European Atherosclerosis Society Research Articles

OPA1 affects lipid metabolism and atherosclerosis progression

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): European Atherosclerosis Society Introduction Mitochondria are involved in cellular metabolism, energy generation, calcium homeostasis, sterol and bile acids (BAs) production. Mitochondria continuously undergo biogenesis, fusion, fission and mitophagy, maintaining a continuous balance between all forms. Purpose On these premises, we test the impact of OPA1, an inner mitochondria membrane fusion protein, on mitochondrial tethering on lipid metabolism in the liver and the atherosclerotic plaque. Methods OPA1HepKO and OPA1 TG on LDLR KO background were fed with a Western-type diet (WTD) respectively for 12 weeks. Inverse calorimetry, GTT, and LipidToleranceTest (LTT) were performed. Paraffin-embedded tissues were used for histological analysis, frozen tissues were used for OMICs analysis. VSMCs were isolated and cultured with VLDL (50 µg/ml). Results While OPA1HepKO mice display altered systemic metabolism with reduced body weight and reduced circulating lipid levels OPA1 overexpression on LDLR KO background showed significantly high cholesterol levels. OPA1 deficiency impair hepatic bile acid conjugation with significant accumulation of primary unconjugated bile acids in the liver. On the contrary OPA1 overexpression leads to a reduction of unconjugated bile acids and higher percentage of conjugated bile acids. OPA1 reduction leads to a reduced atherosclerotic plaque while, on the contrary, its overexpression doesn’t affect atherosclerosis despite an increase in circulating lipid and lipoprotein levels. OPA1 overexpression is therefore promoting plaque stabilization with VSMCs that are less prone to change their metabolism to synthetic. Conclusion Hepatic Opa1 deficiency alters bile acids production and therefore circulating lipid profile with a consequent reduction in atherosclerotic plaque formation. OPA1 overexpression in the aorta affects plaque stability despite the highest levels of circulating lipids.

Cardiovascular outcomes in patients with homozygous familial hypercholesterolaemia on lipoprotein apheresis initiated during childhood: long-term follow-up of an international cohort from two registries

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by extremely high plasma LDL cholesterol from birth, causing atherosclerotic cardiovascular disease at a young age. Lipoprotein apheresis in combination with lipid-lowering drugs effectively reduce LDL cholesterol, but long-term health outcomes of such treatment are unknown. We aimed to investigate the long-term cardiovascular outcomes associated with lipoprotein apheresis initiated in childhood or adolescence. In this cohort study, data were drawn from the HoFH International Clinical Collaboration (HICC) and the international registry for Children with Homozygous Hypercholesterolemia on Lipoprotein Apheresis (CHAIN). An overall cohort included patients diagnosed with HoFH aged 0-18 years who were alive and in follow-up between Jan 1, 2010, and Nov 8, 2021, and whose high plasma LDL cholesterol concentrations made them eligible for lipoprotein apheresis. To compare cardiovascular outcomes, patients who initiated lipoprotein apheresis in childhood (lipoprotein apheresis group) and patients who only received lipid-lowering drugs (pharmacotherapy-only group) were matched by sex and untreated plasma LDL cholesterol concentrations. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischaemic stroke, percutaneous coronary intervention, coronary artery bypass grafting, aortic valve replacement, peripheral artery disease, carotid endarterectomy, angina pectoris, and supra-aortic or aortic stenosis (collectively referred to as atherosclerotic cardiovascular disease), for which survival analyses were performed in the matched cohort. Cox regression analyses were used to compare disease-free survival between cohorts and to calculate hazard ratio (HR) and 95% CI adjusted for sex, age at diagnosis, untreated plasma LDL cholesterol concentration, and number of lipid-lowering therapies other than lipoprotein apheresis. The overall cohort included 404 patients with a median age at diagnosis of 6·0 years (IQR 3·0-9·5) and median untreated plasma LDL cholesterol of 17·8 mmol/L (14·7-20·8). The matched cohorts included 250 patients (125 patients per group), with a median untreated LDL cholesterol of 17·2 mmol/L (14·8-19·7). Mean reduction in plasma LDL cholesterol concentrations between baseline and final follow-up was greater in the lipoprotein apheresis group (-55% [95% CI -60 to -51] vs -31% [-36 to -25]; p<0·0001). Patients in the lipoprotein apheresis group had longer atherosclerotic cardiovascular disease-free survival (adjusted HR 0·52 [95% CI 0·32-0·85]) and longer cardiovascular death-free survival (0·0301 [0·0021-0·4295]). Cardiovascular death was more common in the pharmacotherapy-only group than in the lipoprotein apheresis group (ten [8%] vs one [1%]; p=0·010), whereas median age at coronary artery bypass grafting was lower in the lipoprotein apheresis group than in the pharmacotherapy-only group (15·0 years [IQR 12·0-24·0] vs 30·5 years [19·0-33·8]; p=0·037). Among patients with HoFH, lipoprotein apheresis initiated during childhood and adolescence is associated with reduced long-term risk of atherosclerotic cardiovascular disease and death, and clear benefits of early initiation of high-frequency treatment on reducing plasma cholesterol were found. Consensus recommendations are now needed to guide more widespread and timely use of lipoprotein apheresis for children with HoFH, and research is required to further optimise treatment and ensure benefits of early and aggressive treatment delivery are balanced against effects on quality of life. Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; European Atherosclerosis Society; and the US National Heart, Lung, and Blood Institute, National Institutes of Health.

It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States.

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.

Simplified Criteria for Identification of Familial Hypercholesterolemia in Children: Application in Real Life.

The diagnosis of familial hypercholesterolemia (FH) in children is primarily based on main criteria including low-density lipoprotein cholesterol (LDL-C) levels, increased in the proband and relatives, and its inheritance. Two other relevant parameters are symptoms, rarely occurring in children, as rare are the FH homozygous patients, and the mutation detection of related genes. The latter allows the final diagnosis, although it is not commonly available. Moreover, the application of diagnostic scores, useful in adults, is poorly applied in children. The aim of this study was to compare the reliability of criteria here applied with different scores, apart from genetic analysis, for FH diagnosis. The latter was then confirmed by genetic analysis. n. 180 hypercholesterolemic children (age 10.2 ± 4.6 years) showing LDL-C levels ≥95th percentile (age- and sex-related), the dominant inheritance pattern of hypercholesterolemia (including LDL-C ≥95th percentile in one parent), were considered potentially affected by FH and included in the study. The molecular analysis of the LDLR, APOB and PCSK9 genes was applied to verify the diagnostic accuracy. Biochemical and family history data were also retrospectively categorized according to European Atherosclerosis Society (EAS), Simon Broome Register (SBR), Pediatric group of the Italian LIPIGEN (LIPIGEN-FH-PED) and Dutch Lipid Clinic Network (DLCN) criteria. Detailed kindred biochemical and clinical assessments were extended to three generations. The lipid profile was detected by standard laboratory kits, and gene analysis was performed by traditional sequencing or Next-Generation Sequencing (NGS). Among 180 hypercholesterolemic subjects, FH suspected based on the above criteria, 164/180 had the diagnosis confirmed, showing causative mutations. The mutation detection rate (MDR) was 91.1%. The scoring criteria proposed by the EAS, SBR and LIPIGEN-FH-PED (resulting in high probable, possible-defined and probable-defined, respectively) showed high sensitivity (~90%), low specificity (~6%) and high MDR (~91%). It is noteworthy that their application, as a discriminant for the execution of the molecular investigation, would lead to a loss of 9.1%, 9.8% and 9.1%, respectively, of FH-affected patients, as confirmed by the genetic analysis. DLCN criteria, for which LDL-C cut-offs are not specific for childhood, would lead to a loss of 53% of patients with mutations. In the pediatric population, the combination of LDL-C ≥95th percentile in the proband and the dominant inheritance pattern of hypercholesterolemia, with LDL-C ≥95th percentile in one parent, is a simple, useful and effective diagnostic criterion, showing high MDR. This pattern is crucial for early FH diagnosis. EAS, SBR and LIPIGEN-FH-PED criteria can underestimate the real number of patients with gene mutations and cannot be considered strictly discriminant for the execution of molecular analysis.

Treatment of pediatric heterozygous familial hypercholesterolemia 7 years after the EAS recommendations: Real-world results from a large French cohort

BackgroundHeterozygous 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. ObjectiveHere, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. MethodsThis 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. ResultsWe 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. ConclusionPediatric 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.

The influence of lipoproteina(a) on cardio-vascular diseases

Introduction&#x0D; The current evidence from 2022 published by European Atherosclerosis Society brings the importance of the level of lipoprotein(a) and its influence on the human health. Especially atherosclerotic cardio-vascular events such as myocardial infarction, heart failure, stroke, atherosclerosis are taken into account. They prove, that the associations between the level of Lp(a) is linear with the occurrence of cardio-vascular events. High level of Lp(a), may contribute to the aortic stenosis, cause has pro-inflammatory and pro-atherosclerotic properties. The newest finding demonstrate that Lp(a) has no link with venous thrombosis. Nonetheless, very low level of may contribute with type 2 diabetes.&#x0D; It is recommended to measure the level of lipoprotein(a) at least once in adults to search the patients with higher value than norm. Even at low level of LDL, high Lp(a) is a risk factor for ASCVD. It brings the clinical importance of early detection of potential cardio-vascular diseases and introduction of management. The newest statement form EAS also brings promising possibilities due to specific Lp(a)-lowering therapies is in phase II/III trials.&#x0D; &#x0D; Aim of the study&#x0D; The following paper aims to present a review of the current knowledge about the influence of the level of Lp(a) on cardio-vascular disease and seeks to enhance knowledge and promote effective management of this prevalent condition.&#x0D; The primary goal is to promote the current problem to health care workers with up-to-date information to facilitate early recognition of cardiovascular events.&#x0D; &#x0D; Materials and methods&#x0D; This article presents the current state of knowledge of lipoprotein(a) found in various scientific articles.&#x0D; The following English keywords and its Polish equivalents were used to search Google Scholar's medical databases: lipoprotein(a), cardio-vascular disease, cardiovascular risk, aortic stenosis. The articles most pertinent to the subject have been chosen.

Retrospective Evaluation of LDL-C Levels Following First Treatment With Inclisiran as Part of Secondary Prevention ASCVD Risk Reduction in a Real-World Primary Care Setting

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide. There is a direct relationship between increasing levels of LDL-C and increased risk of ASCVD. Guidance from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) recommends that high-risk ASCVD patients maintain an LDL-C &lt;1.8 mmol/L (70 mg/dL) and very high-risk patients &lt;1.4 mmol/L (55 mg/dL). National data in England reveals that 71% of high-risk secondary prevention patients have an LDL-C &gt;1.8 mmol/L (70 mg/dL). Methodology: An ASCVD risk reduction approach was initiated in a primary care clinic in December 2021. Of those patients who underwent review between December 2021 and July 2023, 102 patients were started on inclisiran treatment in a real-world setting. These patients were retrospectively reviewed to determine the initial effects of using inclisiran after the first dose as part of the patients’ ASCVD risk reduction management. Results: After 1 injection of Inclisiran, the patients’ mean decrease in LDL-C was 2.00 mmol/L (77.3 mg/dL) after a mean of 87 days. This represented a mean reduction of 61.7% (SD = 19.8) in their LDL-C measurements. The addition of inclisiran resulted in 79.4% of patients achieving an LDL-C target of &lt;1.8 mmol/L (70 mg/dL) and 65.7% of patients attaining an LDL-C of &lt;1.4 mmol/L (55 mg/dL). Conclusion: Healthcare providers working in primary care can achieve recommended LDL-C targets in 4 out of 5 secondary prevention patients after an initial dose of inclisiran as part of their ASCVD risk reduction approach management.

Treatment of pediatric heterozygous familial hypercholesterolemia: Where do we stand in real-world study in France seven years after the recommendations of the european atherosclerosis society (EAS)?

Treatment of pediatric heterozygous familial hypercholesterolemia: Where do we stand in real-world study in France seven years after the recommendations of the european atherosclerosis society (EAS)?

Reporting LDL cholesterol results by clinical biochemistry laboratories in Czechia and Slovakia to improve the detection rate of familial hypercholesterolemia.

This survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations. The web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults. A total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a). Only a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.

Concordance of a High Lipoprotein(a) Concentration Among Relatives

Lipoprotein(a) (Lp[a]) concentrations are a highly heritable and potential causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent consensus statements by the European Atherosclerosis Society and American Heart Association recommend screening of relatives of individuals with high Lp(a) concentrations, but the expected yield of this approach has not been quantified in large populations. To measure the prevalence of high Lp(a) concentrations among first- and second-degree relatives of individuals with high Lp(a) concentrations compared with unrelated participants. In this cross-sectional analysis, pairs of first-degree (n = 19 899) and second-degree (n = 9715) relatives with measured Lp(a) levels from the UK Biobank study and random pairs of unrelated individuals (n = 184 764) were compared. Data for this study were collected from March 2006 to August 2010 and analyzed from December 2021 to August 2023. Serum Lp(a) levels, with a high Lp(a) level defined as at least 125 nmol/L. Concordance of clinically relevant high Lp(a) levels in first- and second-degree relatives of index participants with high Lp(a) levels. A total of 52 418 participants were included in the analysis (mean [SD] age, 57.3 [8.0] years; 29 825 [56.9%] women). Levels of Lp(a) were correlated among pairs of first-degree (Spearman ρ = 0.45; P < .001) and second-degree (Spearman ρ = 0.22; P < .001) relatives. A total of 1607 of 3420 (47.0% [95% CI, 45.3%-48.7%]) first-degree and 514 of 1614 (31.8% [95% CI, 29.6%-34.2%]) second-degree relatives of index participants with high Lp(a) levels also had elevated concentrations compared with 4974 of 30 258 (16.4% [95% CI, 16.0%-16.9%]) pairs of unrelated individuals. The concordance in high Lp(a) levels was generally consistent among subgroups (eg, those with prior ASCVD, postmenopausal women, and statin users). The odds ratios for relatives to have high Lp(a) levels if their index relative had a high Lp(a) level compared with those whose index relatives did not have high Lp(a) levels were 7.4 (95% CI, 6.8-8.1) for first-degree relatives and 3.0 (95% CI, 2.7-3.4) for second-degree relatives. The findings of this cross-sectional study suggest that the yield of cascade screening of first-degree relatives of individuals with high Lp(a) levels is over 40%. These findings support recent recommendations to use this approach to identify additional individuals at ASCVD risk based on Lp(a) concentrations.

European guidelines for the treatment of dyslipidaemias: New concepts and future challenges

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity worldwide. Low-density lipoprotein cholesterol (LDL-C) is one of the most important causal factors for ASCVD. Based on the evidence of the clinical benefits of lowering LDL-C, the current 2019 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines provide guidance for optimal management of people with dyslipidaemia. These guidelines include new and revised concepts, with a general tightening of LDL-C goals to be achieved, especially for patients at high and very high cardiovascular risk, based on the results of clinical trials of the recently approved drugs for the treatment of hypercholesterolaemia. However, some issues are still open for discussion. Among others, the concept of lifetime exposure to elevated LDL-C levels will probably drive the pharmacological approach and future guidelines. In addition, other factors such as non-HDL-C, apolipoprotein B, and lipoprotein(a) are becoming increasingly important in determining cardiovascular risk. Finally, there is the question of whether combination therapy should be used as the first step to maximise the effectiveness of the pharmacological approach, avoiding the stepwise approach, which is likely to have a detrimental effect on adherence. Given the ever-changing landscape and the availability of new drugs targeting other important lipids, future guidelines will need to consider all these issues.

Long-term safety and effectiveness of alirocumab and evolocumab in familial hypercholesterolemia (FH) in Belgium

Background: In 2019, the European Atherosclerosis Society (EAS) published updated guidelines, recommending even lower blood cholesterol targets than previously. In patients with familial hypercholesterolaemia (FH), who have very elevated blood cholesterol levels and are at (‘Very’) ‘High risk’ of atherosclerotic cardiovascular disease (ASCVD), this represents a real challenge. Anti-Proprotein convertase subtilisin/kexin type 9 monoclonal antibody (anti-PCSK9 mAb) has been commercially available for FH in Belgium since 2015. Our study aims to investigate the real-life efficacy of anti-PCSK9 mAb in FH patients. Method: We sourced patients from the EAS FH Studies Collaboration database (an international database on FH in which Belgium participates). We only retained patients using anti-PCSK9 mAb and followed at our Lipid Clinic. Results: Of the 239 subjects included in this study (mean age: 56 years), 85% were considered at ‘Very High Risk’ (56% with a history of ASCVD), the remaining 15% were at ‘High Risk’. The PCSK9 mAb treatment reduced LDL-C levels by 54% within the first year. This reduction was maintained over the follow-up (FU) period (3.0 ± 1.8 years). The EAS targets were reached in 50% of the subjects, 93% of whom were also treated with statins. The treatment was very well tolerated. At the end of the observation period, 96% patients continued receiving PCSK9 mAb. Conclusions: Anti-PCSK9 mAb are a safe and effective therapeutic option for lowering LDL-C levels in FH patients. It allowed a significant portion of our FH patients to reach their lipid targets, mainly in those with combined therapy with statin and/or ezetimibe.

Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in type 1 diabetes and type 2 diabetes: Lipid goal attainment in a large German-Austrian diabetes registry.

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. 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. 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. 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.

Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension?

Elevated plasma lipoprotein(a) [Lp(a)] is a relatively common and highly heritable trait conferring individuals time-dependent risk of developing atherosclerotic cardiovascular disease (CVD). Following its first description, Lp(a) triggered enormous scientific interest in the late 1980s, subsequently dampened in the mid-1990s by controversial findings of some prospective studies. It was only in the last decade that a large body of evidence has provided strong arguments for a causal and independent association between elevated Lp(a) levels and CVD, causing renewed interest in this lipoprotein as an emerging risk factor with a likely contribution to cardiovascular residual risk. Accordingly, the 2022 consensus statement of the European Atherosclerosis Society has suggested inclusion of Lp(a) measurement in global risk estimation. The development of highly effective Lp(a)-lowering drugs (e.g., antisense oligonucleotides and small interfering RNA, both blocking LPA gene expression) which are still under assessment in phase 3 trials, will provide a unique opportunity to reduce "residual cardiovascular risk" in high-risk populations, including patients with arterial hypertension. The current evidence in support of a specific role of Lp(a) in hypertension is somehow controversial and this narrative review aims to overview the general mechanisms relating Lp(a) to blood pressure regulation and hypertension-related cardiovascular and renal damage.

Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society.

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women.

Clinical Approach in the Management of Paediatric Patients with Familial Hypercholesterolemia: A National Survey Conducted by the LIPIGEN Paediatric Group.

Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3-4 months (29.2% and 23.3%) or 6-12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.

Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study.

The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study. Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed. In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) (n=962), 27.0% (n=259) and 57.0% (n=548) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD (n=74), 88.1% (n=65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD (n=1520), 12.0% (n=183), 42.1% (n=641) and 93.2% (n=1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively. Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk. Amgen.

Exploring the implemented guidelines for dyslipidemia treatment and care among nurses and physicians in jordanian hospitals

Abstract Funding Acknowledgements Type of funding sources: None. Background Dyslipidemia is a major risk factor for ischemic heart disease in the world. The last updated American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/ European Atherosclerosis Society (ESC/EAS) guidelines for dyslipidemia management aimed to control blood cholesterol and reduce cardiovascular risk. In Jordan, no national guidelines have been published to date, so these guidelines are commonly used. There are a few studies exploring the implementation of these guidelines in Jordan. Purpose To explore the implementation of updated ACC/AHA and ESC/EAS guidelines for the treatment and care of dyslipidemia among nurses and physicians in Jordan. Methods: A mixed-method study was utilized with a convenience sample from three hospitals in Jordan to provide a comprehensive understanding for the investigated concepts in the current study. The quantitative part, the researcher developed a questionnaire. A questionnaire was completed by 150 nurses and 50 physicians, and moreover, 250 patients' medical records were reviewed. The qualitative part, three focus group with open-ended questions was conducted. Results The total mean scores to implement the guidelines among nurses were (1.67, 1.6 out of 4) for ACC/AHA and ESC/EAS guidelines respectively. The percentages for implementing dyslipidemia management guidelines among physicians were 22.6% consistent with ACC/AHA and 29.6% with ESC/EAS. There were high percentages of uncontrolled lipids among patients with dyslipidemia as observed in medical records. Focus group interviews revealed many barriers, like workload and limited resources and many suggestions to implement dyslipidemia management guidelines. Conclusion Results indicated limited implementation of any dyslipidemia management guidelines among Jordanian nurses and physicians in their clinical practices.

CORRELATION OF LIPOPROTEIN(a) AND CORONARY ARTERY DISEASES

&lt;div&gt;&lt;p&gt;&lt;strong&gt;INTRODUCTION:&lt;/strong&gt; Cardiovascular diseases (CVD) continue to be one of the leading causes of mortality worldwide. While factors such as diabetes, sedentariness, psychostress, genetic predisposition, hypertension, smoking, and hyperlipidemia are well-known in the etiology of atherosclerosis (Ath) of coronary arteries. Recent studies have also identified high concentrations of lipoproteins (a) [Lp(a)] as a risk factor. In fact, high concentrations of Lp(a) above 30mg/dl (reference value-30mg/dl) have been found to be a risk factor for Ath, leading experts to develop medications aimed at reducing Lp(a) concentrations and preventing atherosclerotic manifestations. &lt;a href="https://eas-society.org/"&gt;&lt;em&gt;The European Atherosclerosis Society&lt;/em&gt;&lt;/a&gt; has also released clinical guidelines for testing and treating high concentrations of Lp(a) as part of the global assessment of cardiovascular risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;THE GOAL OF THE STUDY:&lt;/strong&gt; The goal of this study is to investigate the concentration of Lp(a) in patients with coronary disease and its connection to the presentation of atherosclerosis of the coronary arteries in patients with CVD compared to a control group of healthy individuals. Through this study, we hope to gain a better understanding of the role of Lp(a) in CVD and its potential as a target for prevention and treatment. By identifying and addressing risk factors like high Lp(a) concentrations, we can work towards reducing the global burden of CVD and improving health outcomes for individuals around the world.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;THE AIM OF THE STUDY:&lt;/strong&gt; The aim of this study is to determine the concentration of lipoprotein(a) in patients with coronary disease, its connectivity and role in the presentation of atherosclerosis of the coronary arteries in patients with CVD compared to the control group of healthy individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;MATERIAL AND METHODS:&lt;/strong&gt; As working material, the blood taken from the vein of patients with coronary disease was used - N0=80, (with an identical average age of 55.70±6.00 years old, of which 35 were female while 45 were male. In the study, there was also a control group: N0=80 healthy volunteers (45 were male and 35 female) with the same age as the patients. Blood for analysis was taken at 8 o'clock in the morning, at room temperature of 19-24°C, every three months in a period of 12 months.&lt;/p&gt;&lt;p&gt;Echocardiography and EKG were also performed on all the patients with Toshiba SSH-140A machine, color Doppler probe 3.7Hz, sectorial type, taking into account as key parameters the thickness of the back wall of the left ventricle and the thickness of-Left ventricular internal diameter end diastole (LVPVd) and interventricular septal end diastole (IVSd&amp;gt;12 mm). Together with the examination of Lp(a) concentrations, the lipid profile was also analyzed. The analyzes were done at the Clinical Laboratory Institute at the University Clinical Center of the Faculty of Medicine – Skopje, North Macedonia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;STATISTICAL PROCESSING OF THE MATERIAL:&lt;/strong&gt; From the statistical methods, arithmetic mean value, standard deviation X±SD were used. The comparative statistics of the lipid parameters between the analyzed groups were analyzed with students ‘t’ dependent and independent samples according to the Mann-Whitney U-test and Wilcoxon - test. The results of the lipid fractions will be shown tabularly (see table 3) with the statistical program SPSS V26.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;RESULTS:&lt;/strong&gt; The obtained values of lipids (Col.Total, TG, HDL-ch, LDL-ch) and lipoprotein (a) in both groups are presented with mean values and standard deviation X-SD. Due to the fact that in the obtained results of Lp(a) in both sexes, in patients with coronary disease, we did not notice any significant difference, we will present them as common for both groups, with CVD with maximum values of 78.00-16,00 mg/dl while in the control group =15.20-4.30 mg/dl, with a statistically significant difference with p&amp;lt;0.000. The same difference was found from the obtained results of lipid concentrations between the two groups with p &amp;lt;0.0001 (as presented in the tables below).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;CONCLUSION:&lt;/strong&gt; The results obtained in the paper proved that high concentrations of Lp(a) &amp;gt; 30 mg/dl are risk factors for the occurrence of Ath of the coronary arteries and that these patients are at a 5-8 times higher risk for the development of Ath of coronary arteries, compared to individuals with normal Lp(a) values, therefore the treatment of high concentrations of Lp(a) should be started at the beginning of their appearance. In conclusion, we can suggest that the adequate treatment of high Lp(a) concentrations and the balancing of the lipid profile can apparently affect the prevention of atherosclerotic processes of the coronary arteries, therefore we prefer that in individuals with a history of CAD and those with coronary disease, the examination of Lp(a) and lipid profile should be one of the initial examinations during the management of patients with CAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Keywords: &lt;/strong&gt;Lipoprotein (a), atherosclerosis, Cardiovascular Arterial Diseases (CAD), lipid profile.&lt;/p&gt;&lt;/div&gt;

Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database

Background and aimsFamilial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets. MethodsWe performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH. ResultsProbable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18–29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels. ConclusionsThis nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients.