Hypercholesterolemic Patients Research Articles

Comparative Analysis between Martin’s Formula and Friedewald’s Formula with Direct Homogenous Assay for Estimating Low Density Lipoprotein Cholesterol Level in Nepalese Population

Background: Low density lipoproteinforms a basis of decision making in treatment of hypercholesterolemic patients and primary target of intervention. Its cost effective and accurate measurementis a need for every clinical laboratories and different calculation methods has been adopted as a replacement to direct assays. This study aims to evaluate the Martin’s formula and Friedewald’s formula in a sample of Nepalese population compared against direct homogenous assay.
 Materials and Methods: This is a cross-sectional study conducted in Department of Biochemistry from Feb 2020 to January 2021. Serum samples of the participants were analysed for total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein. Martin’s and Friedewald’s formula were applied to get calculated value of low density lipoprotein from both methods. Passing and Bablok regression analysis was used for methods comparison.
 Results: The mean age of participants was 54.2 ± 8.9 years. Passing-Bablok regression analysis showed Friedewald’s formula performed better than Martin’s formula as per systematic and proportional bias when compared with directassay. However at lowerserum low density lipoprotein level, underestimation of low density lipoprotein compared to direct assay was more common in Friedewald’s formula. At high triglyceride level more percentage error of difference of mean from direct assay was found for Friedewald’s formula.
 Conclusion: When compared to direct assay, Friedewald’s formula was found to be in better agreement than Martin’s formula. Martin’s formula had advantage over Friedewald’s formula at lower serum low density lipoprotein level and higher triglyceride level where Friedewald’s formula mostly underestimated low density lipoprotein.

Beyond Statins and PCSK9 Inhibitors: Updates in Management of Familial and Refractory Hypercholesterolemias.

Elevation in apolipoprotein B-containing lipoproteins in the blood is a cause of atherosclerosis. Statins have changed the preventive cardiology scenario, and more recently monoclonal proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors were added as robust agents to further reduce pro-atherogenic lipoproteins and therefore prevent cardiovascular events. However, despite this many dyslipidemic individuals persist with inadequate LDL-C levels and still at risk. The purpose of this review was to discuss current status and describe advances in therapies beyond statins and monoclonal PCSK9 inhibitors. Ezetimibe and lomitapide have been used for many years to further reduce LDL-C and longer term data reinforce their safety. Bempedoic acid, an inhibitor of adenosine triphosphate-citrate lyase, has been shown to add LDL-C reduction on top of statins and ezetimibe, furthermore it may be an alternative for statin intolerant patients. Inclisiran is a small interfering ribonucleic acid inhibitor that reduces the hepatic production of PCSK9 that induces robust LDL-C lowering, similar to monoclonal antibodies, with the advantage of 2 or 3 injections per year. So far, no safety signs were seen with its use. Evinacumab, a monoclonal antibody that binds angiopoietin-like protein 3 (ANGPTL3), induces robust LDL-C lowering in either homozygous familial hypercholesterolemia or severe hypercholesterolemia patients with good tolerability. Many high-risk individuals persist with elevated LDL-C, newer medications further lower LDL-C on top of standard lipid-lowering therapies and are well tolerated. Ongoing clinical trials may prove if these novel medications will reduce cardiovascular events with safety.

Efektivitas Pengetahuan Keluarga dalam Pemberian Jus Buah Alpukat pada Pasien Hiperkolesterolemia

Consuming avocado can maintain heart health. Avocados are rich in compounds called beta-sitosterol which have been shown to be effective in lowering blood cholesterol levels. This literature review aimed to analyze the effectiveness of family knowledge in administering avocado juice to hypercholesterolemic patients. The quantitative this study explores evidence published in electronic databases such as Google Scholar and Pubmed, using a search strategy, we identified 4 articles that are objectives potentially and relevant to the research objectives and these articles were included in the final analysis. This study showed the effectiveness of family knowledge in administering avocado juice to hypercholesterolemic patients. in results of research from several articles in in literature review indicate to family knowledge is effective in administering avocado juice to hypercholesterolemic patients.

Integrated analysis of microRNA and mRNA expression profiles in homozygous familial hypercholesterolemia patients and validation of atherosclerosis associated critical regulatory network

Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder characterized by an extremely elevated serum level of low-density lipoprotein cholesterol (LDL-C) and accelerated premature atherosclerotic cardiovascular diseases (ASCVD). However, the detailed mechanism of how the pathogenic mutations of HoFH trigger the acceleration of ASCVD is not well understood. Therefore, we performed high-throughput RNA and small RNA sequencing on the peripheral blood RNA samples of six HoFH patients and three healthy controls. The gene and miRNA expression differences were analyzed, and seven miRNAs and six corresponding genes were screened out through regulatory network analysis. Validation through quantitative PCR of genes and miRNAs from 52 HoFH patients and 20 healthy controls revealed that the expression levels of hsa-miR-486-3p, hsa-miR-941, and BIRC5 were significantly upregulated in HoFH, while ID1, PLA2G4C, and CACNA2D2 were downregulated. Spearman correlation analysis found that the levels of ID1, hsa-miR-941, and hsa-miR-486-3p were significantly correlated with additional ASCVD risk factors in HoFH patients. This study represents the first integrated analysis of transcriptome and miRNA expression profiles in patients with HoFH, a rare disease, and as a result, six differentially expressed miRNAs/genes that may be related to atherosclerosis in HoFH are reported. The miRNA–mRNA regulatory network may be the critical regulation mechanism by which ASCVD is accelerated in HoFH.

Association between testosterone and lipid profiles under statin therapy and its clinical impact on the cardiovascular event risk.

Statin therapy may decrease the levels of serum steroid hormones, including testosterone and cortisol, accompanied by lowering low-density lipoprotein cholesterol (LDL-C) levels, which remains to be investigated. The aim of this study is to examine the association between steroid hormones and lipids under statin therapy and its clinical impact on the cardiovascular event risk from a viewpoint of steroid hormone metabolism. Using a population dataset extracted from the standard versus intEnsive statin therapy for hyper-cholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) study, we analyzed the correlation between steroid hormones and lipid profiles at registration and 1year after registration, comparing between malepatients with or without cardiovascular events (CV events) within 4years (CV events + ; n = 100, and CV events-; n = 100, respectively) after prognostic score matching. The risk for CV events was evaluated using conditional logistic regression analysis. Testosterone levels were lower in the CV events + group than in the CV events - group at registration (5.2 ± 2.2 vs. 7.6 ± 4.1ng/mL, p < 0.001). Testosterone levels were lowered to 5.1ng/mL on average in proportion with LDL-C lowering, and Δtestosterone was correlated with ΔLDL-C during 1year after registration. Cortisol levels were not correlated with LDL-C levels. In addition, testosterone levels at 1year after registration were not associated with cardiovascular event risk. In male hypercholesterolemic patients with diabetic retinopathy, testosterone levels were positively correlated with LDL-C levels, which were mildly lowered in proportion with LDL-C lowering under mild statin therapy. This decrease in testosterone levels under statin therapy was not related to the increase in cardiovascular event risk.Clinical trial registration: UMIN 000003486. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004199.

Antiplatelet Effects of PCSK9 Inhibitors in Primary Hypercholesterolemia.

Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel group of hypolipidemic drugs that are recommended particularly for high-risk hypercholesterolemia patients, including those with primary hypercholesterolemia (PH), where lifelong exposure to high low-density lipoprotein (LDL) cholesterol levels results in an elevated risk of atherosclerosis at an early age. The onset and progression of atherosclerosis is significantly influenced by activated platelets. Oxidized LDL influences platelet activation by interacting with their surface receptors and remodeling the composition of their cell membrane. This results in platelet aggregation, endothelial cell activation, promotion of inflammation and oxidative stress, and acceleration of lipid accumulation in atherosclerotic plaques. PCSK9 inhibitors reduce platelet activation by both significantly lowering LDL levels and reducing the LDL receptor-mediated activation of platelets by PCSK9. They also work synergistically with other hypolipidemic and antithrombotic drugs, including statins, ezetimibe, acetylsalicylic acid, clopidogrel, and ticagrelor, which enhances their antiplatelet and LDL-lowering effects. In this review, we summarize the currently available evidence on platelet hyperreactivity in PH, the effects of PCSK9 inhibitors on platelets, and their synergism with other drugs used in PH therapy.

MicroRNA-33b is a Potential Non-Invasive Biomarker for Response to Atorvastatin Treatment in Chilean Subjects With Hypercholesterolemia: A Pilot Study

Evidence accumulated so far indicates that circulating levels of microRNAs (miRNAs) are associated with several pathologies. Therefore, differential expression of extracellular miRNAs exhibits promising potential for screening and diagnosis purposes. We evaluated plasma miRNAs in response to the lipid-lowering drug atorvastatin in patients with hypercholesterolemia (HC) and controls. Methods: We selected miRNAs based on previous data reported by our group and also by employing bioinformatics tools to identify 10 miRNAs related to cholesterol metabolism and statin response genes. Following miRNA identification, we determined plasma levels of miRNA-17-5p, miRNA-30c-5p, miRNA-24-3p, miRNA-33a-5p, miRNA-33b-5p, miRNA-29a-3p, miRNA-29b-3p, miRNA-454-3p, miRNA-590-3p and miRNA-27a-3p in 20 HC patients before and after 1 month of 20 mg/day atorvastatin treatment, evaluating the same miRNA set in a group of 20 healthy subjects, and employing qRT-PCR to determine differential miRNAs expression. Results: HC individuals showed significant overexpression of miRNA-30c-5p and miRNA-29b-3p vs. NL (p = 0.0008 and p = 0.0001, respectively). Once cholesterol-lowering treatment was concluded, HC individuals showed a substantial increase of three extracellular miRNAs (miRNA-24-3p, miRNA-590, and miRNA-33b-5p), the latter elevated more than 37-fold (p = 0.0082). Conclusion: Data suggest that circulating miRNA-30c-5p and miRNA-29b-3p are associated with hypercholesterolemia. Also, atorvastatin induces a strong elevation of miRNA-33b-5p levels in HC individuals, which could indicate an important function that this miRNA may exert upon atorvastatin therapy. Additional studies are needed to clarify the role of this particular miRNA in statin treatment.

Effectiveness of statin intensive therapy in type 2 diabetes mellitus with high visit-to-visit blood pressure variability.

Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, the evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. We investigated the effectiveness of intensive versus standard statin therapy in the primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability. The standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy study was the first trial comparing statin intensive therapy targeting low-density lipoprotein cholesterol (LDL-C) <70 mg/dl and standard therapy targeting LDL-C ≥100 to <120 mg/dl in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within the initial 6 months. In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45-0.90) and 1.21 (95% CI 0.82-1.80) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (P = 0.018). The analysis using ARV of SBP showed similar results. Statin intensive therapy targeting LDL-C <70 mg/dl had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit-to-visit SBP variability.

Small Dense Low-Density Lipoprotein Cholesterol is a Potential Marker for Predicting Laser Treatment for Retinopathy in Diabetic Patients.

Aim: We explored the superiority of small dense low-density lipoprotein cholesterol (sdLDL-C) as a marker for predicting not only the occurrence of cardiovascular (CV) events but also the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy. Methods: We performed a sub-analysis of the intEnsive statin therapy for hyper-cholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) study (n=5042), in which patients were assigned randomly to intensive or standard statin therapy targeting low-density lipoprotein cholesterol ＜70 mg/dl or 100-120 mg/dl. Using the survival analysis, the risks for CV events and the need for laser treatment were evaluated according to the lipids one year after registration. Results: The patients were 63±11 years old. LDL-C and sdLDL-C levels were 98±25 and 32±14 mg/dl, respectively, one year after registration. The sdLDL-C level had a strong positive correlation with apolipoprotein B level (r=0.83 at registration). SdLDL-C was a sensitive marker for predicting CV events when comparing among the quartiles according to sdLDL-C levels (hazard ratios: HR for quartiles 1-4 were 1.0, 1.4, 1.6, and 2.5, respectively;p for trend ＜0.01). Also, sdLDL-C was a sensitive marker for predicting the need for laser treatment among lipids (log rank,p=0.009), especially in patients with elderly (≧65 yrs) and obesity (BMI ≧25 kg/m2). Conclusions: SdLDL-C is a sensitive target marker to predict cardiovascular events as well as the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy.

Effect of Lactobacillus paracasei HII01 Supplementation on Total Cholesterol, and on the Parameters of Lipid and Carbohydrate Metabolism, Oxidative Stress, Inflammation and Digestion in Thai Hypercholesterolemic Subjects

Hypercholesterolemia is one of the leading causes of cardiovascular disease. Probiotics can help to improve high blood lipid levels in hypercholesterolemia patients. Lactobacillus paracasei has been reported to have beneficial effects in several subjects; however, there is a lack of studies on Thai hypercholesterolemic subjects. Thus, this study was conducted in order to investigate the effect of L. paracasei HII01 on cholesterol, oxidative stress, and other biomarkers. Fifty-two subjects were randomized into two groups: the L. paracasei treatment group and the placebo group. The study was conducted over an intervention period of 12 weeks of supplementation. The results show that L. paracasei HII01 significantly reduced the total cholesterol (TCH), triglycerides (TGs), tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS) of the patients, and increased their HDL, total antioxidant capacity (TAC) and propionic acid compared to the placebo group. Moreover, the supplementation of L. paracasei HII01 significantly increased lactic acid, IL-10 and IFN-γ, and substantially decreased malondialdehyde (MDA) at the end of the treatment. The results suggest that L. paracasei HII01 improves the blood lipid profile, reduces oxidative stress, and is beneficial for health among Thai hypercholesterolemic subjects.

Anti-PCSK 9 antibodies increase the ratios of the brain-specific oxysterol 24S-hydroxycholesterol to cholesterol and to 27-hydroxycholesterol in the serum.

The serum ratios of the brain-specific oxysterol 24S-hydroxycholesterol (24S-OHC) to cholesterol and to 27-OHC reflect brain cholesterol turnover. We studied the effect of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) that enhance low-density lipoprotein receptor activity on serum cholesterol and oxysterol concentrations. Twenty-eight hypercholesterolaemic patients (15 males and 13 females) responding insufficiently to maximally tolerated statin and/or ezetimibe therapy were additionally subcutanously treated biweekly with either the PCSK9ab alirocumab (150 mg, n =13) or evolocumab (140 mg, n =15). Fasting serum cholesterol was measured by gas chromatography and the oxysterols 24S-OHC and 27-OHC using gas chromatography-mass spectrometry before, after 1-month (n =28) and after 3-month (n =13) treatment. As expected, PCSK9ab treatment lowered serum cholesterol and oxysterol levels after 1 month. The serum ratio of 24S-OHC to cholesterol increased after 1 month by 17 ± 28% (mean ± standard deviation; 95% confidence interval [CI]: 5.8 to 28%; P< .01) and 24S-OHC to 27-OHC by 15 ± 39% (95% CI: 0.2 to 30%; P< .01). Within 3 months, 24S-OHC to cholesterol increased by 2.8 μg g-1 mo-1 (95% CI: 2.1 to 3.6; P< .01) and 24S-OHC to 27-OHC by 0.019 mo-1 (95% CI: 0.007 to 0.032; P< .01). The serum ratios of 24S-OHC to cholesterol and to 27-OHC increased after treatment with PCSK9ab. We hypothesize that this is caused by a reduced entrance of 27-OHC into the brain, increased synthesis of brain cholesterol, increased production of 24S-OHC and its secretion across the blood-brain barrier.

Diet-Responsive Hypercholesterolemia With Cardiofaciocutaneous Syndrome Type 3

Background: Molecular basis of diet responsive hypercholesterolemia remains unclear. We report diet-responsive severe hypercholesterolemia in a young female with cardiofaciocutaneous syndrome type 3 (CFC3) due to a heterozygous pathogenic MAP2K1 variant, suggesting a role of common MAPK variants in LDL-cholesterol (LDL-C) response to diet. Clinical case: A 3-year-old Caucasian female with CFC3 (macrocephaly, frontal bossing, wide nasal root with depressed bridge, anteverted nares, low set fleshy ears, congenital pulmonic valve stenosis, postnatal growth deficiency, hypotonia, and neurocognitive impairment) due to a de novo heterozygous c.389A>G, p.Tyr130Cys pathogenic variant in MAP2K1, presented with extremely elevated serum total cholesterol of 446 mg/dL, triglycerides of 239 mg/dL, HDL-cholesterol of 53 mg/dL, LDL-C of 335 mg/dL (normal range < 110 mg/dL) and serum apolipoprotein B level 219 mg/dL (normal range < 90 mg/dL). Her LDL-C was 252 mg/dL a year ago and 215 mg/dL one month prior to presentation. Reducing total dietary fat to 20–25% of total energy and saturated fat to <6% of total energy over the next 4 months lowered LDL-C to 104 mg/dL. However, her weight decreased by 0.5 kg and liberalization of fat intake again increased LDL-C to 222 mg/dL. Her father has mildly elevated LDL-C of 160 mg/dL and her mother had normal LDL-C of 80 mg/dL. Her plasma phytosterol levels were normal and she had ApoE3/E3 genotype. Targeted genetic testing of the patient and parents showed a benign heterozygous LDL receptor (LDLR) variant c.2242G>A; p.Asp748Asn, (Minor allele frequency 0.00008) in the patient and her father. Whole exome sequencing of the patient and both parents showed no known disease-causing variants in LDLR, APOB, PCSK9, LDLRAP1, APOE, STAP1, LIPA, ABCG5, ABCG8 and other known hyperlipidemia-related genes. There are no previous reports of hypercholesterolemia in patients with CFC3. MAP2K1 stimulates various MAP kinases upon wide variety of extra- and intracellular signal and is involved in cell proliferation, differentiation, transcription regulation and development. Previous studies of the relationship between p42/44MAPK activation and LDLR expression in human hepatoma HepG2-derived cell line showed that that activation of the Raf-1/MEK/p42/44MAPK cascade induces LDLR expression and modulation of the Raf-1 kinase signal strength can determine LDLR expression levels. Thus, extent of MAPK activation can alter signaling of LDLR, resulting in hypercholesterolemia. Conclusion: Our case report suggests that MAP2K1 may play a significant role in LDLR signaling, and some MAP2K1 variants may be associated with diet-responsive hypercholesterolemia. Larger studies are required to assess dietary response to LDL-C in subjects with MAP2K1 variants.

Identification of a Positive Association between Mammary Adipose Cholesterol Content and Indicators of Breast Cancer Aggressiveness in a French Population

BackgroundSeveral studies have recently highlighted important roles for adipose tissue in cancer. However, few have examined adipose tissue cholesterol, and no study has been performed in breast adipose tissue associated with breast tumors. ObjectivesThe present work was designed to determine if breast adipose tissue cholesterol from the tumor-surrounding area is associated with breast cancer aggressiveness. MethodsBetween 2009 and 2011, 215 breast adipose tissue samples were collected at the Tours University Hospital (France) during surgery of women (aged 28–89 y) with invasive breast cancer. Associations of free cholesterol (FC), esterified cholesterol (EC), and total cholesterol (TC) amounts with clinical variables (age, BMI, and treated or untreated hypercholesterolemia) and tumor aggressiveness parameters [phenotype, grade, presence of inflammatory breast cancer (IBC), and multifocality] were tested using Student’s t test and after ANOVA. ResultsThe predominant form of cholesterol in adipose tissue was FC, and 50% of patients had no detectable EC. The adipose tissue FC content (μg/mg total lipid) was 18% greater in patients >70 y old than in those 40–49 y old (P < 0.05) and the TC content tended to be 12% greater in untreated hypercholesterolemic patients than in normocholesterolemic patients (P = 0.06). Breast adipose cholesterol concentrations were increased in tissues obtained from patients with human-epidermal-growth-factor-receptor-2 (HER2) phenotype (+13% FC; P < 0.05 compared with luminal A), IBC (+15% FC; P = 0.06 compared with noninflammatory tumors), as well as with multifocal triple-negative tumors (+34% FC, P < 0.05; +30% TC, P < 0.05, compared with unifocal triple-negative tumors). Among patients with triple-negative tumors, hypercholesterolemia was significantly more common (P < 0.05) in patients with multifocal tumors (64%) than in patients with unifocal tumors (25%). ConclusionsThis study is the first of this magnitude that analyzes cholesterol concentrations in adipose tissue from female breast cancer patients. An increase in breast adipose tissue cholesterol content may contribute to breast cancer aggressiveness (HER2 phenotype, multifocality of triple-negative tumors, and IBC).

Evaluation of the combination of Kemuning Leaves Extracts and Simvastatin on Blood fatty acids and amino acids of Hyperlipidemic Model Rats

Introduction: Hypercholesterolemia is an increase in cholesterol levels and a high risk of cardiovascular disease. Simvastatin, a cholesterol-lowering agent, is commonly applied in hypercholesterolemic patients. Simvastatin is metabolized by CYP3A4 so that any drugs that block CYP3A4 will elevate the statin level in the blood. Kemuning leaves (Murraya paniculata L.) contain Mahanimbine, has been known to have an antihyperlipidemic effect. Some people used Kemuning leaves besides to simvastatin treatment so that the interaction between the two substances can occur. The aims of this study to determine the effects of the combination of Kemuning leaves extracts with simvastatin. Method: Six-weeks-old male Wistar rats were randomly divided into nine experimental groups (n = 5 per group). The rat of two groups was fed with a regular diet or with a high-fat diet (HFD) for five weeks. The daily food and HFD groups were administered with 0.5% Carboxymethylcellulose (CMC) as a vehicle or suspension of Simvastatin 2.04 mg/kg of body weight or Kemuning leaves extracts 100, 200, and 400 mg/kg body weight. During the whole treatment, body weight and food intake were recorded every week. Lipid profile was evaluated by spectrophotometric method; amino acid concentration and fatty acid concentration were determined using LCMS-MS. Results: In vivo experiment showed that a single administration of simvastatin and three different doses of Kemuning extracts could reduce the high level of total cholesterol, LDL-cholesterol, and Triglyceride in the hyperlipidemic model rat. But when simvastatin was combined with three kinds of doses of Kemuning extracts, the value had the tendency to show lower than a single administration of simvastatin either Kemuning extracts. We confirmed the lipid and amino acid profiles in plasma and found that similar results. Conclusion: This study indicated that the single administration of simvastatin or Kemuning extract was better than combining them because the combination was causing interaction of each of them by influence fatty acid and amino acids metabolism.

Familial hypercholesterolemia and statins in the COVID-19 era: Mitigating the risk of ischemic stroke.

There is a continuing need for research about the underlying mechanisms behind ischemic strokes in COVID-19 patients. Pre-existing endothelial dysfunction, especially if it is accompanied by a viral infection of the endothelial cells may present an important mechanism behind the immunothrombotic/thromboembolic complications of the COVID-19 illness. Here we emphasize that pharmacotherapy with statins could partly counteract such pathophysiological scenarios. Accordingly, using familial hypercholesterolemia (FH) as a pertinent example of a lifelong endothelial dysfunction, we aim to make the clinicians and consulting neurologists aware of statins as a possible adjuvant therapy in the context of an increased risk of ischemic stroke in patients with COVID-19. Based on recent clinical evidence, there is a need to encourage clinicians and consulting neurologists to continue or initiate effective statin treatment to prevent an ischemic stroke, particularly when they encounter a hypercholesterolemic COVID-19 patient with FH.

Clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia

BackgroundAbnormal lipid metabolism manifests as hypercholesterolemia in patients with obstructive jaundice due to lipoprotein X (LpX). Our aim was to explore the clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia in a large number of samples. MethodsA total of 665 patients with obstructive jaundice were included and categorized into two groups (with/without dyslipidemia) based on the ratio of the sum of HDL-c and LDL-c to total cholesterol [(HDL-c + LDL-c)/TC] with a cut-off value of 0.695. Laboratory liver, kidney, and blood lipid parameters were determined. Cholesterol composition assessment was performed by ultracentrifugation and high-performance liquid chromatography (UC-HPLC), and serum protein profiles were analyzed by capillary electrophoresis. ResultsLiver function in patients with obstructive jaundice accompanied by dyslipidemia was more aggravated than that in patients with simple obstructive jaundice (P < 0.05). The (HDL-c + LDL-c)/TC ratio was negatively correlated with bilirubin levels (P < 0.05). In addition, the difference in ApoB/LDL-c ratios was statistically significant between the obstructive jaundice accompanied by dyslipidemia group and healthy control group (P < 0.05). The LDL-c concentration determined by the UC-HPLC method was more than five times that determined by the enzymatic method (P < 0.05). Bisalbuminemia was found in 43 of 60 patients with obstructive jaundice accompanied by hypercholesterolemia. ConclusionsIn patients with obstructive jaundice, the decreased (HDL-c + LDL-c)/TC ratio may be a novel marker to identify dyslipidemia secondary to LpX. The decreased ratio was associated with poor liver function and indicated disease progression.

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients.

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting. Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state. Design: A commercial liquid preparation of long-chain triglycerides (Supracal®; ω6/ω3 ratio >20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after administration (postprandial state). Flow cytometry was employed to determine platelet and leukocyte activation, and the levels of circulating platelet-leukocyte aggregates. Soluble markers were determined by ELISA, and the parallel-plate flow chamber was employed to study leukocyte adhesion to the dysfunctional arterial endothelium. Results: The PH group had a lower percentage of activated platelets and circulating type 1 monocytes, and blunted neutrophil activation after the OUFL, accompanied by a significant increase in the percentage of regulatory T lymphocytes. In this group, the OUFL led to a significant impairment of leukocyte adhesion to the dysfunctional [tumor necrosis factor α (TNFα)-stimulated] endothelium and reduced the plasma levels of soluble P-selectin, platelet factor-4 (PF-4)/CXCL4, CXCL8, CCL2, CCL5, and TNFα. Conclusion: The OUFL has a beneficial impact on the pro-thrombotic and pro-inflammatory state of PH patients and might be a promising macronutrient approach to dampen the systemic inflammation associated with PH and the development of further cardiovascular events.

Reduced global longitudinal strain at rest and inadequate blood pressure response during exercise treadmill testing in male heterozygous familial hypercholesterolemia patients

BackgroundHeterozygous familial hypercholesterolemia (heFH) is a genetic disorder leading to premature coronary artery disease (CAD). We hypothesized that the subclinical pathophysiologic consequences of hypercholesterolemia may be detected before the occurrence of clinically overt CAD by stress testing and myocardial strain imaging. Patients-methodsWe evaluated the treadmill tests (ETTs) of 46 heFH men without known arterial hypertension/diabetes mellitus/vasculopathy like CAD and of 39 healthy men matched for age, baseline systolic/diastolic blood pressure (BP) and heart rate (HR), using Bruce protocol. Global longitudinal strain (GLS) of the left ventricle (LV) additionally to ejection fraction was obtained. ResultsheFH men reached a significantly higher peak systolic and diastolic BP compared to controls (p = 0.002 and p < 0.001, respectively). Mean rate pressure product was significantly higher in heFH patients (p = 0.038). Both duration of the ETT and workload in metabolic equivalents was lower in the heFH group (p < 0.001 and p < 0.001, respectively). Baseline to peak rise of systolic and diastolic BP in heFH men was higher (p = 0.008 and p < 0.001 for systolic and diastolic BP, respectively). Furthermore, heFH men had higher rise of HR from baseline to peak, compared to controls; (p = 0.047). GLS in heHF men was slightly decreased (p = 0.014), although the ejection fraction was similar in both groups. ConclusionheFH men have a higher rise in systolic/diastolic BP during ETT, which may reflect early, preclinical hypertension. Furthermore, slight impairment of LV GLS is present, despite the absence of apparent myocardial dysfunction in conventional 2D echocardiography.

Screening of PCSK9 and LDLR genetic variants in Familial Hypercholesterolemia (FH) patients in India.

Familial Hypercholesterolemia (FH) is an autosomal, dominant, inherited disorder characterized by severely elevated LDL-cholesterol (LDL-C) levels with high risk for Coronary Artery Disease (CAD). There are limited genetic studies especially on genes other than Low Density Lipoprotein receptor (LDLR) conducted in Indian population. Thus, our aim was to screen the entire Proprotein Convertase Subtilisin/Kexin type 9 gene (PCSK9) gene & hotspot exons 3, 4 and 9 of LDLR gene in FH cases and controls. 50 FH cases were categorized into definite, probable and possible cases according to Dutch Lipid Network Criteria (DLNC) who were gender matched with 50 healthy controls. All 12 exons of PCSK9, and hotspot exons 3, 4 & 9 of LDLR gene were screened through High Resolution Melt (HRM) curve analysis. Enzyme linked immunosorbent assay was performed to measure circulating PCSK9 levels. Total cholesterol and LDL-C were significantly high in all three groups of cases. Total 8 nonpathogenic variants in exon 1, 5, 7 and 9 of the PCSK9 gene were detected. In LDLR gene, 3 known pathogenic and 1 benign variant were found in exon 3 & 4. In FH cases, PCSK9 levels were significantly high compared to controls (P = 0.0001), and were directly correlated to LDL-C (P = 0.0001) and Total Cholesterol (P = 0.0001). Our study is first to screen the entire PCSK9 gene in western part of India. Since no pathogenic variants were identified, it is possible that PCSK9 variants are clinically less relevant. However, 3 known pathogenic variants were found in the LDLR gene. These findings support our understanding of the genetic spectrum of FH in India.

Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force

Background and aimsThis European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients. MethodsEvidence-based review. ResultsStatin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus. ConclusionsThis guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.