Primary Dyslipidemia Research Articles

Effects of lipid-lowering therapies on lipoprotein(a) levels in patients with dyslipidemia: a systematic review and network meta-analysis of 64 randomised controlled trials

Abstract Background Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease. However, there has yet to be a drug approved specifically for lowering Lp(a). There is paucity of studies evaluating the use of current lipid-lowering agents, and their effects, if any, on Lp(a). Purpose We aimed to identify and compare the effects of lipid-lowering therapies on Lp(a) levels, cardiovascular and safety outcomes, in patients with dyslipidemia. Methods A systematic search was performed across four databases (PubMed, Embase, Scopus, Cochrane) for randomised controlled trials (RCTs) published from inception to 3 January 2023. The percentage change of serum Lp(a) levels, cardiovascular and safety outcomes were compared among statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin), fibrates, ezetimibe, niacin, PCSK9 inhibitors (alirocumab, evolocumab, bococizumab) and inclisiran, in patients with primary dyslipidemia. Frequentist network meta-analysis was performed to compare the treatment effects among different drug classes, stratified by use of background statin therapy. Results A total of 64 RCTs were included, comprising 55,256 patients. In patients on background statin therapy, PCSK9 inhibitors significantly lowered Lp(a) levels, compared with placebo (mean difference [MD] -26.8, 95% confidence intervals [95%CI] -30.8 to -22.7), ezetimibe (MD -21.6, 95%CI -31.4 to -11.8), fibrates (MD -19.4, 95%CI -37.4 to -1.5), and niacin (MD -13.8, 95%CI -25.6 to -2.1). PCSK9 inhibitors were associated with lower risk of major adverse cardiovascular events and similar risk of treatment-related adverse events than placebo. Comparing the PCSK9 inhibitors, evolocumab achieved greater Lp(a)-lowering than alirocumab in patients on background statin therapy (MD -11.4, 95%CI -18.6 to -4.1), including those with heterozygous familial hypercholesterolemia. Niacin also achieved 12.9% (95%CI 1.8 to 24.0) reduction in Lp(a) compared with placebo, but had a higher risk of treatment-related adverse effects than fibrates. Statin monotherapy did not affect Lp(a) levels, regardless of type or intensity of statin therapy. Ezetimibe and fibrate had no effect on Lp(a) levels. Conclusions PCSK9 inhibitors produced the greatest effect on Lp(a) levels, compared with other lipid-lowering therapies. Further studies into PCSK9 inhibitors are necessary to characterise their efficacy and safety specifically for Lp(a)-lowering, and elucidate the impact of Lp(a) reduction on cardiovascular risk.% change in Lp(a) levels

Feasibility study to boost ascertainment of FH in diverse primary care populations using FAMCAT tool and pharmacist review

Abstract Background Familial Hypercholesterolaemia (FH) is a greatly underdiagnosed genetic lipid disorder with high risk of morbidity from premature cardiovascular disease. However, early diagnosis can significantly reduce cardiovascular risk with lipid-lowering medicines. Patients identified with high risk primary dyslipidaemia are recommended for lipid clinic referral to inform patient management. Improving FH identification and addressing ethnic disparities in dyslipidaemia management, is a current NHS priority in the UK. Aim We aimed to explore inequalities in the FH care pathway within and across areas with different socio-demographic UK populations. Methods The study was carried out in 6 general practices in the South East of England with divergent ethnic densities and socioeconomic status. Eligible patients aged 18 years or over, fulfilling the NICE (1), Simon-Broome (2) and current NHS Directed Enhanced Service criteria (3) for possible FH were screened using our previously validated PRIMIS FAMCAT2 tool (4) to prioritise those most likely to have FH. The PRIMIS FAMCAT2 tool generated a report highlighting patients with a "High Risk" of FH Tier 1 and a "Higher Risk if family history is positive" of FH- Tier 2. Tier 1 patients were assessed for FH using local lipid pathways. For the 243 Tier 2 patients, an online family history questionnaire/telephone enquiry was administered. The accuracy of the information collected was assessed by a practice-based clinical pharmacist (overseen by the GP). This included repeat testing for full lipid profile, excluding secondary causes of raised cholesterol. New patients meeting the criteria for FH were referred to a lipid/specialist clinic to assess for genetic testing. Patients who did not meet the FH criteria were managed accordingly to the local lipid pathways. Results 131,930 records from 6 general practices in South East England were screened using the PRIMIS FAMCAT tool. In total, the high priority list yielded 369 patients (126 Tier 1 and 243 Tier 2). Ethnicity breakdown was White (40%), Asian (8%), Black African/Caribbean (22%), Mixed (14%), Other (16%) NS (1%). A total of 25/369 (7%) patients were previously referred to lipid clinics (4 underwent genetic testing, 2 had confirmed FH, 12 did not have FH, and 7 were not seen/missed appointments). There were 14/244 (4%) new referrals to lipid clinics. Only 1 patient had received a coded FH diagnosis in the primary care record. For Tier 2 patients, 65/243 (27%) patients completed an online family history questionnaire, the remainder were ascertained by phone (75% response rate overall). Conclusion Incorporating enhanced case-finding from electronic medical records based on current guidelines, and online family history questionnaire can enhance FH identification. However large inequalities remain in referral, attendance and testing at lipid clinics, and further work is underway to evaluate the FH care pathway in diverse populations.

A UK multicentre audit of the management of patients with primary hypercholesterolaemia or mixed dyslipidaemia with bempedoic acid against published lipid-lowering treatment targets.

Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC) <5 mmol/L and low-density lipoprotein cholesterol (LDL-C) <3 mmol/L or ≥25% reduction in TC and ≥30% reduction in LDL-C) at 12 weeks post-initiation. At week 12, the mean absolute change in LDL-C was -1.0 mmol/L; the mean percentage reduction from baseline was 22.0%. Additionally, 52% (96/185) of patients had an LDL-C of <3 mmol/L and 10% (18/185) an LDL-C of <1.8 mmol/L at 12 weeks (as per JBS3). This audit highlights the role of bempedoic acid as part of combination therapy for a population with previously limited treatment options.

PCSK9 inhibition: from effectiveness to cost-effectiveness.

Dyslipidaemia is a complex disorder characterised by abnormal lipid levels in the blood, including cholesterol and triglycerides, and plays an important role in the development of atherosclerotic cardiovascular disease. Most risk factors for cardiovascular disease are modifiable, and dyslipidaemia is a key factor among them. It can result from a combination of genetic and environmental factors. A distinction is made between primary dyslipidaemia, which is mainly caused by inherited genetic changes, and secondary dyslipidaemia, which is due to underlying diseases or certain medications. The treatment of dyslipidaemia has evolved over the years. In the past, statins were the first choice, but newer drugs, such as proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, have gained prominence due to their effectiveness in lowering lipids. Although recent guidelines recommend PCSK9 inhibitors for high-risk patients and patients who cannot tolerate statins, their widespread use is limited because of cost. Several meta-analyses have confirmed the efficacy and safety of PCSK9 inhibitors and have shown a significant reduction in low-density lipoprotein (LDL) cholesterol levels. However, the long-term side effects and interactions with other risk factors for cardiovascular disease remain uncertain. In addition, cost-effectiveness analyses have shown mixed results, with some countries considering PCSK9 inhibitors to be cost-effective for certain patient groups, while others consider them less economical. Meanwhile, initial data from patients using PCSK9 inhibitors support the results of the clinical trials. To summarise, PCSK9 inhibitors represent a revolutionary solution for lowering LDL cholesterol, but their cost-effectiveness remains controversial. Despite the controversy, they offer clear benefits for high-risk patients and should therefore be considered in the treatment of dyslipidaemia.

Evaluation of arterial stiffness in primary atherogenic dyslipidemias

Evaluation of arterial stiffness in primary atherogenic dyslipidemias

Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia.

A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia. A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; P<0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; P<0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups. Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.

Transitional Medicine of Intractable Primary Dyslipidemias in Japan.

Transitional medicine refers to the seamless continuity of medical care for patients with childhood-onset diseases as they grow into adulthood. The transition of care must be seamless in medical treatment as the patients grow and in other medical aids such as subsidies for medical expenses in the health care system. Inappropriate transitional care, either medical or social, directly causes poorer prognosis for many early-onset diseases, including primary dyslipidemia caused by genetic abnormalities. Many primary dyslipidemias are designated as intractable diseases in the Japanese health care system for specific medical aids, as having no curative treatment and requiring enormous treatment costs for lipid management and prevention of complications. However, there are problems in transitional medicine for primary dyslipidemia in Japan. As for the medical treatment system, the diagnosis rate remains low due to the shortage of specialists, their insufficient link with generalists and other field specialists, and poor linkage between pediatricians and physicians for adults. In the medical care system, there is a mismatch of diagnostic criteria of primary dyslipidemias between children and adults for medical care expense subsidization, as between The Program for the Specific Pediatric Chronic Diseases and the Program for Designated Adult Intractable Diseases. This could lead some patients subsidized in their childhood to no longer be under the coverage of the aids after transition. This review intends to describe these issues in transitional medicine of primary dyslipidemia in Japan as a part of the efforts to resolve the problems by the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare of Japan.

Cardioprotective Effects of Aloysia polystachya Essential Oil on a Rat Model with Multiple Cardiovascular Risk Factors.

Traditional medicine is a frequently utilized method to treat cardiovascular disease and its primary risk factors, including hypertension and dyslipidemia. Aloysia polystachya is a species that is commonly employed to treat various pathological conditions, and it has already been identified as having some cardioprotective effects. This study aimed to investigate the protective effects of the essential oil extracted from the leaves of A.polystachya in a rat model that simulates multiple cardiovascular risk factors. We evaluate the acute toxicity, as well as the cardioprotective effects, by giving different doses of A.polystachya essential oil (1.47 mg/kg, 4.40 mg/kg, and 13.20 mg/kg) over a period of 42 days. The control group was treated with rosuvastatin (5 mg/kg). At the end of the treatments, the renal function, electrocardiography, blood pressure, vascular reactivity, serum biochemical profile, and organ histopathology were evaluated. The main compounds identified in the essential oil of A.polystachya using gas chromatography coupled with mass spectrometry were beta-myrcene (1.08%), limonene (40.13%), and carvone (56.47%). The essential oil of A.polystachya not only lacks acute toxicity but also mitigates the reduction in the excretion of sodium, chloride, and creatinine in urine. Furthermore, it reduces electrocardiographic abnormalities and decreases blood pressure levels. Moreover, this treatment prevents an elevation in markers of inflammation and oxidative stress in the bloodstream. Our findings indicate significant cardioprotective effects of the essential oil of A.polystachya against multiple risk factors for cardiovascular diseases in hypertensive rats.

Efficacy and safety of ongericimab given by prefilled syringe or autoinjector in primary hypercholesterolemia and mixed hyperlipidemia

Background and aimsLimited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. Methods and resultsA total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were −72.7% (3.9%) for PFS and −71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. ConclusionIn Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. Clinical trial registrationCTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html.

A Computational Approach on Fenofibrate Drug Using Degree-Based Topological Indices and M-polynomials

Fenofibrate is a drug approved by FDA Food and Drugs Administration used to treat patients with Hypertrigly ceridemia primary hypercholesterolemia or mixed dyslipidemia. It reduces low-density lipoprotein cholesterol (LDL-c), total cholesterol, triglycerides, and apolipoprotein B and increases high -density lipoprotein cholesterol (HDL-C) in adults. The sum and multiplicative versions of several topological indices such as General Zagreb, General Randic, Arithmetic Geometric Index, Inverse sum (Indeg) Index, Symmetric Division (Deg) Index, Forgotten Indices M-polynomials of Fenofibrate are computed in this article.

Genetic epidemiology of monogenic dyslipidemia and statin-associated adverse drug phenotypes in Indian population from whole-genomes of 1029 self-declared healthy individuals

BackgroundMonogenic dyslipidemia is a group of inherited genetic disorders characterized by abnormal levels of lipids and lipoproteins in blood, contributing to a significant risk for coronary artery diseases (CAD) and stroke. There is a paucity of prevalence estimates and genetic epidemiology of monogenic dyslipidemia in South Asian populations. The availability of population-scale genome sequencing datasets could potentially enable a better understanding of the genetic epidemiology of the disease. MethodsWe analyzed whole-genome sequence data of 1029 healthy individuals from India to identify pathogenic variants in 24 genes associated with 26 primary monogenic dyslipidemias. The American College of Medical Genetics and Genomics (ACMG) guidelines was used to classify the variants. We also inferred statin-associated adverse drug phenotypes from SLCO1B1, ABCG2, and CYP2C9 genotypes/haplotypes. ResultsOur analysis identified 12 pathogenic (P) and 9 likely pathogenic (LP) variants in 10 different genes. Autosomal dominant monogenic dyslipidemia prevalence ranged from 0.1% to 0.9%, while autosomal recessive disorder ranged from 0.000005% and 0.0005%. An infrequent ε4/ε4 APOE genotype associated with hypercholesterolemia was found in 1% of samples. Our pharmacogenomic analysis revealed that 10% may require reduced dosage for most statins including atorvastatin, and 1.5% may require reduced dosage for rosuvastatin. ConclusionOur study emphasizes the need for population-scale screening to enable early diagnosis and appropriate treatment of monogenic dyslipidemia in India. By identifying variants and estimating prevalence, our findings can inform healthcare providers in developing targeted prevention and management strategies to reduce cardiovascular disease risk.

Effectiveness and safety of bempedoic acid in routine clinical practice: 1-year follow-up snapshot of the MILOS German cohort

Abstract Background Low-density lipoprotein cholesterol (LDL-C) has an established role in the development of atherosclerotic cardiovascular disease. The 2019 ESC/EAS dyslipidaemia guidelines recommended more intensive treatment goals, however, many patients do not reach them. Bempedoic acid (BA) is a first-in-class ATP citrate lyase inhibitor that lowers LDL-C levels. There is limited data on the use of BA and BA + ezetimibe (EZE) fixed-dose combination (FDC) in clinical practice. Purpose The purpose of this snapshot of 1-year follow-up data from the MILOS study is to evaluate the effectiveness and safety of BA and its FDC in routine clinical practice in Germany. Methods MILOS is a European, prospective, observational, non-interventional study in adult patients with primary hypercholesterolaemia or mixed dyslipidaemia. Patients were recruited from 126 sites in Germany between January 2021 and January 2022, and are followed up for 1–2 years after baseline measurements. Here, we summarise 1-year follow-up data from a snapshot taken on January 13th, 2023. Results Of 992 patients enrolled in Germany, 714 had either completed their 1-year follow-up or discontinued the study prematurely, and 524 of these 714 patients attended their 1-year follow-up visit. For this snapshot, 714 patients are used when determining cardiovascular (CV) outcomes and safety endpoints, and 524 patients are used when reporting efficacy data. The overall mean (SD) age of the population (n=524) was 64.7 (10.0) years, and 60.7% were male. Patients treated with BA/BA+EZE FDC had an overall mean LDL-C level of 2.18 mmol/L (84.1 mg/dL) at 1 year compared with 3.20 mmol/L (123.6 mg/dL) pre-treatment, representing a mean relative LDL-C reduction of 27.3%. Overall, 25.8% (135/524) of patients had reached their LDL-C goal after 1 year of treatment compared with 4.0% (21/524) pre-treatment (Figure 1A and 1B). The overall incidence rate of the composite endpoint of major adverse cardiovascular event (4-component MACE) including CV death, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularisation (n=714) was 3.36%. At 1-year follow-up, 19% (136/714) of patients had an adverse drug reaction (ADR) suspected to be related to BA/BA+EZE FDC, and 0.8% (6/714) had serious ADRs, as deemed by the investigator. Conclusion This snapshot analysis of 1-year follow-up data suggests that the addition of BA to other lipid-lowering therapies increases the proportion of patients at LDL-C goal by ∼6-fold in the observed cohort. The safety and tolerability profile of bempedoic acid are in line with data from randomised controlled trials.

Abstract 11893: Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia

Background: Ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in the phase 2 trial. A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on background lipid-lowering therapy (LLT). Methods: This was a randomized, double-blind, placebo-controlled, 52-week trial conducted in China (NCT02662569). Eligible patients receiving stable statin (±ezetimibe) therapy but not achieving LDL-C goals were enrolled. Patients were randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or placebo subcutaneously every 2 weeks (Q2W), or ongericimab 300 mg or placebo subcutaneously every 4 weeks (Q4W) for 52 weeks. The primary endpoint was percent change in LDL-C from baseline to week 24. Results: A total of 806 patients were randomized, 802 patients received at least one dose of ongericimab or placebo. The least-squares (LS) mean difference between ongericimab and placebo in LDL-C from baseline to week 24 was -67.7% (95% CI: -72.49%, -62.99%; p &lt; 0.0001) in Q2W group and -61.2% (95% CI: -67.09%, -55.21%; p &lt; 0.0001) in Q4W group. LDL-C reductions were maintained to Week 52. Ongericimab also favorably altered other lipid parameters (Table 1). The overall incidence of adverse events was similar between ongericimab and placebo. Conclusion: Ongericimab on stable background LLT significantly reduced LDL-C and was well tolerated in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia.

Tafolecimab: First Approval.

Tafolecimab (SINTBILO®), a subcutaneously administered anti-proprotein convertase subtilisin/kexin type 9 enzyme(PCSK9) monoclonal antibody, is being developed by Innovent for the treatment of hypercholesterolemia and mixed hyperlipidemia. Tafolecimab was approved in August 2023 in China as an adjunct to diet, in combination with a statin or statin with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, for the treatment of adults with primary hyperlipidemia [including heterozygous familial hypercholesterolemia (HeFH) and non-familial hypercholesterolemia (non-FH)] and mixed dyslipidemia who have failed to achieve LDL-C goals despite moderate or higher doses of statins, to reduce LDL-C, total cholesterol (TC), and apolipoprotein B (ApoB) levels. This article summarizes the milestones in the development of tafolecimab leading to this first approval for the treatment of adults with primary hyperlipidemia and mixed dyslipidemia.

Racial Disparities in Lipid Screening Among Patients With Coronary Artery Disease Narrowed in Primary Care Settings Supportive of Nurse Practitioners

Coronary artery disease (CAD) is the most prevalent heart disease in the United States, and it disproportionately affects Black compared to White patients. Regular primary care and dyslipidemia screening and management are essential for optimal CAD care. Nurse practitioners (NPs) increasingly provide primary care services, though unsupportive practice environments may constrain their ability to do so. To examine whether disparities in lipid screening between Black and White patients with CAD were associated with the NP practice environment scores. Cross-sectional survey data from NPs in primary care practices and Medicare claims were linked to evaluate outcomes among 111,911 CAD patients (94% White, 6% Black) across 456 primary care practices in four states (California, Florida, New Jersey, and Pennsylvania) in 2016. The NP-Primary Care Organizational Climate Questionnaire, which provides a score on the supportiveness of a respondent's practice, was used to evaluate the NP practice environment. Multilevel regression models that accounted for patient and practice characteristics were used to evaluate the study aim. Compared to White patients with CAD, Black patients with CAD less frequently received annual lipid screening (77.0% vs. 70.6%; p < .001). In logistic regression models accounting for patient and practice characteristics, for every standard deviation increase in the practice environment score, Black patients experienced a 5% increase in odds of receiving lipid screening. Investing in the NP practice environment, including increasing NP role visibility and strengthening relationships with physicians and administrators, may narrow racial disparities in CAD management.

Rosuvastatin effects on the HDL proteome in hyperlipidemic patients.

The advancements in proteomics have provided a better understanding of the functionality of apolipoproteins and lipoprotein-associated proteins, with the HDL lipoprotein fraction being the most studied. The focus of this study was to evaluate the HDL proteome in dyslipidemic subjects without an established cardiovascular disease, as well as to test whether rosuvastatin treatment alters the HDL proteome. Patients with primary hypercholesterolemia or mixed dyslipidemia were assigned to 20 mg/day rosuvastatin and blood samples were drawn at study entry and after 12 weeks of treatment. A label-free LC-MS/MS protein profiling was conducted, coupled with bioinformatics analysis. Sixty-nine HDL proteins were identified, belonging to four main biological function clusters: lipid transport and metabolism; platelet activation, degranulation, and aggregation, wound response and wound healing; immune response; inflammatory and acute phase response. Five HDL proteins showed statistically significant differences in the abundance (Anova ≤ 0.05), before and after rosuvastatin treatment. Platelet factor 4 variant (PF4V1), Pregnancy-specific beta-1-glycoprotein 2 (PSG2), Profilin-1 (PFN1) and Keratin type II cytoskeletal 2 epidermal (KRT2) showed decreased expressions, while Integrin alpha-IIb (ITGA2B) showed an increased expression after treatment with rosuvastatin. The ELISA validation of PFN1 segregated the subjects into responders and non-responders, as PFN1 levels after rosuvastatin were shown to mostly depend on the subjects' inflammatory phenotype. Findings from this study introduce novel insights into the HDL proteome and statin pleiotropism.

Dyslipidemia in Pediatric Patients: A Cross-Sectional Study.

There is an increasing interest in dyslipidemia in adult patients since it is known to contribute to early cardiovascular disease. Often, dyslipidemia starts in childhood, and it is associated with aggravating lifestyle choices concerning eating habits, such as the tendency to consume processed food and fast food, as well as the tendency to be more and more sedentary. We conducted a retrospective cross-sectional study describing the prevalence of dyslipidemia in a single medical center in Romania and the associated pathology. We evaluated all lipid profiles that were ordered in our clinic over nine years. We included 2413 patients that were evaluated in our clinic in the timeframe 2011-2020. Out of them, 18.23% had high values for LDL-cholesterol. More than a quarter (25.91%) were diagnosed with obesity. 11.37% of the patients with high LDL-cholesterol levels had various metabolic disorders including primary dyslipidemia. A small number of patients with hypercholesterolemia had thyroid disorders (4.10%). Patients with high LDL-cholesterol had various diagnoses ranging from metabolic to neurologic disorders, keeping in mind that there are multiple pathologies that can lead to dyslipidemia. Evaluating children for dyslipidemia is at hand for medical professionals. Screening for dyslipidemia in children would provide the opportunity to prevent rather than treat cardiovascular events.

Familial Hypercholesterolemia in Children. The Current State of the Problem

Cardiovascular diseases are the leading cause of disability and mortality worldwide. Cardiovascular mortality rate is steadily increasing despite the large-scale preventive measures. Familial hypercholesterolemia is the most common genetically determined disorder of lipid metabolism as the major cause of blood circulatory system diseases development and progression. Worldwide, there are 6.8–8.5 million children with this primary dyslipidemia. Early (in childhood) diagnosis of familial hypercholesterolemia is crucial for the timely initiation of lipid-lowering therapy in order to reduce the atherosclerosis progression and the risk of life-threatening cardiovascular events. New screening programs have been implemented, new biomarkers of the disease have been studied, and lipid-lowering drugs with new mechanisms of hypolipidemic action have been developed to increase the efficacy of these activities in economically developed countries.

ANMCO Position paper: Inclisiran: an innovative therapeutic approach for the clinical management of hypercholesterolemia

Research focused on lipid-lowering treatments has led to the development of new therapeutic options aimed at cardiovascular risk reduction. Gene silencing represents one of the most innovative approaches to reduce low-density lipoprotein cholesterol (LDL-C). Inclisiran is a small interfering RNA that inhibits proprotein convertase subtilisin/kexin type 9 synthesis and promotes LDL-C clearance by enhancing LDL-C receptor expression on hepatocyte cell surface. Several clinical studies have demonstrated inclisiran efficacy in terms of LDL-C reduction (~50%) with a dosage regimen of 300 mg administered twice a year after the first two doses administered at time 0 and after 90 days. Inclisiran use has recently been approved by the European and American drug regulatory agencies as a therapeutic option in addition to the maximum tolerated statin therapy in adults with primary hypercholesterolemia or mixed dyslipidemia who need further LDL-C reduction.

P361 SMALL INTERFERING RNA: REAL–LIFE DATA WITH A NEW FRONTIER IN HYPOLIPIDEMIC THERAPY

Abstract Inclisiran (Leqvio® 284 mg) is a new small interfering RNA that acts on the mRNA coding for the gene PCSK9. Inclisiran is indicated in adults with primary hypercholesterolemia (heterozygous familial and non–familial) or mixed dyslipidemia as an adjunct to diet alone or in combination with a statin or other lipid–lowering therapies in patients unable to reach LDL–cholesterol goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid–lowering therapies in patients who are statin–intolerant/contraindicated. The drug is administered subcutaneously and should be performed by a healthcare professional. After the initial dose, a second dose is given at 3 months followed by every 6 months. Real–life data with inclisiran is very limited. Herein, we present real–life data on 6 patients with a mean age of 71 years who started therapy with inclisiran in September 2022 (Fig. 1). Three patients were receiving combined lipid–lowering therapy with a statin and exetimibe, 2 were on ezetimibe alone because they were statin–intolerant, 1 patient was not receiving any therapy because intolerant. All patients had high to very high cardiovascular risk according to current ESC guidelines, and the lipid target was not met on optimized oral lipid–lowering therapy. Following initiation of inclisiran, lipids were assessed at 1 week, and at 1, 2, and 3 months. Changes in serum levels of LDL–cholesterol are shown in Figure 2. Reduction in LDL–cholesterol was seen as early as week 1. The mean percentage reduction in LDL–cholesterol at 1 month was 50% in patients not receiving statin therapy and 40% in those receiving a statin. The greatest reduction in LDL–cholesterol was seen in patients receiving combined therapy with a statin and ezetimibe. There was a clear reduction in LDL–cholesterol regardless of the type of statin and dosage. All patients receiving combined therapy with a statin reached their lipid target within 1 week after the start of treatment. No adverse effects were observed in any patient. From these preliminary observations, in a real–life setting therapy with inclisiran therapy appears to be safe and effective in lowering LDL–cholesterol in patients with high cardiovascular risk, especially when given in combination with a statin.