Lower Low-density Lipoprotein Cholesterol Research Articles

Abstract 16434: 104-Week Safety and Effectiveness of Low-Density Lipoprotein Cholesterol-Lowering Therapy With Evolocumab in Patients With Familial Hypercholesterolemia/Hypercholesterolemia in Japan: Results of Post-Marketing Surveillance

Introduction: Evolocumab is the first monoclonal antibody against proprotein convertase subtilisin/kexin type 9 approved in Japan for familial hypercholesterolemia (FH) and hypercholesterolemia (HC). Aims: This study assessed the 104-week safety and effectiveness of low-density lipoprotein cholesterol (LDL-C)-lowering therapy with evolocumab in patients with FH (homo/heterozygous) and HC in a real-world setting in Japan. Methods: Overall, 3721 and 2792 patients (108 and 91 homozygous FH, 2007 and 1613 heterozygous FH, 1606 and 1088 HC) from 668 clinical sites comprised the safety and effectiveness analysis sets, respectively. Primary safety endpoints: incidence (%) and number of patients with adverse drug reactions and serious adverse events. Effectiveness endpoints: % change in LDL-C from baseline at Week 12 (n=2386, primary endpoint) and Weeks 4-104 (secondary endpoint). Results: Mean age: 63.2 years; female: 33.8%. The mean±SD follow-up duration was 545.5±218.8 days. Adverse drug reaction subject incidence was 5.2%. Serious adverse event subject incidence was 8.9% (330/3721). The adverse event incidences of myocardial infarction and stroke were 0.6% (n=23/3721) and 0.6% (n=21/3721; 0.3% ischemic stroke [n=12]/0.2% hemorrhagic stroke [n=9]), respectively. Table 1 shows adverse events by lowest achieved LDL-C levels. The mean±SD % change in LDL-C from baseline to Weeks 12 and 104 were –45.7%±28.2% (n=84) and –50.9±21.1% (n=48) in homozygous FH patients ( P <0.001 vs baseline; two-sided paired t -test), –56.0%±28.9% (n=1440) and –54.5±28.3% (n=905) in heterozygous FH patients ( P <0.001), and –63.3%±23.7% (n=862) and –60.8±28.1% (n=352) in HC patients ( P <0.001), respectively. Conclusions: There were no trends between the lowest achieved LDL-C levels and adverse events in Japanese patients. Evolocumab was well tolerated and sustained LDL-C reduction in patients with FH and HC in a real-world clinical setting in Japan.

Statin therapy in individuals with intermediate cardiovascular risk

BackgroundAs intermediate cardiovascular risk group accounts for a large part of the total population, determining appropriate cholesterol target in this population is critical. Herein, we investigated the optimal low-density lipoprotein cholesterol (LDL-C) level in individuals with intermediate cardiovascular risk after statin therapy. MethodsThis was a nationwide observational and validation cohort study (median duration of follow-up: 7.5 and 8.7 years, respectively), using data from the Korean National Health Insurance Service and a tertiary hospital database. Among individuals who underwent regular health examinations, those with ≥2 cardiovascular risk factors except diabetes mellitus, LDL-C 100–189 mg/dL, and newly used statins were enrolled. Of the 358,694 screened people, 57,594 met the inclusion criteria, of whom 27,793 were finally analyzed. The study population was stratified according to post-treatment LDL-C levels as follows: <100, 100–119, 120–139, and ≥ 140 mg/dL. The primary outcome variable was composite cardiovascular events (myocardial infarction, coronary revascularization, and ischemic stroke). From the patients screened of Severance Hospital cohort, 1859 meeting inclusion criteria were used for validation. ResultsThe rates of composite events ranged from 7.74 to 9.10 (mean 8.38)/1000 person-years in the three lower LDL-C groups. Adjusted hazard ratios (aHRs) ranged from 0.78 to 0.95 in the three groups with lower LDL-C, and a lower event risk was more evident in the groups that achieved LDL-C levels <120 mg/dL (p = 0.001–0.009). The total mortality risk did not differ between groups. In the validation cohort, the mean rate of composite events was 10.83/1000 person-years. aHRs ranged from 0.52 to 0.78 in the groups with lower LDL-C, and a lower risk was more obvious in patients who achieved LDL-C levels <100 mg/dL (p = 0.006–0.03). ConclusionsIndividuals with intermediate cardiovascular risk who achieved LDL-C levels <120 mg/dL after statin therapy had lower event risk. This result provides clinically useful evidence on target LDL-C levels in this population.

Impact of Active vs Passive Statin Selection for Primary Prevention: The CorCal Vanguard Trial

BackgroundStatins can improve outcomes in high-risk primary prevention populations. However, application in clinical practice has lagged. ObjectivesThe objective of this study was to compare an active vs a passive strategy (ie, usual care) to statin prescription for primary prevention of atherosclerotic cardiovascular disease (ASCVD). MethodsA total of 3,770 patients ≥50 years of age without a history of ASCVD or statin use were invited to enroll in CorCal, with 601 consenting to participate. These patients were randomized 1:1 to statin initiation guided by the pooled cohort equation or by coronary artery calcium scoring (CACS). Outcomes (2.8-year follow-up) compared patients managed actively vs passively (randomly invited but declined or did not respond). ResultsPatient demographics were well matched. Statin recommendation was common among enrolled patients (41.7%). During follow-up, 25.3% of active patients were taking a statin vs 9.8% managed passively (P < 0.0001). Active patients had more lipid panels (median 2.0 vs 1.0), lower low-density lipoprotein cholesterol (109 vs 117 mg/dL) (both P < 0.0001), and a low rate of major adverse cardiovascular events during follow-up (0.6% vs 1.0%, P = 0.47). Statistical comparisons included t-tests, chi-squared tests, nonparametric tests, and time-to-event tests as appropriate. ConclusionsAn active approach to statin selection for primary ASCVD prevention identified a large treatment opportunity and led to over twice as many patients on statins compared to passive (usual care) management. A large CorCal Outcomes Trial is underway to more definitively assess the impact on outcomes of active management of statins for primary prevention.

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study

AimsLimited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. MethodsHEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. ResultsIn total, 201 patients were included in the Spanish cohort. Median follow-up (Q1–Q3) was 30.0 (12–30) months. A total of 61.7% of patients were men and the mean (standard deviation) age was 59.5 (10.8) years. Most patients (68.7%) had experienced a prior cardiovascular event, 45.3% had coronary artery disease or stable angina, and 60.2% had a diagnosis of familial hypercholesterolemia. Overall, 57.7% of patients were receiving treatment with statins, most of them with high-intensity statins (85.3%); 45.8% of patients were intolerant to statins, and 26.4% of patients did not receive any LLT. At baseline, median (Q1–Q3) LDL-C levels were 151 (123–197) mg/dL. After 3 months of treatment, baseline LDL-C decreased by 66% to a median of 50 (30–83) mg/dL and these levels were maintained over time, with a median LDL-C of 55 (40–99) mg/dL at 30 months. At months 10–12 of treatment, LDL-C levels<55mg/dL were achieved by 56.3% of patients. LDL-C levels<70mg/dL were achieved by 70.1% of patients, and a lowering of LDL-C levels ≥50% was achieved by 76.8% of patients. The percentage of patients on evolocumab treatment was 95% at 12 months and 93% at 30 months. ConclusionsIn the Spanish cohort in routine clinical practice, evolocumab therapy provided a reduction in LDL-C levels consistent with that reported in previous clinical trials, which was sustained during 30 months of follow-up. Treatment with evolocumab was started at LDL-C levels 50% higher than those recommended by The Spanish Society of Arteriosclerosis and the Therapeutic Positioning Report. The probability of achieving the 2019 ESC/EAS LDL-C goals would improve with combination therapy and also with a lower LDL-C threshold when starting evolocumab. Persistence to evolocumab remained high during follow-up, with a very low percentage of discontinuation (5% at 12 months; 7% at 30 months).

Regulation of Glucolipid Metabolism in Mice Using Dendrobium huoshanense Extract and PI3k/Akt Signaling Pathway Activation

The present research is carried out to study the hypoglycemic and hypolipidemic effects of the Dendrobium huoshanense C. Z. Tang et S. J. Cheng extract on type 2 diabetic mice. D. huoshanense extract was prepared using the condensation reflux method. The chemical components were separated by UPLC Triple-TOF MS/MS to further identify the components that mainly exerted hypoglycemic and hypolipidemic effects. Type 2 diabetic C57BL/6 mice were induced by a high-fat diet (HFD) followed by intraperitoneal streptozotocin (STZ) and were daily gavaged with different doses of D. huoshanense extract for 5 weeks. Various methods such as HE staining, ELISA, and Western blot were used to evaluate the hypoglycemic and hypolipidemic effects of D. huoshanense extract on mice with type 2 diabetes mellitus model. The experimental results revealed that the main compounds of D. huoshanense extract were polysaccharides, flavonoids, alkaloids, amino acids, and many other chemical components. Oral administration of 200 mg/kg of the extract of D. huoshanense significantly reduced blood glucose and insulin levels of high-dose group mice and lowered total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, but increased high-density lipoprotein cholesterol (HDL-C) levels and liver glycogen content. In addition, the protein expression levels of insulin receptor (Ins R), phosphatidylinositol-3 kinase (PI3K) and p-protein kinase B (Akt) were upregulated. These results imply that the D. huoshanense aqueous extract can improve insulin resistance and lipid metabolism in type 2 diabetic mice, and it may regulate the function through the PI3K/AKT pathway.

Modelling a two-stage adult population screen for autosomal dominant familial hypercholesterolaemia: cross-sectional analysis within the UK Biobank

BackgroundMost people with autosomal dominant familial hypercholesterolaemia (FH) remain undetected, which represents a missed opportunity for coronary heart disease prevention.ObjectiveTo evaluate the performance of two-stage adult population screening for FH.DesignUsing...

Sex Differences in Cardiovascular Outcomes and Cholesterol-Lowering Efficacy of PCSK9 Inhibitors: Systematic Review and Meta-Analysis

BackgroundGuideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood. ObjectivesThe authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i. MethodsA comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used. ResultsWe identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, P < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, P < 0.001) with no significant sex difference (MD −0.01, 95% CI: −0.14 to −0.13, P = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD −62.57, 95% CI: −70.24 to −54.91, P < 0.001; males: MD −66.19, 95% CI: −72.03 to −60.34, P < 0.001) and 24 weeks (females: MD −47.52, 95% CI: −52.94 to −42.09, P < 0.001; males: MD −54.07, 95% CI: −59.46 to −48.68, P < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD −4.55, 95% CI: −7.34 to −1.75, P < 0.01) and 24 weeks (males vs females: MD −7.11, 95% CI: −9.99 to −4.23, P < 0.001). ConclusionsThe use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.

Randomized Double-blind Sham-controlled Trial of a Novel Silicone-filled Endoscopically Placed Device for Weight Loss

Background and AimsAlthough obesity affects over 40% of adults in the United States and is a driver of preventable chronic diseases and health care costs, most patients are left untreated. MethodsThis was a randomized, double-blind, sham-controlled trial to investigate the safety and efficacy of a novel, endoscopically placed intragastric device for weight reduction, the TransPyloric Shuttle, implanted for 1 year in 270 patients with Class I and II obesity. An additional 32 treatment patients were enrolled in an Open-Label group. The co-primary efficacy endpoints were percent total body weight loss (%TBWL) in the Treatment group compared with the Sham group and a proportion of treatment patients achieving ≥5% TBWL at 12 months. ResultsThe mean %TBWL at 12 months was 9.5% (95% CI, 8.2-10.8) in the Treatment group (n = 181) compared with 2.8% (95% CI, 1.1-4.5) in the Sham group (n = 89). In the Treatment group, 67.0% (95% CI, 59.3-74.4) of patients achieved ≥5% TBWL compared with 29.3% (95% CI, 19.3-39.4) in the Sham group. Patients in the Treatment group achieved lower blood pressure, total cholesterol, and low-density lipoprotein cholesterol compared with the Sham group. Early withdrawals occurred in 22% and 11% patients in the Treatment and Sham groups, respectively. Device- or procedure-related serious adverse events occurred in 6 patients (2.8%), and no deaths occurred. ConclusionTreatment with a novel endoscopically placed intragastric device resulted in meaningful weight loss and improvement in cardiometabolic outcomes in patients with Class I and II obesity (ClinicalTrials.gov number NCT02518685).

Practical Implementation of Lipid Lowering for Cardiovascular Risk Reduction in Primary Care

With the advent of safe lipid-lowering drugs, particularly statins and non-statin agents such as ezetimibe, and with the emergence of newer therapeutics such as monoclonal antibodies and RNA technologies, it has become apparent that major adverse cardiovascular (CV) events can be reduced both in primary and secondary prevention by 20–50% through lowering of low-density lipoprotein cholesterol (LDL-C) by 1–2 mmol/L. The purpose of this paper is to provide a pragmatic approach to the implementation of the 2021 Canadian Cardiovascular Society Guideline for managing dyslipidemia in adults.

Cholesterol Levels, Hormone Replacement Therapy, and Incident Dementia among Older Adult Women.

Previous studies revealed that hormone replacement therapy (HRT) probably has a protective effect for preventing dementia in post-menopausal women. However, the results were still controversial. The association between cholesterol levels and incident dementia in older women is not fully understood either. We conducted a retrospective analysis on a cohort of non-demented women aged older than 50 years, which was registered in the History-based Artificial Intelligence Clinical Dementia Diagnostic System database from September 2015 to August 2021. We followed this cohort longitudinally to examine the rates of conversion to dementia. Using a Cox regression model, we investigated the impact of the quartile of total cholesterol (TC) levels on incident dementia, adjusting for age, sex, education, neuropsychiatric symptoms, neuropsychological assessments, HRT, as well as various vascular risk factors and medications. We examined a cohort of 787 participants, comprising 539 (68.5%) individuals who did not develop dementia (non-converters). Among these non-converters, 68 individuals (12.6%) were treated with HRT. By contrast, there were 248 (31.5%) who did develop dementia (converters). Among the converters, 28 individuals (11.3%) were treated with HRT. The average follow-up durations were 2.9 ± 1.5 and 3.3 ± 1.6 years for non-converters and converters, respectively. Compared to the lowest quartile of TC levels (<153), the hazard ratios (HR) for converting to dementia were 0.61, 0.58, and 0.58 for the second (153-176), third (177-201), and highest (>201) quartiles, respectively (all p < 0.05). However, the low-density lipoprotein cholesterol (LDL-C) level and HRT did not alter the rate of conversion to dementia. In conclusion, the lowest quartile of TC increased incident dementia in post-menopausal women without dementia; however, HRT did not contribute to conversion to dementia. Some studies suggest that post-menopausal women who have reduced estrogen levels might have an increased risk of Alzheimer's disease if they also have high cholesterol. Nonetheless, the evidence is inconclusive, as not all studies support this finding. The "Lower LDL-C is better" strategy for preventing cardiac vascular disease should be re-examined for the possible serial adverse effects of new onset dementia due to very low cholesterol levels.

The Decrease in Serum Total Cholesterol and Low-Density Lipoprotein (LDL) Concentrations With the Initiation of Hemodialysis Despite a Concomitant Increase in Serum Albumin Concentrations.

Background and objective Hemodialysis patients often have lower serum low-density lipoprotein (LDL) and total cholesterol concentrations compared to the general population. It is unclear if this is due to a persistent decline in the values due to kidney disease or if the hemodialysis itself is contributing to the lower values. It is often assumed that malnutrition and anorexia are the main causes of the low lipid concentration in hemodialysis patients. In this study, we aimed to determine the association between hemodialysis initiation and serum lipid and albumin concentrations. Methodology The medical records of all patients initiating hemodialysis over an 11-year period at a single center were retrospectively reviewed. The data of 145 patients who had all the required lab values available were ultimately included in the study. Serum lipid levels at the initiation of hemodialysis were compared to values obtained mostly 6-18 months later. In order to determine if poor nutritional status is the reason for the decline in serum lipid levels, the serum albumin concentration at the initiation of hemodialysis was compared to that obtained during follow-up labs. Results We observed that serum cholesterol concentration declined from an average of 147 mg/dL to 137 mg/dL, while LDL decreased from an average of 78 mg/dL to 68 mg/dL, andserum albumin concentration increased from 3.4 g/dL to 3.8 g/dL after an average follow-up period of 10.8 months. Conclusions Based on our findings, the declinein serum LDL and total cholesterol concentrations with the initiation of hemodialysis may not be attributed to poor nutritional intake.

Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial.

To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease. Randomised, open label, multicentre trial. 12 hospitals in South Korea, September 2016 to November 2019. 4400 adults (age ≥19 years) with coronary artery disease. Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation. The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities. 4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% v 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% v 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups. In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin. ClinicalTrials.gov NCT02579499.

Inclisiran in patients with prior myocardial infarction: A post hoc pooled analysis of the ORION-10 and ORION-11 Phase 3 randomised trials

Background and aimsAmong patients with prior myocardial infarction (MI), the risk of future ischaemic cardiovascular events is increased, and intensive lipid-lowering therapy (LLT) is indicated to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. Here, the efficacy and safety of inclisiran, a small interfering ribonucleic acid, were evaluated in patients with or without prior MI from the pooled ORION-10 and ORION-11 Phase 3 trials. MethodsPatients (n = 2636) were randomised 1:1 to receive 284 mg inclisiran (300 mg inclisiran sodium) or placebo on Day 1, Day 90, and 6-monthly thereafter over 18 months, along with background oral LLT, including statins. Of these, 1643 (62.3%) patients had an MI prior to randomisation, stratified as recent (>3 months to <1 year) or remote (≥1 year), and 993 (37.7%) patients were without a prior MI. The percentage change in LDL-C from baseline and safety were assessed. ResultsBaseline characteristics were well balanced across the treatment arms and MI strata. The mean (95% confidence interval) placebo-corrected LDL-C reductions from baseline to Day 510 with inclisiran were 52.6% (40.1, 65.1), 50.4% (47.0, 53.8), and 51.6% (47.4, 55.9) for recent, remote, and no prior MI, respectively. Corresponding time-adjusted LDL-C reductions were 50.0% (41.4, 58.7), 52.2% (49.8, 54.7), and 51.2% (48.1, 54.2). In each MI stratum, treatment-emergent adverse events (TEAEs) at the injection site (all mild to moderate) were observed more in inclisiran-treated patients than placebo, without an excess of other TEAEs. ConclusionsInclisiran provided effective and consistent LDL-C lowering, irrespective of MI status.

Impact of hypertriglyceridaemia on cardiovascular mortality according to low-density lipoprotein cholesterol in a 15.6-million population.

The aim of this study was to assess the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality concerning low-density lipoprotein cholesterol (LDL-C) and age in the general population. From the Korean National Health Insurance Service database, 15 672 028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios for CVD mortality were calculated using Cox models after adjusting for various confounders. During a mean of 8.8 years of follow-up, 105 174 individuals died of CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold [ischaemic heart disease (IHD)], 1.24-fold [acute myocardial infarction (AMI)], and 1.10-fold (ischaemic stroke) higher CVD mortality. Haemorrhagic stroke and heart failure were not associated with TG levels. The impact of hypertriglyceridaemia (HTG) on CVD weakened but remained present in persons with LDL-C < 100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischaemic stroke) higher CVD mortality. The younger population (18-44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population. Hypertriglyceridaemia independently raises CVD mortality with lingering risks in young and older individuals with low LDL-C levels, suggesting the importance of management of HTG even with controlled LDL-C.

A retrospective study of people with familial hypercholesterolaemia in a Belgian lipid clinic

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

Concordance between low density lipoprotein cholesterol concentration measurement by enzymatic method and calculation by Friedewald formula in cardiovascular risk classification

Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for cardiovascular risk assessment and guiding cholesterol-lowering therapy. Due to the high cost of β-quantification (Gold standard) and time-consuming, direct measurement of LDL-C is an alternative method. However, unlike the calculation of LDL-C by Friedewald formula, there is an additional cost in terms of reagents for performing a direct LDL-C test. The current study aimed to compare direct LDL-C concentration determination to data calculated by Friedewald formula. 752 lipid profiles of 710 people with LDL-C estimated by direct LDL assay, in the Biochemistry laboratory of university hospital center of Angré, were included in the study. In the same group, LDL-C was calculated using Friedewald formula. Lin’s concordance correlation coefficient (ccc) and Passing-Bablok regression analysis using, MedCal software, were performed to assess the strength of concordance between the 2 methods, and identify any possible bias. The concordance between the two methods was moderate (ρc = 0.9466). Passing-Bablok regression analysis revealed a systematic bias between the two methods. The total error observed (TEobs) between the two methods was higher than allowable total error recommended by the NCEP-ATPIII when LDL-C values was less than 159 mg/dL (4.112 mmol/L). The Friedewald formula resulted in lower LDL-C concentration values. Despite its cost-effectiveness in the estimation of LDL-C, an underestimation of LDL-C levels could result in inaccurate cardiovascular diseases (CVD) risk assessments and potentially significant future societal costs due to inadequate prevention and treatment of CVD.

Inclisiran: a new generation of lipid-lowering siRNA therapeutic.

Atherosclerotic heart disease (AHD) is a major cause of morbidity and mortality worldwide. Lowering low-density lipoprotein cholesterol (LDL-C) levels is a key strategy to prevent and treat AHD. Inclisiran is a novel siRNA drug that targets proprotein convertase subtilisin/kexin type 9 (PCSK9) gene expression and reduces LDL-C levels with only two or three injections per year. This review summarizes the mechanism, efficacy, safety, and applications of Inclisiran in various populations and settings, based on recent literature. It also compares Inclisiran with other lipid-lowering drugs, especially other PCSK9 inhibitors. We conclude that Inclisiran is a promising lipid-lowering agent that can provide convenience and effectiveness for patients with high cardiovascular risk. However, some challenges and limitations remain for Inclisiran, such as its long-term safety and efficacy, its cost-effectiveness and accessibility, and its interactions and synergies with other drugs. These issues need further investigation and evaluation in future studies.

Tongxinluo capsule in combination with conventional therapies for stable angina pectoris: A meta-analysis and systematic review.

This study aimed to assess the efficacy and safety of Tongxinluo capsule (TXLC) in combination with conventional therapies for treating stable angina pectoris (SAP) through a comprehensive meta-analysis and systematic review. We conducted a systematic search of the China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Embase, and CENTRAL databases for randomized controlled trials investigating the use of TXLC as adjuvant therapy for SAP published up to June 2023. The Cochrane Handbook was used to evaluate the risk of bias. Meta-analysis was performed using Review Manager 5.4.1, and publication bias was assessed using Begg test and Egger test in the Stata SE 12.0 software. GRADEpro was used to assess the quality of the evidence. This meta-analysis included 26 randomized controlled trials with a total of 2352 patients. TXLC co-administration demonstrated significant reduction in angina attack frequency (mean difference (MD) -0.91, 95% confidence interval (CI) -0.97 to -0.84, P < .00001) and duration (MD -1.71, 95% CI -2.24 to -1.19, P < .00001), decreased use of nitroglycerin tablets (MD -6.28, 95% CI -7.16 to -5.41, P < .00001), lowered C-reactive protein (MD -1.19, 95% CI -1.35 to -1.03, P < .00001) and low-density lipoprotein cholesterol levels (MD -0.68, 95% CI -0.86 to -0.51, P < .00001). TXLC co-administration did not increase gastrointestinal reactions (RR 1.17, 95% CI 0.38 to 3.57, P = .78). The Begg test and Egger test results indicated no publication bias. The evidence quality was rated as very low for frequency of angina attack, duration of angina attack, and nitroglycerin usage, and low for C-reactive protein, low-density lipoprotein cholesterol levels, and gastrointestinal reaction events. This meta-analysis supports TXLC as a beneficial adjunct treatment for SAP.

Rhabdomyolysis or Severe Acute Hepatitis Associated with the Use of Red Yeast Rice Extracts: an Update from the Adverse Event Reporting Systems.

Elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for atherosclerotic cardiovascular disease (ASCVD), and lowering LDL-C reduces the risk of cardiovascular adverse events. Among natural approaches known for their lipid-lowering properties, red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins) that act by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In August 2018, the European Food Safety Authority (EFSA) concluded in its assessment of the use of RYR (further amended in June 2022) that monacolins from RYR raise significant safety concerns when used as a food supplement at a dose of 10 mg/day. In particular, individual cases of serious adverse effects of monacolins from RYR have been reported at intakes as low as 3 mg/day. The EFSA Panel pointed out several uncertainties regarding the available data. We conducted an in-depth and updated analysis of the serious adverse events, with a focus on rhabdomyolysis and acute hepatitis, associated with the consumption of RYR. An analysis of the Food and Drug Administration reporting systems revealed a very small number of cases of rhabdomyolysis or severe acute hepatitis associated with RYR use. In addition, only a few case reports of these serious adverse events associated with RYR use have been published. Based on data from adverse event reporting systems and available case reports, the occurrence of rhabdomyolysis or severe acute hepatitis that could be associated with the use of RYR appears to be extremely rare compared to the occurrence with statins, which is rare to common.

Paradoxical Effects of Prolonged Insufficient Sleep on Lipid Profile: A Pooled Analysis of 2 Randomized Trials.

Background Insufficient sleep is associated with increased cardiovascular disease risk, but causality is unclear. We investigated the impact of prolonged mild sleep restriction (SR) on lipid and inflammatory profiles. Methods and Results Seventy-eight participants (56 women [12 postmenopausal]; age, 34.3±12.5 years; body mass index, 25.8±3.5 kg/m2) with habitual sleep duration 7 to 9 h/night (adequate sleep [AS]) underwent two 6-week conditions in a randomized crossover design: AS versus SR (AS-1.5 h/night). Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and inflammatory markers (CRP [C-reactive protein], interleukin 6, and tumor necrosis factor-α) were assessed. Linear models tested effects of SR on outcomes in the full sample and by sex+menopausal status (premenopausal versus postmenopausal women+men). In the full sample, SR increased high-density lipoprotein cholesterol compared with AS (β=1.2±0.5 mg/dL; P=0.03). Sex+menopausal status influenced the effects of SR on change in total cholesterol (P-interaction=0.04), LDL-C (P-interaction=0.03), and interleukin 6 (P-interaction=0.07). Total cholesterol and LDL-C decreased in SR versus AS in premenopausal women (total cholesterol: β=-4.2±1.9 mg/dL; P=0.03; LDL-C: β=-6.3±2.0 mg/dL; P=0.002). Given paradoxical effects of SR on cholesterol concentrations, we explored associations between changes in inflammation and end point lipids under each condition. Increases in interleukin 6 and tumor necrosis factor-α during SR tended to relate to lower LDL-C in premenopausal women (interleukin 6: β=-5.3±2.6 mg/dL; P=0.051; tumor necrosis factor-α: β=-32.8±14.2 mg/dL; P=0.027). Conclusions Among healthy adults, prolonged insufficient sleep does not increase atherogenic lipids. However, increased inflammation in SR tends to predict lower LDL-C in premenopausal women, resembling the "lipid paradox" in which low cholesterol associates with increased cardiovascular disease risk in proinflammatory conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02835261, NCT02960776.