Hypercholesterolemic Patients Research Articles

Challenges in Improving Adherence to Diet and Drug Treatment in Hypercholesterolemia Patients.

Poor adherence to chronic disease treatment may seriously compromise the effectiveness of therapy, characterizing itself as a critical element for the population's health, both from the point of view of quality of life and health economics. The causes of low adherence are many and can depend on the patient, the physician and the healthcare system. Low adherence to dietary recommendations and lipid-lowering drug therapy for hypercholesterolemia is a widespread phenomenon that may strongly limit the great advantages of serum lipid reduction strategies in primary and secondary cardiovascular prevention. Many patients discontinue treatment, and adherence decreases with time. Increasing therapeutic adherence can have a much greater impact on the health of the population than any other therapeutic advance. There are numerous strategies to increase therapy adherence according to behavior change theories. They concern the doctor and the patient. Some must be implemented at the time of prescription, others later during the follow-up. The active role of the patient in the therapeutic decision and the shared definition of LDL cholesterol targets are of paramount importance. The aim of this narrative review is to summarize evidence on current levels of adherence to lipid-lowering strategies, the causes of the lack of adequate adherence and possible physician-applicable strategies to improve it.

ANMCO position paper on the management of hypercholesterolaemia in patients with acute coronary syndrome.

Patients suffering from acute coronary syndrome (ACS) present a high risk of recurrence and new adverse cardiovascular events after hospital discharge. Elevated plasma LDL-cholesterol (LDL-C) levels have been shown to be a causal factor for the development of coronary heart disease, and robust clinical evidence has documented that LDL-C levels decrease linearly correlates with a reduction in cardiovascular events. Recent studies have also demonstrated the safety and efficacy of an early and significant reduction in LDL-C levels in patients with ACS. In this position paper, Italian Association of Hospital Cardiologists proposes a decision algorithm on early adoption of lipid-lowering strategies at hospital discharge and short-term follow-up of patients with ACS, in the light of the multiple evidence generated in recent years on the treatment of hypercholesterolaemia and the available therapeutic options, considering current reimbursement criteria.

P364 LOW–DENSITY LIPOPROTEIN CHOLESTEROL REDUCTION IN PATIENTS AT VERY HIGH CARDIOVASCULAR RISK

Abstract Background Guidelines of treatment of hypercholesterolemia in patients at very high cardiovascular (CV) risk have progressively lowered the target LDL–cholesterol (LDL–C). In real life LDL–C targets are difficult to reach. Aim of this study was to evaluate the achievement of LDL–C targets and the prescription of lipid–lowering therapy (LLT) in a large cohort of outpatients at very high CV risk. Methods we considered 11350 patients at very high CV risk, mean age 70 years evaluated in Our Center from 2017 to 2020. The study population was divided in 3 groups according to the presence of one or more very high risk CV score components. For each group lipid–lowering therapy, LDL–C goal and prognosis were assessed. Results The very high CV risk population was composed maily by patients with coronary artery disease (CAD). We found an increse of LLT after the index cardiologic visit (from 50,5 to 75,8%) and high–efficacy (HE) LLT from 22% to 27,9%. Consequently we found an increase in the achievement of LDL–C target <55 mg/dl (1.4 mmol/l): from 3,2% to 8,3% 6 months after the visit. In the group with more CV risk components the LLT and HE LLT were more prescribed, the LDL–C target was more reached and the mortality rate were higher (22,3% vs 8,4% in patients with only one CV risk component). Conclusions in the very high CV risk population the target of LDL–C is rarely reached. We identificated patients with more CV risk components with worse prognosis and need of HE LLT.

Characterization of Adenosine A2A receptors expression in hypercholesterolemia to understand the cardiovascular risk

Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity worldwide. Hypercholesterolemia [elevated blood levels of total- and low-density lipoprotein-cholesterol (T-C and LDL-C)] is one of the main CVD risk factors and hypocholesterolemic treatments (statins, PCSK9 inhibitors, LDL-apheresis) are part of the daily patient care. During ischemia, hypoxia and inflammation, adenosine blood concentration increases and activates A2A adenosine receptors (A2AR, expressed by endothelial cells and lymphocytes), thus producing a protective effect via its vasodilatory and immunosuppressive functions. Alterations of A2A receptors expression and properties have been found in CVD patients. In a previous pilot study, we described a lower A2AR expression in peripheral blood mononuclear cells (PBMCs) of a small cohort of patients with heterozygous Familial hypercholesterolemia (HeFH), a severe genetic hyperlipidemia (Vairo et al., 2021). In this project, we would like to extend the characterization of A2AR expression in a larger cohort of patients with hypercholesterolemia (including heterozygous and homozygous FH and polygenic hypercholesterolemia) before and after hypocholesterolemic treatments and to understand whether 1) alterations of A2AR expression are broadly associated with hypercholesterolemia; 2) there is a correlation among A2AR expression, blood T-C and LDL-C levels and patient's clinical status; 3) all A2AR alterations may be rescued by hypocholesterolemic treatments. Hypercholesterolemic patients and healthy subjects are selected by age, gender and clinical status, including blood cholesterol levels (T-C > 240 mg/dL and/or LDL-C > 190 mg/dL). A2AR expression was explored in PBMCs by western blot and cytometry. We show on a small number of patients a decrease in A2A receptors expression compared with healthy subjects and an inverse correlation between A2AR expression and total- and LDL-cholesterol blood levels. Our results suggest that alterations of A2A receptors expression are associated with hypercholesterolemia and might help to better understand the high cardiovascular risk in hypercholesterolemia patients.

A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B

Familial hypercholesterolemia (FH) patients suffer from excessively high levels of Low Density Lipoprotein Cholesterol (LDL-C), which can cause severe cardiovascular disease. Statins, bile acid sequestrants, PCSK9 inhibitors, and cholesterol absorption inhibitors are all inefficient at treating FH patients with homozygous LDLR gene mutations (hoFH). Drugs approved for hoFH treatment control lipoprotein production by regulating steady-state Apolipoprotein B (apoB) levels. Unfortunately, these drugs have side effects including accumulation of liver triglycerides, hepatic steatosis, and elevated liver enzyme levels. To identify safer compounds, we used an iPSC-derived hepatocyte platform to screen a structurally representative set of 10,000 small molecules from a proprietary library of 130,000 compounds. The screen revealed molecules that could reduce the secretion of apoB from cultured hepatocytes and from humanized livers in mice. These small molecules are highly effective, do not cause abnormal lipid accumulation, and share a chemical structure that is distinct from any known cholesterol lowering drug.

Identification and Functional Analysis of APOB Variants in a Cohort of Hypercholesterolemic Patients.

Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.

LDL cholesterol targets rarely achieved in familial hypercholesterolemia patients: A sex and gender-specific analysis

Background and aimsDespite lipid lowering therapy (LLT), reaching LDL-C targets in patients with familial hypercholesterolemia (FH) remains challenging. Our aim was to determine attainment of LDL-C target levels and reasons for not reaching these in female and male FH patients. MethodsWe performed a cross-sectional study of heterozygous FH patients in five hospitals in the Netherlands and Norway. Clinical characteristics and information about LLT, lipid levels and reasons for not being on LDL-C treatment target were retrospectively collected from electronic medical records. ResultsWe studied 3178 FH patients (53.9% women), median age 48.0 (IQR 34.0–59.9) years. Median LDL-C before treatment and on-treatment was higher in women compared to men (6.2 (IQR 5.1–7.3) and 6.0 (IQR 4.9–7.2) mmol/l (p=0.005) and 3.0 (IQR 2.4–3.8) and 2.8 (IQR 2.3–3.5) mmol/L (p<0.001)), respectively. A minority of women (26.9%) and men (28.9%) reached LDL-C target. In patients with CVD, 17.2% of women and 25.8% of men reached LDL-C target. Women received less often high-intensity statins and ezetimibe. Most common reported reasons for not achieving the LDL-C target were insufficient effect of maximum LLT (women 17.3%, men 24.3%) and side effects (women 15.2%, men 8.6%). ConclusionsIn routine practice, only a minority of women and men with FH achieved their LDL-C treatment target. Extra efforts have to be made to provide FH patients with reliable information on the safety of statins and their long-term effects on CVD risk reduction. If statin treatment is insufficient, alternative lipid lowering therapies such as ezetimibe or PCSK9-inhibitors should be considered.

The Effect of 4-Methylcatechol on Platelets in Familial Hypercholesterolemic Patients Treated with Lipid Apheresis and/or Proprotein Convertase Subtilisin Kexin 9 Monoclonal Antibodies.

Elevated low-density lipoprotein (LDL) cholesterol levels lead to atherosclerosis and platelet hyperaggregability, both of which are known culprits of arterial thrombosis. Normalization of LDL cholesterol in familial hypercholesterolemia (FH) is not an easy task and frequently requires specific treatment, such as regularly performed lipid apheresis and/or novel drugs such as proprotein convertase subtilisin kexin 9 monoclonal antibodies (PCSK9Ab). Moreover, a high resistance rate to the first-line antiplatelet drug acetylsalicylic acid (ASA) stimulated research of novel antiplatelet drugs. 4-methylcatechol (4-MC), a known metabolite of several dietary flavonoids, may be a suitable candidate. The aim of this study was to analyse the antiplatelet effect of 4-MC in FH patients and to compare its impact on two FH treatment modalities via whole-blood impedance aggregometry. When compared to age-matched, generally healthy controls, the antiplatelet effect of 4-MC against collagen-induced aggregation was higher in FH patients. Apheresis itself improved the effect of 4-MC on platelet aggregation and blood from patients treated with this procedure and pretreated with 4-MC had lower platelet aggregability when compared to those solely treated with PCKS9Ab. Although this study had some inherent limitations, e.g., a low number of patients and possible impact of administered drugs, it confirmed the suitability of 4-MC as a promising antiplatelet agent and also demonstrated the effect of 4-MC in patients with a genetic metabolic disease for the first time.

Dyslipidemia and its features in primary biliary cholangitis

Primary biliary cholangitis, previously known as primary biliary cirrhosis, is a rare autoimmune liver disease that mostly affects women. Disorder of biliary excretion and enterohepatic circulation of bile acids in patients with primary biliary cholangitis in the early stages of the disease leads to their insufficient flow into the intestine and ingestion of bile acids into the general bloodstream. Insufficient intake of bile acids into the duodenum contributes to malabsorption, energetic malnutrition, and a slowly progressing weight loss. Pathophysiological mechanisms of the development of weight loss are related to impaired emulsification of fats and decreased absorption of hydrolyzed products - fatty acids and monoglycerides, steatorrhea in patients with primary biliary cholangitis as well as to dysbiosis of intestinal microflora. Already in the early stages of the disease, this leads to accelerated ß-oxidation of fatty acids, which is aimed at compensating for the developing nutritional energy deficiency. Entry of bile acids into the general bloodstream in primary biliary cholangitis is accompanied by dyslipidemia. The mechanism of hyperlipidemia in patients with primary biliary cholangitis differs from that in other conditions because along with the increase in total cholesterol, there is an increase in high-density lipoproteins and the appearance of unusual lipoprotein X (Lp-X). The appearance of the latter is most likely a protective reaction of the body aimed at the inactivation of bile acids detergent action on membrane structures of blood-forming elements and vascular endotheliocytes. Exactly bile acids, but not the content of total cholesterol, correlates with the level of lipoprotein X and determine its formation. Concomitant hypercholesterolemia in patients with primary biliary cholangitis is also aimed at neutralizing the detergent action of bile acids that entered the general bloodstream and is most likely a compensatory reaction of the body. “Abnormal” hypercholesterolemia in primary biliary cholangitis can serve as a model system to search for and develop new ways of dyslipidemia treatment, as it proceeds without increasing the frequency of cardiovascular events.

Effect Consumption of Papaya and Jicama Juice to Total Cholesterol Levels in Hypercholesterolemia Patients

Hypercholesterolemia is a metabolic disorder of lipoproteins which is characterized by high total cholesterol levels. Papaya and Jicama juice contains vitamin C. This is benefit to regulate the concentration of lipid plasma by inhibits the micelles forming, binding of bile through feces and produces short chain fatty acid that can reduce cholesterol synthesis. This study aimed to determined the effect of Papaya and Jicama Juice to decreased total cholesterol level of hypercholesterolemia patient at dr. M.Suherman Clinic Jember. This study was Quasy Experimental pretest-posttest with control group design. Total subjects were 24 taken by purposive sampling and divided into 2 group, namely control group (24) and treatment group (24) who consumed 180 ml of papaya and jicama juice, containing 65,45mg vitamin C for 7 days, once a day. The criteria of subjects was aged 30-60 years who had total cholesterol levels 200-240 mg/dl. Measurement of total cholesterol used GCU-meter Easy Touch. Data were analyzed used Independent t-test and paired t-tes. The results was total cholesterol level in treatment group before consumed juice was 226.17 mg/dl decreased 176.25 mg/dl after the juice was given. However, papaya and jicama juice had no significant effect (p=0.0103) on the decrease of total cholesterol levels.

Effect Consumption of Papaya and Jicama Juice to Total Cholesterol Levels in Hypercholesterolemia Patients

Effect Consumption of Papaya and Jicama Juice to Total Cholesterol Levels in Hypercholesterolemia Patients

Exposure to oxLDL impairs TGF-β activity in human tendon cells

BackgroundPrevious studies have shown that patients with hypercholesterolemia experience elevated levels of oxidized LDL (oxLDL), a molecule which triggers inflammation and collagenase activity. In this study we discovered novel mechanistic effects of oxLDL on tendon cells and the mediators regulating matrix remodeling by analyzing the expression and activity of related proteins and enzymes. These effects may contribute to tendon damage in patients with high cholesterol.MethodsIsolated human tendon cells (male and female donors age 28 ± 1.4 age 37 ± 5.7, respectively) were incubated in the presence or absence of oxLDL. The influence of oxLDL on the expression level of key mRNA and proteins was examined using real time quantitative PCR, ELISA and Western blots. The activities of enzymes relevant to collagen synthesis and breakdown (lysyl oxidase and matrix metalloproteinases) were quantified using fluorometry. Finally, the isolated human tendon cells in a 3D construct were exposed to combinations of oxLDL and TGF-β to examine their interacting effects on collagen matrix remodeling.ResultsThe one-way ANOVA of gene expression indicates that key mRNAs including TGFB, COL1A1, DCN, and LOX were significantly reduced in human tendon cells by oxLDL while MMPs were increased. The oxLDL reduced the activity of LOX at 50 µg/ml, whereas conversely MMP activities were induced at 25 µg/ml (P ≤ 0.01). COL1A1 synthesis and TGF-β secretion were also inhibited (P ≤ 0.05). Adding recombinant TGF-β reversed the effects of oxLDL on the expression of collagens and LOX. OxLDL also impaired collagen matrix remodeling (P ≤ 0.01), and adding TGF-β restored the native phenotype.ConclusionExposure to oxLDL in patients with hypercholesterolemia may adversely affect the mechanical and structural properties of tendon tissue through a direct action of oxLDL on tendon cells, including impairment of TGF-β expression. This impairment leads to disturbed matrix remodeling and synthesis, thereby potentially leading to increased risk of acute or chronic tendon injury. Our discovery may provide an opportunity for developing effective treatments for tendon injury in hypercholesterolemia patients by targeting the TGF-β pathway.

Association of triglyceride-glucose index with atherosclerotic cardiovascular disease and mortality among familial hypercholesterolemia patients

BackgroundFamilial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients.MethodsData from National Health and Nutrition Examination Survey (NHANES) 1999–2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: < 8.5, 8.5–9.0, and > 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves.ResultsTyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p < 0.001). The risk of ASCVD increased by 74% with every 1 unit increase of TyG index (95%CI: 1.15–2.63, p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p < 0.05).ConclusionTyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality.

Nephrotic Syndrome and Statin Therapy: An Outcome Analysis.

Background and Objectives: Hypercholesterolemia in patients with nephrotic syndrome (NS) may predispose to cardiovascular events and alter kidney function. We aimed to evaluate statins efficiency in NS patients under immunosuppression using four endpoints: remission rate (RR), end-stage kidney disease (ESKD), major cardiovascular events (MACE), and thrombotic complications (VTE). Materials and Methods: We retrospectively examined the outcome at 24 months after diagnosis of 154 NS patients (age 53 (39-64) years, 64% male, estimated glomerular filtration rate (eGFR) 61.9 (45.2-81.0) mL/min). During the follow-up, the lipid profile was evaluated at 6 months and at 1 and 2 years. Results: The median cholesterol level was 319 mg/dL, and 83% of the patients received statins. Patients without statins (17%) had similar age, body mass index, comorbidities, blood lipids levels, NS severity, and kidney function. The most used statin was simvastatin (41%), followed by rosuvastatin (32%) and atorvastatin (27%). Overall, 79% of the patients reached a form of remission, 5% reached ESKD, 8% suffered MACE, and 11% had VTE. The mean time to VTE was longer in the statin group (22.6 (95%CI 21.7, 23.6) versus 20.0 (95%CI 16.5, 23.5) months, p 0.02). In multivariate analysis, statin therapy was not associated with better RR, kidney survival, or fewer MACE; however, the rate of VTE was lower in patients on statins (HR 2.83 (95%CI 1.02, 7.84)). Conclusions: Statins did not improve the remission rate and did not reduce the risk of MACE or ESKD in non-diabetic nephrotic patients. However, statins seemed to reduce the risk of VTE. Further randomized controlled studies are needed to establish statins' role in NS management.

ASSOCIATION OF THE ALLELIC STATE OF THE GNB3 (RS5443) AND AGT (RS4762) GENES WITH ANTHROPOMETRIC, ME TABOLIC- HORMONAL PARAMETERS AND INDICATORS OF MINERAL METABOLISM IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION

The аim of research – to analyze the dependence of changes in metabolic- hormonalparameters and indicators of mineral metabolism depending on the allelic state of theAGT (rs4762) and GNB3 genes in patients with essential arterial hypertension (EAH).Material and methods. The case-control study involved 100 patients with EAH stageII, 1-3 degrees of blood pressure (BP), high and very high cardiovascular risk. Amongthe patients there were 21% (21) men, 79% (79) women. The mean age of patients was59.86±6.22y.o. The control group consisted of 60 almost healthy individuals, relevantin age (49.13±6.28y.o.) and gender distribution (63% – women, 37% – men). To studyAGT (rs4762) and GNB3 (rs5443) genes polymorphism a qualitative polymerasechain reaction (PCR) was performed in real time. The lipid panel parameters, such as:Total cholesterol (TC), Triglycerides (ТG), Low-density and High-density lipoproteincholesterol (LDL-C, HDL-C) were investigated in the blood plasma, using diagnostickits «Accent 200» (Poland). The atherogenic index (AI) was calculated by the equation:(TC – HDL-C)/ HDL-C. All recruited subjects were tested for serum levels of fastingglucose, ionized calcium, parathyroid (PTH) hormone, 25-hydroxyvitamin D.Results. The activity of certain metabolic processes is associated with the allelic state of theAGT (rs4762) and GNB3 (rs5443) genes in patients with EAH: carriers of the T-allele ofthe AGT gene (rs4762) have a glucose level 27.36% higher than that of owners of the CCgenotype (Р СС = 0.032), while KA, on the contrary, is lower 14.41% (Р СС =0.047) witha probable difference in women – 14.90% (Р СС =0.046); the presence of the TT-genotype ofthe GNB3 gene (rs5443) in patients with EAH is associated with hypercholesterolemia: thecontent of cholesterol probably exceeds that of homozygous owners of the wild C-allele 13.95%(Р СС =0.037). Hormonal- messenger indicators of the regulation of mineral metabolismdo not depend on the allelic state of the GNB3 gene (rs5443), while in the owners of theT-allele of the AGT gene (rs4762) a lower level of total metabolites of vitamin D in the blood(at the " deficiency" level) was established – 14, 97% (Р СС =0.002), againsta background of a compensatory increase in PTH concentration – 29.18% (Р СС =0.025).Conclusions.The mutated T-allele of the AGT gene (rs4762) is associated with hyperglycemia,hypovitaminosis D and a compensatory increase in PTH, and the TT-genotype of the GNB3gene (rs5443) is associated with hypercholesterolemia in patients with EAH.

Cholesterol-Related lncRNAs as Response Predictors of Atorvastatin Treatment in Chilean Hypercholesterolemic Patients: A Pilot Study

Statins are currently the treatment of choice for hypercholesterolemia. However, wide interindividual variability has been observed in the response to treatment. Recent studies have reported the role of lncRNAs in the metabolism of lipids; nevertheless, there are few studies to date that show their role in the response to treatment with statins. Thus, the aim of this study was to assess the levels of expression of three lncRNAs (RP1-13D10.2; MANTIS; lncHR1) associated with genes involved in cholesterol homeostasis in leukocyte cells of hypercholesterolemic patients after treatment with atorvastatin and compare them with levels in subjects with normal cholesterol levels. A secondary aim was to assess the levels of expression in monocytic THP-1 cells differentiated to macrophages. The study included 20 subjects with normal cholesterol (NC) levels and 20 individuals with hypercholesterolemia (HC). The HC patients were treated with atorvastatin (20 mg/day/4 weeks). THP-1 cells were differentiated to macrophages with PMA and treated with different doses of atorvastatin for 24 h. Expression of lncRNAs was determined by RT-qPCR. The lncRNAs RP1-13D10.2 (p < 0.0001), MANTIS (p = 0.0013) and lncHR1 (p < 0.0001) presented increased expression in HC subjects compared with NC subjects. Furthermore, atorvastatin had a negative regulatory effect on the expression of lncHR1 (p < 0.0001) in HC subjects after treatment. In vitro, all the lncRNAs showed significant differences in expression after atorvastatin treatment. Our findings show that the lncRNAs tested present differential expression in HC patients and play a role in the variability reported in the response to atorvastatin treatment. Further research is needed to clarify the biological impact of these lncRNAs on cholesterol homeostasis and treatment with statins.

ANMCO Position paper: Management of hypercholesterolemia in patients with acute coronary syndrome

Patients suffering from acute coronary syndromes (ACS) present a high risk of recurrence and new adverse cardiovascular events after hospital discharge. Elevated plasma LDL-cholesterol (LDL-C) levels have been shown to be a causal factor for the development of coronary heart disease, and robust clinical evidence has documented that a decrease of LDL-C levels correlates linearly with a reduction in cardiovascular events. Recent studies have also demonstrated the safety and efficacy of an early and significant reduction in LDL-C levels in patients with ACS.In this position paper, ANMCO proposes a decision algorithm on early adoption of lipid-lowering strategies at hospital discharge and short-term follow-up of patients with ACS, in the light of the multiple evidence generated in recent years on the treatment of hypercholesterolemia and the available therapeutic options, considering current reimbursement criteria.

Treatment with PCSK9 Inhibitor Evolocumab Improves Vascular Oxidative Stress and Arterial Stiffness in Hypercholesterolemic Patients with High Cardiovascular Risk.

Atherosclerosis and atherosclerotic-related cardiovascular diseases (ASCVD) are characterized by high serum levels of low-density lipoprotein cholesterol (LDL-C) that can promote the generation of reactive oxygen species (ROS). To answer the need for better LDL-C control in individuals at high and very high risk for CVD, a new injectable innovative family of lipid-lowering (LL) monoclonal antibodies against the protein convertase subtilisin/kexin type 9 (PCSK9) has been approved. However, the effect of these drugs on vascular function, such as ROS generation and arterial stiffness, has not already been extensively described. In this report, we present data from 18 males with high to very high CV risk undergoing LL treatment (LLT) with either statin and ezetimibe or ezetimibe monotherapy, who experienced, after a 2-month treatment with Evolocumab, a significant improvement in blood pressure (BP)-adjusted carotid-femoral pulse wave velocity (cfPWV) (p-value = 0.0005 in the whole cohort, p-value = 0.0046 in the sub-cohort undergoing background LLT with statin and ezetimibe, p-value = 0.015 in the sub-cohort undergoing background LLT with ezetimibe monotherapy), which was significantly associated with a decrease in freshly isolated leukocytes (PBMCS)-derived H2O2 production (p-value = 0.004, p-value = 0.02 and p-value = 0.05, respectively, in the whole cohort, in the statin + ezetimibe sub-cohort, and the ezetimibe sub-cohort). Our observations support the role of systemic oxidative stress in atherosclerosis and give a further rationale for using Evolocumab also for its effect in vascular disorders linked to oxidative processes.

Severe Dyslipidemia Mimicking Familial Hypercholesterolemia Induced by High-Fat, Low-Carbohydrate Diets: A Critical Review

Emerging studies in the literature describe an association between high-fat, low-carbohydrate diets and severe hypercholesterolemia consistent with the levels observed in patients with (homozygous) familial hypercholesterolemia (FH). High levels of low-density lipoprotein cholesterol (LDL-C) may result from the reduced clearance of LDL particles from the circulation, the increased production of their precursor, or a combination of both. The increased intake of (saturated) fat and cholesterol, combined with limited to no intake of carbohydrates and fiber, are the main features of diets linked to hypercholesterolemia. However, several observations in previous studies, together with our observations from our lipid clinic, do not provide a definitive pathophysiological explanation for severe hypercholesterolemia. Therefore, we review these findings and possible pathophysiological explanations as well as opportunities for future research. Altogether, clinicians should rule out high-fat, low-carbohydrate diets as a possible cause for hypercholesterolemia in patients presenting with clinical FH in whom no mutation is found and discuss dietary modifications to durably reduce LDL-C levels and cardiovascular disease risk.

The Management of Hypercholesterolemia in Patients with Neuromuscular Disorder.

We describe and discuss the safety of statins and non-statin drugs in neuromuscular disorders (NMDs). We also propose a pragmatic model of care for the management of such cases. Patients with both NMD and hypercholesterolemia may be particularly disadvantaged owing to the toxic effects of cholesterol-lowering therapy and the inability to take medication. Specifically, the management of hypercholesterolemia in patients with NMD is complicated by the increased risk of statin-related myotoxicity and concerns that statins may aggravate or possibly induce the onset of a specific NMD. The most severe form of statin-related myotoxicity is immune-mediated necrotizing myopathy. Management of hypercholesterolemia in patients with NMDs include treating modifiable factors, consideration of toxicity risk of statin, use of non-statin lipid lowering agents, noting possible drug interactions, and careful monitoring.