Hypercholesterolemic Patients Research Articles

Clinical and genetic diagnosis of familial hypercholesterolaemia in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health Study.

To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography. The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US-MEDPED, Simon Broome (SB) criteria, the 'Familial Hypercholesterolaemia Case Ascertainment Tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harboring 944 FH mutations. The study cohort consisted of 3267 patients (78.6% with coronary artery disease [CAD]). FH was diagnosed in 2.8%, 2.2%, 3.9%, and 7.9% using the DLCN, US-MEDPED, SB criteria, and the FAMCAT. The clinical algorithm identified the same patients as the SB criteria. Pathogenic FH mutations were found in 1.2% (1.2% in patients with CAD, 1.0% in patients without CAD). FH was more frequently diagnosed in younger patients. With genetic testing as reference, the clinical criteria achieved areas under the ROC curve (AUCs) in the range of 0.56-0.68. Using only LDL-C corrected for statin intake, an AUC of 0.68 was achieved. FH is up to fourfold more prevalent in patients undergoing coronary angiography than in contemporary cohorts representing the general population. Different clinical criteria yield substantially different diagnosis rates, overestimating the prevalence of FH compared to genetic testing. LDL-C testing alone may be sufficient to raise the suspicion of FH, which then needs to be corroborated by genetic testing.

Evaluation & Assessment of Chest Pain among Dyslipidemic Out-Door Patients without Prior Clinical Ischemic Heart Disease

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular diseases, including ischemic heart disease. However, hypercholesterolemia patients without a history of clinical ischemic heart disease (IHD) may experience chest pain that presents diagnostic and management challenges. This review aims to summarize the existing literature and assess the prevalence of chest pain in this specific patient without having previous heart disease. Bangladesh Heart Journal 2024; 39(1): 57-62

Prevalence and Clinical Characteristics of Familial Hypercholesterolemia in Patients with Acute Coronary Syndrome according to the Current Japanese Guidelines: Insight from the EXPLORE-J study.

Little data exists for evaluating the prevalence and patient characteristics of familial hypercholesterolemia (FH) according to the latest 2022 guidelines for FH published by the Japan Atherosclerosis Society (JAS), which revised the Achilles tendon thickness (ATT) threshold from 9.0 mm in both sexes to 8.0 mm in men and 7.5 mm in women. This study used a nationwide registry of patients with acute coronary syndrome (ACS) to evaluate the prevalence of FH according to the latest diagnostic criteria for FH and to investigate the application of Achilles tendon imaging in the diagnosis of FH.A previous prospective observational study at 59 Japanese centers involving consecutive patients with ACS who were managed between April 2015 and August 8, 2016 was conducted to explore lipid management and persistent risk in patients hospitalized for ACS (EXPLORE-J). The study population consisted of 1,944 EXPLORE-J enrollees. According to the diagnostic criteria for FH in the 2022 JAS guidelines, the prevalence of probable or definite was among patients with ACS was 6.6% (127/1944). Among patients with premature ACS (male, age ＜55 years; female, age ＜65 years), the prevalence of FH was 10.1% (43/427). The mean ages were of the probable FH and definite FH groups were 59.9 and 61.0 years, respectively, while the mean age of the possible-or-unlikely FH group was 66.4 years (significantly older). Relative to the possible-or-unlikely FH group, the low-density lipoprotein cholesterol (LDL-C) levels were similar in the probable FH group and and significantly higher in the definite FH group. The prevalence of FH was considerably higher than previously reported, especially for patients with premature ACS. The age and LDL-C levels of the patients in the probable FH and definite FH groups were similar.

Efficacy and Safety of Alirocumab and Evolocumab as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors in Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.

Familial hypercholesterolemia (FH) is a prevalent and potentially fatal illness that causes a substantial elevation in low-density lipoprotein cholesterol (LDL-C). The aim of this study was to investigate the effects of monoclonal antibodies alirocumab and evolocumab on LDL-C and other lipid parameters, as well as their safety in familial hypercholesterolemia patients. A comprehensive search was done on PubMed/MEDLINE, EMBASE, Web of Science (WOS/ ISI), Scopus, ClinicalTrials (www. gov), and conferences/ congress research papers. Random effect models were used to calculate mean differences (%) and risk ratios (RRs), and confidence intervals (95%). Ten studies (n=1489 patients) were included in this study. PCSK9 inhibitors decreased the levels of LDL-C by -49.59% (95%CI -55.5%, -43.67%) as compared to placebo. They also didn't alter the Treatment-Emergent Adverse Event (TEAE) and neuronal events by RR 0.92 (0.75, 1.13) and 1.31 (0.66, 2.59), respectively. PCSK9 inhibitors were effective and safe in treating patients with FH. There was high-quality evidence showing that monoclonal antibodies (alirocumab & evolocumab) lower LDL-C (GRADE: high), lipoprotein (a) (GRADE: High), triglycerides (TG) (GRADE: High), total cholesterol (GRADE: High), non-high-density lipoprotein cholesterol (non- HDL-C) (GRADE: Moderate), and apolipoprotein B (GRADE: High), and increase the HDL-C (GRADE: High) as well as apolipoprotein A1 (GRADE: High). Comparing PCSK9 inhibitors against placebo, neither TEAE (GRADE: high) nor neuronal events (GRADE: moderate) were changed.

Familial Hypercholesterolemia and Type 2 Diabetes: Diagnostic and Therapeutic Challenges

Familial hypercholesterolemia (FH) is a largely underdiagnosed and undertreated disease. Findings regarding the coexistence and interplay between FH and type 2 diabetes (T2D) are conflicting. Epidemiological data suggest an approximately halved prevalence of T2D in FH and an approximately doubled cardiovascular disease (CVD) risk, dependent on mutation type, age, sex, lifestyle, associated pathologies and therapy.For conference attending physicians involved in hypercholesterolemia management, a FH survey was developed including diagnostic-screening situations, severity assessment, while for hypercholesterolemia patients with premature CVD, a web-based tool was prepared for identification of familial cases. For diagnosis, the Simon Broome, DLCN and MEDPED criteria were used.Physicians showed difficulties in FH identification and risk stratification, overestimating the role of associated metabolic changes and underestimating identified mutations characterized by increased CVD risk at any LDL-C level. In children, neither universal nor early lipid screening in strong family history was recommended, unlike in cases with associated metabolic disturbances. In patients, 21.73% presented definite and/or probable FH diagnosis by at least two scoring systems, 3.84% manifesting also T2D. The case of a 45-year-old patient with gestational diabetes and PCOS, conflicting algorhithms-based FH diagnosis and no means for genetic testing, good cholesterol response to statins but aggravating aorta stenosis exemplifies management challenges.In conclusion, FH identification and individual risk assessment may be assisted by targeting selected patients for diagnosis and physicians for raising awareness, but limited access to mutation analysis and novel non-diabetogenic lipid lowering therapies incumber management of FH and the reduced number of cases with coexisting T2D.

Lomitapide for the treatment of paediatric homozygous familial hypercholesterolaemia patients - Results from the efficacy phase of the APH-19 study

Lomitapide for the treatment of paediatric homozygous familial hypercholesterolaemia patients - Results from the efficacy phase of the APH-19 study

To corroborate Dutch lipid network criteria for diagnosis of Familial Hypercholesterolemia patients in India

To corroborate Dutch lipid network criteria for diagnosis of Familial Hypercholesterolemia patients in India

Lipoproteínas y colesterol total en adultos con colesterolemia normal y elevada en un policlínico de Lima-Perú 2022: Un estudio correlacional

Objective: To evaluate the degree of correlation between high-density, low-density, and very low-density lipoproteins and total cholesterol in patients with normal and high cholesterolemia. Methodology: Observational, analytical and cross-sectional study carried out from January to September 2022 with 207 patients over 18 years of age divided into a group with normal cholesterol and another with hypercholesterolemia. The Spearman correlation test was performed. Results: In normocholesterolemic subjects there was a low and negative correlation between high-density lipoproteins and low-density lipoproteins (-0.263) as well as between high-density lipoproteins and very low-density lipoproteins (-0.220). In hypercholesterolemic patients there was a low and positive correlation between high-density lipoproteins and total cholesterol (0.344). In both groups there was a high correlation between cholesterol and low-density lipoproteins and a low and positive correlation between cholesterol and very low-density lipoproteins. Conclusions: Lipoproteins are correlated in normocholesterolemics and high-density lipoproteins are correlated in hypercholesterolemics.

Effectivity of Sukamond Pudding as A Healthy Snack for Hypercholesterolemia Patients

Background: Hypercholesterolemia is a disorder of cholesterol metabolism caused by cholesterol levels in the blood exceeding normal limits. Sukamond Pudding is a pudding made from milk flour, rice bran, and almonds, which contain high fiber, vitamin C, and Vitamin E. This study aims to analyze the effectiveness of giving Sukamond pudding as a healthy snack in hypercholesterolemia sufferers.
 Method: This type of research is quantitative with a quasi-experimental research design. This research was conducted from December 2022 to January 2023 at the OKU Sekarjaya Health Center. The research sample was selected by systematic random sampling with a total sample of 60 respondents.
 Result: There was an effect of giving Sukamond as a healthy snack to patients with hypercholesterolemia (p=0.000).
 Conclusion: The results of statistical tests showed that there was an effect of giving Sukamond as a healthy snack to people with hypercholesterolemia.

Alterations of ileal mucosa-associated microbiota in hypercholesterolemia patients

Many metabolic diseases have been demonstrated to be associated with changes in the microbiome. However, no studies have yet been conducted to examine the characteristics of the mucosal microbiota of patients with hypercholesterolemia. We aimed to examine mucosa-associated microbiota in subjects with hypercholesterolemia. We conducted a case-control study, in which ileal mucosal samples were collected from 13 hypercholesterolemia patients and 13 controls for 16S rRNA gene sequencing. There were differences in the composition of ileal mucosal microbiota based on beta diversity between the hypercholesterolemia and control groups (P < 0.05). Compared with the control group, the phylum Bacteroidetes and the genera Bacteroides, Butyricicoccus, Parasutterella, Candidatus_Soleaferrea, and norank_f__norank_o__Izemoplasmatales were less abundant in the hypercholesterolemia group (P < 0.05), while the genus Anaerovibrio was enriched in the hypercholesterolemia group (P < 0.05). The relative abundance of Bacteroides was negatively correlated with total cholesterol and low-density lipoprotein cholesterol (P < 0.01). The relative abundance of Coprococcus was negatively correlated with triglycerides and body mass index (all P < 0.05). PICRUSt functional prediction analysis showed that pathways related to Glycerophospholipid metabolism, ABC transporters, Phosphotransferase system, and Biofilm formation - Escherichia coli, and infectious diseases of pathogenic Escherichia coli were enriched in the hypercholesterolemia group. This work suggests a potential role of ileal mucosal microbiota in the development of hypercholesterolemia.

Pharmacokinetic/LDL-C and exposure-response analysis of tafolecimab in Chinese hypercholesterolemia patients: Results from phase I, II, and III studies.

Tafolecimab, a novel fully human monoclonal antibody targeting PCSK9, has been assessed in Chinese healthy volunteers and patients with hypercholesterolemia. This analysis is to develop and qualify a population pharmacokinetics (PopPKs)/LDL-C model to characterize tafolecimab PK and LDL-C profiles, evaluate the impact of potential covariates on tafolecimab, estimate individual predicted exposure, and LDL-C decreasing, furthermore, explore exposure-response relationship to support clinical use. Data from six clinical trials in China were used to develop the PopPK/LDL-C model. A Michaelis-Menten approximation of the target-mediated drug disposition (TMDD) model was used to describe PK data and indirect response (IDR) model was developed to estimate the LDL-C profile. A stochastic approximation expectation maximization algorithm was applied to estimate PopPK/LDL-C parameters. The PK/LDL-C time course data for tafolecimab were well described by TMDD/IDR model. Baseline covariates resulting in statistically significant changes in PK/LDL-C parameters included: body weight and sex on absorption rate constant; body weight, sex, and unbound PCSK9 on central volume; body weight and sex on clearance; baseline LDL-C on first-order rate constants for the removal of an effect); and disease and sex on maximum effect. However, the magnitudes of changes associated with these covariates do not necessitate dose adjustment. Exposure-efficacy relationship indicated that the nadir of LDL-C reduction achieved with the steady-state trough plasma concentration (Ctrough ) of tafolecimab at 5 μg/mL, and no further LDL-C decreasing with the increasing Ctrough . There was no exposure dependency observed in exposure-safety exploration. The PopPK/LDL-C model was successfully developed, validated, and predicted tafolecimab/LDL-C concentrations and individual exposures.

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 &lt;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 &lt;0.001), and –63.3%±23.7% (n=862) and –60.8±28.1% (n=352) in HC patients ( P &lt;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.

Abstract 15073: Response to PCSK9 Inhibition in Homozygous Familial Hypercholesterolemia Patients is Variable in Different Regions of the World and According to Age

Background: Reductions in LDL-C with PCSK9-inhibition in HoFH subjects are highly variable even within populations with the same pathogenic variants. Whilst initial studies were done in HoFH patients of European decent, recent studies from India and other countries with novel pathogenic variants as well as studies in paediatric patients have shown substantially less response to PCSK9 inhibition. In the global phase 3 LIBerate-HoFH trial, we evaluated two different PCSK9 inhibitors, lerodacibep (LIB) 300 mg SC QM and evolocumab (EVO) 420 mg SC QM in genetically confirmed HoFH patients on stable background lipid lowering therapy. Methods: Eligible patients (age ≥10 years) were randomized to either LIB or EVO for 24 weeks (Period A) followed by an 8 week ‘washout’ and crossed over to the alternate drug for the next 24 weeks (Period B). In a post-hoc analysis, the mean reduction in average LDL-C with both drugs were evaluated according to various world regions and age. Results: Of 65 who entered Period A, 56 completed both periods: 31 in USA/Europe/Israel/South Africa; 15 in India and 10 in Turkey. Mean baseline LDL-C was 401 mg/dL; 55% were female and 19(34%) were adolescents aged &lt;18 years. For the total population, the mean (SE) reduction in average LDL-C was -9.6% (3.25) on LIB and -11.7% (3.65) on EVO (p=0.44, NS). LDL-C reductions varied considerably in different regions and response was poorer in the adolescent subjects. However, reductions in LDL-C of ≥15% were seen in 26.8% (n=15) with LIB and 37.5% (n=21) with EVO - Table. Conclusions: Reductions in LDL-C achieved with PCSK9-inhibition in HoFH subjects are highly variable and differ according to region and age. However, given the clinically significant reductions in LDL-C in 1/3 of patients including patients from India and Turkey with null/null or novel variants, PCSK9 inhibition should remain part of standard of care for HoFH patients who remain with elevated LDL-C levels despite treatment with statin and ezetimibe.

Prevalence of familial hypercholesterolemia in patients with acute coronary syndrome

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim &amp;lt;br /&amp;gt;&amp;lt;/strong&amp;gt;To investigate the prevalence of familial hypercholesterolemia in patients with acute coronary syndrome (ACS).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;The study included fifteen patients with first or repeated ACS and treated/nontreated dyslipidaemia admitted to the Department of Cardiovascular Diseases of Clinical Hospital Centre Osijek between 1 January 2020 and 1 January 2021. The cut-off value of low-density lipoprotein (LDL)-C was 4.5mmol/L as a possible cut-off value for familial hypercholesterolemia presence. Data were collected from medical history and during patient&amp;amp;rsquo;s follow-up.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;Included patients that fulfilled criteria were predominantly male &amp;amp;ndash; 14 (93%), mean age 61 years. The median level of LDL cholesterol at admission because of ACS was 5.14 mmol/L, whereas the follow-up level after one year was 2.27 mmol/L (p=0.001). At first follow-up, 7 (46%) patients were treated with atorvastatin 80 mg or rosuvastatin 40 mg, 3 (20%) atorvastatin 80mg + ezetimibe 10mg, 2 (13%) with rosuvastatin 40 mg+ ezetimibe 10 mg, other patients were treated with a lower dose of statin or ezetimibe. According to LDL-C profile and by calculating the&amp;lt;br /&amp;gt;Dutch Lipid Clinic Network Score, one (of 15) patient was categorized as having definite familial hypercholesterolemia and two (of 15) as having probable familial hypercholesterolemia leading to the use of triple hypolipidemic therapy (statin+ezetimibe+PCSK9 inhibitor) in 2 (13%) patients (one female and one male).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;LDL-C level of 4.5 mmol/L and higher represents an indication for screening for familial hypercholesterolemia in patients with ACS. The prevalence of familial hypercholesterolemia in ACS, estimated by the Dutch Lipid Clinic Network Score, could be higher than previously reported.&amp;lt;/p&amp;gt;

Familial hypercholesterolaemia patients in a lipid clinic: Characteristics and outcomes

Familial hypercholesterolaemia patients in a lipid clinic: Characteristics and outcomes

Evaluation of a Nutraceutical Containing Monacolin 2.94 Mg on Lipid Profile in Hypercholesterolemic Patients in Primary Prevention

Evaluation of a Nutraceutical Containing Monacolin 2.94 Mg on Lipid Profile in Hypercholesterolemic Patients in Primary Prevention

Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients

The objective was to determine the effect of lycopene on the total cholesterol levels in patients with hypercholesterolemia at a hospital in Lima in 2018. The type of study was quantitative, and the design was analytical, longitudinal and prospective. The sample consisted of patients with hypercholesterolemia treated at the department of Nutrition of Sanidad de la Policia Nacional del Perú. Tomato juice containing lycopene was administered through a preparation based on tomato juice with olive oil, which was macerated for an average of 8 hours before being consumed. A total of 70 subjects were recruited; however, a total of 50 patients finished the study protocol. 21 received tomato juice with olive oil (TOO), 14 patients only received tomato juice (TJ), and 15 only had nutritional counseling regarding the low-calorie diet (LCD). According to this study, the tomato juice and olive oil preparation, as well as the diet, were related to differences on cholesterol measurement. These recommendations can help to lower cholesterol in patients.

LDL-C rebound after long-term evolocumab treatment and intravascular imaging evidence in a familial hypercholesterolemia patient with early-onset myocardial infarction.

LDL-C rebound after long-term evolocumab treatment and intravascular imaging evidence in a familial hypercholesterolemia patient with early-onset myocardial infarction.

Incidence of familial hypercholesterolemia in patients with acute coronary syndrome

Incidence of familial hypercholesterolemia in patients with acute coronary syndrome

Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trial

Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8mmol/L or non-FH patients with screening LDL-C level ≥3.4mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450mg Q4W, tafolecimab 600mg Q6W, placebo 450mg Q4W, or placebo 600mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n=411) or placebo (n=203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]:-65.0% [97.5% CI:-70.2%,-59.9%] for 450mg Q4W;-57.3% [97.5% CI:-64.0%,-50.7%] for 600mg Q6W; both P<0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8mmol/L, and LDL-C < 1.4mmol/L than placebo group at both dose regimens (all P<0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia. Tafolecimab dosed at 450mg Q4W and 600mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients. This study was sponsored by Innovent Biologics, Inc.