The Impact of Regular Screening and Lifestyle Modification on Cardiovascular Disease Risk Factors in South African Women Living With HIV.

BACKGROUND: The Integration of cardiovascular disease SCreening and prevention in the HIV MAnagement plan for women of reproductive age study set out to determine the effectiveness of screening and lifestyle modification in modifying cardiovascular disease (CVD) risk factors in women living with HIV (WLHIV). METHODS: In this prospective, quasiexperimental, intervention study, WLHIV aged 18-<50 years were enrolled from 2 clinics (intervention [I-arm]) and (control arms [C-arm]) in Umlazi, South Africa, between November 2018 and May 2019. Women in the I-arm received lifestyle modification advice on diet, physical activity, alcohol use, and smoking cessation and underwent annual screening for CVD risk. The CVD risk factors were assessed through standardized questionnaires and clinical and laboratory procedures at baseline and at end of 3 years of follow-up. Prevalence of metabolic syndrome and other CVD indices were compared between arms at end-of-study (EOS). RESULTS: Total of 269 WLHIV (149 I-arm and 120 C-arm) with a mean ± SD age of 36 ± 1 years were included in the EOS analyses after 32 ± 2 months of follow-up. The metabolic syndrome prevalence at EOS was 16.8% (25/149) in the I-arm and 24% (24/120) in the C-arm (risk ratio 0.9; 95% CI: 0.5 to 1.1; P 0.86). Proportion of women with fasting blood glucose >5.6 mmol/L in the I-arm and C-arm were 2.7% (4/149) and 13.3% (16/120) respectively (risk ratio 0.2; 95% CI: 0.069 to 0.646; P < 0.01). High-density lipoprotein improved with the intervention arm from baseline to EOS (95% CI: -0.157 to -0.034; P < 0.05). CONCLUSIONS: Although there was no significant difference in the prevalence of metabolic syndrome between study arms, we observed decreased blood glucose levels in the I-arm compared with the C-arm and improved high-density lipoprotein within the I-arm, following lifestyle modification and regular screening for CVD risk factors in WLHIV.

Comparison of effects of tamoxifen and Toremifene on hepatic function and serum lipids in breast cancer patients during adjuvant endocrine therapy.

To investigate the effects of tamoxifen (TAM) and toremifene (TOR) on hepatic function and serum lipid levels in breast cancer patients receiving adjuvant endocrine therapy. The clinical data of 597 early breast cancer patients treated at the First Affiliated Hospital of Nanjing Medical University between January 2016 and December 2022 were collected. All the patients received standard adjuvant endocrine therapy with TAM or TOR after chemotherapy. Hepatic function and serum lipid data of all patients before and at 6 months and 1, 2, and 3 years after the treatment were collected retrospectively and analyzed statistically. There: no negative effect on hepatic function was observed in patients treated with either TAM or TOR. The triglyceride levels in both groups increased during treatment, and the effect of TAM on improving total cholesterol levels was stronger. Total cholesterol levels were not affected by time or treatment regimen. The low-density lipoprotein cholesterol levels decreased in both groups, and the effect was similar between groups. TAM can decrease the high-density lipoprotein cholesterol levels, whereas TOR can increase the high-density lipoprotein cholesterol levels, and there was a significant difference between groups. In the postoperative adjuvant endocrine therapy, TOR and TAM will not negatively impact the hepatic function of breast cancer patients, and TOR is better than TAM in the management of serum lipids; therefore, it may be a better choice for clinical medication.

Blood glucose level and serum lipid profiles among people living with HIV on dolutegravir-based versus efavirenz-based cART; a comparative cross-sectional study.

BACKGROUND: Antiretroviral therapy-linked metabolic abnormalities have become a growing concern among people living with HIV. There is limited data regarding the effects of dolutegravir-based treatment on blood glucose levels and serum lipid profiles in people living with HIV in Ethiopia. Thus, this study aimed to assess blood glucose levels and serum lipid profiles among people living with HIV on dolutegravir-based versus efavirenz-based therapy. METHOD AND MATERIALS: An institutional-based comparative cross-sectional study was conducted from 30 June 2021 to 30 August 2021. A total of 128 participants (64 in the dolutegravir-based group and 64 in the efavirenz-based group) were enrolled in the study. The Chi-square, independent t-test, Mann-Whitney U-test, and logistic regression were used as appropriate statistical tests using SPSS Version 26.0 for this study. A p-value of <0.05 was considered statistically significant. RESULT: The prevalence of hyperglycemia and dyslipidemia were 17.2% (11/64) and 79.7% (51/64) in the dolutegravir group, and 9.4% (6/64) and 75% (48/64) in the efavirenz group, respectively. The efavirenz group had significantly higher mean values of total cholesterol (190.73 ± 44.13 vs. 175.27 ± 37.67 mg/dl, p = 0.035) and high-density lipoprotein (47.53 ± 14.25 vs. 40.92 ± 13.17 mg/dl, p = 0.007) than the dolutegravir group. For a Kg/m2 increase in BMI and for each month's increase in the duration of HIV, the patients were 66% (AOR = 1.66, 95% CI: 1.13, 2.44), and 13% (AOR = 1.13, 95% CI: 1.03, 1.23) more likely to have hyperglycemia, respectively. In contrast, female patients were 3.04 times more likely to have dyslipidemia (AOR = 3.03, 95% CI: 1.14, 8.05) as compared to male patients, and with an increase in CD4 cell count of 1 cell/mm3, the odds of dyslipidemia increased by 0.3% (AOR = 1.003, 95% CI: 1.001, 1.006). CONCLUSION: Efavirenz-based therapy resulted in higher mean values of total cholesterol and high-density lipoprotein as compared with dolutegravir-based therapy. It is important to consider and evaluate high-density lipoprotein levels in HIV patients on dolutegravir-based therapy, and total cholesterol levels in people living with HIV on efavirenz-based therapy.

The long-term use of ART is thought to be one of the potential causes of metabolic abnormalities such as dysregulation of glucose and lipid metabolism.The burden of DTG-based cART-related metabolic abnormalities in resource-limited settings has not been well characterized.This study aimed to address these gaps by assessing blood glucose levels and serum lipid profiles among people living with HIV on DTG-based versus EFV-based regimens and identifying factors associated with hyperglycemia and dyslipidemia.

Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV.

Background Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. Methods and Results In 1814 individuals with a median (interquartile range) age of 53 (44-60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57-0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. Conclusions Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high- and very high-risk patients for cardiovascular disease is recommended. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03994835.

The anti-dyslipidemia property of saffron petal hydroalcoholicextract in cardiovascular patients: A double-blinded randomized clinical trial.

BACKGROUND AND AIMS: Dyslipidemia is one of the most important risk factors of cardiovascular diseases (CVDs). Despite developments in pharmacological treatments for dyslipidemia there are several challenges. Recently some herbs highly considered to control dyslipidemia due to their low toxicity and high potency. In this study we investigated the effects of saffron petals on the lipid profile of dyslipidemia patients as well as several other biochemical blood factors. METHODS: In this double blind, placebo controlled, clinical trial, we used systematic random sampling to divide 40 patients with at least two abnormalities in the following factors: (high-density lipoproteins (HDL) ≤40, low-density lipoproteins (LDL) ≥130, triglycerides (TG) ≥200, total cholesterol (Cho) ≥200), into 2 groups of 21 ones. At the end of the intervention period, serum lipid factors, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, creatinin (CR) and fasting blood sugar (FBS) were measured and statistically compared with their values just before the intervention. RESULTS: We found that the saffron petal pills markedly (P < 0.001) decreased the serum lipid levels of patients (TG, Cho and LDL) in the intervention group (113.81 ± 12.93, 56.52 ± 4.68 and 48.28 ± 3.70) as compared to the placebo group (18.42 ± 15.79, 4.57 ± 4.40 and 7.38 ± 3.54). Also, comparing the mean value of differences in two groups before and after the intervention showed significant reduction in TG (113.81 ± 26), Cho (56.53 ± 0.30) and LDL (48.28 ± 4.30) levels (P < 0.001). CONCLUSIONS: The saffron petal pills considerably reduced blood serum lipid profile and as well as urea and CR of dyslipidemia patients. So, this plant may be used as a potent phytomedicine for treatment and prevention of dyslipidemia and cardiovascular disorders. However, the results indicated that no statistical change was observed in the level of other biochemical blood factors such as ALT, AST, ALP and FBS.

Clinical Pharmacokinetics and Pharmacodynamics of CSL112.

Cardiovascular diseases are the leading cause of death worldwide. Although there have been substantial advances over the last decades, recurrent adverse cardiovascular events after myocardial infarction are still frequent, particularly during the first year of the index event. For decades, high-density lipoprotein (HDL) has been among the therapeutic targets for long-term prevention after an ischemic event. However, early trials focusing on increasing HDL circulating levels showed no improvement in clinical outcomes. Recently, the paradigm has shifted to increasing the functionality of HDL rather than its circulating plasma levels. For this purpose, apolipoprotein-AI-based infusion therapies have been developed, including reconstituted HDL, such as CSL112. During the last decade, CSL112 has been extensively studied in Phase 1 and 2 trials and has shown promising results. In particular, CSL112 has been studied in the Phase 2b AEGIS trial exhibiting good safety and tolerability profiles, which has led to the ongoing large-scale Phase 3 AEGIS-II trial. This systematic overview will provide a comprehensive summary of the CSL112 drug development program focusing on its pharmacodynamic, pharmacokinetic, and safety profiles.

Deciphering structural aspects of reverse cholesterol transport: mapping the knowns and unknowns.

Atherosclerosis is a major contributor to the onset and progression of cardiovascular disease (CVD). Cholesterol-loaded foam cells play a pivotal role in forming atherosclerotic plaques. Induction of cholesterol efflux from these cells may be a promising approach in treating CVD. The reverse cholesterol transport (RCT) pathway delivers cholesteryl ester (CE) packaged in high-density lipoproteins (HDL) from non-hepatic cells to the liver, thereby minimising cholesterol load of peripheral cells. RCT takes place via a well-organised interplay amongst apolipoprotein A1 (ApoA1), lecithin cholesterol acyltransferase (LCAT), ATP binding cassette transporter A1 (ABCA1), scavenger receptor-B1 (SR-B1), and the amount of free cholesterol. Unfortunately, modulation of RCT for treating atherosclerosis has failed in clinical trials owing to our lack of understanding of the relationship between HDL function and RCT. The fate of non-hepatic CEs in HDL is dependent on their access to proteins involved in remodelling and can be regulated at the structural level. An inadequate understanding of this inhibits the design of rational strategies for therapeutic interventions. Herein we extensively review the structure-function relationships that are essential for RCT. We also focus on genetic mutations that disturb the structural stability of proteins involved in RCT, rendering them partially or completely non-functional. Further studies are necessary for understanding the structural aspects of RCT pathway completely, and this review highlights alternative theories and unanswered questions.

Effect Of Tamoxifen On Plasma Lipid Profile In Patients Of Breast Cancer.

BACKGROUND: To evaluate the effect of Tamoxifen on plasma lipid profile in breast cancer patients presenting at tertiary care hospitals. METHODS: It was a longitudinal study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from December 2018 to November 2019. Eighty-eight females aged 26-66 years diagnosed with breast cancer were included in the study using a non-probability consecutive sampling technique. Detailed gynaecological and clinical investigations and detailed history were taken. The blood samples of all the patients were collected and the plasma lipid profile was measured before initiation of Tamoxifen treatment and three- and six-months post-treatment at the clinical laboratory. The plasma lipid profile includes the measurement of Total cholesterol (mg/dl), Triglyceride(mg/dl), High-density Lipoprotein (mg/dl) & Low-density Lipoprotein (mg/dl). SPSS version 23 was used to analyse data. RESULTS: After treatment, there was a significant reduction in serum cholesterol & Low-density Lipoprotein level by 20.54 mg/dl & 16.46 mg/dl at 3 months (p<0.05), moreover there was a significant increase in Triglyceride by 22.14 at 3 months (p<0.05). No significant difference was observed in High density lipoprotein level at 3 months after using Tamoxifen. At 6 months there was a significant reduction in serum cholesterol and low-density lipoprotein by 32.29mg/dl and 24.11 mg/dl at 6 months (p<0.05), moreover there was a significant increase in Triglyceride level by 42.19 mg/dl at 6 months (p<0.05). No significant difference was observed in High-density lipoprotein level at 6 months after using Tamoxifen. CONCLUSIONS: Total cholesterol and Low-density Lipoprotein levels showed significant reduction over the period of six months from the baseline with the use of Tamoxifen. Hence Tamoxifen should be considered to have an added advantage on lipid metabolism and therefore, can reduce the risk of cardiovascular events.

Effect of Obesity and High-Density Lipoprotein Concentration on the Pathological Characteristics of Alzheimer's Disease in High-Fat Diet-Fed Mice.

The typical pathological features of Alzheimer's disease (AD) are the accumulation of amyloid plaques in the brain and reactivity of glial cells such as astrocytes and microglia. Clinically, the development of AD and obesity are known to be correlated. In this study, we analyzed the changes in AD pathological characteristics in 5XFAD mice after obesity induction through a high-fat diet (HFD). Surprisingly, high-density lipoprotein and apolipoprotein AI (APOA-I) serum levels were increased without low-density lipoprotein alteration in both HFD groups. The reactivity of astrocytes and microglia in the dentate gyrus of the hippocampus and fornix of the hypothalamus in 5XFAD mice was decreased in the transgenic (TG)-HFD high group. Finally, the accumulation of amyloid plaques in the dentate gyrus region of the hippocampus was also significantly decreased in the TG-HFD high group. These results suggest that increased high-density lipoprotein level, especially with increased APOA-I serum level, alleviates the pathological features of AD and could be a new potential therapeutic strategy for AD treatment.

Antidiabetic effects of nerolidol through promoting insulin receptor signaling in high-fat diet and low dose streptozotocin-induced type 2 diabetic rats.

The present study was designed to investigate the antidiabetic effect of nerolidol on high-fat diet and streptozotocin-induced diabetic rats. Type 2 diabetes was induced in animals by feeding them a high-fat diet for 4 weeks and administering a single intraperitoneal dose of streptozotocin (35 mg/kg body weight). Diabetic rats were treated with nerolidol (25 mg/kg BW) for 28 days. Results showed that nerolidol treatment significantly reduced (p < 0.05) the level of elevated glucose, glycosylated hemoglobin and improved (p < 0.05) the body weight and insulin level. Nerolidol also considerably improved (p < 0.05) the carbohydrate metabolic enzyme activities and increased the glycogen storage in the liver of diabetic rats. Increased serum triglycerides, total cholesterol (C), low-density lipoproteins-C and very low-density lipoproteins-C levels were significantly lowered (p < 0.05), while reduction of serum high-density lipoprotein-C was alleviated after administration of nerolidol. In addition, nerolidol attenuated oxidative stress markers by significantly increasing (p < 0.05) the levels of superoxide dismutase, catalase, reduced glutathione, and lowering (p < 0.05) the level of thiobarbituric acid reactive substances, and lipid hydroperoxide. Similarly, nerolidol showed its pharmacological effects against hepatic markers via restoring (p < 0.05) the alleviated level of alanine transaminase, aspartate aminotransferase, and alkaline phosphatase. Finally, it improved insulin-dependent glucose transport in skeletal muscle by enhancing and activating glucose transporter protein-4. These findings confirmed the antidiabetic potential of nerolidol in type 2 diabetic rats. This may be related to a high antioxidant capacity, the restoration of plasma insulin and lipid levels, and the activation of insulin signaling in STZ/HFD-induced diabetic rats.

A Study of Peripheral Blood Parameters to Predict Response to Induction Chemotherapy and Overall Survival in Advanced Laryngeal Squamous Cell Carcinoma.

PURPOSE: the purpose of this study was to screen peripheral blood parameters and construct models predicting the prognosis and induction chemotherapy (IC) response in locally advanced laryngeal squamous cell carcinoma (LSCC) patients. METHODS: A total of 128 stage III/IVa LSCC patients (who required a total laryngectomy) were enrolled in a retrospective study from January 2013 to September 2020 at Beijing Tongren Hospital of Capital Medical University. Among them, 62 patients received IC (IC group), and 66 patients immediately underwent a total laryngectomy (TL) after diagnosis (surgery group). Demographic information and peripheral blood parameters were collected for further analysis. The overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) were compared between the two groups. The prognosis and survival were also compared between patients with laryngeal function preservation (LFP) and those with TL. RESULTS: The Receiver Operating Characteristic (ROC) curve for IC response in the IC group showed that the AUC of the blood model based on the four peripheral blood parameters of fibrinogen (FIB), platelet (PLT), high-density lipoprotein cholesterol (HDL), and albumin (ALB) was significantly higher than the TNM stage model's AUC (0.7932 vs. 0.6568). We constructed a nomogram blood model to predict IC response (C-Index = 0.793). Regarding the OS of all patients, an ROC analysis for overall survival, the Kaplan-Meier (K-M) method with a log-rank test, and multivariate analysis indicated age, clinical stage, FIB, and hemoglobin (HGB) were independent prognostic factors for the OS of LSCC patients. The blood-clinical logistic model (AUC = 0.7979) was constructed based on the four prognosis factors, which were superior to the blood (AUC = 0.6867) or clinical models (AUC = 0.7145) alone to predict OS. We constructed a nomogram model based on age, clinical stage, FIB, and HGB to predict OS for LSCC patients (C-Index = 0.792). Besides this, there were no significant differences in OS, PFS, and DSS between IC and surgery groups or LFP and TL groups. CONCLUSION: Peripheral blood parameters help predict IC response and overall survival. Furthermore, induction chemotherapy significantly improves laryngeal function preservation without lowering the survival prognosis.

Efficacy of Yishen Huashi Granules Combined with Linagliptin Tablets on Blood Glucose and Renal Function in Patients with Type 2 Diabetic Nephropathy.

Objective: To probe into the efficacy of Yishen Huashi granules combined with linagliptin tablets in the treatment of type 2 diabetic nephropathy (DN) and its effect on blood glucose and renal function in patients. Methods: 70 patients with type 2 DN at our hospital between May 2020 and May 2022 were chosen as the research objects and separated into the control group and the research group based on their treatments. With 35 cases in each group, the patients treated with initial therapy and linagliptin tablets were enrolled in the control group, and those who received the above treatments and also Yishen Huashi granules were included in the research group. Their clinical indexes such as blood glucose and renal function were compared with both groups after treatment. Results: After treatment, the research group had remarkably lower fasting blood glucose (FPG), 2 h-postprandial blood glucose (2 h-PBG), and glycosylated hemoglobin A1c (HbA1c) levels than those in the control group (P < 0.05). After treatment, the research group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) (P < 0.05) and higher high-density lipoprotein (HDL) levels (P < 0.05) than those in the control group. After treatment, the urinary microalbumin (u-mALB) level was remarkably lower in both groups (P < 0.05) and was distinctly lower in the research group than in the control group (P < 0.05). After treatment, the research group had remarkably lower renal function indexes such as serum creatinine (SCr), blood urea nitrogen (BUN), urinary protein (UPro), and urinary albumin excretion rate (UAER) (P < 0.05) and a higher estimated glomerular filtration rate (eGFR) level (P < 0.05) than those in the control group. The efficacy was evaluated by the traditional Chinese medicine (TCM) syndrome score after treatment. There were no patients in complete remission between both the groups, where slight differences were found in the proportion of significant remission (P > 0.05), with the total effective rate of the research group remarkably higher than that of the control group (P < 0.05). Conclusion: The combination of Yishen Huashi granules and linagliptin tablets can reduce the blood glucose and blood lipid levels in patients with type 2 DN and lower UPro and protect renal function at the same time, which provides a new idea and a method for clinical treatment of type 2 DN with integrated traditional Chinese and Western medicine.

Cucumis melo var. momordica as a Potent Antidiabetic, Antioxidant and Possible Anticovid Alternative: Investigation through Experimental and Computational Methods.

Diabetes mellitus is a typical life threatening of disease, which generate due to the dysfunction of ß cells of pancreas. In 2014, WHO stated that 422 million people were infected with DM. The current pattern of management of diabetes included synthetic or plant based oral hypoglycemic drugs and insulin but drug resentence is become a very big issues in antidiabetic therapy. Thus, it's very earnest to discover now medication for this disease. Now the days, it is well acknowledged that diabetic patients are more prone towards covid and related complications. Thus, medical practitioners reformed the methodology of prescribing medication for covid infected antidiabetic therapy and encouraging the medication contains dual pharmacological properties. It is also well know that polyphenols specifically hold a significant role in oxidative stress and reduced the severity of many inflammatory diseases. Cucumis melo has rich history as ethano-pharmacological use in Indian subcontinent. The fruit and seed are well-known for the treatment of various diseases due to the presence of phenolics. Therefore, in this study, the combined mixture of flower and seeds were used for the extraction of polyphenolic rich extract and tested for antidiabetic activity through the antioxidant and in vivo experiments. The antioxidant potential measurement exhibited that the selected plant extract has the significant competence to down-regulate oxidative stress (DPPH scavenging IC50 at 60.7±1.05 µg/mL, ABTS IC50 at 62.15±0.50 µg/mL). Furthermore, the major polyphenolic phyto-compounds derived from the Cucumis melo were used for in silico anticovid activity, docking, and complementarity studies. The anticovid activity prognosis reflected that selected phyto-compounds amentoflavone and vanillic acid have optimal possibility to interact with 3C-like protease and through this moderate anticovid activity can be exhibit. The docking experiments established that the selected compounds have propensity to interact with protein tyrosine phosphatase 1B, 11ß-Hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, and catalase ß-glucuronidase receptor. In vivo experiments showed that 500 mg/kg, Cucumis melo extract ominously amplified body weight, plasma insulin, high-density lipoprotein levels, and biochemical markers. Furthermore, extract significantly downregulate the blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein.

Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model.

High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p < 0.01), increased HDL particles numbers 2.8-fold (p < 0.0001), reduced HDL-bound APOM (−23%; p < 0.0001), and increased LDL oxidation 1.7-fold (p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content.

Effects of omega-3 supplementation on quality of life, nutritional status, inflammatory parameters, lipid profile, exercise tolerance and inhaled medications in chronic obstructive pulmonary disease.

BACKGROUND: The omega-3 polyunsaturated fatty acids (PUFAs) have an anti-inflammatory effect, beneficial for allergies, asthma, chronic obstructive pulmonary disease (COPD), reduce cholesterol and triglyceride levels and blood inflammatory parameters [C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α)]. The aim of our cross-sectional study was to monitor omega-3 supplementation in patients with severe COPD and assess its association with quality of life, nutritional status, inflammatory parameters, lipid profile, comorbidities, exercise tolerance and inhaled medications. METHODS: Our questionnaire on dietary supplement habits and our validated self-completion questionnaires were filled in by 400 patients with COPD at the National Koranyi Institute of Pulmonology, Hungary, mean age 67 [61-73] years; forced expiratory volume in one second (FEV1) (ref%): 46 [34-58]; 47.5% male, 52.5% female. We used the disease-specific COPD Assessment Test (CAT) questionnaire to measure quality of life. RESULTS: More than half of the study participants (61%) did not consume fish or oilseeds at all. Nineteen patients (4.75%) took omega-3 supplementation regularly, mainly on medical advice (0.5 g/day). We observed significantly lower serum CRP levels [6.0 (1-7.3) vs. 9.7 (7.4-14.4); P=0.044], more favourable lipid profile [triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol] with higher mean body mass index (BMI) [28.1 (22.0-35.3) vs. 24.7 (24.5-30.1); P=0.118], better quality of life {CAT: 25 [21-30.5] vs. 26 [20-31]; P=0.519}, lower inhaled short-acting bronchodilators use [short-acting beta-agonists (SABAs): 6 (31.58) vs. 209 (54.86); P=0.047], lower number of exacerbations in the previous half year [0 (0-1) vs. 1 (0-2); P=0.023], and higher 6-minute walking distance (6MWD) {300 [177-387] vs. 251 [150-345]; P=0.120} in the group with omega-3 supplementation. CONCLUSIONS: PUFAs are anti-inflammatory and affect the immune system. Our study shows that omega-3 intake of COPD patients is insufficient, and there is an urgent need to develop new anti-inflammatory strategies because only one drug (such as corticosteroids) cannot ease the chronically progressive inflammatory process of COPD.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Association between preconception serum lipid concentrations and treatment outcomes in women with PCOS who underwent ovulation induction.

RESEARCH QUESTION: What is the association between preconception serum lipid concentrations and reproductive outcomes after ovulation induction in women with polycystic ovary syndrome (PCOS)? DESIGN: A secondary analysis of a randomized controlled trial with 1000 PCOS women undergoing ovulation induction with clomiphene with or without acupuncture. Preconception serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) were measured. Outcomes were ovulation, conception, pregnancy, live birth and miscarriage. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: In total, 780 women ovulated; 320 women achieved conception, 218 had a clinical pregnancy, 205 had a live birth and 115 had a miscarriage. Serum lipid concentrations per one unit increment were independently associated with reproductive outcomes after controlling for confounders. Increasing LDL-C (OR 0.79, 95% CI 0.63-0.99) was independently associated with a lower chance of ovulation. Increasing total cholesterol (OR 0.76, 95% CI 0.62-0.92), LDL-C (OR 0.73, 95% CI 0.57-0.93), triglycerides (OR 0.74, 95% CI 0.58-0.95) and ApoB (OR 0.34, 95% CI 0.16-0.74) were independently associated with a lower chance of clinical pregnancy. Increased total cholesterol (OR 0.78, 95% CI 0.64-0.96), LDL-C (OR 0.77, 95% CI 0.60-0.99), triglycerides (OR 0.76, 95% CI 0.59-0.96) and ApoB (OR 0.39, 95% CI 0.18-0.86) were independently associated with a lower chance of live birth. Furthermore, increased total cholesterol (OR 1.43, 95% CI 1.06-1.93), LDL-C (OR 1.51, 95% CI 1.04-2.19) and ApoB (OR 3.82, 95% CI 1.17-12.41) were independently associated with a higher chance of miscarriage. CONCLUSIONS: Increased serum lipids were negatively associated with the reproductive outcomes of PCOS women undergoing ovulation induction with clomiphene with or without acupuncture.

Predicting incident heart failure among patients with type 2 diabetes mellitus: The DM-CURE risk score.

AIM: Early identification and prediction of incident heart failure (HF) is important because of severe morbidity and mortality. This study aimed to predict onset of HF among patients with diabetes. METHODS: A time-varying Cox model was derived from ACCORD clinical trial to predict the risk of incident HF, defined by hospitalization for HF (HHF). External validation was performed on patient-level data from the Harmony Outcome trial and Chronic Renal Insufficiency Cohort (CRIC) study. The model was transformed into an integer-based scoring algorithm for 10-year risk evaluation. A stepwise algorithm identified and selected predictors from demographic characteristics, physical examination, laboratory results, medical history, medication and health care utilization, to develop a risk prediction model. The main outcome was incident HF, defined by HHF. The C statistic and Brier score were used to assess model performance. RESULTS: In total, 9649 patients with diabetes free of HF were used, with median follow-up of 4 years and 299 incident hospitalization of HF events. The model identified several predictors for the 10-year HF incidence risk score 'DM-CURE': socio-Demographic [education, age at type 2 diabetes (T2DM) diagnosis], Metabolic (glycated haemoglobin, systolic blood pressure, body mass index, high-density lipoproteins), diabetes-related Complications (myocardial infarction, revascularization, cardiovascular medications, neuropathy, hypertension duration, albuminuria, urine albumin-to-creatinine ratio, End Stage Kidney Disease), and health care Utilization (all-cause hospitalization, emergency room visits) for Risk Evaluation. Among them, the strongest impact factors for future HF were age at T2DM diagnosis, health care utilization and cardiovascular disease-related variables. The model showed good discrimination (C statistic: 0.838, 95% CI: 0.821-0.855) and calibration (Brier score: 0.006, 95% CI: 0.006-0.007) in the ACCORD data and good performance in the validation data (Harmony: C statistic: 0.881, 95% CI: 0.863-0.899; CRIC: C statistic: 0.813, 95% CI: 0.794-0.833). The 10-year risk of incident HF increased in a graded fashion, from ≤1% in quintile 1 (score ≤14), 1%-5% in quintile 2 (score 15-23), 5%-10% in quintile 3 (score 24-27), 10%-20% in quintile 4 (score 28-33) and ≥20% in quintile 5 (score >33). CONCLUSIONS: The DM-CURE model and score were useful for population risk stratification of incident HHF among patients with T2DM and can be easily applied in clinical practice.

The utility of laboratory testing for pediatric patients undergoing isotretinoin treatment.

Isotretinoin, the most effective treatment for severe cystic acne, involves laboratory monitoring. In this retrospective case series of 130 pediatric patients taking isotretinoin, there were significant increases in cholesterol (143.9 mg/dl to 155.3 mg/dl), triglycerides (81.8 mg/dl to 115.2 mg/dl), and low-density lipoprotein (82.0 mg/dl to 98.1 mg/dl), and a decrease in high-density lipoprotein (50.0 mg/dl to 44.7 mg/dl) from baseline to follow-up (p < .05); there were no significant changes in liver enzymes. None of the patients had clinical sequelae (triglyceride-induced pancreatitis, retinoid-induced hepatotoxicity) related to their abnormal lab values. These findings question the utility of laboratory monitoring for prevention of severe clinical sequelae in pediatric patients, and suggest testing based on individualized risk factors may be more appropriate.

Cyclodextrin boostered-high density lipoprotein for antiatherosclerosis by regulating cholesterol efflux and efferocytosis.

A promising therapy for atherosclerosis treatment was designed by targeting LXR receptor (LXR) on atherosclerotic macrophage, where LXR activation could regulate cholesterol efflux and efferocytosis. Herein, a sequential-targeting nanoplatform (HT-rHDL) was constructed to deliver LXR agonist into macrophage, which was composed of discoidal reconstituted high-density lipoprotein (d-rHDL) core for agonist encapsulation and external modifications: (i) the outermost hyaluronan, targeting injured endothelium; (ii) modified ß-cyclodextrin of d-rHDL, accelerating cholesterol efflux of foam cells; (iii) conjugated apolipoprotein A-I of d-rHDL, targeting macrophage. This design underlines that the nanoplatform could increase its plaque accumulation, accomplish cholesterol efflux-remodeling-drug delivery behavior and specifically activate LXR in macrophage. After a 3-month treatment with HT-rHDL, 31.47% plaque area reduction, 56.0% lipid accumulation decrease, obvious inflammation resolution and enhanced plaque stability were observed. Furthermore, the atherosclerosis intervention was demonstrated to benefit from the upregulations of ABC transporters and Mer tyrosine kinase. Collectively, HT-rHDL provides new strategies to regress atherosclerosis.