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Background: Recent data from European studies (EUROASPIRE V, DA VINCI, SANTORINI) indicate that achieving the LDL cholesterol (LDL-C) target in patients at very high cardiovascular risk is uncommon. Additionally, using a combination therapy involving statins and ezetimibe remains infrequent. Methods: A single-center assessment of a pre-defined lipid lowering treatment algorithm's effectiveness at achieving the LDL-C target in patients at very high cardiovascular risk one month and one year after hospitalization. Results: 81 patients were included, all in secondary prevention. The average age of the patient was 66.9 years, and the main cardiovascular risk factors included hypertension, diabetes mellitus, and smoking history. Following the predefined lipid-lowering algorithm specific to our study, which involves initiating high-intensity statin therapy or a combination of statin and ezetimibe depending on initial LDL-C levels and patient history; 30 (37%) patients initiated high-intensity statin therapy (Atorvastatin (40 mg, 80 mg) or Rosuvastatin (20 mg, 40 mg)), while 51 (63%) started combination therapy with high-intensity statin and ezetimibe 10 mg. After one year, 57 (70.4%) remained adherent to their initial treatment, achieving a mean LDL-C of 49.5 ± 16.9 mg/dL, with 36 (63.2%) of them reaching the LDL-C target of <55 mg/dL. A total of 13 patients discontinued treatment, and 9 were lost to follow-up, withdrew from the study, or died. Conclusion: Initiating dual statin and ezetimibe therapy or high-intensity statin therapy early, based on the expected treatment efficacy, holds the potential to more rapidly and effectively achieve LDL-C targets in a larger proportion of very high-risk cardiovascular patients. [ABSTRACT FROM AUTHOR]

Background and Aims Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297). Methods MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH. Results Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio.74, 95% confidence interval.66–.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio.85, 95% confidence interval.74–.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality. Conclusions Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care. [ABSTRACT FROM AUTHOR]

Purpose: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Since the first functional and morphologic changes of the arterial wall occur in childhood, treatment should start early in childhood to mitigate the elevated risk of ASCVD. Pediatricians play an important role in the detection and care of children with FH. In this study, we aim to explore potential gaps in FH care amongst Dutch pediatricians, in order to enhance their knowledge and awareness of detecting and treating children with FH. Methods: An anonymous online survey, deployed using Google Forms, including 26 closed and semi-closed questions on FH care in children was distributed by the Dutch Association of Pediatrics via a newsletter to which the majority of the practicing Dutch pediatricians subscribe. In addition, we requested that the pediatric departments of all Dutch hospitals in the Netherlands distribute this survey personally among their employed pediatricians. Respondents were instructed to answer the questions without any help or use of online resources. Results: Between September 1st, 2023 and November 1st, 2023, 158 (an estimated 11% response rate) Dutch pediatricians completed the survey. They reported a median (IQR) of 15.0 (6.0–22.0) years of experience as a pediatrician, and 34 (21.5%) were working in academic hospitals. The majority (76.6%) of pediatricians correctly identified a typical FH lipid profile but 68 (43.0%) underestimated the true prevalence of FH (1:300). Underestimation and unawareness of the increased risk of FH patients for ASCVD were reported by 37.3% and 25.9% of pediatricians, respectively. Although 70.9% of the pediatricians correctly defined FH, only 67 (42.4%) selected statins and ezetimibe to treat severe hypercholesterolemia. Conclusions:The results of this study suggest significant gaps in knowledge and awareness of FH in children among Dutch pediatricians. FH care in children needs improvement through educational and training initiatives to mitigate the life-long risk of ASCVD from early life. What is Known: • Familial hypercholesterolemia (FH) leads to elevated LDL-cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). • The process of atherosclerosis starts in childhood • Pediatricians play an important role in the detection and treatment of children with FH. What is New: • Our results highlight significant gaps in care for children with FH amongst pediatricians and this may lead to suboptimal detection and treatment. • FH care in children needs improvement by educational initiatives to ultimately prevent ASCVD in adulthood. [ABSTRACT FROM AUTHOR]

Background and Objectives: Patients with previous acute myocardial infarction are at significantly higher risk of recurrent events. Early and intensive lipid-lowering therapy targeting low-density lipoprotein cholesterol is a key strategy for reducing cardiovascular risk in post-acute myocardial infarction patients worldwide. This study aimed to assess patients' real-life lipid-lowering treatment gaps after acute myocardial infarction using a global network, TriNetX, of anonymous, real-time patient data. The uniqueness of the study was the use of the novel, evolving, and constantly improving TriNetX platform and the evaluation of its feasibility for clinical research. Materials and Methods: A retrospective study was conducted on global repository patients in 2020, diagnosed with acute myocardial infarction, with a three-year follow-up. Results: After acute myocardial infarction, the prescribing rate of lipid-lowering medication (statins, ezetimibe and PCSK9I) was insufficient to reach target LDL-C values. The mean LDL-C level decreased from 2.7 mmol/L (103 mg/dL) as measured on the day of AMI to 1.97 mmol/L (76 mg/dL) between 31D and 3M. During the second and third years, the mean LDL-C value was stable (around 2.0 mmol/L (78 mg/dL)). LDL-C goals were not sufficiently reached, as only 7–12% of patients were reported to have LDL-C values < 55 mg/dL (1.4 mmol/L) and 13–20% of patients were reported to have LDL-C values < 70 mg/dL (1.8 mmol/L) during the follow-up periods. This means that a substantial number of patients remain at a very high risk for CV complications and mortality. Most cardiovascular complications happen within three months after acute myocardial infarction. Conclusions: Gaps remain between the recommendations for managing LDL-C in guidelines and what occurs in real life. The TriNetX platform is an innovative platform with significant potential and should be further developed for clinical research, as it enables the use of valuable interinstitutional data. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of hyperlipidemia and lipid-lowering therapy on the prognosis of postoperative patients with hepatitis B related hepatocellular carcinoma. Methods The clinical data of the patients with hepatitis B related hepatocellular carcinoma who were operated in our hospital from January 2012 to January 2021 were retrospectively collected. The effect of blood lipid level and related lipid-lowering therapy on the prognosis of postoperative patients with hepatitis B related hepatocellular carcinoma was analyzed. Results Among 166 patients with hepatitis B related hepatocellular carcinoma, there were 63 cases had hyperlipidemia, of which 33 cases were treated by statins. The median postoperative disease free survival time in the hyperlipidemia group was significantly lower than that in the normal blood lipid group (24.8 months vs. 38.5 months, P

Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8–10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking. Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. This was a retrospective and prospective multicenter cohort study (2015–2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD. We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (−44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal. Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Patients with previous acute myocardial infarction are at significantly higher risk of recurrent events. Early and intensive lipid-lowering therapy targeting low-density lipoprotein cholesterol is a key strategy for reducing cardiovascular risk in post-acute myocardial infarction patients worldwide. This study aimed to assess patients’ real-life lipid-lowering treatment gaps after acute myocardial infarction using a global network, TriNetX, of anonymous, real-time patient data. The uniqueness of the study was the use of the novel, evolving, and constantly improving TriNetX platform and the evaluation of its feasibility for clinical research. Materials and Methods: A retrospective study was conducted on global repository patients in 2020, diagnosed with acute myocardial infarction, with a three-year follow-up. Results: After acute myocardial infarction, the prescribing rate of lipid-lowering medication (statins, ezetimibe and PCSK9I) was insufficient to reach target LDL-C values. The mean LDL-C level decreased from 2.7 mmol/L (103 mg/dL) as measured on the day of AMI to 1.97 mmol/L (76 mg/dL) between 31D and 3M. During the second and third years, the mean LDL-C value was stable (around 2.0 mmol/L (78 mg/dL)). LDL-C goals were not sufficiently reached, as only 7–12% of patients were reported to have LDL-C values < 55 mg/dL (1.4 mmol/L) and 13–20% of patients were reported to have LDL-C values < 70 mg/dL (1.8 mmol/L) during the follow-up periods. This means that a substantial number of patients remain at a very high risk for CV complications and mortality. Most cardiovascular complications happen within three months after acute myocardial infarction. Conclusions: Gaps remain between the recommendations for managing LDL-C in guidelines and what occurs in real life. The TriNetX platform is an innovative platform with significant potential and should be further developed for clinical research, as it enables the use of valuable interinstitutional data.

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A linear reduction in cardiovascular adverse events has been shown even when LDL-C reduction surpassed recommended treatment goals, thus postulating 'the lower, the better for longer' as a therapeutic strategy in patients with acute coronary syndrome (ACS). It was linked with more and more data on dual lipid lowering therapy (LLT) with statin and ezetimibe that showed to be associated with additional reduction of inflammatory markers as compared with statin alone. Thus, we recommend dual LLT consisted of high dose of potent statin and ezetimibe to be applied from the very beginning of hospitalization in all ACS patients. We recommended further increase the education of patients and improve the standards of care by physicians/cardiologists with the discharge letter recently suggested by the Polish Cardiac Society and Polish Lipid Association added to the standardized discharge letter. At the first follow-up study visit, achievement of the therapeutic LDL-C target should be assessed. Patients who did not achieve and are not expected to achieve this target, and those who have been diagnosed with statin intolerance should be referred to a lipidological consultation. Lipoprotein (a) [Lp(a)] has pro-inflammatory and pro-atherosclerotic properties. Concentration of Lp(a) is predominantly determined by genetics (> 90%), more than any other lipoprotein. Elevated concentration of Lp(a) is associated with increased risk of atherosclerotic cardiovascular disease, aortic stenosis, cardiovascular and all-cause mortality. Therefore, Lp(a) should be assessed once during hospitalization in patients with ASC. Patients with Lp(a) > 50 mg/dL (> 125 nmol/L) should be referred to a lipidological consultation. These recommendations regarding LLT apply to patients enrolled in to the ELECTRA-SIRIO 2 trial, however, we encourage to consider them for treatment of other patients with ACS. [ABSTRACT FROM AUTHOR]

Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48–0.92, p = 0.01), CAC score > 100 (1.59; 1.08–2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19–3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population. [ABSTRACT FROM AUTHOR]

Background: Greece was recently reclassified from low- to medium-risk country in terms of cardiovascular disease, with 27% of cardiovascular deaths attributed to hypercholesterolemia. EMENO nationwide survey (2013-2016) assessed the epidemiology of dyslipidemia in the general population in Greece. Methods: A random sample of adults was drawn by multistage stratified random sampling based on 2011 census. Standardized questionnaires and blood tests for total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and triglycerides were used. Hypercholesterolemia was defined as TC ≥ 240/200 mg/dL and/or the use of lipid-lowering drugs, hyper-LDL-cholesterolemia as LDL-C ≥160/130/100 mg/dL and/or the use of drugs, hypo-HDL-cholesterolemia as HDL-C

Background and aims: Heterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL). Methods: We studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system. Results: The database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention. Conclusions: The incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.

Abstract Background Although potent lipid-lowering therapies are available, patients commonly fall short of recommended low-density lipoprotein cholesterol (LDL-C) levels. The aim of this study was to examine the relationship between familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] and LDL-C goal attainment, as well as the prevalence and severity of coronary artery disease (CAD). Moreover, we characterized patients failing to meet recommended LDL-C goals. Methods We performed a cross-sectional analysis in a cohort of patients undergoing cardiac catheterization. Clinical FH was determined by the Dutch Clinical Lipid Network Score, and Lp(a) ≥ 50 mg/dL (≈ 107 nmol/L) was considered elevated. Results A total of 838 participants were included. Overall, the prevalence of CAD was 72%, and 62% received lipid-lowering treatment. The prevalence of clinical FH (probable and definite FH) was 4%, and 19% had elevated Lp(a) levels. With 35%, LDL-C goal attainment was generally poor. Among the participants with clinical FH, none reached their LDL-C target. Among patients with elevated Lp(a), LDL-C target achievement was only 28%. The prevalence and severity of CAD were higher in participants with clinical FH (86% prevalence) and elevated Lp(a) (80% prevalence). Conclusion Most participants failed to meet their individual LDL-C goals according to the ESC 2016 and 2019 guidelines. In particular, high-risk patients with clinical FH or elevated Lp(a) rarely met their target for LDL-C. The identification of these patients and more intense treatment approaches are crucial for the improvement of CAD primary and secondary prevention.

Atherosclerosis and atherosclerotic-related cardiovascular diseases (ASCVD) are characterized by high serum levels of low-density lipoprotein cholesterol (LDL-C) that can promote the generation of reactive oxygen species (ROS). To answer the need for better LDL-C control in individuals at high and very high risk for CVD, a new injectable innovative family of lipid-lowering (LL) monoclonal antibodies against the protein convertase subtilisin/kexin type 9 (PCSK9) has been approved. However, the effect of these drugs on vascular function, such as ROS generation and arterial stiffness, has not already been extensively described. In this report, we present data from 18 males with high to very high CV risk undergoing LL treatment (LLT) with either statin and ezetimibe or ezetimibe monotherapy, who experienced, after a 2-month treatment with Evolocumab, a significant improvement in blood pressure (BP)-adjusted carotid–femoral pulse wave velocity (cfPWV) (p-value = 0.0005 in the whole cohort, p-value = 0.0046 in the sub-cohort undergoing background LLT with statin and ezetimibe, p-value = 0.015 in the sub-cohort undergoing background LLT with ezetimibe monotherapy), which was significantly associated with a decrease in freshly isolated leukocytes (PBMCS)-derived H2O2 production (p-value = 0.004, p-value = 0.02 and p-value = 0.05, respectively, in the whole cohort, in the statin + ezetimibe sub-cohort, and the ezetimibe sub-cohort). Our observations support the role of systemic oxidative stress in atherosclerosis and give a further rationale for using Evolocumab also for its effect in vascular disorders linked to oxidative processes. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is an inherited metabolic defect leading to increased total cholesterol and low-density cholesterol (LDL) from birth onwards. Homozygous FH, presenting with clear clinical features, has a prevalence of ~ 1 per million. Prevalence of heterozygous FH is 1/500 European population. Atherosclerotic burden depends on the degree and duration of high LDL exposure. In severe cases, early detection is critical, and aggressive lipid-lowering therapies should begin in early childhood to reduce coronary heart disease risk. Pediatric therapeutic concepts correspond to adults and are orientated at LDL plasma concentration. Mean LDL plasma target value during treatment is < 135 mg/dL. Medication in childhood consists of ezetemibe, statins, resins, and PCSK-9 inhibitors, with consideration for age restrictions. Only a minority achieve the treatment target with drug therapy alone. Therapeutic apheresis for the treatment of hypercholesterolemia selectively removes lipoproteins from blood (lipid apheresis (LA)). LA has a long tradition in adult medicine and is also safely used in children by a variety of methods, if customized to special pediatric needs. LA reduces cholesterol levels independently of residual LDL-receptor function and not only achieves reduction or disappearance of xanthomas but also inhibits progression of or mitigates aortic valve stenosis and supravalvular aortic stenosis as well as coronary artery and other atherosclerotic lesions. Cardiovascular prognosis of patients with otherwise untreatable FH depends largely on timely use of LA. Taking into account LA as a lifelong treatment, starting early in childhood, it is important to accommodate therapy modalities, such as treatment frequency and point of time, into the life of the individual. [ABSTRACT FROM AUTHOR]

Background: Although potent lipid-lowering therapies are available, patients commonly fall short of recommended low-density lipoprotein cholesterol (LDL-C) levels. The aim of this study was to examine the relationship between familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] and LDL-C goal attainment, as well as the prevalence and severity of coronary artery disease (CAD). Moreover, we characterized patients failing to meet recommended LDL-C goals. Methods: We performed a cross-sectional analysis in a cohort of patients undergoing cardiac catheterization. Clinical FH was determined by the Dutch Clinical Lipid Network Score, and Lp(a) ≥ 50 mg/dL (≈ 107 nmol/L) was considered elevated. Results: A total of 838 participants were included. Overall, the prevalence of CAD was 72%, and 62% received lipid-lowering treatment. The prevalence of clinical FH (probable and definite FH) was 4%, and 19% had elevated Lp(a) levels. With 35%, LDL-C goal attainment was generally poor. Among the participants with clinical FH, none reached their LDL-C target. Among patients with elevated Lp(a), LDL-C target achievement was only 28%. The prevalence and severity of CAD were higher in participants with clinical FH (86% prevalence) and elevated Lp(a) (80% prevalence). Conclusion: Most participants failed to meet their individual LDL-C goals according to the ESC 2016 and 2019 guidelines. In particular, high-risk patients with clinical FH or elevated Lp(a) rarely met their target for LDL-C. The identification of these patients and more intense treatment approaches are crucial for the improvement of CAD primary and secondary prevention. [ABSTRACT FROM AUTHOR]

Nowdays a small proportion of patients with high/very high/extreme atherosclerotic cardiovascular disease risk achieves the optimal target of LDL-cholesterol, because of drug intolerance, poor adherence to the therapy, or inapplicability of the stepwise strategy in lipid lowering therapy, recommended by the current guidelines. The new oral agent bempedoic acid lowers plasma LDL-cholesterol by inhibiting adenosine triphosphate-citrate lyase, an enzyme involved in the synthesis of cholesterol, and, ultimately, by up-regulating the LDL receptors. Several clinical trials in patients with atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia demonstrated that bempedoic acid alone or combined with statins and/or ezetimibe significantly reduced LDL-cholesterol and high-sensitivity C-reactive protein. Bempedoic acid is well tolerated with no significant increase in muscle-related symptoms, since it can be activated only in the liver but not in the skeletal muscles. Bempedoic acid provides an effective tool to further reduce LDL-cholesterol as add on therapy in patients unable to reach the target despite maximally tolerated lipid lowering therapy. [ABSTRACT FROM AUTHOR]

• Defining FH patients destined not to develop disease has significant implications. • This study shows that a low SAFEHEART-Risk Equation score was predictor of OR-FH. • This risk equation may be useful to detect who may require less intensive treatment. Defining patients with familial hypercholesterolemia (FH) destined not to develop clinical atherosclerotic cardiovascular disease (ASCVD) has significant implications for precision and discovery medicine. We investigated the predictors of resilience to ASCVD in a cohort of 248 octogenarian patients with FH enrolled in the SAFEHEART study. Median age at the time of analysis was 84.7 years (82.3–88.1) and 83.6 years (81.9–86.4) in the octogenarian resilient FH (OR-FH) and octogenarian controls non-resilient FH (OCNoR-FH) groups, respectively (p =0.073); 92 (80.0%) and 68 (51.1%) patients were female in the first compared with the second group (p <0.001). Multivariate logistic regression showed that a low 10-year score in SAFEHEART-Risk Equation was the only independent predictor of OR-FH. Application of this simple and validated risk equation may potentially be useful for predicting patients ultra-resilient to the ASCVD sequelae of FH who may require less intensive use of healthcare resources. [ABSTRACT FROM AUTHOR]

Background & Aims: The effect of lipid-lowering treatment (LLT) on metabolic dysfunction associated steatotic liver disease (MASLD) is unclear. This is relevant for patients with familial hypercholesterolemia (FH) who are on lifelong LLT. We aimed to evaluate the effect of LLT on MASLD indices in this population., Methods: Patients with at least possible diagnosis of FH were included into the Hellenic FH Registry (HELLAS-FH) registry. We analyzed the effect of statin monotherapy, statin/ezetimibe and statin/ezetimibe/proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) on MASLD indices, i.e., original triglyceride-glucose index (TyGO) and triglyceride-glucose index (TyG). We compared changes of TyG and TyGO before any treatment and after at least one year of stable LLT., Results: We included 1289 patients: n = 569 in the statin monotherapy group (mean age = 51 ± 15 years, 52.7 % males), n = 629 in the statin/ezetimibe group (52 ± 14 years, 51.8 %), and n = 91 in the statin/ezetimibe/PCSK9i group (54 ± 13 years, 58.2 %). Compared with baseline, TyGO and TyG decreased significantly following statin monotherapy (8.61 vs 8.49 and 4.65 vs 4.59, respectively, both p < 0.01), statin/ezetimibe (8.59 vs 8.41 and 4.64 vs 4.55, respectively, both p < 0.01) and statin/ezetimibe/PCSK9i (8.79 vs 8.55 and 4.74 vs 4.62, respectively, both p < 0.01). There was no difference regarding the change of TyGO and TyG between groups after adjusting for baseline levels. A greater percentage of patients in the statin/ezetimibe and statin/ezetimibe/PCSK9i groups exhibited TyGO-defined MASLD resolution compared with statin monotherapy (p < 0.05). After adjustment for possible confounders, LLT was significantly associated with MASLD resolution., Conclusions: MASLD indices were significantly improved in all LLT groups in FH patients. Statin/ezetimibe and statin/ezetimibe/PCSK9i were associated with greater TyGO-defined MASLD resolution compared with statin monotherapy., Competing Interests: Conflict of interest CB, CVR, GL, AG, GS, PA, VK, GA, EP, CV, ID, FG, KAP, AA, VK, CK, DA, CA has nothing to declare. IS has given talks, received honoraria, and participated in clinical trials sponsored by MSD, AMGEN, SANOFI. LR has received research grants and honoraria from Amgen, Sanofi-Aventis, Viatris, Novartis, Vianex and Servier. GK has given talks, attended conferences and participated in trials sponsored by Amgen, Angelini, MSD, Lilly, Vianex and Sanofi and has also accepted travel support to conferences from Amgen, Sanofi and MSD. KT has participated in educational, research and advisory activities sponsored by AMGEN, ANGELINI, ASTRA-ZENECA, BAYER, BOEHRINGER-INGELHEIM, ELPEN, LILLY, MSD, MYLAN, NOVO NORDISK, SANOFI and VIANEX. ES has participated in educational and advisory activities sponsored by AstraZeneca, Medtronic, MSD, Sanofi and Servier. VK has given talks and attended conferences sponsored by AstraZeneca, MSD, Sanofi-Aventis, and Vianex. MD has participated in educational, research and advisory activities sponsored by Menarini, Elpen, AstraZeneca, MSD, Bayer, Sanofi, Novartis, and Servier. KS has received honoraria from Amgen. VL has given lectures, attended conferences and participated in trials sponsored by Novo Nordisk, Sanofi-Aventis, Novartis, AstraZeneca, Boehringer-Ingelheim, MSD, GSK, Vianex, Elli Lilly, ELPEN, Mylan and Aegereon. AB has received honoraria from Vianex, Amarin and Sanofi. EL has participated in educational, research and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer-Ingelheim, Novartis, Novo Nordisk, Valeant and Servier. EZ has received honoraria for lectures from Amgen. Sanofi, MSD, and Astra Zeneca. HM participated in educational, research and consulting activities supported by healthcare companies, including Amgen, AstraZeneca, Boehringer Ingelheim, Elpen, Novartis, Sanofi, Vianex, Ultragenyx, Winmedica. EL has participated in educational, research and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer-Ingelheim, Novartis, Novo Nordisk, Valeant and Servier. CSM reports grants through his institution from Merck, Massachusetts Life Sciences Center, and Boehringer Ingelheim, has been a shareholder of and has received grants through his institution and personal consulting fees from Coherus Inc. and AltrixBio; he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Genfit, Lumos, Amgen, Corcept, Aligos, Intercept, 89 Bio, Madrigal, and Regeneron, reports travel support and fees from TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to the work presented herein. ENL has participated in educational, research and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer Ingelheim, Novartis, Novo Nordisk, Valeant and Servier., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction and Objectives: Lipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease, and to assess its influence on the achievement of LDL-C targets., Method: We conducted a cross-sectional study in a cardiology department in Spain. A total of 870 patients with stable coronary artery disease had their lipid profile determined, including Lp(a). Patients were stratified into 2 groups according to Lp(a)>50mg/dL and Lp(a)≤50mg/dL. The association of Lp(a)>50mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis., Results: The prevalence of Lp(a)>50mg/dL was 30.8%. Patients with Lp(a)>50mg/dL had higher baseline (142.30±47.54 vs. 130.47±40.75mg/dL; p=0.0001) and current (72.91±26.44 vs. 64.72±25.30mg/dL; p=0.0001), despite the fact that they were treated with more high-potency statins (77.2 vs. 70.9%; p=0.058) and more combination lipid-lowering therapy (37.7 vs. 25.7%; p=0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a)>50mg/dL. Independent predictors of having elevated Lp(a) levels>50mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08-2.14), combination lipid-lowering therapy with ezetimibe (OR 2.0; 95% CI 1.45-2.73) and failure to achieve a LDL-C ≤55mg/dL (OR 2.3; 95% CI 1.63-3.23)., Conclusions: Elevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients., (Copyright © 2024 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48–0.92, p = 0.01), CAC score > 100 (1.59; 1.08–2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19–3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population.

Background The effectiveness of lipid‐lowering therapy (LLT) is affected by both intensity and adherence. This study evaluated the associations of LLT intensity, adherence, and the combination of these 2 aspects of LLT management with the risk of major adverse cardiovascular events (MACE) in people with coronary heart disease. Methods and Results This is an observational study of all adults who suffered a myocardial infarction or had coronary revascularization during 2012 to 2018 and initiated LLT in Stockholm, Sweden. Study exposures were LLT adherence (proportion of days covered), LLT intensity (expected reduction of low‐density lipoprotein cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity during the previous 12 months were calculated. The primary outcomes were MACE (nonfatal myocardial infarction or stroke and death); secondary outcomes were low‐density lipoprotein cholesterol goal attainment and individual components of MACE. We studied 20 490 patients aged 68±11 years, 75% men, mean follow‐up 2.6±1.1 years. Every 10% increase in 1‐year adherence, intensity, or adherence‐adjusted intensity was associated with a lower risk of MACE (hazard ratio [HR], 0.94 [95% CI, 0.93–0.96]; HR, 0.92 [95% CI, 0.88–0.96]; and HR, 0.91 [95% CI, 0.89–0.94], respectively) and higher odds of attaining low‐density lipoprotein cholesterol goals (odds ratio [OR],1.12 [95% CI, 1.10–1.15]; OR, 1.42 [95% CI, 1.34–1.51], and OR, 1.16 [95% CI, 1.19–1.24], respectively). Among patients with good adherence (≥80%), the risk of MACE was similar with low‐moderate and high‐intensity LLT despite differences in the low‐density lipoprotein cholesterol goal attainment with the treatment intensities. Discontinuation ≥1 year increased the risk markedly (HR,1.66 [95% CI, 1.23–2.22]). Conclusions In routine care, good adherence to LLT was associated with the greatest benefit for patients with coronary heart disease. Strategies that improve adherence and use of intensive therapies could substantially reduce cardiovascular risk.

Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event. Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment. Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62–68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure. In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions. [Display omitted] • Less than 70 % of patients with coronary heart disease used high-intensity statin therapy with only small changes over time. • Only one in four patients used additional treatment with ezetimibe. • More than one in five had poor long-term adherence to lipid lowering drugs. • There is a major potential for improving long-term lipid management in secondary prevention. [ABSTRACT FROM AUTHOR]

Purpose: Low-density lipoprotein (LDL) cholesterol reduction by statin therapy is dose-dependent, varies among different statins, and has wide inter-individual variability. The present study aimed to compare mean LDL cholesterol reduction and its variability achieved with different doses of the three statins most frequently used in monotherapy or combined with ezetimibe in a real clinical setting. Methods: Of 5620 cases with primary hypercholesterolemia on the Spanish Arteriosclerosis Society Registry, 1004 with non-familial hypercholesterolemia and complete information on drug therapy and lipid profile were included. Results: The lowest mean percentage LDL cholesterol reduction was observed with simvastatin 10 mg (32.5 ± 18.5%), while the highest mean percentage LDL reduction was obtained with rosuvastatin 40 mg (58.7 ± 18.8%). As to combined treatment, the lowest and highest mean percentage LDL cholesterol reductions were obtained with simvastatin 10 mg combined with ezetimibe (50.6 ± 24.6%) and rosuvastatin 40 mg combined with ezetimibe (71.6 ± 11.1%), respectively. Factors associated with a suboptimal response were male sex, lower age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol reduction (OR 0.603, p < 0.001). Conclusion: In a real clinical setting, rosuvastatin was superior to the other statins in lowering LDL cholesterol, both as monotherapy or combined with ezetimibe. Factors associated with a suboptimal response in LDL cholesterol decline were male sex, age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol improvement. [ABSTRACT FROM AUTHOR]

Bempedoic acid (BA) is a novel first-in-class oral lipid-lowering therapy. BA has been approved by the European Medicinal Agency and Food and Drug Administration and has been commercialised throughout Europe since the end of 2020 as an add-on therapy in patients at high/very-high cardiovascular risk that are not at LDL-C goals with current lipid-lowering treatments. Recently, Italian lipid management experts gathered to discuss several open questions on BA characteristics and BArelated practical clinical issues. The panel permitted collection of its opinions in a ten Q&A format.Aim: The aim of this viewpoint is to discuss and answer several open questions on BA characteristics and BA-related practical clinical issues.Data Synthesis: The data includes main phase III studies, subanalysis and meta-analysis on BA.Conclusions: The panel permitted collection of its opinions in a ten Q&A format. [ABSTRACT FROM AUTHOR]

Abstract Hyperlipidemia is correlated with a series of health problems. Notably, aside from its established role in promoting cardiovascular morbidity and mortality, hyperlipidemia has also been considered for modulating the risk and the severity of multiple metabolic disorders. According to the results of epidemiologic investigations, several certain circulating lipoprotein species are correlated with the prevalence of diabetic retinopathy, suggesting that the physiological and pathological role of these lipoproteins is analogous to that observed in cardiovascular diseases. Furthermore, the lipid-lowering treatments, particularly using statin and fibrate, have been demonstrated to ameliorate diabetic retinopathy. Thereby, current focus is shifting towards implementing the protective strategies of diabetic retinopathy and elucidating the potential underlying mechanisms. However, it is worth noting that the relationship between major serum cholesterol species and the development of diabetic retinopathy, published by other studies, was inconsistent and overall modest, revealing the relationship is still not clarified. In this review, the current understanding of hyperlipidemia in pathogenesis of diabetic retinopathy was summarized and the novel insights into the potential mechanisms whereby hyperlipidemia modulates diabetic retinopathy were put forward.

Han Yang, 1, 2 Nan Li, 3 Youlian Zhou, 1, 4 Zhilan Xiao, 4 Haoming Tian, 1 Ming Hu, 2 Sheyu Li 1 1Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2West China School of Pharmacy, Sichuan University, Chengdu 610041, People’s Republic of China; 3Department of Informatics, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 4West China School of Medicine, Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Sheyu LiDepartment of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu 610041, Sichuan, People’s Republic of ChinaEmail lisheyu@gmail.comMing HuWest China School of Pharmacy, Sichuan University, 17 Renmin South Road (3rd Section), Chengdu 610041, People’s Republic of ChinaEmail huming@scu.edu.cnBackground: For patients with inadequate control of cholesterol using moderate-dose statins in the secondary prevention of cardiovascular diseases (CVD), either doubling the dose of statins or adding ezetimibe should be considered. The cost-effectiveness of them is unknown in the Chinese context. The aim of this study is to compare the cost and effectiveness of the two regimens, and estimate the incremental cost-effectiveness ratio (ICER).Methods: A Markov model of five health statuses were used to estimate long-term costs and quality-adjusted life-years (QALYs) of the two treatment regimens from the healthcare perspective. The effectiveness data used to calculate the transition probability was based on a previously published randomized trial. The utility data was gathered from literature and the costs were gathered from the electronic medical record system of West China Hospital in Chinese Yuan (CNY) in 2017 price. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted.Results: The ICER for ezetimibe plus moderate-dose rosuvastatin was 47,102.99 CNY per QALY for 20 years simulation, which did not reach the threshold of per capita gross domestic product (GDP) of 59,660 CNY per QALY in 2017 in China. Non-CVD-related mortality and CVD-related mortality contributed most to the ICER.Conclusion: Adding ezetimibe to the moderate-dose statin in secondary prevention for CVD is cost-effective, compared with the high-dose statin in the Chinese context whose low-density lipoprotein cholesterol (LDL-c) was not inadequately controlled by moderate-dose statin alone.Keywords: ezetimibe, rosuvastatin, lipid-lowering treatment, cost-effectiveness analysis, Markov model, secondary prevention of cardiovascular diseases

Atherosclerosis and atherosclerotic-related cardiovascular diseases (ASCVD) are characterized by high serum levels of low-density lipoprotein cholesterol (LDL-C) that can promote the generation of reactive oxygen species (ROS). To answer the need for better LDL-C control in individuals at high and very high risk for CVD, a new injectable innovative family of lipid-lowering (LL) monoclonal antibodies against the protein convertase subtilisin/kexin type 9 (PCSK9) has been approved. However, the effect of these drugs on vascular function, such as ROS generation and arterial stiffness, has not already been extensively described. In this report, we present data from 18 males with high to very high CV risk undergoing LL treatment (LLT) with either statin and ezetimibe or ezetimibe monotherapy, who experienced, after a 2-month treatment with Evolocumab, a significant improvement in blood pressure (BP)-adjusted carotid–femoral pulse wave velocity (cfPWV) (p-value = 0.0005 in the whole cohort, p-value = 0.0046 in the sub-cohort undergoing background LLT with statin and ezetimibe, p-value = 0.015 in the sub-cohort undergoing background LLT with ezetimibe monotherapy), which was significantly associated with a decrease in freshly isolated leukocytes (PBMCS)-derived H2O2 production (p-value = 0.004, p-value = 0.02 and p-value = 0.05, respectively, in the whole cohort, in the statin + ezetimibe sub-cohort, and the ezetimibe sub-cohort). Our observations support the role of systemic oxidative stress in atherosclerosis and give a further rationale for using Evolocumab also for its effect in vascular disorders linked to oxidative processes.

Background: The need for conversional metabolic and bariatric surgery (CMBS) is still growing. No large-scale prospective cohort studies have assessed changes in lipid-lowering treatment (LLT) after CMBS., Objectives: This study assesses and compares the effectiveness of the 4 main CMBS sequences after sleeve gastrectomy (SG) and adjustable gastric banding (AGB) on reimbursement and cost of LLT., Setting: France., Methods: This nationwide observational population-based cohort study analyzed data from the French National Health Insurance database. It included all patients who had undergone primary SG and AGB in France between January 1, 2012, and December 31, 2014, and followed until December 31, 2020. The study assessed LLT reimbursement evolution and costs across 4 different CMBS sequences., Results: During follow-up, 6396 patients underwent the 4 CMBS sequences: SG-RYGB (Roux-en-Y gastric bypass) (n = 2400), AGB-SG (n = 2277), AGB-RYGB (n = 1173), and SG-SG (n = 546), with a rate of LLT reimbursement of 9.8%, 3.6%, 6.6%, and 7.9%, respectively, in the year before CMBS. The rates of discontinuation of treatment at 2 and 4 years were 41.9%, 35.4%, 45.6%, 20.5% and 45.6%, 31.3%, 64.3%, 31.6%, respectively. At 4 years, the median [interquartile range] annual costs (euros) per patient were significantly lower (P < .01) than the costs in the year before CMBS for each sequence: 86.8 [57.3; 136.1] versus 38.0 [.0; 64.6], 79.1 [50.5; 120.1] versus 50.4 [15.6; 64.1], 89.0 [66.5; 139.6] versus .0 [.0; 58.8], and 89.8 [66.1; 121.4] versus 63.1 [.0; 93.4]., Conclusions: Our study underlines the effectiveness of CMBS in significantly reducing the need and associated costs of LLT for patients with dyslipidemia over a 4-year period., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

• PCSK9 inhibitors reduce LDL-C by 58% in heterozygous familial hypercholesterolemia. • Response was significantly higher when maximally tolerated statin therapy is used. • Most patients reach an LDL cholesterol goal according guidelines. • PCSK9 inhibitors are highly effective in FH patients in clinical practice setting. [Display omitted] PCSK9 inhibitors are a treatment option for patients with familial hypercholesterolemia not on low-density lipoprotein cholesterol goals despite the use of maximally tolerated high intensity-statins dose. To evaluate the efficacy of alirocumab and evolocumab in LDL-C reduction and targets attainment in patients with heterozygous familial hypercholesterolemia in clinical practice setting. SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of familial hypercholesterolemia. This study analyze subjects ≥ 20 years of age on stable lipid-lowering therapy, who received PCSK9 inhibitors during the period 2016 to January 2020. 433 patients (mean age 55 years, 53% male, 39% with cardiovascular disease) were included and followed-up for a median of 2.5 years (IQR 1.6–3.0). Median LDL-C level prior to PCSK9 inhibitors was 145 mg/dL (IQR 125–173). The addition of PCSK9 inhibitors (211 alirocumab, 222 evolocumab) reduced LDL-C by 58% (IQR 41–70) p <0.001, in men and women, achieving a median LDL-C level of 62 mg/dL (IQR 44–87) without differences between both PCSK9 inhibitors. Out of them 67% with and 80% without cardiovascular disease reached 2016 ESC/EAS LDL-C targets, and 46% very high risk and 50% high risk patients achieved 2019 ESC/EAS LDL-C goals. Independent predictor factors for attainment of 2019 ESC/EAS LDL-C goals were to be male, smoking and the use of statins with ezetimibe. Both inhibitors were well tolerated. PCSK9 inhibitors on top of maximum lipid-lowering treatment significantly reduced LDL-C levels in patients with familial hypercholesterolemia and improved the achievement of LDL-C targets. [ABSTRACT FROM AUTHOR]

This study investigates whether informing patients about their own results of a double-blinded atorvastatin challenge, combined with tailored lipid-lowering treatment, improved statin use and lipid control in coronary heart disease (CHD) patients with self-perceived SAMS. Keywords: coronary heart disease; lipid-lowering treatment; low-density lipoprotein cholesterol; statins; statin-associated muscle symptoms EN coronary heart disease lipid-lowering treatment low-density lipoprotein cholesterol statins statin-associated muscle symptoms 891 893 3 05/11/22 20220601 NES 220601 Dear Editor, Statin discontinuation due to self-perceived statin-associated muscle symptoms (SAMS) is a prevalent challenge associated with unfavourable lipid control and adverse outcomes [1, 2]. Tailored clinical management after blinded statin challenge improved the lipid control in coronary patients with self-perceived muscle side effects. [Extracted from the article]

The aim of this review was to present the recently published results of ODYSSEY OUTCOMES trial and discuss the clinical perspective of these data. Patients with acute coronary syndrome are at very high risk of recurrent ischemic cardiovascular complications, especially during the first year after the event. The use of high-intensity statin therapy in this group of patients does not always lead to the achievement of target levels of atherogenic lipoproteins. PCSK9 inhibitors, administered in addition to statins, can provide additional reduction of low-density lipoprotein cholesterol, which leads to further improvements of outcomes in patients with atherosclerotic cardiovascular disease. According to the latest results from ODYSSEY OUTCOMES trial, among patients with recent acute coronary syndrome, who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who were treated with alirocumab then among those who received placebo. The treatment with alirocumab in patients with recent acute coronary syndrome was associated with reduction in death from any causes. The absolute risk reduction with alirocumab was the most prominent in the subpopulation of patients with low-density lipoprotein cholesterol ≥2,6 mmol/l at baseline. These results have implication for clinical practice and may play an important role for the improvement of outcomes in patients at highest cardiovascular risk after acute cardiovascular syndrome.

Background and Aims: Cardiovascular risk in heterozygous familial hypercholesterolaemia (HeFH) is driven by LDL cholesterol levels. Since lipid response to statin therapy presents individual variation, this study aimed to compare mean LDL and non-HDL cholesterol reductions and their variability achieved with different types and doses of the most frequently prescribed statins.Methods and Results: Among primary hypercholesterolaemia cases on the Spanish Arteriosclerosis Society registry, 2894 with probable/definite HeFH and complete information on drug therapy and lipid profile were included. LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg. After the addition of ezetimibe, an additional 26, 24, 21 and 24% reduction in LDL cholesterol levels was obtained for rosuvastatin, 5, 10, 20 and 40 mg, respectively. Subjects with definite HeFH and a confirmed genetic mutation had a more discrete LDL cholesterol reduction compared to definite HeFH subjects with no genetic mutation. A suboptimal response (<15% or <30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects.Conclusion: According to the LDL cholesterol reduction in HeFH patients, the ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent. HeFH subjects with positive genetic diagnosis had a lower lipid-lowering response. Approximately 1 in 5 patients on high-intensity statin therapy presented a suboptimal response. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies 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.)

Nowdays a small proportion of patients with high/very high/extreme atherosclerotic cardiovascular disease risk achieves the optimal target of LDL-cholesterol, because of drug intolerance, poor adherence to the therapy, or inapplicability of the stepwise strategy in lipid lowering therapy, recommended by the current guidelines. The new oral agent bempedoic acid lowers plasma LDL-cholesterol by inhibiting adenosine triphosphate-citrate lyase, an enzyme involved in the synthesis of cholesterol, and, ultimately, by up-regulating the LDL receptors. Several clinical trials in patients with atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia demonstrated that bempedoic acid alone or combined with statins and/or ezetimibe significantly reduced LDL-cholesterol and high-sensitivity C-reactive protein. Bempedoic acid is well tolerated with no significant increase in muscle-related symptoms, since it can be activated only in the liver but not in the skeletal muscles. Bempedoic acid provides an effective tool to further reduce LDL-cholesterol as add on therapy in patients unable to reach the target despite maximally tolerated lipid lowering therapy.

It is therefore impossible to know whether their cancer was caused by their abnormal lipid values or by statin treatment A more accurate appraisal is therefore to relate the number of cancer cases to the achieved blood cholesterol concentration, as in the study by Matsuzaki et al. ([18]). Keywords: cancer; LDL-cholesterol; ox-LDL; lipid-lowering treatment; microorganisms; immune system EN cancer LDL-cholesterol ox-LDL lipid-lowering treatment microorganisms immune system 1 3 3 05/05/22 20220502 NES 220502 Introduction As demonstrated by Deng et al. ([1]), the association between cancer and LDL-cholesterol is an utterly complicated issue. Cancer, LDL-cholesterol, ox-LDL, lipid-lowering treatment, microorganisms, immune system. [Extracted from the article]

In Italy, the clinical and genetic characteristics of familial hypercholesterolemia (FH) have been extensively assessed in various lipid clinics, although no studies on long-term cardiovascular outcomes in heterozygous patients (He-FH) have been conducted. This study evaluated the incidence of atherosclerotic cardiovascular disease (ASCVD) in He-FH before and after a long-term period of lipid-lowering treatments to ascertain the interference of other risk factors. A total of 294 genetically characterised He-FH subjects from 1989 to 2019 were retrospectively analysed. General characteristics, lipid profiles, ASCVD prevalence, and ultrasound carotid atherosclerosis assessment were evaluated. Primary end points were ASCVD outcomes and the percentage of patients reaching recommended LDL-C targets. During follow-up, despite a significant improvement in plasma lipid profiles, the ESC/EAS 2016 and 2019 recommended LDL cholesterol (LDL-C) goals were attained in only a few patients treated with anti-PCSK9 monoclonal antibodies added to the maximum tolerated oral therapy with statins plus ezetimibe. Forty-seven subjects had an ASCVD event before starting lipid-lowering therapy (LLT). During follow-up (median 13 years) on LLT, 28 patients had a first ASCVD event and 16 had recurrent ASCVD. In basal conditions and during follow-up, higher LDL-C levels were associated with increased ASCVD risk (p < 0.001). Prevention of recurrent ASCVD events was recorded with a long-term reduction of LDL-C below 100 mg/dl with statins plus ezetimibe. PCSK9 inhibition is the only therapeutic option to achieve LDL-C goals as recommended for He-FH and can prevent ASCVD events as reported in large clinical trials. Long-term treatment with statins and ezetimibe seems to be effective at preventing ASCVD recurrence when LDL-C is maintained below 130 and 100 mg/dL for primary and secondary prevention, respectively. Image 1 • An early diagnosis is advisable to ensure the best LLT in subjects affected by HE-FH and reduces LDL-C burden on vessels. • Reaching lipid targets can reduce ASCVD risk, but if impossible, an early, lasting and lower LDL-C reduction is useful. • PCSK9 inhibitors allow to reach therapeutic targets more easily, but early oral LLT may reduce the onset of ASCVD. • HE-FH patients carrying LDL receptor variants without residual activity had higher ASCVD risk and need a more intense LLT. [ABSTRACT FROM AUTHOR]

Copyright of Der Kardiologe 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.)

The guidelines for the treatment of dyslipidemias include the use of nutraceuticals (NUTs) in association with lifestyle modifications to achieve therapeutic goals. In NUT pill, different substances may be associated; in this study we investigated a combined NUT containing monacolin K (MonK)+KA (1:1), berberine (BBR), and silymarin. The aim of the study was to evaluate low-density lipoprotein cholesterol (LDL-C) reduction in 53 patients suffering from polygenic hypercholesterolemia, characterized by a low/intermediate cardiovascular risk calculated with SCORE algorithm. The effects on lipid profile of 2-month treatment with NUT containing MonK+KA (1:1), BBR, and sylimarin, were compared with Atorvastatin (ATO) 10 mg administrated in a matched control group. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the cholesterol loading capacity (CLC) were determined at baseline and at the end of the study in NUT-treated group; variations were assessed. NUT was effective as lipid-lowering agent with a wide interindividual response variability (mean LDL-C from 170.8 ± 19.9 to 123.8 ± 20.0 with a change of −47.0 ± 21.5 mg/dL; P < .001) and the effect was similar to that induced by ATO. The use of NUT significantly modified PCSK9 levels (P < .01) and CLC (P < .001), ultimately suppressing the serum-mediated foam cell generation directly measured on human macrophages. NUT reduces LDL-C levels with an effect similar to what is induced by 10 mg of ATO and ex vivo improves the functional profile of lipoproteins with antiatherogenic action. [ABSTRACT FROM AUTHOR]

Abstract Background and aims The aim of this work was to compared the effect of lipid lowering drugs among familial hypercholesterolemia (FH) subjects with a functional mutation in LDLR (LDLR FH) and FH with the p.(Leu167del) mutation in APOE. Methods We retrospectively selected all adults with the p.(Leu167del) mutation on lipid-lowering treatment (n = 22) attending the Lipid Unit at the Hospital Miguel Servet. Age and sex matched LDLR FH from the same Unit were randomly selected as a control group (n = 44). Results The mean percentage reduction in LDLc was significantly higher in the p.(Leu167del) carriers (−52.1%) than in the LDLR FH (−39.7%) (p = 0.040) when on high intensity statins. Similar differences between groups were observed in non-HDLc −49.4% and −36.4%, respectively (p = 0.030). Conclusions Subjects with p.(Leu167del) mutation have a higher lipid-lowering response to statins with or without ezetimibe than LDLR FH. This supports the use of genetics for a more efficient management of FH. Highlights • The p.(Leu167del) mutation in APOE has been described as a new cause of familial hypercholesterolemia (FH). • The p.(Leu167del) carriers were on significantly lower dose of statin than LDLR FH. • The p.(Leu167del) carriers had higher lipid-lowering effect to statins than LDLR FH. • Our results support the use of genetics for a more efficient management of FH. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of potent lipid-lowering drugs. Oxidized low-density lipoprotein (ox-LDL) is the key pathogenic factor leading to atherosclerosis. However, its effect on ox-LDL levels has not been clinically reported. The clinical data of 290 very high-risk atherosclerotic cardiovascular disease (ASCVD) patients diagnosed in the First Affiliated Hospital of Zhengzhou University from May 2022 to October 2022 were collected retrospectively. According to whether evolocumab (a PCSK9 inhibitor) was used after percutaneous coronary intervention (PCI), they were divided into evolocumab group (153 cases) and statin monotherapy group (137 cases). At hospital admission, ox-LDL, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteinA1 (apoA1), apolipoprotein B-100 (apoB), lipoprotein (a) [Lp(a)], and high-sensitivity reactive protein (hs-CRP) levels were collected and used as baseline data. After two weeks of treatment, ox-LDL in the evolocumab group and statin monotherapy group were significantly lower than those before treatment ( p <0.05). The decrease of ox-LDL in the evolocumab group was more than in the stain monotherapy group ( p <0.05). In conclusion, PCSK9 inhibitors reduce ox-LDL levels in very high-risk ASCVD patients in a short time., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2023 JCBN.)

Objective: Despite current standard of care, the overall lipid goal attainment rate for hyperlipidemia patients, especially those who have experienced acute coronary syndrome (ACS), is suboptimal, which predisposes them to a higher residual risk of atherothrombotic events. This study aimed to describe characteristics of Chinese patients who recently experienced an ACS event and were on lipid-lowering treatment, yet failing to reach targeted goal.Methods: A multicenter, cross-sectional study was conducted to recruit 2,034 Chinese patients who experienced an ACS (ST segment elevation myocardial infarction [STEMI], non-STEMI, or unstable angina) event within the past 4-40 weeks and were on statin treatment (>2 weeks) from March 2015 to December 2016. All eligible patients underwent a fasting lipid test after enrollment and data on medical history were collected.Results: The mean age of 1,994 eligible patients was 61.0±9.84 years. Among them, 1,493 (74.9%) patients received intensive statin therapy (defined as atorvastatin 40 or 80 mg, or rosuvastatin 20 mg per protocol) and 499 (25.0%) patients were on maximum tolerated dose statin. Of the 1,994 eligible subjects, 1,273 (63.8%) patients did not achieve the lipid goal at the time of enrollment. Among the not-at-goal patients, 910 (71.5%) received intensive statin therapy; the majority (73.4%) of them were male; the mean age was 61.2±10.1 years old; 699 (54.9%) patients had a history of hypertension; 25.3% had diabetes mellitus; and 29.5% were current smokers. The mean low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and ApoB levels at enrollment of this group of patients were 2.460±0.7139 mmol/L, 3.094±0.8861 mmol/L, and 0.840±0.3015 g/L, respectively.Conclusion: The study result demonstrates that overall more than half of the patients who recently (4-40 weeks) experienced ACS who were treated did not reach the guideline-recommended LDL-C and non-HDL-C goal. These results highlight the potential necessity for a new drug beyond statins to further reduce disease burden in the future. [ABSTRACT FROM AUTHOR]

Stroke is associated with a heavy burden of mortality and disability, underscoring the importance of effective primary and secondary prevention measures. Dyslipidemia as a risk factor for ischemic stroke has long been disputed. Nevertheless, accumulating epidemiological evidence supports a role of lipid abnormalities in increasing ischemic stroke risk and representing a potential target for therapeutic interventions. 3-hydroxy-3-methyl-glutaryl-(HMG-) CoA reductase inhibitors (i.e., statins) are currently the mainstay of therapy for the management of hypercholesterolemia in patients with cardiovascular disease and stroke. Although their beneficial effects on stroke risk have been attributed chiefly to their lipid-lowering capacity, they also have pleiotropic effects. Other lipid lowering modalities have been shown to reduce the risk of ischemic stroke in individuals at high cardiovascular risk, but data regarding their use in secondary stroke prevention are lacking. [ABSTRACT FROM AUTHOR]

The paper considers the problem of lipid-lowering therapy for chronic kidney disease, by using different groups of drugs, the expediency, efficiency, and safety of the therapy at different disease stages, including end-stage renal failure, and replacement treatments.