wide independent variants). We did not find evidence of a causal relationship between LDL-C levels and PD risk in females [OR (95% CI) = 1.01 (0.60, 1.69), IVW random-effects] or males [OR (95% CI) = 0.93 (0.55, 1.56)]. The sex-specific standard MR analysis also supported this conclusion. We encourage future work assessing sex-specific effects using causal inference techniques to better understand factors that may contribute to complex disease risk differently between the sexes. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the link between the neutrophil to HDL-C ratio (NHR) and the degree of coronary stenosis in patients with stable coronary artery disease (CAD).Materials and methodsTotally 766 individuals who attended our clinic for coronary angiography between January 2019 and January 2021 were included in this study. The participants were divided into two groups, including the CAD group and control group. Spearman correlation analysis was used to investigate the association between NHR and Gensini score and logistic regression analysis was performed to determine the influence of NHR on CAD and severe CAD. Receiver operating characteristic (ROC) curve was constructed to analyze the predictive value of NHR for severe CAD.ResultsThe CAD group had a substantially higher median NHR than the control group (3.7 vs. 3.2, P < 0.01). There was a positive correlation between NHR and Gensini score, as well as the frequency of coronary artery plaques. Logistic regression demonstrated that NHR was an independent contributor for CAD and severe CAD. In ROC analysis, the area under the ROC curve (AUC) for NHR was larger than that for neutrophil, HDL-C or LDL-C/HDL-C, and the differences were statistically significant (all P < 0.05). The NHR limit that offered the most accurate prediction of severe CAD according to the greatest possible value of the Youden index, was 3.88, with a sensitivity of 62.6% and a specificity of 66.2%.ConclusionNHR was not only associated with the occurrence and seriousness of CAD, but also a better predictor of severe CAD than neutrophil, HDL-C or LDL-C/HDL-C.

Purpose: Cardiovascular disease (CVD) is a major worldwide health burden. As the risk factors of CVD, hypertension, and hyperlipidemia are most mentioned. Early stage hypertension in the population with dyslipidemia is an important public health hazard. This study was the application of data-driven machine learning (ML), demonstrating complex relationships between risk factors and outcomes and promising predictive performance with vast amounts of medical data, aimed to investigate the association between dyslipidemia and the incidence of early stage hypertension in a large cohort with normal blood pressure at baseline. Methods: This study analyzed annual health screening data for 71,108 people from 2005 to 2017, including data for 27 risk-related indicators, sourced from the MJ Group, a major health screening center in Taiwan. We used five machine learning (ML) methods—stochastic gradient boosting (SGB), multivariate adaptive regression splines (MARS), least absolute shrinkage and selection operator regression (Lasso), ridge regression (Ridge), and gradient boosting with categorical features support (CatBoost)—to develop a multi-stage ML algorithm-based prediction scheme and then evaluate important risk factors at the early stage of hypertension, especially for groups with high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels within or out of the reference range. Results: Age, body mass index, waist circumference, waist-to-hip ratio, fasting plasma glucose, and C-reactive protein (CRP) were associated with hypertension. The hemoglobin level was also a positive contributor to blood pressure elevation and it appeared among the top three important risk factors in all LDL-C/HDL-C groups; therefore, these variables may be important in affecting blood pressure in the early stage of hypertension. A residual contribution to blood pressure elevation was found in groups with increased LDL-C. This suggests that LDL-C levels are associated with CPR levels, and that the LDL-C level may be an important factor for predicting the development of hypertension. Conclusion: The five prediction models provided similar classifications of risk factors. The results of this study show that an increase in LDL-C is more important than the start of a drop in HDL-C in health screening of sub-healthy adults. The findings of this study should be of value to health awareness raising about hypertension and further discussion and follow-up research. [ABSTRACT FROM AUTHOR]

BackgroundThe role of longitudinal temporal trends in LDL-C in cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) and diabetes is unclear. This study categorized the long-term LDL-C trajectory and determined its association with the incidence of atherosclerotic CVD in patients with CKD according to diabetes status and estimated glomerular filtration rate (eGFR).MethodsThe risk of atherosclerotic CVD was estimated in 137,127 Taiwanese patients with CKD using six LDL-C trajectory classes determined by the latent class mixed model as optimal, near optimal, above optimal, borderline, sustained high, and declined high over 5 years.ResultsThe risk of CVD was higher in the sustained high LDL-C [>160 mg/dL over time; adjusted hazard ratio (aHR) = 1.68, 95% CI = 1.45–1.94], declined high LDL-C (>160 to 120 mg/dL).ConclusionThe LDL-C trajectory pattern was associated with the phenotype of CVD risk. The degree of risk varied according to eGFR and diabetes status. A stable low LDL-C over time was potentially beneficial for prevention of CVD. Intensive lipid management and periodic assessment of LDL-C is essential to reduce the risk of CVD in patients with CKD and diabetes.

BackgroundIn dialysis patients, lowering low-density lipoprotein cholesterol (LDL-C) did not provide benefits, which seemed implausible in clinical practice. We hypothesized a U-shaped association between LDL-C and mortality in dialysis patients.MethodsIn this multi-center retrospective real-world cohort study, 3,565 incident Chinese peritoneal dialysis (PD) patients between January 1, 2005, and May 31, 2020, were included. The associations between baseline LDL-C and mortality were examined using cause-specific hazard models.ResultsOf 3,565 patients, 820 died, including 415 cardiovascular deaths. As compared with the reference range (2.26-2.60 mmol/L), both higher levels of LDL-C (> 2.60 mmol/L) and lower levels of LDL-C (< 2.26 mmol/L) were associated with increased risks of all-cause mortality (hazard ratio [HR],1.35, 95% confidence index [CI], 1.09-1.66; HR 1.36, 95%CI, 1.13-1.64) and cardiovascular mortality (HR, 1.31, 95% CI, 1.10-1.72; HR, 1.64; 95% CI, 1.22-2.19). Malnutrition (albumin < 36.0 g/L) modified the association between LDL-C and cardiovascular mortality (P for interaction = 0.01). A significantly increased risk of cardiovascular mortality was observed among patients with malnutrition and lower levels of LDL-C (HR 2.96, 95%CI 1.43-6.12) or higher levels of LDL-C (HR 2.81, 95%CI 1.38-5.72).ConclusionLow and high levels of LDL-C at the start of PD procedure were associated with increased all-cause and cardiovascular mortality risks. Malnutrition may modify the association of LDL-C with cardiovascular mortality.

Background and Aims: Familial hypercholesterolemia (FH) is a common inherited disorder of low-density lipoprotein (LDL) catabolism that causes elevated LDL-cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Despite the availability of effective treatments, FH remains underdiagnosed and undertreated. The aims of the study were to identify putative FH subjects using data from laboratory and cardiology databases, genetically characterize suspected FH patients referred to the Lipid Clinic and monitor attainment of treatment goals in identified patients.Methods and Results: We retrieved the electronic health records of 221,644 individuals referred to laboratory for routine assessment and of 583 ASCVD patients (age ≤65) who underwent percutaneous transluminal coronary angioplasty (PTCA). We monitored the lipid profiles of subjects with LDL-C ≥ 250 mg/dl identified by laboratory survey (LS-P), PTCA patients and patients from the Lipid Clinic (LC-P). The laboratory survey identified 1.46% of subjects with LDL-C ≥ 190 mg/dl and 0.08% with LDL-C ≥ 250 mg/dl. Probable/definite FH was suspected in 3% of PTCA patients. Molecularly-confirmed FH was found in 44% of LC-P subjects. Five new LDLR mutations were identified. The 50% LDL-C reduction target was achieved by 70.6% of LC-P patients. Only 18.5% of PTCA patients reached the LDL-C < 55 mg/dl target.Conclusion: By using a combined approach based on laboratory lipid profiles, documented ASCVD and Lipid Clinic data, we were able to identify subjects with a high probability of being FH. Attainment of LDL-C goals was largely suboptimal. Efforts are needed to improve FH detection and achievement of lipid targets. [ABSTRACT FROM AUTHOR]

Objective: To compare and rank the clinical effects of different acupuncture and related therapies on hyperlipidemia patients. Methods: We used network meta-analysis (NMA) to evaluate direct and indirect effects in studies of acupuncture and related therapies for hyperlipidemia. Databases PubMed, EMBASE, Cochrane Library, the China Biology Medicine (CBM), the China National Knowledge Infrastructure (CNKI), Wanfang Data and the Chinese Scientific Journal Database (VIP) were searched to collect randomized controlled trials (RCTs) of acupuncture and related therapies in the treatment of hyperlipidemia. The data were analyzed using Stata 15.0 and WinBUGS 1.4.3 software after two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Results: We analyzed a total of 36 eligible studies that included 3 124 patients, involving 12 types of acupuncture and related therapies and comprehensive therapies. The results of the NMA showed that: for the total cholesterol (TC), acupoint catgut embedding (ACE), simple acupuncture (ACU), acupoint injection (AI), electroacupuncture (EA), western medicine of statins (WM), and combination of acupuncture and related therapies (combined therapies) were all more effective than placebo (P < 0.05). For triacylglycerol (TG), ACU, EA, warming acupunc-ture (WA), WM and combined therapies were better than placebo (P < 0.05), while WA was better than Chinese herb (CH) (P < 0.05). For low-density lipoprotein cholesterol (LDL-C), combined therapies were more effective than lifestyle modification (LM) (P < 0.05). For high-density lipoprotein choles-terol (HDL-C), auricular acupoint stimulation (AAS), ACE, ACU, AI, CH, EA, LM, moxibustion (MOX), WM, combined therapies and placebo were all worse than WA (P < 0.05), while WM and combined therapies were better than ACU (P < 0.05). Combined ranking results suggest that ACU and combined therapies may be the optimal intervention. Conclusions: The efficacy of all kinds of acupuncture-related therapies in patients with hyperlipidemia is better than lifestyle changes. However, for different outcome indicators, all kinds of acupuncture-related therapies have their advantages and disadvantages, and comprehensive ranking results suggest that ACU and combined therapies may be the optimal intervention.

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. A major risk factor for this condition is increased serum low-density lipoprotein cholesterol (LDL-C) levels for which statins have been successful in reducing serum LDL-C to healthy concentrations. However, patients who are statin intolerant or those who do not achieve their treatment goals while on high-intensity statin therapy, such as those with familial hypercholesterolemia, remain at risk. With the discovery of PCSK9 inhibitors, the ability to provide more aggressive treatment for patients with homozygous and heterozygous familial hypercholesterolemia has increased. Ezetimibe reduces LDL-C by 15%-20% when combined with statin. 2 , 3 Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been found to achieve profound reductions in LDL-C (54%-74%) when added to statins. They have shown dramatic effects at lowering major adverse cardiovascular events (MACE) in high-risk patients 4 with LDL-C levels ≥70 mg/dL and can be used in populations that are statin intolerant or not at goal levels with maximally tolerated statin therapy. PCSK9 inhibitors also produce minimal side effects. Myopathy, a common side effect for patients on statins, has been rare in patients on PCSK9 inhibitors. Randomized trials have shown that reduction in LDL-C has translated to clinical benefits even in patients who have not achieved their LDL-C target. [ABSTRACT FROM AUTHOR]

High-intensity statins have been recommended to initiate in patients after acute coronary syndrome (ACS) to reduce the risk of death and recurrent cardiovascular events. There have been few studies comparing the effectiveness of high-intensity statins in Vietnam. Therefore, we conducted a randomized controlled trial to compare the effects of rosuvastatin versus atorvastatin in Vietnamese patients with ACS. A total of 96 ACS patients were randomized into 2 groups at a ratio of 1:1 to receive rosuvastatin 20 mg/day or atorvastatin 40 mg/day in addition to the standard treatment of ACS. LDL-c and hs-CRP levels were measured before and after the intervention for analysis. No significant differences were found between the two groups at baseline. LDL-c levels were significantly reduced from baseline to 4-day in both groups (p<0.001 in both groups), but the difference in LDL-c levels at 4-day between the groups was not statistically significant (p=0.251). hs-CRP did not increase significantly in the rosuvastatin group but significantly in the atorvastatin group (p=0.209 and p<0.001, respectively). hs-CRP at 4-day was not significantly different between the two groups (p=0.250). The proportion of LDL <1.8 mmol/L after 4 days in the rosuvastatin group was significantly higher than that of the atorvastatin group (OR=4.592; 95% CI 1.365-15.449; p=0.014). There was no significant difference in the LDL-c reduction ≥50% and hs-CRP ≤3 mg/L at 4-day between two groups. In conclusion, rosuvastatin is more effective than atorvastatin in achieving LDL-c targets of <1.8 mmol/L after 4 days in Vietnamese patients with ACS. [ABSTRACT FROM AUTHOR]

• Postprandial LDL-C decline largely underestimate the postprandial atherogenicity. • Postprandial LDL-C is not well suitable for clinical decision. • Postprandial PCSK9 decrease may be secondary to the increased intrahepatic lipids. Serum concentration of low-density lipoprotein cholesterol (LDL-C) is markedly reduced after a meal. Does postprandial cholesterol in LDL truly decline via clearance of LDL particles or is there simply a redistribution of cholesterol in LDL subclasses? Thus, we sought to evaluate whether postprandial decline of LDL-C reflects a reduction of LDL particle and to assess the correlation between proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration and postprandial atherogenic lipoproteins profile. Eighty-seven persons were enrolled in this study. We measured lipid profiles by enzymatic and nuclear magnetic resonance (NMR)-based methods and serum PCSK9 concentration by enzyme-linked immunosorbent assays before and after a meal. Plasma samples were collected after a 10-h fasting and 2 and 4 h post-meal. Compared to the fasting status, there was significant postprandial decline of LDL-C measured enzymatically (LDL-Ce) at 2nd and 4th h [99.38 (80.43, 120.65) vs 95.51 (74.25, 117.17) vs 87.01 (69.99, 108.28) mg/dl, p < 0.000]. But there was no significant reduction in LDL particle and its cholesterol content (LDL-Cn) determined by NMR. Just the postprandial large LDL particle [186.45 (151.36, 229.42) vs 176.92 (147.43, 220.91) vs 181.77 (149.05, 224.17), p < 0.000] and its cholesterol content [19.10 (15.09, 22.37) vs 18.28 (14.59, 21.84) vs 17.79 (14.62, 22.14), p < 0.000] were greatly decreased at 2nd and 4th h compared to the fasting one. Interestingly, postprandial serum PCSK9 was decreased at 2nd and 4th h compared with fasting concentration [298.75 (233.25, 396.92) vs 257.34 (207.52, 342.36) vs 250.57 (215.02, 339.66) ng/ml, p < 0.000]. The postprandial percent decrease in serum PCSK9 at 4th h was positively correlated to the percent decline in postprandial LDL-Ce (r = 0.252, p = 0.019) but was independently associated with the percent increase in remnant cholesterol (r = 0.262, p = 0.016). Postprandial decline of LDL-C determined enzymatically was not confirmed by NMR-based methods. Indeed, there exists cholesterol redistribution in LDL subclasses following a meal. The decrease of postprandial PCSK9 may be secondary to the increase in intrahepatic lipids following food intake. [ABSTRACT FROM AUTHOR]

Background: Previous studies revealed a linear relationship between body mass index (BMI) and repeat coronary revascularization rate in patients who underwent percutaneous coronary intervention (PCI). However, this relationship has not been demonstrated in Korean patients who meet old and new target low-density lipoprotein cholesterol (LDL-C) levels of Korean dyslipidemia guidelines. Therefore, we conducted this study to find out the effect of BMI on repeat coronary revascularization rate in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL., Methods: This cohort study was followed for 42 months in Daegu Catholic Medical Center, Korea. We included 429 patients with LDL-C <70 mg/dL 1 year after PCI. We compared repeat revascularization rates using Kaplan-Meier survival curves between the normal weight group (18.5 kg/m 2 ≤ BMI < 23 kg/m 2 ) and the pre-obesity and obesity group (23 kg/m 2 ≤ BMI) in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL., Results: During a follow-up period, there was no significant difference in repeat coronary revascularization-free survival between a group with LDL-C <55 mg/dL and a group with LDL-C <70 mg/dL (79.6% vs. 76.2%, P=0.32). In normal weight patients, LDL-C <55 mg/dL group showed higher repeat coronary revascularization-free survival than LDL-C <70 mg/dL group (89.3% vs. 77.1%, P=0.05). There was no significant difference in repeat revascularization-free survival between the normal weight group and the pre-obesity and obesity group in patients with LDL-C <70 mg/dL (77.1% vs. 75.7%, P=0.67). However, the normal weight group showed significantly higher repeat revascularization-free survival compared to the pre-obesity and obesity group in patients with LDL-C <55 mg/dL (89.3% vs. 74.3%, P=0.03). Normal body weight and LDL-C <55 mg/dL [hazard ratio (HR): 0.421, 95% confidence interval (CI): 0.193-0.916, P=0.02] was the only independent predictor for repeat revascularization., Conclusions: In Korean PCI patients with normal body weight whose LDL-C level is less than 70 mg/dL, but more than 55 mg/dL, should be treated with more intensive therapy to lower LDL-C to less than 55 mg/dL. For obese patients who have succeeded in reducing LDL-C below 55 mg/dL, it seems that weight loss should be attempted to a normal body weight level., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-27/coif). The authors have no conflicts of interest to declare., (2024 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein that regulates cholesterol levels by lysosomal low-density lipoprotein receptor (LDLR) degradation and has recently been associated with the production of neuronal oxidative stress and age-associated cardiovascular dysfunction. Since increased oxidative stress and vascular dysfunction are implicated in the pathology of aging and various neurodegenerative disorders, targeting PCSK9 may offer a promising therapeutic avenue for addressing these conditions. While the precise mechanisms through which PCSK9 contributes to vascular and neuronal oxidative stress in the brain remain elusive, preclinical studies have highlighted a neuroprotective effect linked to PCSK9 inhibition. This inhibition has shown promise in reducing oxidative stress, mitigating neuroinflammation, and alleviating neuropathological changes, thus underscoring the therapeutic potential of this approach in addressing neurodegenerative conditions.

Background: Cerebrovascular accident (CVA), also commonly known as stroke, is an acute condition characterized by jeopardized perfusion of the brain tissue. Atherosclerosis is a common converging point for the various risk factors for CVA. It is a chronic, evolving condition of the vessel wall characterized by peculiar lesions known as atheromas. Low-density lipoprotein cholesterol (LDL-C) has been one of the established and traditional risk factors for the development of plaques in atherosclerosis. Small dense LDL-C (sdLDL-C) is a subclass of LDL-C that is considered more atherogenic, and its role in atherosclerotic plaque formation has been very well established. Hence, in this study, we aimed to find the association between calculated sdLDL-C and atherosclerotic carotid plaque (including various plaque characteristics)., Materials and Methods: This retrospective cross-sectional study was conducted at Sri Ramachandra Medical College and Research Institute between December 2022 and December 2023 after getting ethics approval from the Institutional Ethics Committee. Patients who underwent CT angiogram (312) were included in the study, and their lipid profile data were collected from the Laboratory Information System. Participants were divided into groups depending on the presence or absence of carotid plaque, the characteristics of the plaque, and the narrowing caused by the plaque. sdLDL-C was calculated using Sampson formula from the lipid parameters in these groups. Statistical analysis was done using SPSS Statistics version 16.0 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). A p-value of <0.05 was considered significant., Results: sdLDL-C was significantly higher in the plaque group (37.25 ± 13.69 mg/dL) when compared to the group without plaques on CT angiogram (34.09 ± 11.64 mg/dL) (p<0.05), wherein the LDL-C wasn't significantly different between the two groups. sdLDL-C was also elevated in the soft plaque sub-group (39.46 ± 13.63 mg/dL) when compared to the calcific plaque sub-group (35.41 ± 13.05 mg/dL), which was statistically significant (p<0.05)., Conclusion: sdLDL-C is associated with atherosclerotic carotid plaques, especially the soft plaques on CT angiogram, which are considered to be vulnerable plaques. Thus, calculated sdLDL-C can be utilized as a cost-effective tool to assess plaque vulnerability and monitor hypolipidemic treatment in addition to LDL-C., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Sri Ramachandra Institute of Higher Education and Research issued approval CSP-MED/24/JAN/97/15. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rajan et al.)

Abstract Background The serum lipid profile, including LDL-C level, is associated with hypertension which is the major cause of cerebrovascular disease (CVD) amounting 30% of global death rate. Previous work also demonstrated important roles of genetic variants of SLC12A3 gene on human CVD, hypertension and other diseases in Mongolian population. However, the relationship between SLC12A3 gene polymorphisms on individuals’ lipid profile is still unknown. Methods A panel of 15 SNPs of SLC12A3 gene was genotyped within a 424 Mongolians pedigree cohort. The associations between SLC12A3 polymorphisms and four lipid profiles were analyzed by family-based association test (FBAT) and confirmed with haplotype analysis. Results From both single site and haplotype analyses, the results demonstrated a close relationship between SLC12A3 polymorphisms and LDL-C level. Two SNPs, rs5803 and rs711746 showed significant associations with individuals’ serum LDL-C level (z = − 2.08, P -e = 0.038; z = 2.09, P -e = 0.023, respectively), and distribution of haplotypes constructed by two SNPs also associated with participants’ serum LDL-C level, significantly (Global Chi 2 = 9.06 df = 3, P = 0.028). Conclusion Our results demonstrated the importance of SLC12A3 polymorphisms in individuals’ difference about their serum lipid profiles, thereby providing evidence that the genetic variants may contribute to CVD development via modulating person’s LDL-C level and blood pressure, in certain contexts.

Previous studies have explored the relationship between homocystein (Hcy) and lipid profiles. However, the results from these studies have been inconsistent. The current study investigated the correlation between Hcy and lipid profiles in Chinese community‐based population. The participants were composed of 4012 Chinese people aged 30–92 years old, who were recruited from rural and urban communities in the Hunan Province. Non‐parametric test and logistic regression were used to examine the distribution of Hcy and lipid profiles (triglyceride [TG], total cholesterol [TC], low‐density lipoprotein cholesterol [LDL‐C], high‐density lipoprotein cholesterol [HDL‐C]) and the relationship between them. The median age of subjects was 54.50 years old, and 40.98% were male. Median Hcy was 13.20 μmol/L, and 35.39% had hyperhomocysteinemia (HHcy). Median TG was 1.51 mmol/L, TC was 4.77 mmol/L, LDL‐C was 2.62 mmol/L, and HDL‐C was 1.27 mmol/L. In multivariable logistic regression analysis, HHcy was associated with high levels of TG (ORmale = 2.240, p < 0.001; ORfemale = 2.539, p < 0.001), TC (ORmale = 2.237, p < 0.001; ORfemale = 2.202, p < 0.001), and LDL‐C (ORmale = 1.413, p = 0.010; ORfemale = 1.617, p < 0.001) in the different sexes population and low level of HDL‐C in females (OR = 1.326, p = 0.023) after adjusting for confounders. HHcy was independently associated with an increasing risk of low HDL‐C among females. The regression analysis showed that HHcy was also associated with hypertriglyceridemia, hypercholesterolemia, and high level of LDL‐C in males and females from Chinese community‐based population, which provides a basis for the treatment and prevention of abnormal lipid metabolism. [ABSTRACT FROM AUTHOR]

Understanding how blood lipid levels change with age in the general population is a precondition to defining dyslipidemia. To explore age-related trends in LDL-C and non-HDL-C levels in the general population, a large-scale cross-sectional study with 49,201 males and 35,084 females was adopted. Trends of non- HDL-C and LDL-C levels were plotted against each age (18 to 85 years old, one-year increments); the trends, as well as the influence of confounding factors on the trends, were validated and adjusted by linear regression modeling. The trajectory of LDL-C and non-HDL-C levels by age displayed a nonlinear correlation trend. Further multivariate linear regression modeling that incorporated sex-specific age phases showed that age was positively associated with LDL-C and non-HDL-C levels, with coefficients of 0.018 and 0.031, respectively, in females aged ≥18 to ≤56 years and negatively associated with LDL-C and non-HDL-C levels, with coefficients of -0⋅013 and -0.015, respectively, in females aged ≥57 years. The LDL-C and non-HDL-C levels increased with age in males ≥18 to ≤33 years of age, with coefficients of 0.025 and 0.053, respectively; the lipid levels plateaued at ≥34 to ≤56 years of age and subsequently decreased in those ≥57 years of age, with coefficients of -0.008 and -0.018, respectively. In contrast, pooled analyses without age stratification concealed these details. In conclusion, fluctuating increasing and decreasing lipid levels occurred with phases of aging in both sexes. Well-grounded age stratification is necessary to improve lipid-related pathophysiological studies. [ABSTRACT FROM AUTHOR]

Background: People living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and are prone to statin-related adverse events from drug-drug interactions with certain antiretroviral regimens.Objectives: This study sought to evaluate the efficacy and safety of evolocumab in dyslipidemic PLHIV.Methods: BEIJERINCK (EvolocumaB Effect on LDL-C Lowering in SubJEcts with Human Immunodeficiency VirRus and INcreased Cardiovascular RisK) is a randomized, double-blind, multinational trial comparing monthly subcutaneous evolocumab 420 mg with placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia taking maximally-tolerated statin therapy. The primary endpoint was the percent change (baseline to week 24) in low-density lipoprotein cholesterol (LDL-C); secondary endpoints included achievement of LDL-C <70 mg/dl and percent change in other plasma lipid and lipoprotein levels. Treatment-emergent adverse events were also examined.Results: A total of 464 patients were analyzed (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). ASCVD was documented in 35.6% of patients, and statin intolerance/contraindications to statin use were present in 20.7% of patients. Evolocumab reduced LDL-C by 56.9% (95% confidence interval: 61.6% to 52.3%) from baseline to week 24 versus placebo. An LDL-C level of <70 mg/dl was achieved in 73.3% of patients in the evolocumab group versus 7.9% in the placebo group. Evolocumab also significantly reduced other atherogenic lipid levels, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) (all p < 0.0001). Evolocumab was well tolerated, and treatment-emergent adverse events patient incidence was similar among evolocumab and placebo groups.Conclusions: Evolocumab was safe and significantly reduced lipid levels in dyslipidemic PLHIV on maximally-tolerated statin therapy. Evolocumab is an effective therapy for lowering atherogenic lipoproteins in PLHIV with high cardiovascular risk. (Safety, Tolerability & Efficacy on LDL-C of Evolocumab in Subjects With HIV & Hyperlipidemia/Mixed Dyslipidemia; NCT02833844). [ABSTRACT FROM AUTHOR]

Aim: Patients with type 2 diabetes mellitus (T2DM) who have suboptimal control of the triad of glucose (A), blood pressure (B) and lipid profile (C) have an increased risk of cardiovascular disease (CVD). Additionally, the presence of major depressive disorder (MDD) can lead to poor outcomes. Therefore, the aim of this study was to assess the role of MDD with ABC control in patients with T2DM in a South African private healthcare setting., Methods: Healthcare medical claims and electronic health records of 1 211 adult patients with T2DM and/or MDD were analysed for 2019., Results: Only 24% of the T2DM ± MDD patients reached a low-density lipoprotein cholesterol (LDL-C) target < 1.8 mmol/l, and only 13% of the T2DM + MDD and 7.1% of T2DM - MDD patients achieved simultaneous ABC targets. The proportion of patients admitted due to macrovascular complications was higher in the T2DM + MDD group (22.8%) compared to the T2DM - MDD (13.1%) and MDD group (9.9%) ( p = 0.012). Multivariate logistic regression analysis showed that older patients with T2DM + MDD achieved better glycated haemoglobin and LDL-C control. Significantly more patients with T2DM + MDD (12%) had repeat macrovascular admissions in 2019 compared to the T2DM - MDD patients (2.9%) ( p = 0.005)., Conclusions: Despite a managed-care environment, the comprehensive ABC control among patients with T2DM was suboptimal, particularly in those with MDD, placing them at greater risk for CVD events.

Introduction: Type 2 diabetes is associated with vascular complications that deteriorate the quality of life and decrease the life expectancy of individuals. We previously reported the efficacy of sitagliptin for glucose control in patients with type 2 diabetes in the Sitagliptin Registration Type 2 Diabetes-Juntendo Collaborating Project (SPIRITS-J). Through the results of the SPIRITS-J study, we expected that optimal comprehensive management of type 2 diabetes according to current clinical practice guidelines in addition to achieving individualized glycemic goals would reduce macrovascular complications and all-cause mortality in Japan. The aim of this study was to evaluate this hypothesis. Methods: We investigated the clinical outcomes prospectively in the extended SPIRITS-J study and compared these to previous Japanese cohort studies in the era before widespread use of guidelines. The primary clinical outcome was a composite of myocardial infarction (MI), stroke, and all-cause mortality. Results: Mean duration of follow-up was 3.5 ± 1.3 years. The crude incidence of the primary outcome per 1000 person-years was 13.9 (non-fatal MI 1.44, non-fatal stroke 4.22, all-cause mortality 8.79 per 1000 person-years, respectively). It is noteworthy that the incidence of MI in the SPIRITS-J study was very much lower than that in a previous Japanese cohort study. In multivariate analysis, both the history of coronary artery disease and low-density lipoprotein cholesterol (LDL-C) were independently associated with incidence of primary clinical outcome. Conclusion: The extended SPIRITS-J study demonstrated that optimal comprehensive management in patients with type 2 diabetes according to the recent practice guidelines has succeeded in preventing macrovascular complications in Japan. This study suggests that more intensive LDL-C-lowering therapy is important for further prevention of macrovascular complications even in Japanese patients with type 2 diabetes (UMIN 000004121). [ABSTRACT FROM AUTHOR]

Objective: Proprotein convertase subtilisin/kexin type 9 antibody inhibitors (PCSK9i) are approved as adjuncts to maximal tolerated statin therapy to lower low-density lipoprotein cholesterol (LDL-C). This study describes real-world use, characteristics of PCSK9i users and non-users, and factors influencing treatment choice.Methods: A physician and patient survey was conducted in Germany, Spain, and the UK from December 2016 to April 2017 through the Adelphi Dyslipidemia Disease Specific Program. Physicians reported patients' lipid-lowering therapy (LLT) history and characteristics. PCSK9i users were systematically over-sampled. Results were summarized using frequencies and proportions.Results: The study included 110, 123, and 117 physicians from Germany, Spain, and the UK, respectively, providing data on 3,073 patients (mean age = 62 years; 60% male). Most patients (63-73%) had prior statin and/or ezetimibe use. Compared to patients receiving other LLT (n = 2686), PCSK9i users (222 in Germany, 97 in Spain, 68 in the UK) were, on average, 5-7.5 years younger and had LDL-C at diagnosis averaging 23-53 mg/dl higher. Familial hypercholesterolemia (FH), coronary heart/artery disease, myocardial infarction, and acute coronary syndrome were more common among PCSK9i users than non-users. PCSK9i users were also more likely to use high-intensity statins in their current LLT regimen (64-89% vs 28-50%). Physicians commonly reported PCSK9i benefits on LDL-C and total cholesterol as reasons for initiating these agents, and PCSK9i users reported good knowledge of cardiovascular disease and treatment options.Conclusions: Results indicate that physicians are prescribing PCSK9i to patients with high cardiovascular risk in accordance with European guidelines and reimbursement requirements. [ABSTRACT FROM AUTHOR]