[First-line treatment of hypercholesterolemia : start with statin monotherapy or ezetimibe-statin combination ?] / Comment je traite...une hypercholestérolémie en première intention : statine seule ou combinaison ézétimibe-statine d'emblée ?

Hypercholesterolemia, especially LDL-C («Low-Density-Lipoprotein - Cholesterol¼), is a major cardiovascular risk factor, especially for coronary artery disease. Patients at high or very high cardiovascular risk should reach LDL concentrations as low as possible («the lower, the better¼), with a reduction of at least 50 % from baseline levels according to the most recent guidelines, especially those in secondary prevention. An ezetimibe-statin combination most often allows to reach this goal thanks to a complementary action. The objectives of this article are to remind the dual actions of these two medications, to summarize the clinical evidence showing not only a remarkable cholesterol-lowering effect but also a reduction in cardiovascular events in both controlled trials and observational real-life studies, to specify the positioning of this combined oral therapy in the last international guidelines and to mention pharmaceutical specialties that combine ezetimibe with a statin available for the practitioner.

L'hypercholestérolémie, en particulier le LDL-C («Low-Density-Lipoprotein - Cholesterol¼), est un facteur de risque cardiovasculaire, notamment coronarien, majeur. Les patients à haut ou très haut risque cardiovasculaire doivent atteindre des concentrations de LDL les plus basses possibles (concept du «the lower, the better¼), avec une diminution d'au moins 50 % des valeurs de base selon les dernières recommandations, tout particulièrement ceux en prévention secondaire. Une combinaison ézétimibe-statine permet souvent d'atteindre cet objectif grâce à une action complémentaire. Le but de cet article est de rappeler la dualité des mécanismes d'action de ces deux approches, de résumer les évidences cliniques montrant non seulement un remarquable effet hypocholestérolémiant mais aussi une réduction des événements cardiovasculaires dans les essais cliniques et dans les études observationnelles de vraie vie, de préciser la position de cette combinaison thérapeutique orale dans les dernières recommandations internationales et de mentionner les spécialités pharmaceutiques associant l'ézétimibe à une statine mises à la disposition du praticien.

Pharmacists as clinical care partners: How a pharmacist-led intervention is associated with improved medication adherence in older adults with common chronic conditions.

BACKGROUND: Hypertension, hyperlipidemia, and type 2 diabetes (T2D) are 3 of the most common chronic conditions, but related medication adherence rates are far below 80%. Consequences of poor adherence include high health care utilization/costs and increased mortality. There is accumulating evidence in support of the benefits of affording pharmacists the opportunity to practice at the full scope of their licensure by engaging in patients' clinical care. OBJECTIVE: To examine the impact of a large national pharmacy chain's pharmacist-led interventions to improve medication adherence among older adults with hypertension, hyperlipidemia, or T2D. A secondary objective was to estimate the potential cost savings associated with improved adherence. METHODS: Participants were Medicare patients aged 18 years or older who had 2 or more prescription fills in at least 1 of the 3 therapeutic classes. The primary outcome, optimal adherence, was defined as proportion of days covered (PDC) of 80% or higher. A difference-in-differences (DID) design with a generalized linear model analytical approach was applied to examine differences between intervention participants and controls. The study period spanned from 2020 to 2022. RESULTS: Intervention participants (n = 317,613, age 70.1 years, female sex 57.0%) had lower baseline optimal adherence than controls (n = 943,389, age 73.3, female sex 56.1%) for diabetes (76.9% vs 79.8%), hypertension (79.0% vs 83.0%), and cholesterol (78.6% vs 82.1%). The DID results showed that between 2020 and 2022, optimal adherence had significant absolute increases for intervention participants (diabetes: +4.0%, hypertension: +6.3%, cholesterol: +6.1%) vs controls who declined in adherence (diabetes: -1.6%, hypertension: -0.4%, cholesterol: -1.4%). All DID models were significant at P < 0.0001. Total cost of care was projected based on improvements in adherence. Based on PDC improvements for the test population, we estimate that the pharmacist consultations were associated with annual total health care cost savings of $10,329,284 ($109 per capita), $31,640,660 ($122 per capita), and $21,589,875 ($75 per capita) for test population patients with diabetes, hypertension, and hyperlipidemia, respectively. CONCLUSIONS: The study found that the pharmacist-led interventions were significantly associated with increased optimal adherence over 2 years. These findings demonstrate the potential of pharmacist-led interventions to improve medication adherence among older adults with chronic conditions. Strategies to expand pharmacist-provided care must be further examined.

Brief communications: changes in inflammatory biomarkers and lipid profiles after switching to long-acting cabotegravir plus rilpivirine.

We assessed whether the impact of cabotegravir plus rilpivirine on inflammation reduction differs from that of oral antiretrovirals, using real-world data. Inflammatory biomarkers and lipid profiles were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. The CD4/CD8 ratio and C-reactive protein did not change. There were transient decreases in CD8 and CD4 counts in the group that switched from the dolutegravir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein (HDL) cholesterol increased, resulting in a decrease in the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol.

Effects of Neonatal Hypoxic-Ischemic Injury on Brain Sterol Synthesis and Metabolism.

BACKGROUND: Neonatal hypoxic-ischemic brain injury (HIBI) results from disruptions to blood supply and oxygen in the perinatal brain. The goal of this study was to measure brain sterol metabolites and plasma oxysterols after injury in a neonatal HIBI mouse model to assess for potential therapeutic targets in the brain biochemistry as well as potential circulating diagnostic biomarkers. METHODS: Postnatal day 9 CD1-IGS mouse pups were randomized to HIBI induced by carotid artery ligation followed by 30 minutes at 8% oxygen or to sham surgery and normoxia. Brain tissue was collected for sterol analysis by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Plasma was collected for oxysterol analysis by LC-MS/MS. RESULTS: There were minimal changes in brain sterol concentrations in the first 72 hours after HIBI. In severely injured brains, there was a significant increase in desmosterol, 7-DHC, 8-DHC, and cholesterol 24 hours after injury in the ipsilateral tissue. Lanosterol, 24-dehydrolathosterol, and 14-dehydrozymostenol decreased in plasma 24 hours after injury. Severe neonatal HIBI was associated with increased cholesterol and sterol precursors in the cortex at 24 hours after injury. CONCLUSIONS: Differences in plasma oxysterols were seen at 24 hours but were not present at 30 minutes after injury, suggesting that these sterol intermediates would be of little value as early diagnostic biomarkers.

The genetics of autosomal dominant familial hypercholesterolemia.

ABSTRACT: Familial hypercholesterolemia (FH) is one of the most common genetic conditions. Affected individuals are unable to metabolize cholesterol due to inherited changes in the low-density lipoprotein (LDL) receptor, which impairs the ability to metabolize cholesterol, resulting in extremely high levels of cholesterol that leads to premature coronary artery disease. Autosomal dominant FH is caused by variants in several genes, which may present as heterozygous FH (less severe) or homozygous FH (more severe). Clinical diagnosis may be more likely when there is a family history of two or more first-degree relatives with total and LDL-cholesterol (LDL-C) level elevations, a child is identified, or the affected individual or close relatives have tendon xanthomas and/or progressive atherosclerosis. This article provides an overview of autosomal dominant FH, including disease prevalence, clinical diagnostic criteria, genetic variants, diagnostic testing, pathognomonic findings, and treatment options. It also shares a brief case, which highlights challenges associated with genetic test interpretation and the importance of including experienced providers in the diagnosis and treatment of this underdiagnosed and often untreated or undertreated genetic condition.

Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke.

Ischemic white matter injury leads to long-term neurological deficits and lacks effective medication. Growth arrest specific protein 6 (Gas6) clears myelin debris, which is hypothesized to promote white matter integrity in experimental stroke models. By the middle cerebral artery occlusion (MCAO) stroke model, we observed that Gas6 reduced infarcted volume and behavior deficits 4 weeks after MCAO. Compared with control mice, Gas6-treatment mice represented higher FA values in the ipsilateral external capsules by MRI DTI scan. The SMI32/MBP ratio of the ipsilateral cortex and striatum was profoundly alleviated by Gas6 administration. Gas6-treatment group manifested thicker myelin sheaths than the control group by electron microscopy. We observed that Gas6 mainly promoted OPC maturation, which was closely related to microglia. Mechanically, Gas6 accelerated microglia-mediated myelin debris clearance and cholesterol transport protein expression (abca1, abcg1, apoc1, apoe) in vivo and in vitro, accordingly less myelin debris and lipid deposited in Gas6 treated stroke mice. HX531 (RXR inhibitor) administration mitigated the functions of Gas6 in speeding up debris clearance and cholesterol transport protein expression. Generally, we concluded that Gas6 cleared myelin debris and promoted cholesterol transportation protein expression through activating RXR, which could be one critical mechanism contributing to white matter repair after stroke.

4,8-Dicarboxyl-8,9-iridoid-1-glycoside inhibits apoptosis in human osteoarthritis chondrocytes via enhanced c-MYC-mediated cholesterol metabolism in vitro.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease related to cholesterol metabolism disorders. However, current therapies for OA are insufficient and no convincing disease-modifying OA drugs exist. Therefore, we aimed to elucidate the mechanism by which borojoa iridoid glycoside (BIG) inhibits chondrocyte apoptosis in OA. METHODS: Borojoa pulp was heated to 70 °C, and the main active substance in borojoa, BIG, was extracted by fractionation at an ultraviolet 254-nm absorption peak. Chondrocytes were identified by immunohistochemistry and visualized by immunofluorescence confocal microscopy. The proliferation of chondrocytes cultured with BIG was determined by MTS assay. The apoptosis of chondrocytes cultured with BIG was tested by Annexin V-FITC/PI, and the cytokine, protein, and cholesterol levels in chondrocytes were detected by ELISA, RT‒qPCR, Western blot, and biochemistry analyses. Protein‒protein interactions were verified by a coimmunoprecipitation (Co-IP) assay. RESULTS: BIG promoted chondrocyte proliferation and reduced apoptosis in vitro. BIG induced an alteration of the total RNA profiles in chondrocytes, and bioinformatic analysis showed that BIG inhibited chondrocyte apoptosis by promoting c-MYC expression; KEGG analysis confirmed that BIG-inhibited apoptosis was enriched in the cell cycle pathway. Flow cell cycle experiments confirmed that BIG promoted chondrocyte proliferation by significantly increasing the S phase cell number. The c-MYC inhibitor 10058-F4 stimulated the increased expression of IL-1ß, IL-6, TNF-α, and AGEs and suppressed the cholesterol metabolism, which promoted chondrocyte apoptosis and autophagy. Co-IP analysis showed that BIG promoted the interaction of c-MYC and CH25H, Bcl-2, which suggests that BIG could inhibit chondrocyte apoptosis in part by enhancing c-MYC-mediated cholesterol metabolism. CONCLUSIONS: This study confirmed that BIG promotes chondrocyte proliferation and inhibits apoptosis and autophagy, and BIG improving OA is associated with cholesterol metabolism. The results identify a potential mechanism by which BIG enhances c-MYC-mediated CH25H regulation of cholesterol metabolism in vitro and suggest that BIG might be a promising new drug against OA.

Potential anti-obesity effects of two-graded doses of Iraqi Hibiscus tiliaceus leaves extract, alone and in combination with orlistat, on high-fat diet-induced obesity in male rats.

Obesity is a world health concern and a serious risk factor for several chronic diseases. Hibiscus tiliaceus is a plant with reported anti-obesity properties. However, the preclinical anti-obesity effect of ethanolic extract of Iraqi Hibiscus tiliaceus has not been studied yet. This study aimed to evaluate the preclinical anti-obesity properties of Iraqi Hibiscus tiliaceus extract, alone or in combination with orlistat, on high-fat diet-induced obesity in male rats. Male rats were divided into five groups: control, induction, ethanolic extract of Iraqi Hibiscus tiliaceus (250 mg/kg and 500 mg/kg), orlistat (Xenical) alone (10 mg/kg), and a combination of the extract (250 mg/kg) with Xenical. The rats were fed a high-fat diet to induce obesity, and treatments were given orally for 8 weeks. Body weight, food intake, serum lipid profile, and liver enzymes were measured. Administration of ethanolic extract of Iraqi Hibiscus tiliaceus (250 mg/kg and 500 mg/kg), Xenical alone (10 mg/kg), and combination with the extract (250 mg/kg) for 8 weeks significantly reduced body weight, food intake, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and liver enzymes (aspartate transaminase and alanine transaminase) when compared to the induction group. The ethanolic extract of Iraqi Hibiscus tiliaceus showed anti-obesity effects and could be a potential therapeutic agent in managing obesity. However, further studies are needed to evaluate its clinical efficacy and safety.

Effect of systemic atorvastatin on bone regeneration in critical-sized defects in hyperlipidemia: an experimental study.

PURPOSE: Hypocholesterolemic medications similar to atorvastatin are efficient in lowering blood lipid levels; however, compared to other medications in the statin family, their impact on bone metabolism is claimed to be insufficient. The impact of atorvastatin on bone regeneration in dental implantology in individuals with hyperlipidemia who received atorvastatin in the clinic is doubtful. METHODS: In the study, 16 male New Zealand rabbits of 6 months were used. All rabbits were fed a high-cholesterol diet for 8 weeks, and hyperlipidemia was created. It was confirmed that the total cholesterol level in rabbits was above 105 mg/dl. A critical-sized defect was created in the mandible. The defect was closed with xenograft and membrane. Oral 10 mg/kg atorvastatin was started in the experimental group, and no drug was administered in the control group. At 16th week, animals were sacrificed. For histomorphological examination, the new bone area, osteoclast, and osteoblast activities were evaluated. RESULTS: While new bone area (45,924 µm2, p < 0.001) and AP intensities (105.645 ± 16.727, p = 0.006) were higher in the atorvastatin group than in the control group, TRAP intensities in the control group (82.192 ± 5.346, p = 0.021) were higher than that in the atorvastatin group. CONCLUSIONS: It has been found that high blood lipid levels will adversely affect bone graft healing and the use of systemic atorvastatin contributes to bone healing. Clinicians should pay attention to the selection of surgical materials, considering the importance of questioning drug use in their patients and the risks in cases of non-use.

Impact of Dyslipidemia Medications on the Prevalence of Diabetic Retinopathy Among a Large US Cohort.

BACKGROUND AND OBJECTIVE: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. PATIENTS AND METHODS: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022. Prevalence and prevalence odds ratios (POR) were calculated. RESULTS: Patients taking pitavastatin (OR 0.64, 95% CI 0.49, 0.84), fenofibrate (OR 0.83, CI 0.79, 0.87), or evolocumab (OR 0.80, CI 0.68, 0.95) had lower POR of proliferative DR compared to nonproliferative DR. Patients taking any cholesterol medication had a lower POR of vitreous hemorrhage. Patients taking fibrates also had lower POR of neovascular glaucoma. CONCLUSION: This exploratory study highlights positive associations between DR and dyslipidemia and medications that may have fewer worsening events in DR patients. [Ophthalmic Surg Lasers Imaging Retina 2023;54:626-633.].

Effect of Grape Seed Procyanidins Combined with Allicin on Lipid Levels in Hyperlipidemic Rats.

OBJECTIVES: To study the effects of grape seed proanthocyanidins (GSP) combined with allicin on serum lipids level and vascular damage in a rat model of hyperlipidemia. MATERIALS AND METHODS: SD rats(male, 170-220 gn= 40) were randomized into five groups (n = 8/group): modelhigh fat and cholesterol diet; controlnormal diet; model+low-dose (GSP+allicin )(GSP 45mg/kg, allicin 30mg/kg, orally); model+high-dose (GSP+allicin) (GSP180mg/kg, allicin 90mg/kg, orally) and positive control (model+simvastatin (4 mg/kg)). Normal control group was fed conventionally, and remaining four groups were fed high cholesterol and fat food to replicate the high fat model. After 9 weeks, the normal control group continued to receive regular feeding, while the other groups continued to receive high-fat feeding. At the same time, model and normal control groups were given equal volume of physiological saline by gavage, and the other treatment groups began to receive corresponding drugs by gavage once a day. After 4 weeks, serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) as well as high-density lipoprotein cholesterol (HDL-C) in rats were determined. And the body weight of rat, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA)in serum were identified. The level of endothelin-1(ET-1) was quantitative analysis by ELISA assay. RESULTS: In comparison to normal controls, the model group displayed a marked rise in body weight, an increment in serum concentrations of LDL-C, TG and TC, as well as a decline in HDL (P<0.01), demonstrating successful model replication; All doses of GSP in combination with allicin resulted in a reduction in TG, LDL-C, and TC and an enhancement in HDL-C in contrast to the model control (all P<0.05). High-dose (GSP+allicin ) decreased MDA, and increased T-AOC and SOD activity(all P<0.01). All doses of GSP combined with allicin decreased ET-1 (all P<0.05). In addition, the protective effect of GSP combined with allicin was dose-dependent. CONCLUSIONS: Studies have shown that GSP combined with allicin can significantly improve blood lipids in hyperlipidemic rats, and this mechanism may be related to antioxidants and reduced endothelial damage.

Targeting cholesterol metabolism in Cancer: From molecular mechanisms to therapeutic implications.

Cholesterol is an essential component of cell membranes and helps to maintain their structure and function. Abnormal cholesterol metabolism has been linked to the development and progression of tumors. Changes in cholesterol metabolism triggered by internal or external stimuli can promote tumor growth. During metastasis, tumor cells require large amounts of cholesterol to support their growth and colonization of new organs. Recent research has shown that cholesterol metabolism is reprogrammed during tumor development, and this can also affect the anti-tumor activity of immune cells in the surrounding environment. However, identifying the specific targets in cholesterol metabolism that regulate cancer progression and the tumor microenvironment is still a challenge. Additionally, exploring the potential of combining statin drugs with other therapies for different types of cancer could be a worthwhile avenue for future drug development. In this review, we focus on the molecular mechanisms of cholesterol and its derivatives in cell metabolism and the tumor microenvironment, and discuss specific targets and relevant therapeutic agents that inhibit aspects of cholesterol homeostasis.

Predictors of HbA1c treatment response to add-on medication following metformin monotherapy: a population-based cohort study.

Evidence on the influence of patient characteristics on HbA1c treatment response for add-on medications in patients with type 2 diabetes (T2D) is unclear. This study aims to investigate the predictors of HbA1c treatment response for three add-on medications (sulfonylureas (SU), dipeptidyl peptidase-4 (DPP-4) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor) in metformin monotherapy treated patients with T2D. This retrospective cohort study was conducted using the electronic health record data from six primary care clinics in Singapore. A total of 9748 adult patients with T2D on metformin monotherapy receiving SU, DPP-4 or SGLT-2 add-on were 1:1 propensity score matched to patients receiving other add-on medications. Patient demographics, laboratory results, diabetes related complications, comedications, and treatment response at two endpoints (HbA1c reduction ≥ 1% at 6th month, HbA1c goal attainment < 7% at 12th month) were examined. Multiple logistic regression analyses were used to identify patient characteristics associated with the treatment responses. After matching, there were 1073, 517, and 290 paired cohorts of SU, DPP-4 and SGLT-2 respectively. Besides baseline HbA1c, patients with longer hypertension disease duration and higher cholesterol HDL were associated with better treatment response to SU medication add-on. Lower estimated glomerular filtration rate (eGFR), and angiotensin-II receptor medications were associated with better treatment response to DPP-4 add-on. Lower cholesterol HDL, higher creatinine serum, absence of renal complications and beta-blockers medications were associated with better treatment response to SGLT-2 add-on. The cholesterol HDL, creatinine serum, eGFR, hypertension disease duration, angiotensin-II receptors and beta-blockers class of medications can influence the HbA1c treatment response for SU, DPP-4 and SGLT-2 add-on medications. Knowing the patients' characteristics that influence treatment response can assist in guiding clinical decisions when selecting the appropriate add-on medication, ultimately helping to prevent the development of diabetes-related complications.

Efficacy of Poria cocos and Alismatis rhizoma against diet-induced hyperlipidemia in rats based on transcriptome sequencing analysis.

Hyperlipidemia, a common metabolic disease, is a risk factor for cardiovascular diseases, Poria cocos (PC) and Alismatis rhizoma (AR) serve as a potential treatment. A systematic approach based on transcriptome sequencing analysis and bioinformatics methods was developed to explore the synergistic effects of PC-AR and identify major compounds and potential targets. The phenotypic characteristics results indicated that the high dose (4.54 g/kg) of PC-AR reduced total cholesterol (TC), elevated high-density lipoprotein cholesterol (HDL-C) levels, and improved hepatocyte morphology, as assessed via hematoxylin and eosin (H&E) staining. Transcriptomic profiling processing results combined with GO enrichment analysis to identify the overlapping genes were associated with inflammatory responses. The cytokine-cytokine receptor interaction pathway was found as a potential key pathway using geneset enrichment analysis. Core enrichment targets were selected according to the PC-AR's fold change versus the model. Real-time quantitative PCR analysis validated that PC-AR significantly downregulated the expression of Cxcl10, Ccl2, Ccl4, Cd40 and Il-1ß mRNA (P < 0.05). Molecular docking analysis revealed the significant compounds of PC-AR and the potential binding patterns of the critical compounds and targets. This study provides further evidence that the therapeutic effects of PC-AR on hyperlipidemia in rats through the regulation of inflammation-related targets.

Dynamical modeling the effect of glucagon-like peptide on glucose-insulin regulatory system based on mice experimental observation.

As an emerging global epidemic, type 2 diabetes mellitus (T2DM) represents one of the leading causes of morbidity and mortality worldwide. Existing evidences demonstrated that glucagon-like peptide-1 (GLP-1) modulate the glucose regulatory system by enhancing the ß-cell function. However, the detailed process of GLP-1 in glycaemic regulator for T2DM remains to be clarified. Thus, in this study, we propose an Institute of Cancer Research (ICR) mice high fat and cholesterol dietary experimental data-driven mathematical model to investigate the secretory effect of GLP-1 on the dynamics of glucose-insulin regulatory system. Specifically, we develop a mathematical model of GLP-1 dynamics as part of the interaction model of ß-cell, insulin, and glucose dynamics. The parameter estimation and data fitting are in agreement with the data in mice experiments In addition, uncertainty quantification is performed to explore the possible factors that influence the pathways leading to the pathological state. Model analyses reveal that the high fat or high cholesterol diet stimulated GLP-1 plays an important role in the dynamics of glucose, insulin and ß cells in short-term. These results show that enhanced GLP-1 may mitigate the dysregulation of glucose-insulin regulatory system via promoting the ß cells function and stimulating secretion of insulin, which offers an in-depth insights into the mechanistic of hyperglycemia from dynamical approach and provide the theoretical basis for GLP-1 served as a potential clinical targeted drug for treatment of T2DM.

Lipid profile changes associated with antiretroviral therapies in a real-world cohort. / [Artículo traducido] Cambios en el perfil lipídico asociados con las terapias antirretrovirales en una cohorte de vida real.

OBJECTIVE: To compare lipid profile changes and cardiovascular events among HIV naïve and experienced patients from a real-world cohort treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. METHOD: A retrospective cohort study in HIV naïve and experienced people at a reference hospital in Spain was done. During the follow-up (March 2015-June 2019), patients were treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. Epidemiological, clinical and immunovirological variables were recorded. A statistical analysis of the lipid profile at baseline, 48 and 120 weeks after initiating the study therapy, cardiovascular events (myocardial infarction, heart failure, cerebrovascular accident, deep venous thrombosis, myocardiopathy, non-ST- segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction) and cardiovascular risks factors was performed. Data were analysed in naïve and experienced patients from each of the study treatments. The data was obtained from the medical history. The statistical analysis was performed with SPSS v.24 software. RESULTS: A total of 266 and 191 patients receiving treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine were included in the study, respectively. After 120 weeks of treatment, a worsening of the lipid profile was found in the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group, both in naïve and experienced patients, whereas not so conspicuously observed in the dolutegravir/abacavir/lamivudine group. Statistically significant differences between both groups were found in experienced patients favoring dolutegravir/abacavir/lamivudine; in total cholesterol (204.1 ± 38.2 vs. 187.3 ± 29.4, p < 0.001) and LDL-C (126.1 ± 31.9 vs. 113.5 ± 28.5, p = 0.001) at week 48, and in total cholesterol (201.1 ± 33.4 vs. 188.7 ± 33.9, p = 0.013) and HDL-C (54.2 ± 15.6 vs. 48.3 ± 14.3, p = 0.01) at week 120. No significant differences in cardiovascular events were found, neither in naïve nor in experienced patients. CONCLUSIONS: The lipid profile among elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group worsened throughout the follow-up, both in naïve and experienced patients, not so remarkable in the dolutegravir/abacavir/lamivudine group. Both regimens were well tolerated, with similar rates of cardiovascular events.

The role of the ATP-Binding Cassette A1 (ABCA1) in neurological disorders: a mechanistic review.

INTRODUCTION: Cholesterol homeostasis is critical for normal brain function. It is tightly controlled by various biological elements. ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that effluxes cholesterol from cells, particularly astrocytes, into the extracellular space. The recent studies pertaining to ABCA1's role in CNS disorders were included in this study. AREAS COVERED: In this comprehensive literature review, preclinical and human studies showed that ABCA1 has a significant role in the following diseases or disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, neuropathy, anxiety, depression, psychosis, epilepsy, stroke, and brain ischemia and trauma. EXPERT OPINION: ABCA1 via modulating normal and aberrant brain functions such as apoptosis, phagocytosis, BBB leakage, neuroinflammation, amyloid ß efflux, myelination, synaptogenesis, neurite outgrowth, and neurotransmission promotes beneficial effects in aforementioned diseases. ABCA1 is a key molecule in the CNS. By boosting its expression or function, some CNS disorders may be resolved. In preclinical studies, liver X receptor agonists have shown promise in treating CNS disorders via ABCA1 and apoE enhancement.

Determinants of arterial stiffness in patients with type 2 diabetes mellitus: a cross sectional analysis.

In patients with type 2 diabetes mellitus (T2DM) arterial stiffness is associated with increased cardiovascular and total mortality. Little is known about determinants of arterial stiffness in clinical routine. Identification of potential determinants of arterial stiffness will help to address treatment targets for patients in the early state of T2DM. This is a cross-sectional analysis of arterial stiffness in 266 patients in the early stage of T2DM who did not have cardiovascular or renal complications. Parameters of arterial stiffness such as central systolic blood pressure (cSBP), central pulse pressure (cPP) and pulse wave velocity (PWV) were measured with the SphygmoCor System (AtCor Medical). We investigated the influence of parameters of glucose metabolism, lipid status, body constitution, blood pressure (BP) and inflammation on the stiffness parameters using multivariate regression analysis. The study cohort consisted of male and female patients aged 61 ± 8 years with mean diabetes duration of 6.4 ± 5.1 years, mean HbA1c 7.1 ± 0.9%, mean cSBP 121 ± 12 mmHg, mean cPP 44 ± 10 mmHg and mean PWV 8.9 ± 1.8 m/s. Multiple regression analysis identified waist circumference (WC) (beta = 0.411, p = 0.026), LDL-cholesterol (beta = 0.106, p = 0.006), systolic office BP (beta = 0.936, p < 0.001) and diabetes duration (beta = 0.233, p = 0.043) as potential determinants of cSBP. cPP was determined by sex (beta = 0.330, p = 0.008), age (beta = 0.383, p < 0.001), systolic office BP (beta = 0.370, p < 0.001) and diabetes duration (beta = 0.231, p = 0.028) whereas for PWV the following determinants could be identified: age (beta = 0.405, p < 0.001), systolic office BP (beta = 0.421, p < 0.001) and diabetes duration (beta = 0.073, p = 0.038). In addition to the known parameters age, sex and systolic office BP serum LDL-cholesterol, WC and diabetes duration have been identified as determinants of arterial stiffness in patients with T2DM. Treatment of patients in the early stage of T2DM should focus on these clinical parameters to prevent progression of arterial stiffness and as a consequence reduce cardiovascular mortality.Trial registration: The patients included in the analysis participated in one of the following clinical trials NCT02752113 (registered 26.4.2016), NCT02383238 (09.03.2015), NCT02471963 (15.06.2015), NCT01319357 (21.03.2011) ( http://www.clinicaltrials.gov ).

Lipid profile changes associated with antiretroviral therapies in a real-world cohort.

OBJECTIVE: To compare lipid profile changes and cardiovascular events among HIV naïve and experienced patients from a real-world cohort treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. METHOD: A retrospective cohort study in HIV naïve and experienced people at a reference hospital in Spain was done. During the follow-up (March 2015-June 2019), patients were treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate or dolutegravir/abacavir/lamivudine. Epidemiological, clinical, and immunovirological variables were recorded. A statistical analysis of the lipid profile at baseline, 48, and 120 weeks after initiating the study therapy, cardiovascular events (myocardial infarction, heart failure, cerebrovascular accident, deep venous thrombosis, myocardiopathy, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction), and cardiovascular risks factors was performed. Data were analysed in naïve and experienced patients from each of the study treatments. The data were obtained from the medical history. The statistical analysis was performed with SPSS v. 24 software. RESULTS: A total of 266 and 191 patients receiving treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine were included in the study, respectively. After 120 weeks of treatment, a worsening of the lipid profile was found in the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group, both in naïve and experienced patients, whereas not so conspicuously observed in the dolutegravir/abacavir/lamivudine group. Statistically significant differences between both groups were found in experienced patients favouring dolutegravir/abacavir/lamivudine; in total cholesterol (204.1±38.2 vs. 187.3±29.4, P < .001) and LDL-C (126.1±31.9 vs. 113.5±28.5, P = .001) at week 48, and in total cholesterol (201.1±33.4 vs. 188.7±33.9, P = .013) and HDL-C (54.2±15.6 vs. 48.3±14.3, P = .01) at week 120. No significant differences in cardiovascular events were found, neither in naïve nor in experienced patients. CONCLUSIONS: The lipid profile among elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate group worsened throughout the follow-up, both in naïve and experienced patients, not so remarkable in the dolutegravir/abacavir/lamivudine group. Both regimens were well tolerated, with similar rates of cardiovascular events.

Risk of dyslipidemia in chronic hepatitis B patients taking tenofovir alafenamide: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to demonstrate how tenofovir alafenamide (TAF) and other hepatitis B treatment drugs differentially impact lipid profiles in chronic hepatitis B patients. METHODS: We searched PubMed, Ovid MEDLINE, EMBASE, and the Cochrane Library to identify studies on the changes in cholesterol level in hepatitis B patients who underwent TAF therapy. The changes in lipid profiles (e.g., HDL-c, LDL-c, total cholesterol [TC], and triglyceride [TG]) were compared between the TAF treatment group and the baseline, other nucleoside analogs (NAs), and tenofovir disoproxil fumarate (TDF)-only treatment groups. In addition, risk factors for worsening cholesterol level when treated with TAF were examined. RESULTS: Twelve studies involving 6,127 patients were selected. After 6 months of TAF treatment, LDL-c, TC, and TG were increased by 5.69 mg/dL, 7.89 mg/dL, and 9.25 mg/dL, respectively, from the baseline level. In particular, with the treatment of TAF, levels of LDL, TC, and TG rose by 8.71 mg/dL, 18.34 mg/dL, and 13.68 mg/dL, respectively, showing a greater deterioration of cholesterol when the TAF treatment was implemented compared to other NAs (e.g., TDF or entecavir). When TAF was compared to TDF, LDL-c, TC, and TG worsened with a mean difference of 14.52 mg/dL, 23.72 mg/dL, and 14.25 mg/dL, respectively. As a result of a meta-regression analysis, risk factors for worsening lipid profiles were found to be treatment-experienced, previous diabetes, and hypertension. CONCLUSIONS: TAF continues to worsen lipid profiles including LDL-c, TC, and TG after 6 months of use compared to the other NAs.