Low-density Lipoprotein Cholesterol Measurement Research Articles

Intercomparison study between the measurement of LDL cholesterol in the Atellica Solution® analyser and the estimation of LDL cholesterol using the Martin-Hopkins equation

Intercomparison study between the measurement of LDL cholesterol in the Atellica Solution® analyser and the estimation of LDL cholesterol using the Martin-Hopkins equation

Intercomparison study between the measurement of LDL cholesterol in the Atellica Solution® analyser and the estimation of LDL cholesterol using the Friedewald equation

Intercomparison study between the measurement of LDL cholesterol in the Atellica Solution® analyser and the estimation of LDL cholesterol using the Friedewald equation

Integrating Patient-Based Real-Time Quality Control (PBRTQC) in a New Field: Inter-Comparison between Biochemical Instrumentations with LDL-C.

Patient-based real-time quality control (PBRTQC) can be a valuable tool in clinical laboratories due to its cost-effectiveness and constant monitoring. More focus is placed on discovering and improving algorithms that compliment conventional internal control techniques. The practical implementation of PBRTQC with a biochemical instrument comparison is lacking. We aim to evaluate PBRTQC's efficacy and practicality by comparing low-density lipoprotein cholesterol (LDL-C) test results to ensure consistent real-time monitoring across biochemical instrumentations in clinical laboratories. From 1 September 2021 to 30 August 2022, the First Affiliated Hospital of Xi'an Jiaotong University collected data from 158,259 both healthy and diseased patients, including 84,187 male and 74,072 female patients, and examined their LDL-C results. This dataset encompassed a group comprising 50,556 individuals undergoing health examinations, a group comprising 42,472 inpatients (IP), and a group comprising 75,490 outpatients (OP) for the PBRTQC intelligent monitoring platform to conduct daily tests, parameter configuration, program development, real-time execution, and performance validation of the patients' data. Moreover 40 patients' LDL-C levels were assessed using two biochemical analyzers, designated as the reference and comparator instruments. A total of 160 LDL-C results were obtained from 40 both healthy and diseased patients, including 14 OP, 16 IP, and 10 health examination attendees, who were selected to represent LDL-C levels broadly. Two biochemical instruments measured LDL-C measurements from the same individuals to investigate consistency and reproducibility across patient statuses and settings. We employed exponentially weighted moving average (EWMA) and moving median (MM) methods to calculate inter-instrument bias and ensure analytical accuracy. Inter-instrument bias for LDL-C measurements was determined by analyzing fresh serum samples, different concentrations of quality control (QC), and commercialized calibrators, employing both EWMA and MM within two assay systems. The assessment of inter-instrumental bias with five different methods adhered to the external quality assessment standards of the Clinical Laboratory Center of the Health Planning Commission, which mandates a bias within ±15.0%. We calculated inter-instrument comparison bias with each of the five methods based on patient big data. The comparison of fresh serum samples, different concentrations of QC, commercialized calibrators, and EWMA were all in the permissive range, except for MM. MM showed that the bias between two biochemical instruments in the concentration ranges of 1.5 mmoL/L-6.2 mmoL/L exceeded the permissible range. This was mainly due to the small number of specimens, affected by variations among individual patients, leading to increased false alarms and reduced effectiveness in monitoring the consistency of the inter-instrumental results. Moreover, the inter-comparison bias derived from EWMA was less than 3.01%, meeting the 15% range assessment criteria. The bias result for MM was lower than 24.66%, which was much higher than EWMA. Thus, EWMA is better than MM for monitoring inter-instrument comparability. PBRTQC can complement the use of inter-comparison bias between biochemical analyzers. EWMA has comparable inter-instrument comparability monitoring efficacy. The utilization of AI-based PBRTQC enables the automated real-time comparison of test results across different biochemical instruments, leading to a reduction in laboratory operating costs, enhanced work efficiency, and improved QC. This advanced technology facilitates seamless data integration and analysis, ultimately contributing to a more streamlined and efficient laboratory workflow in the biomedical field.

Guidelines of the Polish Society of Laboratory Diagnosticsand the Polish Lipid Association on laboratory diagnosticsof lipid metabolism disorders. 2024

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area – the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

2024 Guidelines of the Polish Society of Laboratory Diagnostics and the Polish Lipid Association on laboratory diagnostics of lipid metabolism disorders.

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area - the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

Evaluation of common carotid artery wall stiffness by shear wave elastography in smokers and non-smokers.

Smoking is one of the most important preventable causes of cardiovascular diseases. Vascular disease caused by smoking is associated with vascular endothelial damage, platelet aggregation, and adhesion. In our study, we examined the effect of chronic smoking on vessel wall stiffness in smokers and control group by measuring carotid artery wall stiffness by shear wave ultrasonography. Sixty-two smokers of similar ages and genders, and 67 people who never smoked in the last ten years were included as the control group in this cross-sectional study. Arterial wall stiffness over the common carotid arteries of all participants was measured by shear wave elastography (SWE). In addition, each patient's blood pressure, fasting blood glucose, body mass index (BMI), HDL and LDL cholesterol measurements were recorded. Arterial wall stiffness values in smokers were found to be statistically significantly higher than in non-smokers. The mean of SWE measurements of the smokers was 47.3 ± 6.2 kPa, and that of the control group was 42.9 ± 4 kPa. The mean values of HDL and LDL of the smokers were 46.9 ± 5.6 mg/dL and 147.3 ± 9.3 mg/dL, respectively, and those of the control group were 50.3 ± 5.1 mg/dL and 136.9 ± 5.9 mg/dL. The LDL cholesterol values were statistically significantly higher in smokers compared to the control group, and HDL cholesterol values were statistically significantly lower in smokers. In our study, the arterial wall stiffness values measured by the SWE technique were higher in smokers than non-smokers.

Prevalence of Metabolic Syndrome and its Components in Patients with Controlled Graves’ Disease

Abstract Aim: Our aim was to assess the prevalence of the metabolic syndrome (MetS) and its components in patients with controlled Graves’ disease (GD). Methods: This was a cross-sectional study involving 95 consecutive patients with GD referred to our tertiary care inpatient clinical center meeting the following inclusion criteria: controlled hyperthyroidism, treatment with antithyroid drugs, untreated Graves’ orbitopathy (GO), if present. Patients’ anthropometric parameters were evaluated and laboratory tests were performed with measurement of fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, thyroid hormone and antibody levels. The presence of the MetS and its components as defined by the International Diabetes Federation from 2009 were evaluated. Results: In our patient cohort 82.1% were females, 17.9% were males, mean age 50.2 ± 13 years, with median duration of GD 16.5 months. The MetS was observed in 32.6% of our patients, obesity – in 34.7%, hyperglycemia in 38.9%, arterial hypertension – in 36.8%, low HDL-cholesterol – in 23.2% and hypertriglyceridemia – in 13.7%. There was not statistical difference neither between the prevalence of the MetS, nor between the prevalence of its individual components in female and male GD patients. The MetS was significantly more frequent in older patients, as well as abdominal obesity, hyperglycemia and arterial hypertension. There was not statistical difference in the frequency of the MetS and its components between GD patients with and without GO, except for waist circumference, which was significantly higher in patients with GO. Conclusions: The presence of the MetS and its components among GD patients are to great extent similar to those reported in the general population, which underlines the need for their screening and proper treatment in this subpopulation.

Monitoring and treatment of hypercholesterolemia after an atherosclerotic cardiovascular disease event in Denmark from 2015 to 2020

Background and Aims.Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event. MethodsDanish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured. ResultsA total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated. ConclusionsMany Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.

An improved method for estimating low LDL-C based on the enhanced Sampson-NIH equation

BackgroundThe accurate measurement of Low-density lipoprotein cholesterol (LDL-C) is critical in the decision to utilize the new lipid-lowering therapies like PCSK9-inhibitors (PCSK9i) for high-risk cardiovascular disease patients that do not achieve sufficiently low LDL-C on statin therapy.ObjectiveTo improve the estimation of low LDL-C by developing a new equation that includes apolipoprotein B (apoB) as an independent variable, along with the standard lipid panel test results.MethodsUsing β-quantification (BQ) as the reference method, which was performed on a large dyslipidemic population (N = 24,406), the following enhanced Sampson-NIH equation (eS LDL-C) was developed by least-square regression analysis:eSLDL-C=TC1.15-HDL-C1.25-TG6.99-TG×NonHDL-C1120+TG28910+TG×ApoB1240+ApoB4.54-4.73\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$eS\\,LDL-C= \\frac{TC}{1.15}-\\frac{HDL-C}{1.25}-\\frac{TG}{6.99}-\\frac{\\left(TG\ imes NonHDL-C\\right)}{1120}+\\frac{{TG}^{2}}{8910}+\\frac{\\left(TG\ imes ApoB\\right)}{1240}+\\frac{ApoB}{4.54}-4.73$$\\end{document}ResultsThe eS LDL-C equation was the most accurate equation for a broad range of LDL-C values based on regression related parameters and the mean absolute difference (mg/dL) from the BQ reference method (eS LDL-C: 4.51, Sampson-NIH equation [S LDL-C]: 6.07; extended Martin equation [eM LDL-C]: 6.64; Friedewald equation [F LDL-C]: 8.3). It also had the best area-under-the-curve accuracy score by Regression Error Characteristic plots for LDL-C < 100 mg/dL (eS LDL-C: 0.953; S LDL-C: 0.920; eM LDL-C: 0.915; F LDL-C: 0.874) and was the best equation for categorizing patients as being below or above the 70 mg/dL LDL-C treatment threshold for adding new lipid-lowering drugs by kappa score analysis when compared to BQ LDL-C for TG < 800 mg/dL (eS LDL-C: 0.870 (0.853–0.887); S LDL-C:0.763 (0.749–0.776); eM LDL-C:0.706 (0.690–0.722); F LDL-C:0.687 (0.672–0.701). Approximately a third of patients with an F LDL-C < 70 mg/dL had falsely low test results, but about 80% were correctly reclassified as higher (≥ 70 mg/dL) by the eS LDL-C equation, making them potentially eligible for PCSK9i treatment. The M LDL-C and S LDL-C equations had less false low results below 70 mg/dL than the F LDL-C equation but reclassification by the eS LDL-C equation still also increased the net number of patients correctly classified.ConclusionsThe use of the eS LDL-C equation as a confirmatory test improves the identification of high-risk cardiovascular disease patients, who could benefit from new lipid-lowering therapies but have falsely low LDL-C, as determined by the standard LDL-C equations used in current practice.

Prevalence and management of familial hypercholesterolaemia in patients with chest pain admitted to hospital: a retrospective observational study

ObjectivesPatients with familial hypercholesterolaemia (FH) are genetically burdened by a lifelong elevation of the low-density lipoprotein cholesterol (LDL-C) level, putting them at a very high risk of premature ischaemic heart...

Differences between repeated lipid profile measurements in a tertiary hospital over a short time period

BackgroundMeasurement of the plasma lipid profile, mainly low-density lipoprotein cholesterol (LDL-C), is widely used in the management of hospitalized patients as part of their cardiometabolic risk assessment. In common practice, LDL-C is calculated indirectly by the Friedewald equation. For many years, fasting of 8–14 h is needed to obtain an accurate lipid profile measurement, although recent guidelines do not necessitate it. The aim of this study was to find patients with two consecutive LDL-C measurements taken over a short time period on the same admission to see if a significant difference exists and to suggest reasons that may explain it. We also aim to define whether the difference between LDL-C calculated by the Friedewald equation is diminished while using the newer Martin/Hopkins, de Cordova or Sampson/NIH equations.MethodsThis was a retrospective cohort study performed in one medical center in Israel. In a five-year time period, 772 patients with two repeated LDL-C measurements taken on the same admission were found. The median time gap between tests was 2 days. Correlations between laboratory results and LDL-C measurements were determined.ResultsA total of 414 patients (53.6%) had a difference greater than the acceptable total error of 8.9% in LDL-C calculation using the Friedewald equation, with a mean 25.8% difference between the two tests. Newer LDL-C calculations showed less diversity. Non-HDL-C was found as the only variable with a major correlation with LDL-C results in all equations. A weaker correlation was found with HDL-C. Triglycerides showed an even weaker correlation, and glucose differences had no correlation with LDL-C differences.ConclusionsRepeated LDL-C measurements can vary widely, even during a short period of hospitalization. In this study, more than half of the patients had a significant difference between their consecutive LDL-C results. This wide difference between two consecutive tests was diminished using newer calculations, yet not well explained. The fasting state likely has no effect on LDL-C levels. The results of this study might emphasize that many factors influence LDL-C calculation, especially in the disease state. Further research is needed, especially in looking for a more accurate LDL-C calculation from existing formulas.

New Advances in Rapid Pretreatment for Small Dense LDL Cholesterol Measurement Using Shear Horizontal Surface Acoustic Wave (SH-SAW) Technology.

Atherosclerosis is an inflammatory disease of the arteries associated with alterations in lipid and other metabolism and is a major cause of cardiovascular disease (CVD). LDL consists of several subclasses with different sizes, densities, and physicochemical compositions. Small dense LDL (sd-LDL) is a subclass of LDL. There is growing evidence that sd-LDL-C is associated with CVD risk, metabolic dysregulation, and several pathophysiological processes. In this study, we present a straightforward membrane device filtration method that can be performed with simple laboratory methods to directly determine sd-LDL in serum without the need for specialized equipment. The method consists of three steps: first, the precipitation of lipoproteins with magnesium harpin; second, the collection of effluent from a 100 nm filter; and third, the quantification of sd-LDL-ApoB in the effluent with an SH-SAW biosensor. There was a good correlation between ApoB values obtained using the centrifugation (y = 1.0411x + 12.96, r = 0.82, n = 20) and filtration (y = 1.0633x + 15.13, r = 0.88, n = 20) methods and commercially available sd-LDL-C assay values. In addition to the filtrate method, there was also a close correlation between sd-LDL-C and ELISA assay values (y = 1.0483x - 4489, r = 0.88, n = 20). The filtration treatment method also showed a high correlation with LDL subfractions and NMR spectra ApoB measurements (y = 2.4846x + 4.637, r = 0.89, n = 20). The presence of sd-LDL-ApoB in the effluent was also confirmed by ELISA assay. These results suggest that this filtration method is a simple and promising pretreatment for use with the SH-SAW biosensor as a rapid in vitro diagnostic (IVD) method for predicting sd-LDL concentrations. Overall, we propose a very sensitive and specific SH-SAW biosensor with the ApoB antibody in its sensitive region to monitor sd-LDL levels by employing a simple delay-time phase shifted SH-SAW device. In conclusion, based on the demonstration of our study, the SH-SAW biosensor could be a strong candidate for the future measurement of sd-LDL.

LDL cholesterol target attainment in cardiovascular high- and very-high-risk patients with statin intolerance: a simulation study

The inability to tolerate sufficient doses of statins, statin intolerance (SI), contributes to the non-achievement of guideline-recommended low-density lipoprotein cholesterol (LDL-C) treatment targets. Patients with SI require alternative lipid-lowering therapies (LLT). We conducted a simulation study on LDL-C target achievement with oral LLT (ezetimibe, bempedoic acid) in patients with SI, using representative data of 2.06 million German outpatients. SI was defined using literature-informed definitions based on electronic medical records (EMR). Among n = 130,778 patients with hypercholesterolaemia, available LDL-C measurement, and high or very-high cardiovascular risk, 8.6% met the definition of SI. Among patients with SI, 7.7% achieved the LDL-C target at baseline. After simulation of the stepwise addition of treatment with ezetimibe and bempedoic acid, 22.6 and 52.0% achieved the LDL-C target, respectively. The median achieved LDL-C was 80 and 62 mg/dL, the corresponding reductions from baseline were 20.0 and 38.0%, respectively. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1 vs. 49.9%). In conclusion, in patients with increased cardiovascular risk meeting the definition of SI based on EMR, combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions.

Effectiveness of low-density lipoprotein cholesterol reduction with lipid lowering therapy for secondary prevention amongst older individuals: a nationwide cohort study.

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

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron.

Phenotypes Associated with HFE p.C282Y Homozygosity, the Main Hereditary Hemochromatosis Genotype, in Four Large Genetic Cohorts

Introduction Hereditary hemochromatosis (HH) is the most common known recessive hereditary disease in people of northern European descent. HH is most commonly caused by the HFE-C282Y homozygosity. Disease penetrance is highly variable (1-20%). We have examined the association between C282Y homozygosity and multiple phenotypes, both case-control and quantitative, across 4 international cohorts (deCODE genetics, UK Biobank, Denmark (Copenhagen Hospital Biobank / Danish Blood Donor Study) and Intermountain Healthcare) in an effort to shed a new light on the pathophysiology of this common hereditary disease. Methods We preformed a phenome wide association study meta-analyses for C282Y homozygosity across the 4 beforementioned cohorts, comprising around 970.000 individuals, of those 5928 were homozygous for the C282Y mutation (746 in deCODE/Iceland MAF 6.71%, 2865 in UK Biobank MAF 7.94%, 1703 in CHB MAF 5.6% and 614 in Intermountain Healthcare MAF 6.19%). The analyses comprised both case-control phenotypes (approximately 7000), cases being defined by ICD-10 codes, and continuous quantitative phenotypes (approximately 5500), both results from blood tests and proteome data from deCODE and UK Biobank. Results C282Y homozygotes had a higher prevalence of the following liver, hematological and rheumatic diseases compared to a control group with no copy of the C282Y variant. Diagnosed fibrosis and cirrhosis of liver (odds ratio 4.30, 95% confidence interval 3.35 to 5.51, p=1.77x10 -30), liver cell carcinoma (9.04, 6.01 to 13.58, p=3.24x10 -26) and fatty liver disease (1.75, 1.45 to 2.11, p=5.42x10 -09) were strikingly more common in C282Y homozygotes. Unsurprisingly C282Y homozygotes also had higher liver parameters. Notably C282Y homozygotes had a higher prevalence of diagnosed polycythemia vera (7.24, 4.93 to 10.62, p=4.37x10 -24) yet no association was found with clonal hematopoiesis (1.09, 0.88 to 1.34, p=4.47x10 -01). Strong association was found between C282Y homozygosity and increased hemoglobin (0.41 standard deviations, 95% confidence interval 0.38 to 0.45, p=6.84x10 -142), MCH (0.98, 0.93 to 1.03, p=&amp;lt;1.00x10 -300) and MCV (0.82, 0.78 to 0.86, p=&amp;lt;1.00x10 -300). Red blood cell count (RBC) was decreased (-0.27, -0.30 to -0.23, p=1.06x10 -50), while reticulocyte count (0.30, 0.26 to 0.34, p=1.42x10 -54) and percentage (0.36, 0.32 to 0.40, p=7.91x10 -79) were increased. Erythropoietin (EPO) measurements were markedly decreased in C282Y homozygotes (-0.31, -0.40 to -0.22, p=1.77x10 -11). Homozygous individuals had an increased risk of being diagnosed with osteoarthritis of hip (1.83, 1.63 to 2.07, p=4.30x10 -23) and were more likely to undergo total hip replacement (2.00, 1.69 to 2.29, p=5.81x10 -18). In contrast to these risk enhancing effects C282Y homozygotes had a lower prevalence of cardiovascular disease (CVD). C282Y homozygotes had decreased risk of coronary artery disease (CAD) (0.79, 0.72 to 0.86, p=4.26x10 -07) and angina pectoris (0.77, 0.69 to 0.86, p=4.28x10 -06) and were less likely to undergo coronary artery bypass graft (0.60, 0.49 to 0.74, p=2.39x10 -06). Pure hypercholesterolemia (0.76, 0.69 to 0.83, p=2.52x10 -09) and disorders of lipoprotein metabolism (0.75, 0.66 to 0.85, p=8.41x10 -06) was less commonly diagnosed. C282Y homozygotes were less likely to take cholesterol lowering statin drugs (0.74, 0.67 to 0.81, p=1.45x10 -09). Unsurprisingly with regard to these results strong association was found with lower cholesterol measurements in C282Y homozygotes, the effects being most pronounced on LDL cholesterol (-0.38, -0.42 to -0.35, p=1.61x10 -99). Total cholesterol was also markedly lowered (-0.35, -0.38 to -0.31, p=1.38x10 -91), as well as non HDL cholesterol (-0.34, -0.37 to -0.30, p=2.36x10 -81). No significant association was found with HDL cholesterol and triglyceride measurements. Conclusions C282Y homozygosity was associated with significantly increased risk of liver disease, liver cell carcinoma and osteoarthritis of hip. Homozygous individuals had increased risk of non-clonal primary polycythemia, association with polycythemia vera likely due to misdiagnosis or early diagnosis exacerbated by significantly increased hemoglobin. C282Y homozygotes had a significant decrease in LDL, non-HDL and total cholesterol measurements and were protected against cardiovascular disease.

Triglyceride level as a potential marker of residual cardiovascular risk and its relation to HeartScore.

Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in Bosnia and Herzegovina. Elevated LDL-cholesterol is established as a strong marker of cardiovascular risk. Some researchers believe that measuring triglyceride levels gives a good assessment of the residual risk for ASCVD besides the measurement of LDL-cholesterol. The aim of this study was to evaluate the overall prevalence of major risk factors for ASCVD, lipid profile and 10-year fatal cardiovascular risk using the HeartSCORE scoring system. Further, we want to evaluate the prevalence and relationship between elevated triglyceride levels and high 10-year fatal cardiovascular risk calculated as a HeartSCORE. This is a cross-sectional study conducted on 832 volunteers aged between 40 and 65 years without a diagnosis of diabetes and without known preexisting cardiovascular disease, as a part of the preventive program conducted at the Family Medicine office. Data were collected for ASCVD risk factors and lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides). 10-year fatal cardiovascular risk was calculated using the HeartSCORE scoring system for countries with high CV risk. Among 832 participants included, 565 (67.9%) were female, and 267 (32.1%) were male. We found high prevalence of hypertension (27.7%), obesity (32.2%), and smoking (36.2%). All lipid parameters, except HDL-C, were not optimal. Only 17.4% of participants had normal estimated HeartSCORE risk, while more than one-third (33.9%) had high or very high estimated HeartSCORE risk. Although we found a higher percentage of participants with elevated triglycerides in groups with higher HeartSCORE, there was a very weak positive correlation between values of triglycerides and the 10-year risk of a fatal cardiovascular event (r= 0.249, p= 0.000). The high prevalence of major known risk factors and high estimated HeartSCORE risk indicate a high overall risk for ASCVD in the sample. The proportion of participants with elevated triglycerides was increased in patients with high HeartSCORE risk what implicates importance of triglyceride measurement.

Clinical characteristics and treatment patterns in patients with atherosclerotic cardiovascular disease with hypercholesterolemia: a retrospective analysis of a large US real-world database cohort

Objective Guidelines developed by the American College of Cardiology/American Heart Association (ACC/AHA) recommend lipid-lowering therapies (LLTs) to reduce low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. This study described LLT utilization patterns and LDL-C goal achievement (to <70 mg/dL) among patients with ASCVD in the United States. Methods This retrospective study was conducted using Optum’s de-identified Clinformatics Data Mart Database (CDM). Patients with their first ASCVD diagnosis (index date) in the CDM database between July 1, 2015, and December 31, 2018, were followed for ≥12 months to assess LLT utilization patterns and change in LDL-C. LLTs included were statins and non-statin LLTs (ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 inhibitors). Adherence was measured as the proportion of days covered (PDC), defined as the number of days with drug on-hand (or number of days exposed to drug) divided by the 12-month follow-up period. Patients with PDC ≥0.8 were considered adherent. Results Among the patients with ASCVD (N = 1,424,893) included in this study, only 621,978 (43.7%) had at least one LDL-C measurement at baseline (6 months prior to and 3 months after the index date). The mean age was 71.5 years, and almost half of the patients were female. Patients were followed for a mean (standard deviation [SD]) duration of 30.6 (11.4) months (median of 29.9 months). During the follow-up, about one-quarter of the patients did not receive any LLT. Among treated patients, 89.5% received statins and 10.5% received non-statin LLT. Less than half (47.6%) of the patients were adherent to the index treatment during the 12-month follow-up. Even in patients receiving combination therapy (statin + non-statin LLT), a sizable proportion (35.8%) showed an increase in LDL-C over the follow-up period. Conclusions This retrospective study highlighted limited LDL-C monitoring in patients with ASCVD, and unmet need in terms of suboptimal utilization of non-stain LLTs, limited adherence to LLTs, and inadequate lipid control after treatment (among those with LDL-C measurements during the follow-up period) need to be addressed to improve outcomes in this patient cohort.

Low-density-lipoprotein cholesterol target attainment in high-risk patients with history of diabetes or major adverse cardiac and cerebrovascular event: an (un)expected gender bias

Abstract Background Lowering low-density lipoprotein cholesterol (LDL-C) is the cornerstone of cardiovascular disease prevention, especially after the occurrence of a major adverse cardiac and cerebrovascular event (MACCE). Collection of epidemiological data is crucial for monitoring healthcare appropriateness and the fulfillment of guidelines recommendations. Purpose This analysis aimed to evaluate the proportion of high-risk patients who achieved LDL-C goal as suggested by the international guidelines by analyzing regional administrative data and to explore the predictors of therapeutic failure, with a focus on the role of gender. Methods By linking health administrative and laboratory data, we collected data from seven Local Health Districts on residents aged ≥45 years. Inclusion criteria were: 1) at least one LDL-C measurement in the year; 2) a history of MACCE (defined as myocardial infarction and/or stroke and/or revascularization of the coronary, carotid, or peripheral arteries) and/or type 2 diabetes mellitus (T2DM). Cohorts were defined at 1st January 2019 and 1st January 2020. Lipid lowering therapy use (defined as ≥2 prescription fillings or ≥75% coverage of treatment days) over the past 6 months if LDL-C data were available or over the past year if no LDL-C data were available was monitored. The outcome was the number of patients with on-treatment LDL-C optimal levels, as defined by levels &amp;lt;55 mg/dl for patients with MACCE and &amp;lt;70 mg/dl for patients with T2DM without MACCE. Results A cohort of 174,200 individuals was analyzed (55% males). As regards subjects on lipid-lowering therapies, we found that female gender was associated with a significantly lower probability to have LDL-C levels at target (OR: 0.58±0.01; p&amp;lt;0.0001) in patients with MACCE with or without T2DM, in a model adjusted for age, district area, and the presence of cardiovascular risk factors and comorbidities (renal failure, heart failure, atrial fibrillation). This result was confirmed also in the analysis conducted in subjects without lipid-lowering therapies (OR: 0.56±0.01; p&amp;lt;0.0001). No significant differences were documented by stratifying for the presence of clinical pathways aimed to the active call of the patients by clinicians ("Initiative Health"). Conclusions These results demonstrated that females have a significantly lower probability to reach LDL-C levels recommended targets. This datum is confirmed even in the absence of lipid-lowering therapies. These results call for action aimed to: 1) education for general population and for patients with MACCE with a specific target on females; 2) information for clinicians for the need of assessing adequate lipid-lowering therapy prescription and adherence irrespectively of gender; 3) organization of clinical pathways - from admission to recovery and follow-up - with a specific focus on secondary prevention target attainment.

Abstract 16180: The Adherence and LDL-C Lowering Effect of Inclisiran Among Patients Who Received Treatment at Outpatient Clinics

Introduction: Inclisiran is a novel small interfering RNA (siRNA) indicated as an adjunct to diet and maximally tolerated statin to lower LDL-C among adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) in the US. It is administered subcutaneously initially, again at 3 months, and then every six months by an HCP. Subsequent doses may be administered within three months after the scheduled dose without restarting a new dose schedule. Metro Infusion Center (MIC) is one of the largest infusion centers across the US with over 200 centers in 38 states and has clinician oversight over each administration. Hypothesis: To describe the real-world adherence to inclisiran and changes in low-density lipoprotein cholesterol (LDL-C) levels associated with inclisiran use at MICs. Methods: Patient charts for those who initiated inclisiran from March 1, 2022 to November 31, 2022 were reviewed retrospectively. Demographics and clinical characteristics at initiation were collected and patients were followed until May 2023 for the current analysis. The study outcomes included the proportion of eligible patients who received the 2 nd or 3 rd dose and the percent change in LDL-C levels from baseline to the latest available data. Results: A total of 562 patients were included in the analysis from 107 different MICs in over 21 states. Mean (SD) age was 70.6 (9.6) years; 51% were female. The majority of patients (80%) were covered by Medicare. 492 (88%) had a history of ASCVD and 60 (11%) had HeFH. Mean (SD) baseline LDL-C was 147.6 (59.9) mg/dl. Of the 562 patients initiated inclisiran, 531 (95%) received their 2 nd dose, and 91% received the 2 nd dose within ±7 days of the schedule. There were 233 patients eligible to receive a 3 rd dose, 196 (84%) of them had received the 3 rd dose. Among 274 patients who had the LDL-C measured after inclisiran initiation, the average LDL-C reduction from baseline was 46.3%. On average, the first LDL-C measurement was taken at 3 months after receiving at least one dose of Inclisiran. Conclusions: These real-world data demonstrate high adherence to inclisiran with LDL-C reductions of 46.3% at 3 months. This finding was consistent with the ORION clinical development program.