Decrease In Low-density Lipoprotein Cholesterol Research Articles

Effect of avocado seed extract on lipid profile and atherogenic index in cyclosporine-treated rats

Hypertension is a global health issue because of its high prevalence and its association with increased risk of cardiovascular disease. This work evaluated the anti-dyslipidemic potential of aqueous extract of avocado seed (APE) (50 – 100 mg/kg) in adult male wistar rats. Twenty-five rats were used for this work and divided into five groups of 5 rats each (n= 5). Group 1 (normal control), group 2 (cyclosporine alone), group 3 (cyclosporine + 5 mg of lisinopril), group 4 and 5 (cyclosporine + 50 mg/kg and 100 mg/kg b.wt of extract respectively). Treatments lasted for 7 days and the rats were sacrificed by cervical dislocation. Plasma samples from the rats were used for lipid profile analysis such as; total cholesterol, triglyceride, and high density lipoprotein. The results showed significant (p < 0.05) increase in triglyceride (TG), low density lipoprotein (LDL), and total cholesterol (TCH), as well as significant (p < 0.05) decrease in HDL and atherogenic index in cyclosporine only treated rats compared with the normal control group. However, treatment with aqueous extract of avocado seed (APE) caused a significant decrease in TG, LDL, and total cholesterol, with concomitant increase in HDL concentration and atherogenic index in a dose-dependent manner. The findings of this study suggest that avocado seed extract has anti-dyslipidemic potential which could be useful in the management of hypertension and other diseases arising from dyslipidemia.

LDL lowering effect of PCSK9 inhibition is reduced in women.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the sex-differential effect of either pharmacological or genetic inhibition of PCSK9 on LDL-C levels. We meta-analyzed six real-life studies (1216 men and 641 women) that investigated the effects of PCSK9 monoclonal antibodies (mAbs) on LDL-C reduction in men and women. Despite higher LDL-C levels in women at baseline [mean difference (MD)=17.4mg/dL, P<0.0001, women = 175mg/dL vs. men = 152mg/dL], the LDL-C reduction under PCSK9 mAb treatment was significantly greater in men (MD=7.6mg/dL, 95% confidence interval: 2.7-12.4, P=0.002) than in women.We tested the sex-related association of the loss-of-function variant PCSK9-R46L with LDL-C plasma levels in 382 813 individuals (219 301 women and 163 512 men) free of lipid-lowering drugs from the UK Biobank general population cohort. The magnitude of LDL-C reduction was larger in men than in women (mean LDL-C difference: -35mg/dL vs. -26mg/dL, when comparing homozygous carriers with non-carriers in men and women, respectively). The relationship between PCSK9-R46L and LDL-C was significantly dependent on sex (P for interaction=7.2e-04). These results demonstrate by complementary approaches that the decrease in LDL-C mediated by PCSK9 inhibition is slightly, but significantly, less marked in women than in men. These data reinforce the need for specific studies to develop sex-specific recommendations for the management of ASCVD in women.

A Systematic Review of the Effects of Plant Compared with Animal Protein Sources on Features of Metabolic Syndrome

Dietary protein may play an important role in the prevention of metabolic dysfunctions. However, the way in which the protein source affects these dysfunctions has not been clearly established. The aim of the current systematic review was to compare the impact of plant- and animal-sourced dietary proteins on several features of metabolic syndrome in humans. The PubMed database was searched for both chronic and acute interventional studies, as well as observational studies, in healthy humans or those with metabolic dysfunctions, in which the impact of animal and plant protein intake was compared while using the following variables: cholesterolemia and triglyceridemia, blood pressure, glucose homeostasis, and body composition. Based on data extraction, we observed that soy protein consumption (with isoflavones), but not soy protein alone (without isoflavones) or other plant proteins (pea and lupine proteins, wheat gluten), leads to a 3% greater decrease in both total and LDL cholesterol compared with animal-sourced protein ingestion, especially in individuals with high fasting cholesterol concentrations. This observation was made when animal proteins were provided as a whole diet rather than given supplementally. Some observational studies reported an inverse association between plant protein intake and systolic and diastolic blood pressure, but this was not confirmed by intervention studies. Moreover, plant protein (wheat gluten, soy protein) intake as part of a mixed meal resulted in a lower postprandial insulin response than did whey. This systematic review provides some evidence that the intake of soy protein associated with isoflavones may prevent the onset of risk factors associated with cardiovascular disease, i.e., hypercholesterolemia and hypertension, in humans. However, we were not able to draw any further conclusions from the present work on the positive effects of plant proteins relating to glucose homeostasis and body composition.

Effectiveness and safety of Inclisiran in hyperlipidemia treatment: An overview of systematic reviews.

This paper aimed to comprehensively evaluate the effectiveness and safety of Inclisiran in treating hyperlipidemia through an overview of systematic reviews (SRs). The Cochrane Library, EMBASE, PubMed, CNKI, WANGFANG database, VIP database, ClinicalTrials.gov, and ICRT were searched electronically to collect SRs and meta-analysis of Inclisiran in hyperlipidemia treatment from the establishment of the database till May 2022. Two researchers independently screened the relevant literature, then the assessment of multiple systematic reviews tool was made into assess the methodological quality of the included studies. Data extracted were used to perform the study through RevMan5.3 software. The grading of recommendations assessment, development, and evaluation tool was used to grade the quality of the evidence of the outcomes included in the SRs. Prospero ID: CRD 42022326845. A total of 10 relevant SRs were included, involving 7 randomized controlled trials. The assessment results of the assessment of multiple systematic reviews tool suggested that the quality of the SRs included needed to be improved. The reduced level of low-density lipoprotein cholesterol of the experimental group was lower than the control group, and the difference in the amount of effectiveness was statistically significant (MD = -50.13, 95%CI: -56.2 to -44.06, P < .00001). The grading of recommendations assessment, development, and evaluation results showed that out of 27 outcomes, 8 were high-quality, 3 were of medium quality, 6 were of low quality, and 10 were of the most inferior quality. 300mg Inclisiran with 2 injections a year has the best therapeutic effect, which can significantly reduce low-density lipoprotein cholesterol and total cholesterol, and increase high-density lipoprotein cholesterol levels in patients with hyperlipidemia. Inclisiran has a favorable safety profile, with no significant difference in the incidence of adverse reactions compared to a placebo. Most of the adverse effects were associated with the reaction on the injection site.

Growth performance, meat quality, and blood characteristics of finisher crossbred pigs fed diets supplemented with different levels of green tea (Camellia sinensis) by-products.

Dietary supplementation with green tea by-product shows special effects on animal parameters. This study aimed to assess the effects of green tea by-products (GTBP) in the diet on some blood parameters, growth performance, and carcass characteristics of finishing pigs and on meat quality, and nutritional composition of pork. One hundred and sixty crossbred pigs with an initial body weight of 65.15 ± 0.38 kg, were distributed into four dietary treatments, with four replicates of 10 pigs each. The dietary treatments were a basal diet (control diet, CON), and three experimental diets (GTBP8, GTBP16, and GTBP24) based on the CON diet supplemented with GTBP at 8, 16, and 24 g/kg of feed. The studied parameters were examined during the experimental period of 10 weeks. No statistical differences in average daily feed intake, average daily gain, and feed conversion ratio were observed between the diet treatments (p > 0.05). Backfat thickness decreased (linear, p < 0.05) according to the GTBP levels but no other carcass parameters. Meat quality was not influenced by the GTBP levels (p > 0.05). However, pigs fed with GTBP had a decrease in cholesterol content and an increase in crude protein and total omega-3 content of pork compared to the CON diet (p < 0.05). Moreover, dietary supplementation with GTBP significantly decreased plasma cholesterol (p < 0.05), and trends for the decrease in low-density lipoprotein cholesterol and urea nitrogen were observed (linear, p = 0.08). Up to 24 g/kg GTBP in the diet for finishing pigs does not impair animal performance and makes carcass leaner with softer meat as well as positive effects on cholesterol and fatty acid metabolism. Further experiments are needed to determine the optimal levels of GTBP addition in finishing pig diet to produce higher meat quality.

Сравнительная оценка комбинированной гиполипидемической терапии у пациентов с очень высоким сердечно-сосудистым риском

Aim: to assess the efficacy and safety of combined lipid-lowering therapy including statin and ezetimibe in patients with acute coronary syndrome (ACS) who are followed up in a short-term study. Patients and Methods: a prospective cohort study involved 50 patients who were divided into 2 groups (25 patients in each group) by sequential inclusion. In group 1, atorvastatin (80 mg) plus ezetimibe (10 mg) were prescribed. In group 2, pitavastatin (4 mg) plus ezetimibe (10 mg) were prescribed. Over a 6-month follow-up period, changes in the clinical signs and parameters of carbohydrate and lipid metabolism were evaluated. Results: at baseline, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and glucose levels were similar in the groups. After 1 month, LDL-C &lt;1.4 mmol/L were reported in less than 50%. Meanwhile, a decrease in LDL-C &lt;1.4 mmol/L or a decrease in LDL-C by ≥50% occurred in 17 (68%) patients in each group. After 6 months, glucose levels in group 1 were significantly higher than those in group 2 (p=0.034). Intragroup analysis of blood glucose changes over time revealed a significant increase after 6 months in group 1 (p=0.005) but no significant changes in group 2. Over a 6-month follow-up period, diabetes was newly diagnosed in four patients, with no significant differences between the groups. Conclusion: a comparable clinical lipid-lowering efficacy of both treatment regimens was demonstrated. Significantly higher blood glucose levels were reported in the atorvastatin group than in the pitavastatin group, with no significant differences between the groups in newly diagnosed carbohydrate metabolism disorders. The most significant limitation of this study was the small sample size and relatively short follow-up period. KEYWORDS: diabetes, acute coronary syndrome, atorvastatin, pitavastatin, ezetimibe, lipid metabolism, carbohydrate metabolism. FOR CITATION: Druk I.V., Korennova O.Yu., Yukhina Yu.E., Savchenko M.V., Podol'naya S.P., Shukil L.V. Comparative assessment of combined lipid-lowering therapy in patients with very high cardiovascular risk. Russian Medical Inquiry. 2023;7(9):572–579 (in Russ.). DOI: 10.32364/2587-6821-2023-7-9-3.

Nigella sativa supplementation normalizes serum LDL cholesterol in healthy women volunteers

Objective: To determine the effect of the powder of Nigella sativa seeds (NSS) on serum low-density lipoprotein cholesterol (LDL-C) in female volunteers. Methodology: This study included 159 female volunteers aged 30-35 years determe effect of various doses of Nigella sativa (NS) on LDL-C serum levels of eight groups for the duration of nine months. Subjects in the first month (October 2021) were considered as the control (C) subjects. Same subjects in the remaining eight months (November 2021 to June 2022) were administered equal daily doses (1 gram/day) of the powder of Kalonji/NSS. Blood samples were obtained and Friedewald formula was employed for determining the levels of serum LDL-C. Results: The groups 1 to 8 altogether had significant decrease in LDL-C. Analysis of variance showed highly significant variations. Intergroup variations had p&gt;0.0001. Various groups of LDL-C control range from 80-129.9 mg/dl under the influence of various doses of NS supplementation gave highly significant negative linear correlation. Conclusion: Administration of NS showed the levels of LDL-C in the central range of 80-100 mg/dl that might be considered as the physiological normal serum levels of LDL-C. Further studies are required in healthy subjects and patients having various hyperlipidaemic and other related disorders to understand the diagnostic and therapeutic significance of NS.

Beta 1,3-1,6 Glucans Produced by Two Novel Strains of Aureobasidium Pullulans Exert Immune and Metabolic Beneficial Effects in Healthy Middle-aged Japanese Men: Results of an Exploratory Randomized Control Study.

In this pilot study, we have evaluated the specific metabolic and immune-related benefits of the AFO-202 strain and N-163 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in healthy human subjects. Sixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta-glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta-glucan (2 sachets of 1 g each) and N-163 beta-glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days. Decrease in HbA1C and glycated albumin (GA), significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I between pre- and post-treatment. Decrease in total and LDL cholesterol, a decrease of CD11b, serum ferritin, galectin-3 and fibrinogen were profound in Group II between pre- and post-treatment. However, there was no statistically significant difference between day 21 and day 35 among the groups. This outcome warrants larger clinical trials to explore the potentials of these safe food supplements in the prevention and prophylaxis of diseases due to dysregulated metabolism, such as fatty liver disease, and infections such as COVID-19 in which balanced immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases.

Perindopril prevents development of obesity and hypertension in middle aged diet-induced obese rat models of metabolic syndrome

AimsThe therapeutic properties of anti-hypertensive medications that extend beyond blood pressure lowering have started to become important clinical targets in recent years. This study aimed to assess the cardioprotective effects of perindopril in attenuating complications associated with metabolic syndrome in diet induced obese rats. Main methodsMale Wistar-Kyoto (WKY) rats aged 16 weeks were fed either standard rat chow (SC) or given a high-fat-high-carbohydrate (HFHC) diet for 20 weeks. Perindopril treatment (1 mg/kg/day) was administered to a subset of WKY rats commencing at week 8 of the 20 week HFHC feeding period. Body weights, food, water and energy intakes, blood pressure, heart rate and glucose tolerance were measured throughout the treatment period. Oxidative stress and inflammatory markers, lipid levels, cardiac collagen deposition, vascular function, aortic and cardiac electrical function were examined after the treatment. Key findingsWKY rats developed metabolic syndrome after 20 weeks of HFHC feeding, evidenced by the presence of abdominal obesity, dyslipidaemia, glucose intolerance and hypertension. Perindopril treatment prevented the development of obesity and hypertension in WKY-HFHC. Perindopril improved blood lipid profiles in HFHC rats with decreases in LDL cholesterol, triglycerides and total cholesterol. Type I collagen levels were decreased in WKY-HFHC rats along with decreases in left ventricle mass. Perindopril treated rats also showed improved cardiac electrical function indicated by decreases in action potential at 90 % of repolarisation in WKY-HFHC rats. SignificanceThese results show that perindopril has a profound effect on preventing the development of metabolic syndrome in animals fed a HFHC diet.

516 SAFETY OF PCSK9I IN A SINGLE COUNTRY, MULTICENTER, OBSERVATIONAL STUDY: A POST-HOC ANALYSIS OF THE AT-TARGET-IT STUDY

Abstract Introduction PCSK9 inhibitors (PCSK9i) significantly decrease LDL cholesterol (LDL-C), either as monotherapy or in addition to the maximally tolerated dose of statin and/or ezetimibe. Yet, few data are available in real-world observations. Purpose AT-TARGET-IT is an Italian multicenter registry involving 9 Italian centers, designed to assess efficacy, adherence, and persistence of PCSK9i, as well as prescribing doctors’ behavior in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). The aim of the present analysis was to assess differences between evolocumab and alirocumab on safety in patients on PCSK9i in a real-world single country observational study. Methods From June through November 2021, we enrolled patients with PCSK9i first prescription from 6 months before inclusion through starting of PCSK9i use. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at the latest observation preceding inclusion in the study. Results Of 798 patients enrolled, 566 (70.9%) patients took Evolocumab and 232 (29.1%) Alirocumab (of them, 117 patients Alirocumab 75 mg and 115 Alirocumab 150 mg). The LDL-C values reductions did not significantly differ between Evolocumab and Alirocumab groups (65.1% for Evolocumab; 64.5% for Alirocumab, p=ns). Regarding safety events, after a median observation period of 19.3 months (6; 57), 19 patients (2.4%) had acute coronary syndrome, 18 (2.3%) hospitalization for CV causes, 3 (0.4%) stroke, 6 (0.8%) new-onset heart failure (HF) and 68 (4.9%) the composite endpoints of ACS, CV hospitalization, new onset HF, new onset chronic kidney disease, stroke and cerebrovascular insufficiency. Comparing events between patients in Alirocumab and in Evolocumab, no significant difference was found between the two groups. Combined endpoint of adverse events occurred more frequently in patients in Alirocumab (27; 11.6%), in comparison with those in Evolocumab (41; 7.2%) (p=0.044) (Figure). Conclusion AT-TARGET-IT study shows that between evolocumab and alirocumab there was a statistically significant difference on the combined endpoint of adverse events.

Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk

Randomized controlled trials (RCTs) show that decreases in low-density lipoprotein cholesterol (LDL-C) by the use of statins cause a significant reduction in the development of cardiovascular disease (CVD). However, one of our previous studies showed that, among eight RCTs that investigated the effect of statins vs. a placebo on CVD development, 56-79% of patients had residual CVD risk after the trials. In three RCTs that investigated the effect of a high dose vs. a usual dose of statins on CVD development, 78-87% of patients in the high-dose statin arms still had residual CVD risk. The risk of CVD development remains even when statins are used to strongly reduce LDL-C, and this type of risk is now regarded as statin residual CVD risk. Our study shows that elevated triglyceride (TG) levels, reduced high-density lipoprotein cholesterol (HDL-C), and the existence of obesity/insulin resistance and diabetes may be important metabolic factors that determine statin residual CVD risk. Here, we discuss atherogenic lipoproteins that were not investigated in such RCTs, such as lipoprotein (a) (Lp(a)), remnant lipoproteins, malondialdehyde-modified LDL (MDA-LDL), and small-dense LDL (Sd-LDL). Lp(a) is under strong genetic control by apolipoprotein (a), which is an LPA gene locus. Variations in the LPA gene account for 91% of the variability in the plasma concentration of Lp(a). A meta-analysis showed that genetic variations at the LPA locus are associated with CVD events during statin therapy, independent of the extent of LDL lowering, providing support for exploring strategies targeting circulating concentrations of Lp(a) to reduce CVD events in patients receiving statins. Remnant lipoproteins and small-dense LDL are highly associated with high TG levels, low HDL-C, and obesity/insulin resistance. MDA-LDL is a representative form of oxidized LDL and plays important roles in the formation and development of the primary lesions of atherosclerosis. MDA-LDL levels were higher in CVD patients and diabetic patients than in the control subjects. Furthermore, we demonstrated the atherogenic properties of such lipoproteins and their association with CVD as well as therapeutic approaches.

Potential lipid-lowering effects of Ulmus macrocarpa Hance extract in adults with untreated high low-density lipoprotein cholesterol concentrations: A randomized double-blind placebo-controlled trial.

Ulmus macrocarpa Hance extract (UME) has demonstrated an antilipidemic effect via upregulation of the adenosine monophosphate-activated protein kinase pathway and regulation of lipid metabolism in both laboratory and animal studies. Therefore, we examined the effects and safety of UME on plasma lipids in adults with untreated high, low-density lipoprotein cholesterol (LDL-C) concentrations. In the current double-blind placebo-controlled randomized clinical trial, 80 patients with untreated high LDL-C concentrations (130-190 mg/dl) were randomly allocated to either the "UME group" (received 500 mg UME as two capsules per day) or the "Placebo group" (received placebo containing cornstarch as two capsules per day) for 12 weeks. The primary outcome was the change in LDL-C concentration within the 12-week treatment period; secondary outcomes included changes in total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B (ApoB) concentrations. UME over 12 weeks led to a greater decrease in LDL-C, TC, and ApoB concentrations than did the placebo as follows: by 18.1 mg/dl (P < 0.001); 23.3 mg/dl (P < 0.001); 9.3 mg/dl (P = 0.018), respectively. When LDL-C, TC, and ApoB concentrations were expressed as a lsmeans percentage of the baseline concentration, they after 12 weeks of UME had greater % differences compared to the placebo as follows: by 11.9% (P < 0.001); 10.0% (P < 0.001); 8.6% (P < 0.05), respectively. However, no significant inter- and intra-group changes in liver enzyme, free fatty acid, anti-inflammatory marker, and fasting glucose concentrations were observed. None of the participants experienced notable adverse events. UME causes a significant improvement in lipid profiles in adults with untreated high LDL-C concentrations. [www.clinicaltrials.gov/], identifier [NCT03773315].

Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia

Abstract Background Familial hypercholesterolemia (FH) is characterised by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Previous studies show that carotid intima-media thickness (cIMT) is increased in children with FH, an indicator of early ASCVD. Add-on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, evolocumab, substantially reduced atherosclerotic lipid levels in children with heterozygous FH (HeFH) and was safe and well tolerated. The effect of evolocumab on cIMT in paediatric patients (pts) has not been investigated. Purpose To investigate the effect of evolocumab treatment on cIMT progression in paediatric pts with HeFH. Methods HAUSER-RCT was a multicenter, randomised, placebo-controlled study in which paediatric FH pts (ages 10–17 years) received monthly subcutaneous injections of evolocumab 420 mg or placebo. Of 157 pts, 150 continued to an open-label extension study (HAUSER-OLE) during which all received up to 80 weeks of monthly evolocumab 420 mg on top of stable background statin therapy. cIMT was measured by B-mode ultrasound scanning at baseline, week 24 of the RCT, and weeks 24, 48, and 80 of the OLE. cIMT was measured on anterior, lateral, and posterior imaging angles of the right and left common carotid artery. Mean thickness at each visit and mean changes from baseline were summarised by treatment received during the RCT and artery location. In addition, the largest measurements (anterior, lateral, or posterior) from a patient's left and right carotid artery were averaged to calculate a summary score. Results Mean baseline cIMT summary score was 0.568 mm (SD=0.06) for 46 placebo pts and 0.586 mm (SD=0.06) for 82 evolocumab pts. During the RCT, 37 placebo pts had a mean increase of 0.006 mm (SD=0.05) from baseline to week 24; in contrast, 76 evolocumab pts had a mean decrease of 0.003 mm (SD=0.05). Although this treatment group difference was not statistically significant (P=0.403), the pattern of increased cIMT for placebo and decreased cIMT for evolocumab was consistent across artery locations (Table). During the OLE, for pts who initially received placebo, mean cIMT summary score decreased by 0.019 mm (SD=0.04, n=34) from baseline to week 80 (P=0.007) (Figure). Pts who received evolocumab in both the RCT and OLE showed continued improvement during the OLE; at week 80, mean cIMT summary score decreased by 0.012 mm (SD=0.05, n=59) from baseline (P=0.067). For all pts at week 80 (n=128), the mean decrease in LDL-C from baseline was 35.3% (SD=28.0). Conclusions Open-label evolocumab treatment for up to 80 weeks led to reductions in mean cIMT. In this small sample of pts with FH, the data suggest that the addition of PCSK9 inhibition to background lipid-lowering therapy has the potential to reduce the risk of ASCVD progression and future cardiovascular events in this vulnerable paediatric population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen, Inc.

PCSK9 inhibitors: effectiveness of treatment and changes in background lipid-lowering therapy in a real world Italian population. The AT-TARGET-IT study

Abstract Introduction PCSK9 inhibitors (PCSK9i) significantly decrease LDL cholesterol (LDL-C), either as monotherapy or in addition to the maximally tolerated dose of statin and/or ezetimibe. Yet, few data are available on efficacy and background lipid-lowering therapy (LLT) adjustment in patients treated with PCSK9i in real-world observations. Purpose AT-TARGET-IT is an Italian multicenter registry involving 9 Italian centers, designed to assess efficacy, adherence, and persistence of PCSK9i, as well as prescribing doctors' behavior in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). The aim of the present analysis was to assess efficacy and changes in background LLT therapy in patients on PCSK9i in a real-world single country observation. Methods From June through November 2021, we enrolled patients with PCSK9i first prescription from 6 months before inclusion through starting of PCSK9i use. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at the latest observation preceding inclusion in the study. Background therapy was assessed at baseline and during follow-up, evaluating treatment withdrawal, reduction of doses, or changes from statin-ezetimibe association to single drug therapy. Results We enrolled 798 patients (27% with FH) receiving either alirocumab or evolocumab and followed for a median time of 19.3 months. At the time of PCSK9i first prescription LDL-C was 147.6 mg/dl and reached 51.5 mg/dl at the time of latest observation (64% reduction), and 129 patients (16%) were not receiving any LLT, 669 patients received background LLT, of them 246 (31%) were taking ezetimibe alone and 423 (53%) were taking statins with or without ezetimibe. At the end of the observation period, 785 patients (98%) were still receiving PCSK9i and 550 (69%) did not change background LLT. Of 248 patients changing background LLT, 116 (47%) withdrew therapy, 132 (53%) changed dose or type of LLT. After stratification by achievement of LDL-C target according CV risk class, 483 patients achieved the target (60%). Target was achieved at the end of the observation period in 63% of patients taking triple therapy, 65% patients receiving PCSK9i plus statins, 62% of patients receiving PCSK9i plus ezetimibe and 55% receiving PCSK9i alone (Figure 1). No significant differences in terms of percentage of patients changing background LLT during PCSK9i treatment were found between patients at target for LDL-C and those not at target. Conclusion AT-TARGET-IT study shows that PCSK9i therapy is effective in reaching LDL-C target in the majority of patients, yet a sizable number of them (40%) remains undertreated. LLT background therapy is either reduced or withdrawn in 31% of patients, being responsible for not reaching target. Reasons for inappropriate LLT changes in patients receiving PCSK9i should be identified and removed to optimize lipid control. Funding Acknowledgement Type of funding sources: None.

The effects of phytosterol and phytostanol supplementation on the lipid profile in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

Various studies have proven that phytosterols and phytostanols (PS) are lipid-lowering agents. These compounds play a role in regulating high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) metabolism. Although various drugs are available and are currently used to treat dyslipidemia, the management of lipid abnormalities during the postmenopausal period remains a challenge. Thus, scientists are trying to develop new strategies to reduce serum lipids concentrations using natural products. However, the impact of PS administration on serum lipids in postmenopausal women remains unclear. Hence, the purpose of this study was to assess the effect of PS supplementation on the lipid profile in postmenopausal women based on a systematic review of the literature and a meta-analysis of randomized controlled trials. PubMed/Medline, Scopus, Embase, and Web of Science were searched to identify suitable papers published until January 18, 2022. We combined the effect sizes with the DerSimonian and Laird method using a random effects model. PS supplementation resulted in a significant decrease in TC (weighted mean difference [WMD]: -16.73 mg/dl) and LDL-C (WMD: -10.06 mg/dl) levels. No effect of PS supplementation on TG (WMD: -1.14 mg/dl) or HDL-C (WMD: -0.29 mg/dl) concentrations was detected. In the stratified analysis, there was a notable reduction in TC and LDL-C levels when the PS dose was ≥2 g/day (TC: -22.22 mg/dl and LDL-C: -10.14 mg/dl) and when PS were administered to participants with a body mass index ≥25 kg/m2 (TC: -20.22 mg/dl and LDL-C: -14.85 mg/dl). PS administration can decrease TC and LDL-C, particularly if the dose of administration is ≥2 g/day and if the participants are overweight or obese. Further high-quality studies are needed to firmly establish the clinical efficacy of PS usage in postmenopausal females.

Antidyslipidemic, Antioxidant, and Anti-inflammatory Effects of Jelly Drink Containing Polyphenol-Rich Roselle Calyces Extract and Passion Fruit Juice with Pulp in Adults with Dyslipidemia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Oxidative stress and inflammation play key roles in the pathophysiology in the pathophysiology of dyslipidemia, which are positive risks that increase atherosclerosis leading to important healthcare problems. Therefore, we aimed to study the antioxidant, anti-inflammatory, and lipid-lowering effects of jelly drink containing polyphenol-rich roselle calyces extract and passion fruit juice with pulp concentrate (RP jelly drink) in comparison to a placebo jelly drink for 8 weeks. Forty-three adults with dyslipidemia were randomly assigned into two groups: the RP jelly drink group and the placebo group. Glucose, total cholesterol (TC) triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), oxidative stress biomarkers, inflammatory parameters, and monocyte chemotactic protein-1 (MCP-1) were measured with fasting blood samples at baseline, 4 weeks and 8 weeks of intervention. Results showed a significant decrease in LDL-C and TG, respectively, after 8 weeks of RP jelly drink consumption (LDL-C: 107.63 ± 22.98 mg/dL; TG: 109.79 ± 38.83 mg/dL) compared to baseline measurements (LDL-C: 128.43 ± 32.74 mg/dL; TG: 132.33 ± 75.11 mg/dL). These may be possible due to reduced inflammation and improvements in oxidative stress, as demonstrated by the reduction of tumor necrosis factor- (TNF-) α and malondialdehyde (MDA), and the enhancement of glutathione (GSH) after consuming the RP jelly drink for 8 weeks. However, no significant differences of treatment on glucose, total cholesterol, MCP-1, interleukin-6, and interleukin-10 were observed. In conclusion, daily consumption of RP jelly drink for 8 weeks resulted in significant improvement in lipid profiles in subjects with dyslipidemia. However, more research is needed to assess its nutritional and functional potential.

Investigation of the Effect and Possible Mechanism of Antihypertensive Activity of Lycopene-rich Extract of Solanum lycopersicon in Wistar Rats

Background and Aim: Hypertension is a common debilitating illness among people in both developed and developing countries. This study investigated the effect and possible mechanism of the antihypertensive activity of lycopene-rich extract of Solanum lycopersicon (LRESL) on Wistar rats. Methods: Sixty hypertensive Wistar rats were divided into seven experimental groups viz: Group A served as a normotensive group and received food and clean distilled water ad libitum. Group B was the hypertensive untreated group; Groups C-E served as hypertensive group administered with 100, 200, and 400 mg/kg LRESL, respectively. While group F was hypertensive and received 10 mg/kg amlodipine and group G received 200 mg/kg of LRESL+0.5 mg/kg Lisinopril respectively. Results: There was a statistical significant decrease (P&lt;0.05) in the systolic and diastolic blood pressure and the decrease was in a dose-dependent manner. The heart rate showed no statistical significant difference among the groups. The total cholesterol (TC) increased in the positive and normal control compared to other groups. There was a significant decrease in the triglyceride (TG), low density lipoprotein cholesterol (LDL-C) in all hypertensive treated groups. The decrease in the LRESL treated groups was in a dose-dependent manner and there was no significant difference between the groups compared to the normotensive and positive control. Moreover, the high density lipoprotein cholesterol (HDL-C) had a significant reverse effect of the LDL-C as there was a significant increase (P&lt;0.05) in HDL-C and the increase was more significant in group E and G respectively. The serum cardiac arginase (SCAr) activity also decreased significantly (P&lt;0.05) in all groups except group B compared to the normotensive and positive control groups and in a dose-dependent manner. The serum nitric oxide (SNO) concentration also increased in all test groups in a dose-dependent pattern except the positive control group. Conclusion: This study suggests that LRESL has an antihypertensive property and elicited this through multiple mechanisms involving a decrease in SCAr, LDL-C, body weight and marked elevation of SNO and could be used as a novel compound channeled into the production of antihypertensive drugs.

Effect of Vitamin D Supplementation on Cardiometabolic Indices and the Severity of Symptoms in Male Patients With Chronic Schizophrenia

Objectives: Hypovitaminosis D is suggested to be related to the high risk of metabolic disorders and symptoms of schizophrenia. Therefore, this study aimed to evaluate the effect of vitamin D supplementation on cardio-metabolic indices and the severity of symptoms in schizophrenic patients. Materials and Methods: Patients with schizophrenia (N=42) were randomly assigned to 2 groups, i.e., intervention (2000 IU of vitamin D daily; n=21) and placebo groups (n=21). The intervention was administered for 8 weeks. Anthropometric, clinical, and laboratory measures were assessed at both baseline and end of the trial. The Positive and Negative Syndrome Scale (PANSS) was performed to assess the schizophrenia symptoms. Results: Vitamin D supplementation leads to a significant decrease in low-density lipoprotein cholesterol (LDL-C) levels (P=0.006). In addition, a significant improvement was found in the PANSS negative subscale score (PANSS-NSS) and PANSS total score (PANSS-TS; P=0.005 and P=0.015, respectively). At the baseline, there was a significant negative correlation between PANSS-NSS, PANSS positive subscale score (PANSS-PSS), and PANSS-TS with serum levels of vitamin D (r=-0.42, P=0.010; r=-0.34, P=0.041; and r=-0.47, P=0.004, respectively). Conclusions: Vitamin D supplementation may have helpful efficacy on some cardio-metabolic indices and schizophrenia severity.

Effect of a 3-Week Multidisciplinary Body Weight Reduction Program on the Epigenetic Age Acceleration in Obese Adults.

Obesity and aging share common molecular and cellular mechanisms underlying the pathophysiology of cardiovascular diseases (CVD), which occur frequently in both conditions. DNA methylation (DNAm) age, a biomarker of the epigenetic clock, has been proposed as a more accurate predictor of biological aging than chronological age. A positive difference between an individual’s chronological age and DNAm age is referred to as epigenetic age acceleration. The objective of the present study was to evaluate the effects of a 3-week in-hospital body weight reduction program (BWRP) on the epigenetic age acceleration, as well as on other cardiometabolic outcomes, in a cohort of 72 obese adults (F/M: 43/29; (chronological) age: 51.5 ± 14.5 yrs; BMI: 46.5 ± 6.3 kg/m2). At the end of the BWRP, when considering the entire population, BMI decreased, and changes in body composition were observed. The BWRP also produced beneficial metabolic effects as demonstrated by decreases in glucose, insulin, HOMA-IR, total cholesterol, and LDL cholesterol. A post-BWRP improvement in cardiovascular function was also evident (i.e., decreases in systolic and diastolic blood pressures and heart rate). The BWRP reduced some markers of systemic inflammation, particularly C-reactive protein (CRP). Finally, vascular age (VA) and Framingham risk score (FRS) were reduced after the BWRP. When considering the entire population, DNAm age and epigenetic age acceleration did not differ after the BWRP. However, when subdividing the population into two groups based on each subject’s epigenetic age acceleration (i.e., ≤0 yrs or >0 yrs), the BWRP reduced the epigenetic age acceleration only in obese subjects with a value > 0 yrs (thus biologically older than expected). Among all the single demographic, lifestyle, biochemical, and clinical characteristics investigated, only some markers of systemic inflammation, such as CRP, were associated with the epigenetic age acceleration. Moreover, chronological age was correlated with DNAm age and VA; finally, there was a correlation between DNAm age and VA. In conclusion, a 3-week BWRP is capable of reducing the epigenetic age acceleration in obese adults, being the BWRP-induced rejuvenation evident in subjects with an epigenetic age acceleration > 0 yrs. Based on the BWRP-induced decrease in CRP levels, chronic systemic inflammation seems to play a role in mediating obesity-related epigenetic remodeling and biological aging. Thus, due to the strong association of CVD risk with the epigenetic clock and morbidity/mortality, any effort should be made to reduce the low-grade chronic inflammatory state in obesity.

Determination of factors associated with serum cholesterol response to dairy fat consumption in overweight adults: Secondary analysis from an RCT.

Elevated intakes of saturated fatty acids (SFA) can adversely affect serum cholesterol levels. Dairy fat contains ~60% SFA, prompting healthy eating guidelines to recommend low-fat dairy. Physiological, and environmental factors influence inter-individual variance in response to food consumption. Evidence exploring the dairy matrix has differing effects of dairy fat consumption on serum cholesterol levels when consumed in the form of cheese. The extent of this variability and determinants of response to dairy fat are currently unknown. The objective of this study was to determine factors associated with lipid metabolism response to a dairy fat intervention, with a focus on serum cholesterol. A 6-week randomized parallel intervention trial was carried out in healthy volunteers (≥50 years, BMI ≥25 kg/m2). Participants (n = 104) consumed ~40 g dairy fat daily in addition to their usual diet, in 1 of 3 forms: butter, cheese, or reduced-fat cheese and butter. For this analysis, “response” was based on the percentage (%) change in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) from pre- to post-intervention. Participants were divided into tertiles for each lipid response. The upper and lower tertiles were used to categorize participants as “responders” and “non-responders.” For TC and LDL-c, response was classified as a decrease, whereas “response” was defined as an increase for HDL-c. Clinical response was also considered, by calculating pre- and post-intervention prevalence of those meeting target levels of cholesterol recommendations. Participants demonstrating the largest % decrease (Tertile 1; “responders”) in TC had significantly higher levels of TC and HDL-c, at baseline, and lower levels of triglycerides (TAGs) compared to those in tertile 3 (i.e., TC non-responders). Those with the largest % decrease in LDL-c (Tertile 1: LDL-c responders) had higher baseline levels of LDL-c and lower levels of TAGs. Multiple regression analysis revealed that the % change in TC and LDL-c was associated with baseline TC, TAG, body weight and high-sensitivity C-reactive protein (hsCRP; P < 0.05). Previous work has demonstrated the dairy food matrix affects lipid response to dairy consumption. This study suggests that phenotypic differences may also influence response to dairy fat in overweight individuals.