Search

Cardiovascular disease (CVD) is a leading cause of global mortality, with dyslipidemia being a significant modifiable risk factor. Dyslipidemia refers to all abnormalities in blood lipid levels. It plays a fundamental role in the development and progression of atherosclerosis. The reduction of low‐density lipoprotein (LDL) cholesterol has been shown to decrease cardiovascular risk. Cholesteryl ester transfer protein (CETP) plays a role in LDL metabolism, and its inhibition results in lower LDL levels. This study synthesizes and evaluates novel benzene sulfonamide derivatives as CETP inhibitors. Twenty compounds were synthesized and tested for their inhibitory activity using an in vitro bioassay. The results revealed that para‐methylated derivatives exhibited higher inhibitory activity compared to meta‐methylated derivatives, where compound 6n has an IC50 of 24.4 µM. Furthermore, electron withdrawing groups such as chlorine and nitro substitutions on the sulfanamido‐phenyl rings demonstrated superior inhibitory effects compared to electron donating groups. Positional isomerism of the substitutions also influenced inhibitory activity, with para substitutions being more effective. Nitro‐substituted compounds showed greater inhibition than chlorine‐substituted compounds, where compound 6t has an IC50 of 18.3 µM. Overall, this study provides valuable insights into the SAR of CETP inhibitors and identifies promising compounds for further investigation as potential therapeutics for CVD. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non‐alcoholic fatty liver disease, focusing particularly on ferroptosis‐related pathways and its reliance on nuclear factor erythroid 2‐related factor 2.Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis‐related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels.Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low‐density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin‐1β and tumour necrosis factor‐α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high‐fat diet‐induced non‐alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2‐related factor 2 and its downstream ferroptosis‐related genes to inhibit ferroptosis in the livers of rats with non‐alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis‐related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2‐related factor 2.This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2‐related factor 2 regulation, offering novel insights into the treatment of non‐alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

The document titled "2024 ESC Guidelines for the management of chronic coronary syndromes" provides comprehensive guidelines for the diagnosis and management of chronic coronary syndromes. It covers various topics such as initial management, diagnostic testing, medical therapy, revascularization options, and treatment for specific patient groups. The guidelines emphasize shared decision-making, patient education, and adherence to healthy lifestyle behaviors. It also highlights the importance of long-term follow-up and care, including strategies to improve medication adherence. These resources can be useful for library patrons conducting research on chronic coronary syndrome and seeking evidence-based guidance on its diagnosis and treatment. [Extracted from the article]

Background: Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level. Hypothesis: We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons. Methods: Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid‐lowering therapies (LLTs), (ii) per low‐density lipoprotein cholesterol (LDL‐C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL‐C goals, and (iv) LDL‐C reduction per type of LLT was also determined. Results: Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL‐C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL‐C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL‐C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL‐C levels ≥ 100 mg/dL and only 20.7% were at goal. Conclusion: Our study emphasizes the importance of developing strategies to help patients achieve their LDL‐C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice. Practitioner Points: Approximately 25% of patients with ASCVD had no documented LLT (although 64.2% of them exhibited LDL‐C levels ≥ 100 mg/dL), ~60% received monotherapy, and only 15.3% received combination LLT.The greatest improvements in LDL‐C levels were achieved with high‐intensity statin plus ezetimibe. Yet, ~25% of patients receiving statin plus ezetimibe had LDL‐C levels ≥ 100 mg/dL, and only 20.7% were at goal (2021 ESC guidelines).Altogether, the results emphasize the importance of developing strategies to help patients achieve their LDL‐C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice. [ABSTRACT FROM AUTHOR]

Aims: To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata. Materials and Methods: Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3‐month doses up to 18 months, with background oral lipid‐lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m2). Co‐primary endpoints were percentage and time‐adjusted percentage change in low‐density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed. Results: Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo‐corrected) with inclisiran from baseline to Day 510 ranged from −47.6% to −51.9% and from −48.8% to −54.4% across glycaemic/BMI strata, respectively. Similarly, time‐adjusted percentage changes after Day 90 and up to Day 540 ranged from −46.8% to −52.0% and from −48.6% to −53.3% across glycaemic/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of <1.8 mmol/L and <1.4 mmol/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic/BMI strata, a higher proportion of individuals had mild/moderate treatment‐emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%–7.7%) versus placebo (0.2%–2.1%). Conclusion: Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic/BMI strata, with a modest excess of transient mild‐to‐moderate TEAEs at the injection site. [ABSTRACT FROM AUTHOR]

Reducing low-density lipoprotein cholesterol levels lowers the risk of atherosclerotic cardiovascular disease. With the current and future portfolios of emerging lipid-lowering therapies included in various national and international guidelines, the objectives of this study were (i) to investigate the perceptions of UK prescribers', including doctors, pharmacists, and nurses, on current lipid management for cardiovascular diseases and prescriptions of novel lipid-lowering therapies, and (ii) to explore the challenges and facilitating factors of prescribing novel lipid-lowering therapies through qualitative interviews. Qualitative semi-structured interviews with twelve medical and non-medical prescribers were conducted, around 20–30 min in length. The interviews were audio-recorded and transcribed on an online platform. A thematic analysis was deployed. Four major themes emerged from the analysis: (1) prescribing barriers; (2) prescribing enablers; (3) inter-profession variability; and (4) health literacy. These themes highlighted the contrast between the need for optimal shared decision making and the various constraints in practice. Participants expressed their inexperience with novel lipid-lowering therapies and acknowledged the requirement and importance of these agents for primary cardiovascular disease prevention. Participants recognised confidence and competence as key drivers for prescribing therapies and welcomed further education and training to enhance their skillset. Patients' misconceptions towards current lipid-lowering therapies contributed to their refusal of newer agents, highlighting a requirement to improve patient education. Targeting communities through awareness campaigns was identified as a viable solution. [ABSTRACT FROM AUTHOR]

Purpose of Review: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. Recent Findings: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Summary: Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD. [ABSTRACT FROM AUTHOR]

Introduction: Effective management of dyslipidemias is crucial for reducing morbidity and mortality among patients after acute coronary syndrome (ACS). Sex differences in dyslipidemia management after premature ACS in Israeli patients have not been extensively studied. This study aimed to investigate potential disparities between men and women in managing dyslipidemia, considering current guidelines. Methods: This retrospective cohort study examined patients who were 55 years old or younger and admitted to Meir Medical Center for ACS from January 2018 to February 2019. The study aimed to evaluate the use of lipid-lowering therapy (LLT), measure the achievement of target low-density lipoprotein cholesterol (LDL-C) levels, and analyze the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in both male and female patients. Results: The study included a total of 687 participants, of which 23.3% were identified as females. Upon discharge, ∼80% of the patients were prescribed high-intensity statins. After 1 year, it was observed that females had higher levels of LDL-C and lower rates of achieving target LDL-C levels (<70 and 55 mg/dL) as compared with males (45% vs. 54.6% and 30% vs. 42.2%, respectively). The use of non-statin LLT at the 1-year mark was minimal in both groups. Finally, it was found that the occurrence of MACCE was similar between males and females. Conclusion: Sex disparities in dyslipidemia management after a premature ACS were apparent, with females having higher LDL-C levels and lower rates of target achievement. Intervention is necessary to address these disparities and encourage greater use of non-statin LLT. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a major risk factor for atherosclerotic cardiovascular diseases. Recent advancements in lipid-lowering therapies have seen progress with statins, cholesterol absorption inhibitors, PCSK9 inhibitors, and omega-3 fatty acids becoming widely utilized. Emerging new lipid-lowering drugs, including angiopoietin-like protein 3 (ANGPTL3) inhibitors, apolipoprotein C3 inhibitors, monoclonal antibodies, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and cholesterol vaccines, have diversified the therapeutic landscape, showing promising efficacy. This review explores the development and application of these lipidlowering drugs, offering new insights for therapeutic strategies.

The review presents contradictory results from numerous clinical and epidemiological studies, giving reason to doubt the indisputability of ideas about the primary role of low-density lipoprotein (LP) cholesterol in atherogenesis and the efficacy of lipid-lowering therapy. The latter clearly demonstrates the absence of the expected clinical effect in reducing cholesterol levels after surgical correction of lipid metabolism (ileal bypass surgery) or a very modest effect when using drugs devoid of pleiotropic properties. This circumstance finds an explanation in the fact that, according to modern concepts, only modified LP are the molecular substrate of the pathophysiological process at all stages of atherosclerosis development. Native (intact) LP, the concentration of which in the blood does not correlate with the level of modified forms, are not included in the pathogenesis of atherosclerosis. Consequently, the presence of native LP in the blood does not give a true picture of the activity of the atherosclerotic process. Based on the above, in the treatment of atherosclerosis, it should be considered justified not so much to further improve methods of lipid-lowering effects on the body, which do not have a sufficiently reliable evidence base of clinical effect, but to search for means that prevent the generation of atherogenic, modified LP. In this regard, taking into account the important role of systemic inflammation in the pathogenesis of atherosclerosis, the synthesis and clinical use of safe anti-inflammatory drugs, as well as the development and implementation of methods aimed at eliminating the causes of systemic inflammation, should be considered promising.

Abstract Background Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. Methods This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. Results Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients’ prognostic factors, potentially leading to bias when comparing real-world treatment effects. Methods: Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015–June 2020 for patients aged ≥18 years in Optum’s de-identified Clinformatics Data Mart (CDM) and MarketScan, and those aged ≥66 in the US Medicare claims database. We estimated a 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone–censor–weight approach to address time-varying confounding and immortal person-time. Results: PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = −3.6% [95% CI: −4.3%, −2.9%]), decubitus ulcer (RD = −7.7% [95% CI: −11.8%, −3.7%]), fracture (RD = −8.1% [95% CI: −9.6%, −6.6%]), influenza vaccine (RD = −9.3% [95% CI: −17.5%, −1.1%]), and visual test (RD = −0.6% [95% CI: −0.7%, −0.6%]) under the PCSK9 mAb initiation versus no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies. Conclusion: A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge. Between January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed. On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage. Switch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached. • Missing intensity- and dose-titration in statins. • Underuse of add-on lipid therapy for target level achievement. • Insufficient recommendation on lifestyle adaptations as for secondary prevention. • Underwhelming advice on nutrition in ASCVD. [ABSTRACT FROM AUTHOR]

Introduction: European guidelines recommend the implementation of lipidlowering therapies (LLTs) in adults (≥ 65 years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75 years), yet their use in very-old adults (> 75 years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65-74 and ≥ 75 years) at presentation for STsegment elevation myocardial infarction (STEMI) and also to assess evidencebased care delivery to older adults in our region. Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018-2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65 years (n = 152), 65-74 years (n = 104), and ≥ 75 years (n = 113). Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%-23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%-13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70 mg/dL compared to patients < 65 years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55 mg/dL. Low LLT uptake (16%) among older adults aged 64-74 years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70 mg/dL and < 55 mg/dL, respectively. Oldest adults (≥ 75 years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy. Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75 years, with the achievement of riskbased LDL-C targets in 10%-48% of these patients. [ABSTRACT FROM AUTHOR]

Non-culprit lesion-related coronary events are a significant concern in patients with coronary artery disease (CAD) undergoing coronary intervention. Since several studies using intra-coronary imaging modalities have reported a high prevalence of vulnerable plaques in non-culprit lesions at the initial coronary event, the immediate stabilization of these plaques by intensive pharmacological regimens may contribute to the reduction in the adverse events. Although current treatment guidelines recommend the titration of statin and other drugs to attain the treatment goal of low-density lipoprotein cholesterol (LDL-C) level in patients with CAD, the early prescription of strong LDL-C lowering drugs with more intensive regimen may further reduce the incidence of recurrent cardiovascular events. In fact, several studies with intensive regimen have demonstrated a higher percentage of patients with the attainment of LDL-C treatment goal in the early phase following discharge. In addition to many imaging studies showing plaque stabilization by LDL-C lowering drugs, several recent reports have shown the efficacy of early statin and proprotein convertase subtilisin/kexin type 9 inhibitors on the immediate stabilization of non-culprit coronary plaques. To raise awareness regarding this important concept of immediate plaque stabilization and subsequent reduction in the incidence of recurrent coronary events, the term 'Drug Intervention' has been introduced and gradually applied in the clinical field, although a clear definition is lacking. The main target of this concept is patients with acute coronary syndrome as a higher prevalence of vulnerable plaques in non-culprit lesions in addition to the worse clinical outcomes has been reported in recent imaging studies. In this article, we discuss the backgrounds and the concept of drug intervention. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major adverse cardiac events (MACE). Different pharmacological therapies have been implemented to mitigate this risk. Over the last two decades, intravascular imaging modalities have emerged in clinical studies to clarify how these therapies may affect the composition and burden of coronary plaques. Lipid-lowering agents, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were shown not only to reduce low-density lipoprotein levels and MACE but also to directly affect features of coronary plaque vulnerability. Studies have demonstrated that lipid-lowering therapy reduces the percentage of atheroma volume and number of macrophages and increases fibrous cap thickness. Future studies should answer the question of whether pharmacological plaque stabilization may be sufficient to mitigate the risk of MACE for selected groups of patients with atherosclerotic coronary disease. [ABSTRACT FROM AUTHOR]

Background: Statins are lipid‐lowering drugs with favorable anti‐inflammatory effects. This study aimed to explore different statin‐based lipid‐lowering strategies to reduce high‐sensitivity C‐reactive protein (hs‐CRP). Hypothesis: The hypothesis is that different statin‐based lipid‐lowering strategies might reduce hs‐CRP. Methods: This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin‐based lipid‐lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs‐CRP levels and blood lipid indicators were measured at baseline and after 1‐month lipid‐lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid‐lowering strategies, Δhs‐CRP (%) and ΔLDL‐C (%). Results: Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs‐CRP (%) (β = −0.253, 95% CI: [−0.501 to −0.005], p = 0.045). The increased ΔLDL‐C (%) was an independent predictor of elevated levels of Δhs‐CRP (%) (β = 0.487, 95% CI: [0.15−0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (β = −0.300, p < 0.001) and intensive statin therapy (β = −0.032, p = 0.043) had an indirect negative effect on Δhs‐CRP via ΔLDL‐C. Conclusions: Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs‐CRP levels. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the leading cause of mortality in Germany. Cardiovascular risk can be mitigated with long-term lipid-lowering therapies (LLTs) that reduce levels of low-density lipoprotein cholesterol. Although effective, risk mitigation is hindered by poor persistence and adherence. Objective: To investigate real-world persistence and adherence to LLTs through 36 months post-initiation. Methods: This retrospective cohort study included patients with dyslipidemia who were newly prescribed LLTs between July and December 2017, using anonymized prescription data from the Insight Health™ Patient Insight Tool, and followed up until March 2021. Persistence and adherence to the therapies were stratified by age and sex. The proportion of days covered (PDC) was used to measure adherence. Results: Patients with dyslipidemia and newly prescribed statins (n = 865,732), ezetimibe (n = 34,490), or anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (anti-PCSK9 mAbs; n = 1940) were included. Persistence to LLTs declined gradually across all treatment subgroups and was lower in women than men. Adherence, calculated as the mean PDC at the end of the analysis period (July 2017‒March 2021) was 0.84, 0.92, and 0.93 for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Among patients who discontinued treatment, mean treatment duration was 265, 255, and 387 days for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Only ~ 10% of patients persisted between 201 and 300 days. By Day 300, 71% of patients on statins had discontinued treatment. At 36 months, overall persistence rates were lowest with statins (20.6%), followed by ezetimibe (22.3%) and anti-PCSK9 mAbs (50.9%). Conclusions: High non-persistence rates were observed across all LLT regimens analyzed, with the lowest persistence rates observed with statins. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) poses a significant global health and economic challenge, with atherosclerosis being a primary cause. Over the past 40 years, substantial research has been conducted into the prevention and reversal of atherosclerosis, resulting in the development of lipid-lowering agents such as statins and fibrates. Despite the extensive literature and formulation of numerous therapeutic guidelines in this domain, a comprehensive bibliometric analysis of the current research landscape and trends has not been performed. This study aimed to elucidate the evolution and milestones of research into lipid-lowering treatments for coronary heart disease (CHD) in conjunction with hyperlipidemia through bibliometric analysis, offering insights into future directions for treatment strategies. Methods: This study examined publications from 1986 to 2023 retrieved from the Web of Science database (Core Collection). Utilizing tools such as VOSviewer, Pajek, and CiteSpace, we analyzed publication and citation numbers, H-indexes, contributions by countries and institutions, authorship, journal sources, and keyword usage to uncover research trajectories and areas of focus. Results: Our analysis of 587 publications revealed a recent surge in research output, particularly post-2003. The American Journal of Cardiology published the highest number of studies, with 40 articles, whereas Circulation received the highest number of citations (6,266). Key contributors included the United States, Japan, and China, with the United States leading in citation numbers and the H-index. Harvard University and Leiden University emerged as pivotal institutions, and Professors J. Wouter Jukema and Robert P. Giugliano were identified as leading experts. Keyword analysis disclosed five thematic clusters, indicating a shift in research towards new drug combinations and strategies, signaling future research directions. Conclusion: The last 4 decades have seen a notable rise in publications on lipidlowering therapies for CHD and hyperlipidemia, with the United States retaining world-leading status. The increase in international collaboration aids the shift towards research into innovative lipid-lowering agents and therapeutic approaches. PCSK9 inhibitors and innovative combination therapies, including antisense oligonucleotides and angiopoietin-like protein 3 inhibitors, provide avenues for future research, intending to maximize the safety and efficacy of treatment approaches. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost‐effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high‐risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin‐angiotensin‐aldosterone system inhibitors and sodium‐glucose cotransporter‐2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care. [ABSTRACT FROM AUTHOR]

Purpose of Review: In this review, we will discuss the data from early clinical studies of MK-0616 and summarize clinical trials of other oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recent Findings: The success of PCSK9 inhibition with monoclonal antibody injections has fueled the development of additional therapies targeting PCSK9, including oral formulations, the most advanced of which is MK-0616. MK-0616 is a novel, orally administered macrocyclic peptide that binds to PCSK9 and inhibits binding of PCSK9 to the LDL receptor, thereby decreasing plasma levels of LDL-C. Summary: Clinical trial data on the safety and efficacy of MK-0616 are promising and report LDL-C–lowering efficacy comparable to that provided by injectable PCSK9 inhibitors. Ongoing and future studies of oral PCSK9 inhibitors in development will evaluate the safety, efficacy, and effectiveness of these agents and their potential role in preventing cardiovascular disease events. [ABSTRACT FROM AUTHOR]

In patients with acute coronary syndrome (ACS), lipid-lowering therapy plays an important role in the prevention of the recurrence of cardiovascular disease. Recent guidelines recommend the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with ACS if their low-density lipoprotein cholesterol (LDL-C) levels are not adequately controlled with statins and ezetimibe. Based on this, we report a case in which administering a PCSK9 inhibitor successfully lowered the patient's LDL-C level to the target level and managed the coronary artery disease (CAD) recurrence. A 39-year-old man who was taking statins presented to the hospital with chest pain and was diagnosed with unstable angina. He started taking maximum doses of statins and ezetimibe to lower his LDL-C. However, the patient's unstable angina recurred 1 year later, and a de novo lesion with plaque rupture was demonstrated via coronary angiography. The LDL-C failed to reach the target level despite maintaining the maximum dose of statin and ezetimibe. Accordingly, evolocumab was initiated in addition to rosuvastatin/ezetimibe 20/10 mg daily. Subsequently, coronary angiography was performed twice, and on follow-up, the patient remained free of CAD recurrence. This case highlights the efficacy of lipid-lowering therapy with evolocumab in high-risk patients with repeated ACS. [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]

Haonan Guan,&ast; Guoyou Zhang,&ast; Qiqi Li, Jie Lian, Zhaoyang Dong, Lian Zhu, Kaiyan Xiao Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaiyan Xiao, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, People’s Republic of China, Tel +86 021 23271699, Fax +86 021 63136856, Email xky7026@163.comAbstract: Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.Keywords: soft-tissue tumors, lipoprotein, atorvastatin, foam cells, lipid-lowering therapy

Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like "lower is better" and "strike early and strong" should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp(a)) is a unique low-density lipoprotein-like lipoprotein that is considered an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. The Lp(a) molecule also contains apolipoprotein A and apolipoprotein B, which collectively promote atherosclerosis, thrombosis, and inflammation. Lp(a) is highly genetic and minimally responsive to nonpharmacological measures. Lp(a) serum levels =125 nmol/L are associated with increased ASCVD risk, but this threshold has not been accepted universally. Elevated Lp(a) is the most common genetic dyslipidemia affecting approximately 20% of the general population. Certain currently available lipid-lowering drugs, including the proprotein convertase subtilisin/kexin type 9 therapies, produce moderate reductions in Lp(a); however, none are indicated for the treatment of elevated Lp(a). There are currently four investigational RNA-based therapeutic agents that reduce Lp(a) by 70% to 100%. Two of these agents are being evaluated for ASCVD risk reduction in adequately powered outcomes trials, with results expected in 2 to 3 years. Until such therapies become available and demonstrate favorable clinical outcomes, strategies for elevated Lp(a) primarily involve early and intensive ASCVD risk factor management. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of mortality worldwide. Despite the availability of effective low-density lipoprotein cholesterol (LDL-C) lowering agents, an increased cardiovascular risk is still observed in individuals with therapeutic LDL-C levels. One of these cardiovascular risk factors is elevated plasma lipoprotein(a) (Lp(a)) concentration, which maintains chronic inflammation through the increased presence of oxidized phospholipids on its surface. In addition, due to its 90 percent homology with the fibrinolytic proenzyme plasminogen, Lp(a) exhibits atherothrombotic effects. These may also contribute to the increased cardiovascular risk in individuals with high Lp(a) levels that previous epidemiological studies have shown to exist independently of LDL-C and other lipid parameters. In this review, the authors overview the novel therapeutic options to achieve effective Lp(a) lowering treatment, which may help to define tailored personalized medicine and reduce the residual cardiovascular risk in high-risk patients. Agents that increase LDL receptor expression, including statins, proprotein convertase subtilisin kexin type 9 inhibitors, and LDL production inhibitors, are also discussed. Other treatment options, e.g., cholesterolester transfer protein inhibitors, nicotinic acid derivatives, thyroid hormone mimetics, lipoprotein apheresis, as well as apolipoprotein(a) reducing antisense oligonucleotides and small interfering RNAs, are also evaluated. [ABSTRACT FROM AUTHOR]

The article discusses the use of gene editing as a potential therapy for reducing cholesterol levels in individuals with atherosclerotic cardiovascular disease (ASCVD). The current standard treatment for ASCVD involves the use of statins, but low adherence to these medications has led to the need for alternative therapies. The article explores different approaches to targeting PCSK9, a protein that plays a role in cholesterol regulation, including monoclonal antibodies, RNA interference, and gene editing using CRISPR/Cas9. The authors present the results of a phase 1b clinical trial evaluating the safety and tolerability of a gene editing therapy called VERVE-101 in patients with hypercholesterolemia. While the therapy showed promising results in reducing PCSK9 protein levels and LDL cholesterol, there were also some serious adverse events reported. The authors emphasize the need for further research to determine the long-term safety and efficacy of gene editing therapies for lipid-lowering. [Extracted from the article]

Background: Studies utilising genotyping methods report the prevalence of familial hypercholesterolaemia to be as high as one in 137 of the adult population. Aim: To estimate the prevalence of familial hypercholesterolaemia measured by clinically coded diagnosis, associated treatments, and lipid measurements observed in UK primary care. Design and setting: This was a retrospective analysis using the Clinical Practice Research Datalink (CPRD) GOLD database. Method: Patients aged ≥18 years and actively registered on the index date (30 June 2018) formed the study cohort. Point prevalence of familial hypercholesterolaemia for 2018 was estimated overall and for each nation of the UK. Patients with familial hypercholesterolaemia were stratified into primary and secondary prevention groups, defined as those with/without a prior diagnosis of atherosclerotic cardiovascular disease. Prevalence estimates and extrapolations were replicated for these subgroups. Baseline demographic, lipid, and clinical characteristics for the prevalent cohort were presented. Results: In total, 4048 patients with familial hypercholesterolaemia formed the study cohort. The estimated familial hypercholesterolaemia prevalence for the UK was 16.4 per 10 000 (95% confidence interval [CI] = 16.0 to 16.9). Of these, 2646 (65.4%) patients with familial hypercholesterolaemia had a recent prescription for lipid-lowering therapy. Mean lipid levels were lower for those treated with lipid-lowering therapy compared with those untreated: 5.34 mmol/L (SD 1.50) versus 6.25 mmol/L (SD 1.55) for total cholesterol and 3.15 mmol/L (SD 1.34) versus 3.96 mmol/L (SD 1.36) for low-level density lipoprotein cholesterol. Conclusion: The estimated prevalence of familial hypercholesterolaemia was one in 608 of the population, less than expected from other studies, which may indicate that familial hypercholesterolaemia is under-recognised in UK primary care. Over one-third of diagnosed patients were undertreated and many did not achieve target goals, placing them at risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolaemia (FH) is a genetic disease characterised by hypercholesterolaemia and premature cardiovascular events. Early diagnosis and treatment can reduce the cardiovascular burden. We describe the characteristics of patients with heterozygous FH followed in a tertiary hospital in Belgium. We retrospectively studied a population of 321 patients with definite heterozygous FH who visited the UZ Leuven lipid clinic at least once between 1 January 2016 and 31 December 2020. Data are represented as mean ± SD. The age at time of diagnosis of FH was 39 ± 18 years. Patients with atherosclerotic disease (secondary prevention) were older (p <.001), more often male (p <.001), had a higher body mass index (p <.001), prevalence of (pre)diabetes (p <.001) and hypertension (p <.001) and had lower levels of low-density lipoprotein-cholesterol (LDL-C) (p <.001) than individuals without atherosclerotic disease (primary prevention). The average LDL-C in both primary (109 ± 53 mg/dL) and secondary (81 ± 63 mg/dL) prevention did not meet the targets of LDL-C as proposed by the 2019 ESC/EAS guidelines for the management of dyslipidaemias. However, LDL-C levels in the subgroup of patients treated with PCSK9 inhibition therapy, and especially in the triple therapy group (combination of statin, ezetimibe and PCSK9 inhibitor), were markedly lower (p <.001). In this Belgian population, people with heterozygous FH remain undertreated. Reaching treatment targets in FH seems possible, although this requires combination treatment (with PCSK9-targeted therapy) in most patients. Earlier diagnosis of FH, more extensive lipid-lowering treatment and reimbursement options and a more holistic approach are needed to lower LDL-C and cardiovascular risk in patients with FH. [ABSTRACT FROM AUTHOR]

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65 years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75 years), yet their use in very-old adults (> 75 years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65–74 and ≥ 75 years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region.Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018–2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65 years (n = 152), 65–74 years (n = 104), and ≥ 75 years (n = 113).Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%–23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%–13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70 mg/dL compared to patients < 65 years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55 mg/dL. Low LLT uptake (16%) among older adults aged 64–74 years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70 mg/dL and < 55 mg/dL, respectively. Oldest adults (≥ 75 years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy.Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75 years, with the achievement of risk-based LDL-C targets in 10%–48% of these patients.

Introduction: The therapeutic control of LDL-cholesterol is essential in cardiovascular prevention, as recommended by the recent guidelines. Objective: To evaluate gender differences in terms of demographic and clinical characteristics, treatment pattern, treatment adherence and healthcare costs in patients on lipid-lowering therapy, stratified by cardiovascular risk in the Italian real clinical practice. Methods: An observational analysis was conducted on the administrative databases of healthcare institutions, covering about 6.1 million health-assisted subjects. After inclusion of all patients on lipid-lowering therapy between January 2017 and June 2020, the population was investigated in the period before the first prescription of a lipid-lowering drug and followed-up for at least 12 months. Clinical and demographic variables were compared after stratification by gender and by cardiovascular risk (very high/high/other risk). The main outcome measures were treatment adherence and direct healthcare costs during follow-up. Results: Of the 684,829 patients with high/very high cardiovascular risk, 337,394 were men and 347,435 women, aged on average 69.3 years and 72.1 years, respectively (p < 0.001). Men were characterised by a worse comorbidity profile. Regardless of cardiovascular risk, female subjects were associated with larger utilisation of low-potency statins and lower adherence (p < 0.001). The annual healthcare costs per patient during follow-up were higher in men than in women (p < 0.001). Conclusions: The results highlighted larger utilisation of low-potency statins, a lower adherence and a milder comorbidity profile in women, the latter feasibly explaining the reduced healthcare costs compared to men.

Background A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add‐on treatment to optimized lipid‐lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia. Methods and Results A total of 806 patients who were receiving stable and optimized lipid‐lowering therapy but did not achieve their low‐density lipoprotein cholesterol (LDL‐C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL‐C from baseline to week 24. Our findings demonstrated that the least‐squares mean difference of percentage change in LDL‐C from baseline to week 24 was −67.7% (95% CI, −72.5% to −63.0%; P

Dyslipidemia is one of the most significant modifiable cardiovascular risk factors. The change in the modern paradigm for dyslipidemia treatment from high-intensity statin therapy to high-intensity lipid-lowering therapy makes it possible to more often use new drug classes to achieve the target level of low-density lipoprotein cholesterol. The article presents two case reports on the use of inclisiran as part of combination lipid-lowering therapy for secondary prevention in patients at very high cardiovascular risk. Based on the presented cases, following clinical aspects of the management of cardiovascular patients are discussed: the safety of achieving low-density lipoprotein cholesterol levels below 1 mmol/l in a patient with asymptomatic cerebral infarction, the need for adequate dyslipidemia treatment after revascularization, the strategic importance of prescribing lipid-lowering therapy in patients with cerebrovascular disease to reduce the cardiovascular risk, adherence to therapy as a significant aspect of effective dyslipidemia control.

This article discusses a study that examined the effects of empagliflozin and fenofibrate therapies, both individually and in combination, on serum urate concentration in individuals with hyperuricaemic type 2 diabetes. The study found that both therapies led to a reduction in serum urate concentration, with the combination therapy resulting in a greater reduction compared to empagliflozin alone. The study also noted that the treatments were well-tolerated by participants, with only minor side effects reported. These findings suggest that these medications could be effective in managing hyperuricaemia in individuals with type 2 diabetes. However, the combination therapy was associated with a significant reduction in estimated glomerular filtration rate (eGFR), which may have clinical implications. Close monitoring of renal function is recommended when using combination therapy. Overall, the study suggests that combining empagliflozin and fenofibrate could simplify treatment for gout in individuals with diabetes. [Extracted from the article]

We hypothesized that a short-course high-intensity statin treatment during admission for myocardial infarction (MI) could rapidly reduce LDL-C and thus impact the choice of lipid-lowering therapy (LLT) at discharge. Our cohort comprised 133 MI patients (62.71 ± 11.3 years, 82% male) treated with atorvastatin 80 mg o.d. during admission. Basal LDL-C levels before admission were analyzed. We compared lipid profile variables before and during admission, and LLT at discharge was registered. Achieved theoretical LDL-C levels were estimated using LDL-C during admission and basal LDL-C as references and compared to LDL-C on first blood sample 4–6 weeks after discharge. A significant reduction in cholesterol from basal levels was noted during admission, including total cholesterol, triglycerides, HDL-C, non-HDL-C, and LDL-C (−39.23 ± 34.89 mg/dL, p < 0.001). LDL-C levels were reduced by 30% in days 1–2 and 40–45% in subsequent days (R2 0.766, p < 0.001). Using LDL-C during admission as a reference, most patients (88.7%) would theoretically achieve an LDL-C < 55 mg/dL with discharge LLT. However, if basal LDL-C levels were considered as a reference, only a small proportion of patients (30.1%) would achieve this lipid target, aligned with the proportion of patients with LDL-C < 55 mg/dL 4–6 weeks after discharge (36.8%). We conclude that statin treatment during admission for MI can induce a significant reduction in LDL-C and LLT at discharge is usually prescribed using LDL-C during admission as the reference, which leads to insufficient LDL-C reduction after discharge. Basal LDL-C before admission should be considered as the reference value for tailored LLT prescription. [ABSTRACT FROM AUTHOR]

The aim of this study is to present data on the use of lipid-lowering therapy (LLT) in relation to calculated cardiovascular risk (CVR) and an additionally defined target LDL-C concentration. The cohort consisted of 1287 participants in the Polish edition of the Prospective Urban and Rural Epidemiological Study (PURE). CVR was calculated for each participant using the SCORE2 or SCORE2-OP scale, and for patients with diabetes mellitus (DM), chronic kidney disease (CKD) or atherosclerotic cardiovascular disease (ASCVD) according to the respective criteria. In the cohort analysed, 107 of 212 people (50.5%) in the low cardiovascular risk (CVR) group, 284 of 414 people (68.6%) in the moderate CVR group, 562 of 612 people (91.8%) in the high CVR group and 48 of 49 people (98%) in the very high CVR group did not meet the target LDL-c criterion. Of those in the low CVR group, 86% of participants were not receiving lipid-lowering therapy (LLT); in the moderate CVR group, the proportion was 77.8%; in the high CVR group, 68.1% and in the very high CVR group, 75%. In each cardiovascular risk group, participants who did not meet the target LDL-c concentration criterion and did not take LLT made up the larger group. [ABSTRACT FROM AUTHOR]

Background Data about the clinical benefit from initial low-density lipoprotein cholesterol (LDL-C) reduction with lipid lowering treatment for secondary prevention and risk of major vascular events amongst older as compared with younger individuals treated during routine clinical care are limited. We investigated this in a nationwide cohort. Methods Individuals aged ≥ 50 years with a first-time hospitalisation for a cardiovascular event (index event, including acute coronary syndrome, non-haemorrhagic stroke, transient ischaemic attack and coronary revascularisation), 1 January 2008 to 31 October 2018, who subsequently used lipid lowering treatment, and had an LDL-C measurement before and after the event were included. Hazard ratios (HRs) for major vascular events per 1 mmol/L reduction in LDL-C were estimated for the included 21,751 older and 22,681 younger individuals (≥/<70 years old) using Cox regression. Results LDL-C lowering was associated with a 12% lower risk of major vascular events in older individuals per 1 mmol/L reduction in LDL-C (HR 0.88, 95% confidence interval [CI] 0.84–0.93), with no significant difference compared with the risk reduction amongst younger individuals (HR 0.88, 95% CI 0.83–0.93; P -value for difference between age groups: 0.86). The risk reduction was more pronounced when post hoc restricting, as a proxy for compliance, to new users with an LDL-C reduction above the lowest decile for both older (0.81, 95% CI 0.73–0.90) and younger (0.81, 95% CI 0.72–0.91) individuals. Conclusions This study strongly supports a similar relative clinical benefit of LDL-C reduction with lipid lowering treatment for secondary prevention of major vascular events amongst individuals aged ≥70 and <70 years. [ABSTRACT FROM AUTHOR]

Despite considerable evidence that lipid-lowering therapies (LLTs) afford clinical benefit, the control of low-density lipoprotein cholesterol (LDL-C) is suboptimal, and available LLTs are underused, especially in patients at high and very high cardiovascular (CV) risk. This study assesses the real-world LDL-C target attainment rate in patients on LLT before experiencing a first major acute cardiovascular event (MACE). The HEARTBEAT was a retrospective, multicentre observational study. From March to June 2021 a total of 334 patients on LLT who had a first MACE while being on statins were included in the study. Of these patients, 83.2 % had a high (40.7 %) or very high CV risk (29.0 %) prior to MACE. Overall, 87.5 % and 89.7 % of the patients at high and very high CV risk, respectively, failed to reach the LDL-C target. Regarding LLTs, only 11.8 % and 19.6 % of the patients at high and very high risk had received high-intensity LLTs prior to MACE. It was estimated that if these patients had reached their recommended LDL-C targets, the risk of MACE may have been reduced by a median of 24.5 % and 23.2 % in patients at high and very high risk respectively. Patients who suffer a first MACE while on statin therapy often were at high/very high CV risk. Despite their risk, LDL-levels and being on statins they are undertreated, and too far from lipid targets. A proper use of high-intensity LLTs led to an increase attainment of LDL targets and lower CV events. [Display omitted] • Patients taking statins for primary prevention in Spain are too far of lipid target. • This occurs especially in those at high and very high cardiovascular (CV) risk. • High-intensity lipid-lowering therapies (LLTs) are underused in primary prevention. • A proper use of LLTs would increase the number of patients achieving LDL-C targets. • Moreover, the number of CV events would be significantly reduced. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, imposing substantial healthcare economic burdens. Among the modifiable risk factors, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in ASCVD development. Novel therapies such as PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors are emerging to address this concern. These inhibitors offer the potential to reduce ASCVD risk by directly targeting LDL-C levels. The article reviews the structural and functional aspects of PCSK9, highlighting its role in LDL receptor regulation. The pharmacological strategies for PCSK9 inhibition, including monoclonal antibodies, binding peptides, gene silencing, and active immunization, are explored. Clinical evidence from various trials underscores the safety and efficacy of PCSK9 inhibitors in reducing LDL-C levels and potentially improving cardiovascular outcomes. Despite these promising results, challenges such as cost-effectiveness and long-term safety considerations are addressed. Among PCSK9 inhibitors, monoclonal antibodies represent a cornerstone. Many trials have showed their efficacy in reducing LDL-C and the risk for major adverse clinical events, revealing long-lasting effects, with special benefits particularly for statin-intolerant and familial hypercholesterolemia patients. However, long-term impacts, high costs, and patient selection necessitate further research. [ABSTRACT FROM AUTHOR]

Aim: To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid‐lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022. Materials and Methods: Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline‐based low‐density lipoprotein cholesterol (LDL‐C) and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) goal attainment was analysed. Results: In patients with T1D (median age 38.35 [20.51‐57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86‐78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk‐based recommended LDL‐C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk‐based goal of LDL‐C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non‐HDL‐C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively. Conclusion: Approximately 2 years after publication of the guidelines, LDL‐C and non‐HDL‐C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Copyright of Die Kardiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Atherosclerosis, while initially deemed a bland proliferative process, is now recognized as a multifactorial-lipoprotein-mediated inflammation-driven pathway. With the rising incidence of atherosclerotic disease of the lower extremity arteries, the healthcare burden and clinical morbidity and mortality due to peripheral artery disease (PAD) are currently escalating. With a healthcare cost burden of over 21 billion USD and 200 million patients afflicted worldwide, accurate knowledge regarding the pathophysiology, presentation, and diagnosis of the disease is crucial. The role of lipoproteins and their remnants in atherosclerotic vessel occlusion and plaque formation and progression has been long established. This review paper discusses the epidemiology, pathophysiology, and presentation of PAD. PAD has been repeatedly noted to portend to poor cardiovascular and limb outcomes. We discuss major therapeutic avenues for the prevention of major cardiovascular adverse events and major limb adverse events in patients with PAD. [ABSTRACT FROM AUTHOR]

Although great progress has been made in the diagnostic and treatment options for dyslipidemias, unawareness, underdiagnosis and undertreatment of these disorders remain a significant global health concern. Growth in digital applications and newer models of care provide novel tools to improve the management of chronic conditions such as dyslipidemia. In this review, we discuss the evolving landscape of lipid management in the 21st century, current treatment gaps and possible solutions through digital health and new models of care. Our discussion begins with the history and development of value-based care and the national establishment of quality metrics for various chronic conditions. These concepts on the level of healthcare policy not only inform reimbursements but also define the standard of care. Next, we consider the advances in atherosclerotic cardiovascular disease risk score calculators as well as evolving imaging modalities. The impact and growth of digital health, ranging from telehealth visits to online platforms and mobile applications, will also be explored. We then evaluate the ways in which machine learning and artificial intelligence-driven algorithms are being utilized to address gaps in lipid management. From an organizational perspective, we trace the redesign of medical practices to incorporate a multidisciplinary team model of care, recognizing that atherosclerotic cardiovascular disease risk is multifaceted and requires a comprehensive approach. Finally, we anticipate the future of dyslipidemia management, assessing the many ways in which atherosclerotic cardiovascular disease burden can be reduced on a population-wide scale. [ABSTRACT FROM AUTHOR]

• In real life, vast majority of FH patients with established ASCVD are undertreated in cardiology outpatient clinics • The proportion of FH patients receiving high intensity statin therapy is very low • Ezetimibe and PCSK9 inhibitor use is almost non-existent • Drug discontinuation rates are notably high and are mostly media-related • Side effects very rarely cause cessation of LLT. • Patients' knowledge about high cholesterol and its treatment is low. Familial hypercholesterolemia (FH) is a common inherited disease, leading to premature atherosclerotic cardiovascular disease (ASCVD) due to elevated low-density lipoprotein cholesterol (LDL-C) levels. Achieving LDL-C goals is extremely important for preventing the complications of this fatal disease. We evaluated the management of FH patients with ASCVD in cardiology practice. We analyzed patients with ASCVD from the nationwide EPHESUS registry, which was conducted in 40 cardiology outpatient clinics, and compared those with and without FH. Of the 1482 consecutively enrolled patients with ASCVD, 618 (41.7%) had FH, among which 455 were categorized as 'Possible FH' and 163 as 'Probable or Definite FH'. Proposed LDL-C goals were not attained in more than 90% of the patients with FH. The proportion of those on statin therapy was 77% for possible and 91% for probable or definite FH, whereas 34.2 % and 59.4% were in use of high-intensity statins, respectively. None of the patients were on PCSK-9 inhibitors, and only 2 used ezetimibe. Adverse media coverage was the most common cause of statin discontinuation (32.5% in 'possible FH' and 45.7% in 'probable/definite FH'). The negative impact of media in the decision to stop lipid lowering therapy (LLT) was increasing with education level. In real life most of the FH patients with ASCVD are undertreated in cardiology practice regarding statin dosing and combined LLT. Drug discontinuation rates are notably high and are mostly media-related, and side effects very rarely cause cessation of LLT. Urgent measures are needed to increase the awareness of FH among healthcare providers and patients and to develop improved treatment strategies aimed at preventing the complications of FH. [Display omitted] [ABSTRACT FROM AUTHOR]