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Lipid lowering, with the use of statins after an acute coronary syndrome (ACS), is a cornerstone, well-established strategy for the secondary prevention of ischemic events in this high-risk cohort. In addition to the positive effect on lipid levels, statins have also been linked to improved atherosclerotic plaque characteristics, such as plaque regression and inflammation reduction, associated with the extent of reduction in LDL-C. The recent emergence of PCSK9 inhibitors for the management of dyslipidemia and the more extensive lipid lowering provided by these agents may provide better prevention for ACS patients when initiated after the ACS event. Several trials have evaluated the immediate post-ACS initiation of PCSK9 inhibitors, which has shown, to date, beneficial results. Furthermore, PCSK9 inhibitors have been linked with positive plaque remodeling and associated mortality benefits, which makes their use in the initial management strategy of such patients appealing. Therefore, in this review, we will analyze the rationale behind immediate lipid lowering after an ACS, report the evidence of PCSK9 inhibition immediately after the ACS event and the available data on plaque stabilization, and discuss treatment algorithms and clinical perspectives for the use of these agents in this clinical setting. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMPs) play an important role in the pathophysiology of atherosclerosis. Reportedly, statins can decrease MMP activity in patients with atherosclerotic cardiovascular disease, but this effect has not been studied in healthy individuals. Methods: MMPs 2, 7, and 9 and several other parameters were measured before and after a four-week course of moderate-dose atorvastatin (20 mg/day) in 21 healthy individuals. Results: Atorvastatin treatment resulted in lower total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and triglycerides (p < 0.001 for all), but higher levels of plasma enzymes AST, ALT, CK, and LDH (p < 0.05 for all). No effect of atorvastatin on plasma MMP median concentrations was recorded. Before treatment, moderate positive significant correlations were found between MMP-7 and age, blood lipids, and blood count-derived inflammatory markers. Pre-treatment MMP-7 was best predicted by the total cholesterol-to-HDL cholesterol ratio in a remnant cholesterol-weighted least squares regression model. After atorvastatin treatment, MMP-7 no longer correlated with these markers. Conclusions: While the effect of statins on plasma MMPs in atherosclerosis is controversial, short-term moderate-dose atorvastatin treatment does not seem to affect levels of MMPs 2, 7, and 9 in healthy individuals. However, an intriguing correlation between MMP-7 and atherosclerosis-related blood lipids and neutrophil-associated inflammatory biomarkers seems to be disrupted by atorvastatin independently of hsCRP, possibly via pleiotropic effects. [ABSTRACT FROM AUTHOR]

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory autoimmune disease of the oral mucosa that affects between 0.5% and 2% of the general population. In the last decade, several studies have associated cardiovascular diseases (CVDs) with some inflammatory skin diseases such as oral lichen planus, demonstrating the presence of dyslipidemia in these pathologies. The objective of this work is to review whether patients with OLP show higher dyslipidemia and CRP levels compared to a healthy control population without OLP. Methods: Searches were carried out in Medline, Scopus, and Cochrane. The studies had to perform a histopathological diagnosis for OLP and the patients could not take any medication to treat this disorder. Non-lichenoid reactions were included. Results: After an initial search that provided us with 254 papers, this number was reduced to 10 articles after a detailed evaluation. All of them were case–control studies that compared the presence of analytical cardiovascular risk factors in patients affected by OLP and in healthy subjects. Conclusions: There is no scientific evidence of the possible association between OLP and CVDs. The only association we can prove is the one between OPL and CVD risk factors, especially those related to the lipid profile. More studies are needed in order to evaluate this relationship in patients diagnosed with CVDs. [ABSTRACT FROM AUTHOR]

Background/Objectives: Lipid metabolism plays an important role in maternal health and fetal development. There is a gap in the knowledge of how lipid metabolism changes during pregnancy for Black women who are at a higher risk of adverse outcomes. We hypothesized that the comprehensive lipidome profiles would show variation across pregnancy indicative of requirements during gestation and fetal development. Methods: Black women were recruited at prenatal clinics. Plasma samples were collected at 8–18 weeks (T1), 22–29 weeks (T2), and 30–36 weeks (T3) of pregnancy. Samples from 64 women who had term births (≥37 weeks gestation) were subjected to "shotgun" Orbitrap mass spectrometry. Mixed-effects models were used to quantify systematic changes and dimensionality reduction models were used to visualize patterns and identify reliable lipid signatures. Results: Total lipids and major lipid classes showed significant increases with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase from T1 to T2 to T3, while sphingolipids and total sterol lipids displayed a more pronounced increase from T2 to T3. Acylcarnitines, hydroxy acylcarnitines, and Lyso phospholipid levels significantly decreased from T1 to T3. A deviation was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggestive of a potential role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids—non-esterified Linoleic acid, Arachidonic acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, and Docosahexaenoic acid. Conclusions: Mapping lipid patterns and identifying lipid signatures would help develop intervention strategies to reduce perinatal health disparities among pregnant Black women. [ABSTRACT FROM AUTHOR]

Background: Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Methods: Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. Results: We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Conclusions: Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia. [ABSTRACT FROM AUTHOR]

Background: Our study aimed to evaluate the performance of primary healthcare physicians (PCPs) in managing glycemia, lipids, and blood pressure in people with type 2 diabetes mellitus (T2DM) in Catalonia, Spain. Methods: We included 3267 PCPs with 367,132 T2DM subjects in a cross-sectional analysis of the SIDIAP (Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària) database for the year 2017. Results: 63.1% of PCPs were female, with an average practice size of 1512 subjects. T2DM individuals had a mean (standard deviation) age of 70 (±12.2) years old, a mean body mass index (BMI) of 30.2 (±5.21) kg/m2, and a median diabetes duration of 8.8 years. Overall, 42.6% of subjects achieved target glycemic control (glycated hemoglobin < 7%). Notably, 59.2% maintained blood pressure < 140/90 mmHg during the 12-month study period. The multivariable analysis identified positive associations between glycemic control and female PCPs, practice sizes (1000–1500 people), a higher proportion of patients aged ≥ 65 years, and rural practices. Combined glycemic, lipid, and blood pressure target attainment was associated with medium-sized practices and those with a higher proportion of patients aged ≥ 65 years. Conclusions: Practice size, patient age distribution, and rurality are factors associated with the performance of PCPs in the control of glycemia, lipids, and blood pressure in T2DM subjects in primary health care centers in our region. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and lipid alterations. Besides pharmacological treatment, lifestyle modifications and nutraceuticals can be used to manage glucose and lipid profiles, which is crucial for preventing, or avoiding, serious consequences associated with the condition. This randomized controlled clinical trial on 75 patients with T2DM evaluated the effects of a combination of myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc on glucose and lipid profile. The intention-to-treat analysis displayed no significant differences in glucose parameters between the groups; however, the study group displayed reduced levels of total cholesterol (p = 0.01) and LDL (p = 0.03) after 3 months of supplementation. A subgroup analysis involving patients who did not modify their antidiabetic therapy, after 6 months displayed improved levels of total cholesterol (p = 0.03) and LDL (p = 0.04) in the study group versus placebo, along with a greater body weight reduction (p = 0.03) after 3 months. Furthermore, within the study group, levels of HDL (p = 0.03) and triglycerides (p = 0.04) improved after 3 months. These findings support supplementation with myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc as an adjuvant and safe strategy to manage the lipid profiles of patients with T2DM. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a major risk factor for atherosclerosis. Identification of dyslipidemia in athletes has raised interest in establishing preventive strategies and reducing cardiovascular (CV) events. Nowadays, targets or "scores" for athletes are undefined. The aim of our study was to create a "Lipid Athlete Score" based on lipid parameters and derive score indexes to identify high-risk athletes. We retrospectively enrolled 957 Olympic athletes practicing different sporting disciplines (power, skills, endurance, and mixed), analyzing their CV profiles and anthropometrics; 55.4% were male, the mean age was 27.1 ± 5 years, and the mean body mass index (BMI) was 23.1 ± 3.2 kg/m2. Three hundred and forty-three athletes (35.8%) were dyslipidemic (LDL ≥ 115 mg/dL or LDL/HDL ≥ 1.90). Multivariate analysis revealed the following: male p = 0.001, OR 1.88 [0.41–2.51], familiarity for dyslipidemia p = 0.001, OR 2.82 [1.72–4.59], BMI ≥ 30 kg/m2 p = 0.001, OR 2.53 [1.46–4.38], and fat mass p = 0.001, OR 2.29 [1.38–3.80] were significant. Endurance athletes presented the lowest CV risk. We proposed a lipid athlete score including major (LDL ≥ 115 mg/dL and LDL/HDL ≥ 1.90) and minor criteria (male, BMI > 30 kg/m2 or fat mass >22% for males and 32% for females, familiarity for dyslipidemia, and conventional CV risk factors). Twelve athletes (1.2%) were at high risk, 150 athletes (15.7%) at medium risk, 171 athletes (17.9%) at low risk, and 624 (65.2%) were at no risk. Dyslipidemia is very common in elite athletes. We have defined a specific lipid athlete score based on lipid parameters and derived score indexes for the stratification of risk. In accordance with this tool, a substantial proportion of athletes (16.9%) were at medium-to-high risk and need early preventive strategies to improve their lipid profiles and reduce the future development of atherosclerotic CV diseases. [ABSTRACT FROM AUTHOR]

(1) Background: Diabetic retinopathy (DR) remains the leading cause of low vision and blindness in young adults of working age. Although the most important risk factors—such as the duration of diabetes mellitus (DM) and glycemic control measured by HbA1c—are known, the effects of lipids are not as clear. The aim of the present study is to analyze the effects of lipids on the development of DR. (2) Methods: This is a retrospective study of a population of 175,645 DM2 patients, during the period 2010 to 2020, in which the effects of different lipid factors are studied. (3) Results: The variables that most influenced the development of DR in our study, based on significance and cumulative hazard (CH), were arterial hypertension (CH 1.217, p < 0.001), HbA1c levels (CH 1.162, p = 0.001), microalbuminuria (CH 1.012, p < 0.001), LDL-C cholesterol (CH 1.007, p = 0.012), TC/HDL-C index (CH 1.092, p < 0.001), No-HDL-C/HDL-C index (CH 1.065, p = 0.002), the use of statins (CH 1.001, p = 0.005), and body mass index (CH 1.007, p < 0.001). (4) Conclusions: LDL-cholesterol, TC/HDL-C, and No-HDL-C/HDL-C indices are related to the development of DR, and there is a protective effect of HDL-cholesterol and the use of fibrates. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Dyslipidemia Treatment and Lipid Control in US Adults with Diabetes by Sociodemographic and Cardiovascular Risk Groups in the NIH Precision Medicine Initiative All of Us Research Program." The correction addresses an error in reporting in Table 2 and Table 3, where some cells with small percentages implied sample sizes of less than 20, which violated the All of Us policy. The corrected tables are provided, and the authors state that the scientific conclusions are unaffected. The correction was approved by the Academic Editor, and the original publication has been updated. The authors acknowledge the breach of trust with the All of Us participants and apologize for the noncompliance with the data dissemination policy. [Extracted from the article]

The lipid profile is affected following menstrual cessation (MC). We aimed to evaluate the effects of goserelin-induced MC and subsequent menstrual restoration (MR) on lipid metabolism. Premenopausal women with histologically verified endometriosis (n = 15) received goserelin monthly for 6 months (6mο), resulting in MC, and were followed-up for another 6 months after MR (12mο). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a ([Lp(a)] and lipidomics were measured at baseline, 6mo and 12mo. Shotgun quantitative deep lipidomics were determined at the level of lipid class category, subclass, species, and fatty acyl chain lengths and degree of saturation. TC (p = 0.006), LDL-C (p = 0.028), HDL-C (p = 0.002), and apoA1 (p = 0.013) increased during goserelin-induced MC and remained practically unchanged during MR. TG, apoB, and Lp(a) did not change. From the deep lipidomics analysis, multivariate statistical analysis demonstrated profound alterations in lipid species with MC, whereas no statistically valid models could be fitted for the restoration period. In conclusion, GnRH-analog-induced MC alters lipid profiles at various levels, from standard blood lipid and lipoprotein profiles to several lipid species as detected by lipidomics analysis. Changes largely persist for at least 6 m after MR. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that both lipid levels and anti-severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) antibody levels are associated with outcome in coronavirus disease 2019 (COVID-19). While both parameters have separately been implicated in the neutralization and clearance of pathogens during severe infections, it is currently unclear whether the interplay of these parameters affects outcome in COVID-19. We therefore aimed to determine whether there was a relationship between lipoproteins, anti-SARS-CoV-2 antibodies, and COVID-19 mortality. Methods: In this prospective, multicenter cohort study, we recruited 1152 hospitalized patients with COVID-19 from five hospitals. Total cholesterol (TC), LDL-C, HDL-C, triglycerides, and anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The investigated endpoint was in-hospital mortality. Results: LDL-C, HDL-C, and TC were significantly lower in non-survivors than in survivors (mg/dL, 95%CI; 56.1, 50.4–61.8 vs. 72.6, 70.2–75.0, p < 0.001; 34.2, 31.7–36.8 vs. 38.1, 37.2–39.1, p = 0.025; 139.3, 130.9–147.7 vs. 157.4, 54.1–160.6, p = 0.002). Mortality risk increased progressively with lower levels of LDL-C, HDL-C, and TC (aOR 1.73, 1.30–2.31, p < 0.001; 1.44, 1.10–1.88, p = 0.008; 1.49, 1.14–1.94, p < 0.001). Mortality rates varied between 2.1% for high levels of both LDL-C and anti-SARS-CoV-2 antibodies and 16.3% for low levels of LDL-C and anti-SARS-CoV-2 antibodies (aOR 9.14, 95%CI 3.17–26.34, p < 0.001). Accordingly, for total cholesterol and anti-SARS-CoV-2 antibodies, mortality rates varied between 2.1% and 15.0% (aOR 8.01, 95%CI 2.77–23.18, p < 0.001). Conclusion: The combination of serum lipid levels and anti-SARS-CoV-2 antibodies is strongly associated with in-hospital mortality of patients with COVID-19. Patients with low levels of LDL-C and total cholesterol combined with low levels of anti-SARS-CoV-2 antibodies exhibited the highest mortality rates. [ABSTRACT FROM AUTHOR]

Objective: Preeclampsia (PE) is a prevalent pregnancy disorder worldwide with limited preventative treatments available. Obesity triples the risk for PE, yet only 10% of women with obesity develop PE. The factors that distinguish PE from uncomplicated pregnancies in the context of obesity have not been fully established. Methods: We studied a cohort of women with obesity throughout pregnancy to identify lipid mediators and/or biomarkers of PE. Blood samples were collected at each trimester and analyzed by both targeted lipidomics and standard lipid panels. Individual lipid species were compared by PE status at each trimester, as well as by self-identified race (Black vs. White) and fetal sex. Results: Standard lipid panels and clinical measurements revealed few differences between PE and uncomplicated pregnancies. Targeted lipidomics, however, identified plasmalogen, phosphatidylethanolamine, and free fatty acid species that were elevated in the third trimester of women with PE. Furthermore, race and trimester of pregnancy were considerable sources of plasma lipidomic variation in women with obesity. Conclusions: First and second trimester individual plasma lipid species do not predict the development of PE in obese women. In the third trimester, PE patients have elevated levels of plasmalogens—a class of lipoprotein-associated phospholipids that have been implicated in the response to oxidative stress. [ABSTRACT FROM AUTHOR]

To assess the determinants of lipid parameters in primary care patients without diagnosed cardiovascular disease (CVD), a cross-sectional study was conducted during 2018–2019 with a total of 200 patients. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), small, dense LDL (sdLDL-C), and lipoprotein (a) (Lp(a)). Predictors of elevated and adequately controlled lipid parameters were assessed with logistic regression analysis. Older age was related to higher risk of TC ≥ 6.2 mmol/L [OR 1.03 (95% CI 1.0–1.05)], sdLDL-C ≥ 1.0 mmol/L [OR 1.05 (95% CI 1.0–1.1)], and decreased risk of Lp(a) ≥ 50 mg/dL [OR 0.97 (95% CI 0.94–0.99)]. Patients with diabetes mellitus (DM) had increased probability of TG ≥ 2.25 mmol/L [OR 3.77 (95% CI 1.34–10.6)] and Lp(a) ≥ 50 mg/dL [OR 2.97 (1.34–6.10)] as well as adequate control of TG and Lp(a). Higher material status was related to lower risk of TC ≥ 6.2 mmol/L [OR 0.19 (95% CI 0.04–0.82)] and LDL-C ≥ 3.6 mmol/L [OR 0.33 (95% CI 0.12–0.92)]. High BMI was related to increased [OR 1.14 (95% CI 1.02–1.29)], and female gender [OR 0.33 (95% CI 0.12–0.96)] and hypertension [OR 0.29 (95% CI 0.1–0.87)] to decreased risk of TG ≥ 2.25 mmol/L [OR 1.14 (95% CI 1.02–1.29)]. Taking lipid-lowering drugs (LLD) was associated with LDL-C < 2.6 mmol/L [OR 2.1 (95% CI 1.05–4.19)] and Lp(a) < 30 mg/dL [OR 0.48 (95% CI 0.25–0.93)]. Physical activity was related to LDL-C < 2.6 mmol/L [OR 2.02 (95% CI 1.02–3.98)]. Higher abdominal circumference was associated with decreased risk of TG < 1.7 mmol/L [OR 0.96 (95% CI 0.93–0.99)]. Elevated lipid parameters were related to age, gender, material status, BMI, history of DM, and hypertension. Adequate control was associated with age, education, physical activity, LLD, history of DM, and abdominal circumference. [ABSTRACT FROM AUTHOR]

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice. [ABSTRACT FROM AUTHOR]

Intestinal lymphatic, known as lacteal, plays a critical role in maintaining intestinal homeostasis by regulating several key functions, including the absorption of dietary lipids, immune cell trafficking, and interstitial fluid balance in the gut. The absorption of dietary lipids relies on lacteal integrity, mediated by button-like and zipper-like junctions. Although the intestinal lymphatic system is well studied in many diseases, including obesity, the contribution of lacteals to the gut–retinal axis in type 1 diabetes (T1D) has not been examined. Previously, we showed that diabetes induces a reduction in intestinal angiotensin-converting enzyme 2 (ACE2), leading to gut barrier disruption. However, when ACE2 levels are maintained, a preservation of gut barrier integrity occurs, resulting in less systemic inflammation and a reduction in endothelial cell permeability, ultimately retarding the development of diabetic complications, such as diabetic retinopathy. Here, we examined the impact of T1D on intestinal lymphatics and circulating lipids and tested the impact of intervention with ACE-2-expressing probiotics on key aspects of gut and retinal function. Akita mice with 6 months of diabetes were orally gavaged LP-ACE2 (3x/week for 3 months), an engineered probiotic (Lactobacillus paracasei; LP) expressing human ACE2. After three months, immunohistochemistry (IHC) was used to evaluate intestinal lymphatics, gut epithelial, and endothelial barrier integrity. Retinal function was assessed using visual acuity, electroretinograms, and enumeration of acellular capillaries. LP-ACE2 significantly restored intestinal lacteal integrity as assessed by the increased expression of lymphatic vessel hyaluronan receptor 1 (LYVE-1) expression in LP-ACE2-treated Akita mice. This was accompanied by improved gut epithelial (Zonula occludens-1 (ZO-1), p120-catenin) and endothelial (plasmalemma vesicular protein -1 (PLVAP1)) barrier integrity. In Akita mice, the LP-ACE2 treatment reduced plasma levels of LDL cholesterol and increased the expression of ATP-binding cassette subfamily G member 1 (ABCG1) in retinal pigment epithelial cells (RPE), the population of cells responsible for lipid transport from the systemic circulation into the retina. LP-ACE2 also corrected blood–retinal barrier (BRB) dysfunction in the neural retina, as observed by increased ZO-1 and decreased VCAM-1 expression compared to untreated mice. LP-ACE2-treated Akita mice exhibit significantly decreased numbers of acellular capillaries in the retina. Our study supports the beneficial role of LP-ACE2 in the restoration of intestinal lacteal integrity, which plays a key role in gut barrier integrity and systemic lipid metabolism and decreased diabetic retinopathy severity. [ABSTRACT FROM AUTHOR]

Highlights: What are the main finding? Higher serum levels of total cholesterol and low-density lipoprotein cholesterol are associated with the severity of AP, while the persistent inflammation of AP is linked with decreased serum levels of cholesterol-related lipids. What is the implication of the main finding? Cholesterol-related lipids should be recommended both as risk factors and early predictors for studying the severity of AP. Cholesterol-lowering drugs may play a role in the treatment and prevention of AP with hypercholesterolemia. It is well known that hypercholesterolemia in the body has pro-inflammatory effects through the formation of inflammasomes and augmentation of TLR (Toll-like receptor) signaling, which gives rise to cardiovascular disease and neurodegenerative diseases. However, the interaction between cholesterol-related lipids and acute pancreatitis (AP) has not yet been summarized before. This hinders the consensus on the existence and clinical importance of cholesterol-associated AP. This review focuses on the possible interaction between AP and cholesterol-related lipids, which include total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) A1, from the bench to the bedside. With a higher serum level of total cholesterol, LDL-C is associated with the severity of AP, while the persistent inflammation of AP is allied with a decrease in serum levels of cholesterol-related lipids. Therefore, an interaction between cholesterol-related lipids and AP is postulated. Cholesterol-related lipids should be recommended as risk factors and early predictors for measuring the severity of AP. Cholesterol-lowering drugs may play a role in the treatment and prevention of AP with hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Real-world data on lipid levels and treatment among adults with diabetes mellitus (DM) are relatively limited. We studied lipid levels and treatment status in patients with DM across cardiovascular disease (CVD) risk groups and sociodemographic factors. In the All of Us Research Program, we categorized DM as (1) moderate risk (≤1 CVD risk factor), (2) high risk (≥2 CVD risk factors), and (3) DM with atherosclerotic CVD (ASCVD). We examined the use of statin and non-statin therapy as well as LDL-C and triglyceride levels. We studied 81,332 participants with DM, which included 22.3% non-Hispanic Black and 17.2% Hispanic. A total of 31.1% had ≤1 DM risk factor, 30.3% had ≥2 DM risk factors, and 38.6% of participants had DM with ASCVD. Only 18.2% of those with DM and ASCVD were on high-intensity statins. Overall, 5.1% were using ezetimibe and 0.6% PCSK9 inhibitors. Among those with DM and ASCVD, only 21.1% had LDL-C < 70 mg/dL. Overall, 1.9% of participants with triglycerides ≥ 150 mg/dL were on icosapent ethyl. Those with DM and ASCVD were more likely to be on high-intensity statins, ezetimibe, and icosapent ethyl. Guideline-recommended use of high-intensity statins and non-statin therapy among our higher risk DM patients is lacking, with LDL-C inadequately controlled. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis may benefit from fibrates, mixed formulation omega-3 fatty acids, and niacin; however, evidence does not support their use for ASCVD risk reduction in the contemporary statin era. Novel therapeutics including those that target apoC-III and ANGPTL3 have shown to be safe, well-tolerated, and effective for lowering TG levels. Given the growing burden of cardiometabolic disease and risk factors, public health and health policy strategies are urgently needed to enhance access to effective pharmacotherapies, affordable and nutritious food options, and timely health care services. [ABSTRACT FROM AUTHOR]

Cancer resistance to treatments is a challenge that researchers constantly seek to overcome. For instance, TNF-related apoptosis-inducing ligand (TRAIL) is a potential good prospect as an anti-cancer therapy, as it attacks tumor cells but not normal cells. However, treatments based in soluble TRAIL provided incomplete clinical results and diverse formulations have been developed to improve its bioactivity. In previous works, we generated a new TRAIL formulation based in its attachment to the surface of unilamellar nanoliposomes (LUV-TRAIL). This formulation greatly increased apoptosis in a wide selection of tumor cell types, albeit a few of them remained resistant. On the other hand, it has been described that a metabolic shift in cancer cells can also alter its sensitivity to other treatments. In this work, we sought to increase the sensitivity of several tumor cell types resistant to LUV-TRAIL by previous exposure to the metabolic drug dichloroacetate (DCA), which forces oxidative phosphorylation. Results showed that DCA + LUV-TRAIL had a synergistic effect on both lung adenocarcinoma A549, colorectal HT29, and breast cancer MCF7 cells. Despite DCA inducing intracellular changes in a cell-type specific way, the increase in cell death by apoptosis was clearly correlated with an increase in death receptor 5 (DR5) surface expression in all cell lines. Therefore, DCA-induced metabolic shift emerges as a suitable option to overcome TRAIL resistance in cancer cells. [ABSTRACT FROM AUTHOR]

Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.14 ± 9.99 years; HbA1c, 8.66 ± 1.60%; mean body mass index, 35.15 ± 6.65 kg/m2). Plasma lipoprotein particles number and size were determined by nuclear magnetic resonance spectroscopy. Associations of different lipoprotein subpopulations with lipoprotein insulin resistance (LPIR) score and glycoprotein acetylation (GlycA) were assessed using multi-regression analysis. In stepwise regression analysis, VLDL and HDL large particle number and size showed the strongest associations with LPIR (R2 = 0.960; p = 0.0001), whereas the concentrations of the small VLDL and HDL particles were associated with GlycA (R2 = 0.190; p = 0.008 and p = 0.049, respectively). In adjusted multi-regression analysis, small and large VLDL particles and all sizes of lipoproteins independently predicted LPIR, whereas only the number of small LDL particles predicted GlycA. Conventional markers HbA1c and Hs-CRP did not exhibit any significant association with lipoprotein subpopulations. Our data suggest that monitoring insulin resistance-induced changes in lipoprotein subpopulations in T2DM might help to identify novel biomarkers that can be useful for effective clinical intervention. [ABSTRACT FROM AUTHOR]

Contradicting evidence exists regarding the role of lipids in outcomes following intravenous (IV) thrombolysis with tissue plasminogen activator (tPA). Restricted cubic spline curves and adjusted logistic regression were used to evaluate associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratio with poor functional outcome, symptomatic intracranial hemorrhage (SICH) and 90-day mortality, among 1004 acute ischemic stroke (AIS) patients who received IV tPA in a comprehensive stroke center. Quartile (Q) 1, Q2 and Q3 of HDL-C were associated with increased odds of poor functional outcome (adjusted odds ratio (adjOR) 1.66, 95% CI 1.06–2.60, p = 0.028, adjOR 1.63, 95% CI 1.05–2.53, p = 0.027, adjOR 1.56, 95% CI 1.01–2.44, p = 0.048) compared to Q4. Q2 and Q4 of non-HDL-C were associated with increased odds of SICH (adjOR 4.28, 95% CI 1.36–18.90, p = 0.025, adjOR 5.17, 95% CI 1.64–22.81, p = 0.011) compared to Q3. Q1 and Q2 of LDL-C was associated with increased odds of mortality (adjOR 2.57, 95% CI 1.27–5.57, p = 0.011 and adjOR 2.28, 95% CI 1.10–5.02, p = 0.032) compared to Q3. In AIS patients who received IV tPA, low LDL-C was associated with increased odds of mortality while HDL-C may be protective against poor functional outcome. [ABSTRACT FROM AUTHOR]

Background: Annexin A6 (AnxA6) is a lipid-binding protein that regulates cholesterol homeostasis and secretory pathways. However, the correlation of AnxA6 polymorphism with lipometabolism has never been studied in psoriasis. Objectives: To investigate the impact of AnxA6 polymorphism on lipid profiles and the expression of AnxA6 protein in both peripheral blood mononuclear cells (PBMCs) and lipometabolism in psoriasis. Methods: A total of 265 psoriatic patients received methotrexate (MTX) treatment for 12 weeks, after which their lipid profiles were determined by measuring total cholesterol (TC), triglycerides (TGs), lipoprotein (a) [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein (a)1 (ApoA1), and apolipoprotein B (ApoB). In addition, AnxA6 (rs11960458) was genotyped in 262 patients and the expression of AnxA6 in PBMCs was measured by Western blotting at baseline and week 8 post-MTX treatment. Results: The CC genotype carriers of rs11960458 had a lower expression of AnxA6 and lower levels of the pro-atherogenic lipids TC, LDL, and ApoB compared to TC genotype carriers. MTX significantly downregulated the levels of the anti-atherogenic lipids HDL-C and ApoA1 and the level of AnxA6 in TC genotype carriers, as well as the level of TGs in CC genotype carriers. Conclusions: The polymorphism of AnxA6, rs11960458, was statistically associated with the levels of pro-atherogenic lipids and with the downregulation of MTX on the levels of anti-atherogenic lipids and TGs in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Our aim was to systematically investigate the effect of upadacitinib, an oral JAK-1 selective inhibitor, on lipid profile and cardiovascular disease risk. Methods: PubMed, PubMed Central and ClinicalTrials.gov databases were searched for relevant randomized controlled trials (RCTs) up to 31 July 2022. We performed a qualitative synthesis of published RCTs to investigate the associations of upadacitinib with lipoprotein changes, along with a quantitative synthesis of MACE and mean lipoprotein changes where there were available data. Results: Nineteen RCTs were eligible for the present systematic review, which included 10,656 patients with a mean age of 51 years and a follow-up period of 12–52 weeks. Increases in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were noted upon upadacitinib administration (3–48 mg/day) in 15 studies, while the LDL-C:HDL-C ratio remained unchanged. The pooled analyses of three placebo-controlled RCTs (n = 2577) demonstrated that upadacitinib at 15 mg increased the LDL-C by 15.18 mg/dL (95% CI: 7.77–22.59) and HDL-C by 7.89 mg/dL (95% CI: 7.08–8.69). According to the pooled analysis of 15 placebo-controlled RCTs (n = 7695), upadacitinib had no effect on MACE (risk ratio, RR: 0.62; 95% CI: 0.24–1.60). A sub-analysis focusing on upadacitinib at 15 mg (12 studies, n = 5395) demonstrated similar results (RR: 0.67; 95% CI: 0.19–2.36). Conclusions: Treatment with upadacitinib increases both LDL-C and HDL-C levels. Nevertheless, upadacitinib had no significant effect on the cardiovascular disease risk during a ≤52-week follow-up. [ABSTRACT FROM AUTHOR]

The rising prevalence of cardiovascular (CV) risk factors in Portugal has translated into more than 35,000 annual deaths due to CV diseases. We performed a multicenter observational cohort study encompassing clinical activities performed between 2000 and 2019 to characterize the CV risk profile and LDL-C management of patients in every CV risk category using electronic health records of a regional population in Portugal. We analyzed data from 14 health centers and 1 central hospital in the north of Portugal of patients between 40 and 80 years that had at least 1 family medicine appointment at these institutions. Living patients were characterized on 31 December 2019. CV risk assessment was computed according to the 2019 ESC/EAS Guidelines. Lipid-lowering therapy (LLT) and achievement of LDL-C targets were assessed. In total, the analysis included 78,459 patients. Patient proportions were 33%, 29%, 22%, and 17% for low, intermediate, high, and very high CV risk, respectively. Moderate-intensity statins were the most frequently used medication across all CV risk categories. High-intensity statins were used in 5% and 10% of high and very high CV risk patients, respectively. Ezetimibe was used in 6% and 10% of high and very high CV risk patients, respectively. LDL-C targets were achieved in 44%, 27%, 7%, and 3% of low, intermediate, high, and very high CV risk patients, respectively. For uncontrolled patients in the high and very high CV risk categories, a median LDL-C reduction of 44% and 53%, respectively, would be required to meet LDL-C targets. There are clear opportunities to optimize LDL-C management in routine clinical practice. The prescription of LLT according to CV risk represents an important missed treatment opportunity. [ABSTRACT FROM AUTHOR]

Chronic hyperglycemia induces pathophysiologic pathways with negative effects on the metabolism of most substrates as well as lipids and lipoproteins, and thereby induces dyslipidemia. Thus, the diabetic milieu is commonly accompanied by different levels of atherogenic dyslipidemia, which is per se a major risk factor for subsequent complications such as atherosclerosis, coronary heart disease, acute myocardial infarction, ischemic stroke, and nephropathy. Therefore, readjusting lipid metabolism in the diabetic milieu is a major goal for preventing dyslipidemia-induced complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of relatively newly introduced antidiabetes drugs (including empagliflozin, canagliflozin, dapagliflozin, etc.) with potent hypoglycemic effects and can reduce blood glucose by inducing glycosuria. However, recent evidence suggests that they could also provide extra-glycemic benefits in lipid metabolism. It seems that they can increase fat burning and lipolysis, normalizing the lipid metabolism and preventing or improving dyslipidemia. Nevertheless, the exact mechanisms involved in this process are not well-understood. In this review, we tried to explain how these drugs could regulate lipid homeostasis and we presented the possible involved cellular pathways supported by clinical evidence. [ABSTRACT FROM AUTHOR]

Decreased thrombolysis in myocardial infarction (TIMI) flow is associated with poor clinical outcomes. However, its predictors are not fully known. A combination of near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) could be used to detect lesions at high risk of slow TIMI flow. This study evaluated 636 consecutive patients undergoing target-lesion NIRS-IVUS imaging prior to percutaneous coronary intervention (PCI). The maximal lipid core burden index over 4-mm segments (maxLCBI4mm) per target vessel was calculated. The primary endpoint was the association between maxLCBI4mm and post-interventional TIMI flow. A high lipid core burden index (LCBI) cut-off point was determined using receiver-operating characteristic analysis. Decreased TIMI flow (TIMI less than 3) occurred in 90 patients and normal TIMI flow in 546 patients. The decreased TIMI flow group showed significantly higher incidence of cardiovascular events (5.6% vs. 1.5%, log-rank p = 0.010) in three months of composite events including cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization. In multivariable analysis, a high LCBI (≥354) was independently associated with slow TIMI flow (OR, 2.59 (95% CI, 1.33–5.04), p = 0.005). High LCBI measured using NIRS-IVUS imaging was an independent predictor of decreased post-PCI TIMI flow. Performing PCI for high-LCBI lesions may necessitate adjunctive measures to prevent suboptimal post-PCI reperfusion. [ABSTRACT FROM AUTHOR]

Late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) are major causes of neonatal morbidity and mortality. In this prospective, case-control study, we evaluated the metabolic profile of neonates with LOS and NEC. Blood samples were collected from 15 septic neonates and 17 neonates with NEC at the clinical suspicion of the specific diseases. Sixteen gestational and postnatal age-matched neonates without sepsis/NEC served as controls. Serum metabolic profiles were assessed using liquid chromatography–quadrupole time-of-flight mass spectrometry. Metabolomic analysis revealed significant differences in the metabolic profile of neonates with LOS or NEC compared to controls. More specifically, a number of molecules possibly identified as phosphatidylcholines or lysophosphatidylcholines were found to be significantly reduced both in neonates with LOS and those with NEC compared to controls. Additionally, L-carnitine could efficiently discriminate NEC cases from controls. The results of the current study suggest that certain phospholipids and their derivatives could possibly be used as biomarkers for the early detection of LOS and NEC. [ABSTRACT FROM AUTHOR]

Keratoconus (KC) is a progressive corneal disorder characterized by thinning and protrusion, mostly of the inferotemporal and central corneal regions. Dysfunction of the meibomian gland, the excretions of which form the lipid layer of the tear film, has been reported to be associated with KC. Thus, this manuscript investigates the correlation among lipid layer thickness (LLT), partial blink rate (PBR), and KC of different degrees. This retrospective study included 54 patients and 24 healthy controls. The anterior corneal curvature, LLT, and PBR were taken from the unilateral eye of all 78 participants. The difference in those ocular parameters between the moderate and severe groups and the control group is significant. No significant association was found between anterior corneal curvature and LLT (r = −0.2, p = 0.15) across all the patients. However, there was a significant negative correlation between anterior corneal curvature and LLT in moderate (r = −0.6, p < 0.05) and severe (r = −0.7, p < 0.05) keratoconus cases. The results also show a significant negative correlation between anterior corneal curvature and PBR (r = −0.41, p < 0.05). Therefore, we conclude that the severity of keratoconus is associated with the thinning of LLT and the reduction of PBR. This may relate to a further epithelial abnormality with the reduced protection of tear film from the air, leading to the release of proteolytic enzymes that degrade stromal collagen and weaken the cornea. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular mortality in dialysis population remains very high. Saturated fatty acids (SFA) contribute to atherosclerosis and to cardiovascular risk. Aim: The aim of this study was to evaluate the relationship between mortality in dialysis patients and the serum SFA content. Methods: Survival of 54 patients on dialysis was assessed. A total of 21 SFA from patients' sera were measured by gas chromatography-mass spectrometry (GC-MS). Diet was assessed by food frequency questionnaire FFQ-6. The SFA content is presented as fatty acid proportion (%). Results: During the observation time (median 66 months) 22 patients died. There was a significant relationship between elevated SFA (above SFA mean) and mortality (log-rank 3.13; p = 0.0017). Moreover, patients who ingested foods rich in SFA, according to FFQ-6, had a higher mortality risk (log-rank 2.24; p = 0.03). The hazard ratio for mortality associated with increased SFA content equalled 4.47 (1.63–12.26). Addition of age and inflammation (hsCRP > 5 mg/L) into the Cox model did not modify this relationship. However, SFA content turned out to be significantly higher in patients with diabetes mellitus and cardiovascular disease, as compared to patients free from these co-morbidities. Their addition to the model attenuated the relationship between SFA and mortality, making it statistically insignificant. Conclusion: The serum content of SFA turned out to be a strong predictor of mortality in dialysis patients. However, given the significant associations between SFA, DM, and CVD, interventional studies with controlled SFA intake are needed to evaluate the causal links between SFA, co-morbidities and survival. [ABSTRACT FROM AUTHOR]

Background: The brain is rich in lipid content, so a physiopathological pathway in Alzheimer's disease (AD) could be related to lipid metabolism impairment. The study of lipid profiles in plasma samples could help in the identification of early AD changes and new potential biomarkers. Methods: An untargeted lipidomic analysis was carried out in plasma samples from preclinical AD (n = 11), mild cognitive impairment-AD (MCI-AD) (n = 31), and healthy (n = 20) participants. Variables were identified by means of two complementary methods, and lipid families' profiles were studied. Then, a targeted analysis was carried out for some identified lipids. Results: Statistically significant differences were obtained for the diglycerol (DG), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), monoglyceride (MG), and sphingomyelin (SM) families as well as for monounsaturated (MUFAs) lipids, among the participant groups. In addition, statistically significant differences in the levels of lipid families (ceramides (Cer), LPE, LPC, MG, and SM) were observed between the preclinical AD and healthy groups, while statistically significant differences in the levels of DG, MG, and PE were observed between the MCI-AD and healthy groups. In addition, 18:1 LPE showed statistically significant differences in the targeted analysis between early AD (preclinical and MCI) and healthy participants. Conclusion: The different plasma lipid profiles could be useful in the early and minimally invasive detection of AD. Among the lipid families, relevant results were obtained from DGs, LPEs, LPCs, MGs, and SMs. Specifically, MGs could be potentially useful in AD detection; while LPEs, LPCs, and SM seem to be more related to the preclinical stage, while DGs are more related to the MCI stage. Specifically, 18:1 LPE showed a potential utility as an AD biomarker. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population. [ABSTRACT FROM AUTHOR]

Molecular mechanisms behind obesity and sex-related effects in adipose tissue remain elusive. During adipocyte expansion, adipocytes undergo drastic remodelling of lipid membrane compositions. Lipid flippases catalyse phospholipid translocation from exoplasmic to the cytoplasmic leaflet of membranes. The present study aimed to analyse the effect of sex, obesity, and their interactions on the gene expression of two lipid flippases—ATP8A1 and ATP8B1—and their possible microRNA (miR) modulators in visceral adipose tissue (VAT). In total, 12 normal-weight subjects (5 premenopausal women and 7 men) and 13 morbidly obese patients (7 premenopausal women and 6 men) were submitted to surgery, and VAT samples were obtained. Gene expression levels of ATP8A1, ATP8B1, miR-548b-5p, and miR-4643 were measured in VAT. Our results showed a marked influence of obesity on VAT ATP8A1 and ATP8B1, although the effects of obesity were stronger in men for ATP8A1. Both genes positively correlated with obesity and metabolic markers. Furthermore, ATP8B1 was positively associated with miR-548b-5p and negatively associated with miR-4643. Both miRs were also affected by sex. Thus, lipid flippases are altered by obesity in VAT in a sex-specific manner. Our study provides a better understanding of the sex-specific molecular mechanisms underlying obesity, which may contribute to the development of sex-based precision medicine. [ABSTRACT FROM AUTHOR]

To evaluate the stability and permanence of the liquid film created after the instillation of 0.15% crosslinked hyaluronic acid with liposomes and crocin versus the effect of 0.15% standard hyaluronic acid, a prospective, longitudinal, single-blind, single-center study was conducted in symptomatic populations with a novel noninvasive ocular surface analyzer. Limbal and bulbar redness classification, lipid layer thickness, tear meniscus height, and first and mean noninvasive break-up time (FNIBUT and MNIBUT) were performed before and 30 and 45 min after liposome-crosslinked hyaluronic acid (LCHA) and standard hyaluronic acid (HA) eye drop instillations. LCHA had a higher lipid layer thickness than HA (grades 2.00 ± 0.83 and 1.17 ± 0.63 on the Guillon pattern, respectively). LCHA achieved a better tear meniscus height than HA (0.23 ± 0.02 and 0.21 ± 0.02 mm, respectively). LCHA improved FNIBUT and MNIBUT more than HA (for FNIBUT, 6.30 ± 0.94 and 4.77 ± 0.89 s, respectively. For MNIBUT, 17.23 ± 5.11 and 12.41 ± 4.18 s, respectively). Crosslinking hyaluronic acid with liposomes and crocin significantly increases the permanence and stability of the lipid, aqueous, and mucin tear film layers. In a short-term period, liposome and crosslinked hyaluronic acid achieved better first and mean noninvasive break-up times than standard hyaluronic acid. [ABSTRACT FROM AUTHOR]

Lipid peroxidation (LPO) participates in the development of various diseases, including periodontitis, and malondialdehyde (MDA) is its terminal product. Therefore, in the present study, salivary and plasma MDA levels in 30 periodontitis patients were compared to those in 20 healthy controls, as well as in relation to periodontal therapy in order to assess its effectiveness. Periodontal status was assessed via plaque index, gingival index, papilla bleeding index, probing depth and clinical attachment level, while salivary and plasma MDA levels were determined by the ELISA method. The periodontitis group had a significantly greater salivary (2.99 pmol/µL) and plasma (0.50 pmol/µL) MDA levels relative to the healthy controls (1.33 pmol/µL and 0.40 pmol/µL, respectively). Three months after the periodontal therapy completion, although salivary MDA levels were significantly lower than those measured at the baseline (p < 0.001), the reduction in plasma MDA was not statistically significant (p > 0.05). These findings indicate that, while inflammatory processes in periodontium may increase local and systemic lipid peroxidation, periodontal therapy can result in a significant decrease in salivary, but not plasma, MDA levels. [ABSTRACT FROM AUTHOR]

Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stimulate endothelial dysfunction and promote inflammation. Inflammation and growth factors actively promote the synthesis of the extracellular matrix (ECM) and trigger an osteogenic program. The accumulation of ECM proteins promotes lipid adhesion to valve tissue, which could initiate the osteogenic program in interstitial valve cells. Statin treatment has been shown to have the ability to diminish the death rate in subjects with atherosclerotic impediments by decreasing the serum LDL cholesterol levels. However, the use of HMG-CoA inhibitors (statins) as cholesterol-lowering therapy did not significantly reduce the progression or the severity of aortic valve calcification. However, new clinical trials targeting Lp(a) or PCSK9 are showing promising results in reducing the severity of aortic stenosis. In this review, we discuss the implication of lipids in aortic valve calcification and the current findings on the effect of lipid-lowering therapy in aortic stenosis. [ABSTRACT FROM AUTHOR]

Treatment with interferon-free direct-acting antivirals (DAA) has become the gold standard in chronic hepatitis C virus (HCV) infection. Nevertheless, little research about the metabolic impact of achieving sustained virological response (SVR) is available in HCV/HIV co-infected patients. This research aimed to evaluate early anthropometric, lipid and liver parameters changes after achieving SVR 12 weeks after treatment (SVR12). A real-life retrospective descriptive before-after study assessed 128 DAA treatment episodes from 2015 to 2019 in HCV/HIV co-infected patients. Anthropometric parameters (weight, body mass index), lipid profile, genotype (GT) and viral load, liver data (basics laboratory necroinflammatory parameters and transient elastography (TE)) were collected before treatment with DAA (baseline), and when SVR12 was achieved. Significant increases (p < 0.01) were found in the early lipid profile, measured by LDLc (84.6 ± 35.0 vs. 108.6 ± 35.1 mg/dL) and total cholesterol (161.3 ± 41.0 vs. 183.3 ± 41.6 mg/dL). Significant changes (p < 0.05) were found in liver parameters, measured by ALT (58.2 ± 34.0 vs. 22.0 ± 16.0 U/L), bilirubin (0.8 ± 0.6 vs. 0.6 ± 0.5 mg/dL), albumin (4.2 ± 0.4 vs. 4.3 ± 0.3 g/dL) and liver stiffness (LS) (13.7 ± 13.3 vs. 11.8 ± 12.1 kPa). The main conclusions were that the use of DAA has an early negative impact on lipid metabolism. Achieving SVR12 against HCV leads to an early improvement in liver function and LS in HCV/HIV co-infected patients without interference with antiretroviral treatment (ART) and DAA. Short-term close lipid monitoring may be necessary when combining protease inhibitors. HCV-GT-3/HIV co-infected patients might require further close monitoring for residual fibrosis. These findings can be relevant for actual clinical practice. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is defined as a cessation of ovarian function before the age of 40. Such early deprivation of estrogens in women may be associated with several adverse cardiovascular and metabolic consequences. The aim of this retrospective study was to investigate whether women with POI and a serum follicle-stimulating hormone (FSH) level of 25–40 I/U (Group A) have the same metabolic profile as women with POI and a serum FSH level of >40 I/U (Group B). One hundred twenty-three women were included in the study group (Group A; n = 41; Group B; n = 82). The control group comprised 77 healthy women with regular menstruation. In the age- and BMI-adjusted model, no differences were found between the groups with respect to total cholesterol, high-density lipoproteins, triglycerides, HOMA-IR, glucose, and insulin. The only significant difference was found in terms of low-density lipoprotein cholesterol (LDL-C). The highest serum concentration was found in Group B, the second highest was found in Group A, and the lowest was in the controls. In conclusion, changing the threshold of FSH required to establish a POI diagnosis may have an impact on the level of serum LDL-C. [ABSTRACT FROM AUTHOR]

Diabetes in pregnancy, both preexisting type 1 or type 2 and gestational diabetes, is a highly prevalent condition, which has a great impact on maternal and fetal health, with short and long-term implications. Gestational Diabetes Mellitus (GDM) is a condition triggered by metabolic adaptation, which occurs during the second half of pregnancy. There is still a lot of controversy about GDM, from classification and diagnosis to treatment. Recently, there have been some advances in the field as well as recommendations from international societies, such as how to distinguish previous diabetes, even if first recognized during pregnancy, and newer diagnostic criteria, based on pregnancy outcomes, instead of maternal risk of future diabetes. These new recommendations will lead to a higher prevalence of GDM, and important issues are yet to be resolved, such as the cost-utility of this increase in diagnoses as well as the determinants for poor outcomes. The aim of this review is to discuss the advances in diagnosis and classification of GDM, as well as their implications in the field, the issue of hyperglycemia in early pregnancy and the role of hemoglobin A1c (HbA1c) during pregnancy. We have looked into the determinants of the poor outcomes predicted by the diagnosis by way of oral glucose tolerance tests, highlighting the relevance of continuous glucose monitoring tools, as well as other possible pathogenetic factors related to poor pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is associated with dyslipidemia. However, the effects of continuous positive airway pressure (CPAP) treatment on lipid profiles are unclear. Methods: PubMed/Medline, Embase and Cochrane were searched up to July 2021. Randomized controlled trials (RCTs) of CPAP versus controls with ≥4 weeks treatment and reported pre- and post-intervention lipid profiles were included. Weighted mean difference (WMD) was used to assess the effect size. Meta-regression was used to explore the potential moderators of post-CPAP treatment changes in lipid profiles. Results: A total of 14 RCTs with 1792 subjects were included. CPAP treatment was associated with a significant decrease in total cholesterol compared to controls (WMD = −0.098 mmol/L, 95% CI = −0.169 to −0.027, p = 0.007, I2 = 0.0%). No significant changes in triglyceride, high-density lipoprotein nor low-density lipoprotein were observed after CPAP treatment (all p > 0.2). Furthermore, meta-regression models showed that age, gender, body mass index, daytime sleepiness, OSA severity, follow-up study duration, CPAP compliance nor patients with cardiometabolic disease did not moderate the effects of CPAP treatment on lipid profiles (all p > 0.05). Conclusions: CPAP treatment decreases total cholesterol at a small magnitude but has no effect on other markers of dyslipidemia in OSA patients. Future studies of CPAP therapy should target combined treatment strategies with lifestyle modifications and/or anti-hyperlipidemic medications in the primary as well as secondary cardiovascular prevention models. [ABSTRACT FROM AUTHOR]

We analyzed the relationship between egg consumption, body composition, and serum cholesterol levels. We obtained data on egg consumption by using a food frequency questionnaire (FFQ) (13,132 adults) and the 24-h dietary recall (24HR) (13,366 adults) from the fourth and fifth Korea National Health and Nutrition Examination Surveys (2008–2011). In men, consuming 2–3 eggs/week was associated with higher fat mass (FM), percentage body fat (PBF), and fat-to-muscle ratio (FtoM), compared to consuming <1 egg/week. In women, consuming 1–6 eggs/week was associated with higher low-density lipoprotein cholesterol, consuming 2–6 eggs/week was associated with higher total cholesterol, and consuming 4–6 eggs/week was associated with higher FM and high-density lipoprotein cholesterol, compared to consuming <1 egg/week. There was no relationship between egg consumption and the prevalence of dyslipidemia, and there was no relationship between egg consumption, body composition, and serum cholesterol levels according to the 24HR. However, there was some association with other cardiovascular diseases and consumption of certain amounts of eggs. Egg consumption investigated by FFQ was associated with body composition and serum cholesterol levels. However, the egg consumption investigated by the 24HR resulted in no health benefit or harm with respect to body composition and cholesterol. [ABSTRACT FROM AUTHOR]

Heterozygous familial hypercholesterolaemia (FH) is among the most common genetic metabolic lipid disorders characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and a significantly higher risk of developing premature atherosclerotic cardiovascular disease. The majority of the current pediatric guidelines for clinical management of children and adolescents with FH does not consider the impact of genetic variations as well as characteristics of vascular phenotype as assessed by recently developed non-invasive imaging techniques. We propose a combined integrated approach of cardiovascular (CV) risk assessment and clinical management of children with FH incorporating current risk assessment profile (LDL-C levels, traditional CV risk factors and familial history) with genetic and non-invasive vascular phenotyping. Based on the existing data on vascular phenotype status, this panel recommends that all children with FH and cIMT ≥0.5 mm should receive lipid lowering therapy irrespective of the presence of CV risk factors, family history and/or LDL-C levels Those children with FH and cIMT ≥0.4 mm should be carefully monitored to initiate lipid lowering management in the most suitable time. Likewise, all genetically confirmed children with FH and LDL-C levels ≥4.1 mmol/L (160 mg/dL), should be treated with lifestyle changes and LLT irrespective of the cIMT, presence of additional RF or family history of CHD. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the relationship between selected serum sex hormones and lipid profiles in a group of women with polycystic ovary syndrome (PCOS) dividing according to four phenotypes, value of body mass index (BMI), and presence of hyperlipidemia. The study included 606 Caucasian women. Lipids and selected hormones were estimated using commercially available procedures during hospitalization in 2017. Phenotype of PCOS, BMI value, and hyperlipidemia were significant factors that influenced androgen hormone concentrations, such as total and free testosterone and androstenedione as well as the value of free androgen index (FAI). Moreover, significant changes in concentrations of dehydroepiandrosterone sulphate and sex hormone binding globulin (SHBG) were found between those groups. Higher quartiles of triglyceride concentrations increased the odds ratio of decreased concentrations of SHBG or increased values of FAI, while an adverse relation was found in case of HDL-C. The concentration of estradiol in the blood of women with PCOS was not associated with lipid profile parameters in any investigated groups. Probably, irregularities in sex hormone concentrations during PCOS is not directly associated with lipid profile parameters but could be reflective of the concentration of SHBG or the ratio of SHBG and total testosterone and their association with lipids. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduce low-density lipoprotein (LDL) cholesterol and cardiovascular event rates, yet due to their high price remain underutilized and difficult to prescribe in clinical practice. In March 2018, their price was significantly reduced. We evaluated whether the price reduction would improve prescribing patterns of PCSK9 inhibitors in eligible patients with atherosclerotic cardiovascular disease (ASCVD). Methods: We identified the number of eligible ASCVD patients and those prescribed a PCSK9 inhibitor for each year between July 2015 and December 2019. Patient demographics and clinical characteristics for those prescribed a PCSK9 inhibitor were extracted from their electronic health record. Results: In total 1059 patients of eligible patients received a new prescription for a PCSK9 inhibitor. From 2015 to 2019, the rate of new prescriptions among eligible patients increased from 0.5 to 3.3% (p < 0.001) and continuation rates increased from 18 to 60% (p < 0.001). Following the price reduction, patients who were prescribed a PCSK9 inhibitor were younger and more likely to be female, but less likely to have Medicare insurance. Conclusions: Despite the reduction in the cost of PCSK9 inhibitors, most eligible patients are not prescribed one. The reduction in cost has improved adherence, primarily in patients with commercial insurance. Older patients and those on Medicare still face significant barriers in accessing a PCSK9 inhibitor. Further reductions in the price of the PCSK9 inhibitors are needed as is further study of the barriers that exist in prescribing one. [ABSTRACT FROM AUTHOR]

In this study, we aim to explore the effects on lipids of integrase strand transfer inhibitors (INSTIs) in naïve and switch randomised controlled trials, and compare them with protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). We reviewed phase 3/4 randomised clinical trials in the Cochrane and PubMed databases that compare an INSTI with a boosted PI, an NNRTI, or another INSTI plus one or two nucleoside/nucleotide reverse transcriptase inhibitors (NtRTIs) in naïve patients and switching strategies in HIV-infected patients. We reported the baseline plasma concentration of total cholesterol (TC), low and high-density lipoprotein cholesterol (LDL-c, HDL-c), triglycerides (TG), and the TC/HDL-c ratio, as well as the change at weeks 48 and 96, when available. In naïve HIV-infected patients, raltegravir (RAL) and dolutegravir (DTG) have a more favourable lipid profile compared with NNRTI and boosted PI. Elvitegravir (EVG/c) has a superior lipid profile compared with efavirenz and is similar to that observed with ritonavir-boosted atazanavir except in TG, which increases less with EVG/c. In naïve patients, RAL, DTG, and bictegravir (BIC) produce a similar, slight increase in lipids. In switching trials, the regimen change based on a boosted PI or efavirenz to RAL, DTG, or BIC is associated with clinically significant decreases in lipids that are minor when the change is executed on EVG/c. No changes were observed in lipids by switching trials between INSTIs. In summary, RAL, DTG, and BIC have superior lipid profiles compared with boosted-PI, efavirenz, and EVG/c, in studies conducted in naïve participants, and they are associated with a clinically significant decrease in lipoproteins by switching studies. [ABSTRACT FROM AUTHOR]

We assessed sex differences across the life span in the lipid profile of type 2 diabetes (T2D) patients treated and not treated with statins. We used the Groningen Initiative to ANalyze Type 2 diabetes Treatment database, which includes T2D patients from the north of the Netherlands. Patients with a full lipid profile determined between 2010 and 2012 were included. We excluded patients treated with other lipid-lowering drugs than statins. Sex differences in low- and high-density lipoprotein cholesterol (LDL-c and HDL-c) and triglyceride (TG) levels across 11 age groups stratified by statin treatment were assessed using linear regression. We included 26,849 patients (51% women, 55% treated with statins). Without statins, women had significantly lower LDL-c levels than men before the age of 45 years, similar levels between 45 and 49 years, and higher levels thereafter. With statins, similar LDL-c levels were shown up to the age of 55, and higher levels in women thereafter. Women had significantly higher HDL-c levels than men, regardless of age or statin treatment. Men had significantly higher TG levels up to the age of 55 and 60, depending on whether they did not take or took statins, respectively, and similar levels thereafter. When managing cardiovascular risk in patients with T2D, attention is needed for the menopausal status of women and for TG levels in younger men. [ABSTRACT FROM AUTHOR]

In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules. It undergoes quantitative as well as qualitative changes which can be measured using the HDL inflammatory index (HII). Pro-inflammatory, or dysfunctional HDL (dysHDL) lacks the ability to perform these functions, and we have also found it to independently predict adverse outcomes and organ failure in sepsis. Another important class of lipids known as specialized pro-resolving mediators (SPMs) positively affect the escalation and resolution of inflammation in a temporal fashion. These undergo phenotypic changes in sepsis and differ significantly between survivors and non-survivors. Certain subsets of sepsis survivors go on to have perilous post-hospitalization courses where this inflammation continues in a low grade fashion. This is associated with immunosuppression in a syndrome of persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The continuous release of tissue damage-related patterns and viral reactivation secondary to immunosuppression feed this chronic cycle of inflammation. Animal data indicate that dysregulation of endogenous lipids and SPMs play important roles in this process. Lipids and their associated pathways have been the target of many clinical trials in recent years which have not shown mortality benefit. These results are limited by patient heterogeneity and poor animal models. Considerations of sepsis phenotypes and novel biomarkers in future trials are important factors to be considered in future research. Further characterization of lipid dysregulation and chronic inflammation during sepsis will aid mortality risk stratification, detection of sepsis, and inform individualized pharmacologic therapies. [ABSTRACT FROM AUTHOR]