Reductions In Low-density Lipoprotein Levels Research Articles

Apolipoprotein E Genetic Variant and Blood Lipid Responses to Plant Sterols: A Systematic Review and Pooled Analysis of Clinical Trials.

Plant sterols/stanols are effective cholesterol-lowering agents. However, it is unclear whether the apolipoprotein E (ApoE) genetic variants influence it. We investigated whether ApoE genetic variants modulate the responses of blood lipids to dietary intervention plant sterols/stanols in adults and if the intervention dose and duration, as well as the age and status of participants, influence this effect. Randomized clinical trials were identified by searching databases in the Cochrane Library. Random-effect models were used to estimate the pooled effect size of each outcome of interest total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides. Meta-regression and subgroup analysis were used to investigate the effects of potential modifiers on the outcomes of interest. Eleven articles were selected from 3,248 retrieved abstracts. Plant sterol/stanol intervention was associated with a more significant reduction in LDL levels in the E3 group [-0.251 mmol/L; 95% confidence interval (95% CI), -0.488 to -0.015] compared with both the E4 and E2 groups. In E4 carriers, the plant sterol/stanol intervention dose and duration resulted in a larger decrease in LDL levels (-0.088027 mmol/L; 95% CI, -0.154690 to -0.021364). In conclusion, ApoE genetic variants affected the response of blood LDL levels to supplementation with plant sterols/stanols, as individuals with E3 variant showed significantly decreased LDL levels compared with the other genotypes. However, future studies recruiting participants according to their ApoE genetic variants are needed to confirm our conclusion.

PCSK9 Inhibitor Therapy as an Alternative for Statin Intolerance

Scientific relevance. The main cause of cardiovascular pathologies is atherosclerosis, which is secondary to lipid metabolism disorders, in particular, the accumulation of low-density lipoprotein (LDL) cholesterol. Dyslipidaemia treatment with the largest evidence base predominantly includes statins in combination therapy, but their use is limited by into lerance in some patients. Alternatively, the treatment may include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.Aim. The study aimed to analyse the applicability of PCSK9 inhibitors in patients with statin intolerance.Discussion. According to the literature analysis, the most common presentation of statin intolerance is statin-associated muscle symptoms. The pathogenesis of statin-associated adverse events is mainly mediated by HMGCoA reductase inhibition, treatment effects on cellular and subcellular processes and skeletal muscles, and patients’ genetic makeup. The mechanism of action of PCSK9 inhibitors is entirely different and involves binding and inactivation of the PCSK9 protein, which lowers blood LDL cholesterol levels. PCSK9 inhibitors have been associated with some adverse drug reactions, most notably immunogenicity; however, PCSK9 inhibitors effectively reduce LDL levels even if patients develop antibodies.Conclusions. Therefore, PCSK9 inhibitors are a safe, well-tolerated, and effec tive therapeutic strategy for hyperlipidaemia in patients with statin intolerance.

Dietary branched-chain amino acids intake, glycemic markers, metabolic profile, and anthropometric features in a community-based sample of overweight and obese adults

BackgroundExisting research provides conflicting evidence regarding the relationship between estimated branched-chain amino acid (BCAA) intake and metabolic, glycemic markers, and anthropometric characteristics. This research seeks to examine the association between estimated dietary BCAA consumption and glycemic, and metabolic markers, as well as anthropometric parameters in adults classified as overweight or obese.MethodsIn this cross-sectional analysis, we gathered data from 465 overweight and obese individuals aged between 18 and 37 years. To evaluate dietary data, we employed the food frequency questionnaire, and the BCAA content in foods was determined via the United States Department of Agriculture website. We utilized ELISA kits to measure fasting blood glucose (FBS) and lipid profile markers, and additionally calculated low-density lipoprotein (LDL) and insulin sensitivity markers. We assessed sociodemographic status, physical activity (PA), and anthropometric attributes through a method recognized as both valid and reliable. For statistical analysis, we conducted analyses of covariance (ANCOVA), making adjustments for variables including sex, PA, age, energy, and body mass index (BMI).ResultsUpon adjusting for confounders, those in the highest tertiles of BCAA intake exhibited an increase in weight, BMI, waist circumference (WC), waist-to-hip ratio (WHR), and fat-free mass (FFM). Conversely, they demonstrated reduced fat mass (FM) (%) and FM (kg) compared to their counterparts in the lowest tertiles (P < 0.05). Additionally, there was a noted association between greater estimated BCAA intake and reduced LDL levels. Nonetheless, our findings did not reveal a significant relationship between dietary BCAA and glycemic indices.ConclusionsFrom our findings, an increased estimated intake of BCAA seems to correlate with diminished serum LDL concentrations. To gain a more comprehensive understanding of this association, it is imperative that further experimental and longitudinal studies be conducted.

THE NEW PCSK9-INHIBITOR INCLISIRAN: AN EXCEPTIONAL REDUCTION IN LDL CHOLESTEROL FROM THE FIRST PATIENTS OF THE NIGUARDA HOSPITAL

Objective: Dyslipidemia is one of the most prominent risk factors in coronary artery disease. With the new strict target of Low Density Lipoprotein (LDL) cholesterol in secondary prevention in some patients oral medication may not be sufficient. Inclisiran is a small interfiring RNA that inhibits the hepatic PCSK-9 synthesis inducing a reduction in low-density lipoprotein levels up to 50%. Conveniently, it only requires one administration every six months. Design and method: A 53-year-old man, with no previous cardiologic history, presented to our emergency department reporting acute chest pain and left arm paresthesia developed after an emotional stress. Electrocardiogram was normal with a slightly and stable increased of high sensitivity troponin T levels (18 ng/l). The patient had the following cardiovascular risk factors: type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea syndrome, obesity (body mass index 30), sedentary lifestyle. Taking into consideration his clinical presentation and his cardiovascular risk, a coronary computer tomography was performed showing severe stenosis in Left Anterior Descending (LAD) and right coronary arteries. The subsequent coronary angiography confirms the severe stenosis in the proxymal LAD and the mild stenosis (30%) in the right coronary artery. The LAD was treated with a drug eluting stent. At the time of the event the patient was already on therapy with rosuvastatina/ezetimibe 10/10 mg that we increased to a dosage of 20/10 mg. At the first medical examination after the hospitalization, his blood tests showed uncontrolled LDL cholesterol (70 mg/dl). We therefore decided to try lowering his cholesterol levels with addition of inclisiran. Results: After 3 months of inclisiran therapy, his blood test showed a surprisingly decrease in cholesterol levels (total cholesterol 78 mg/dl and LDL 11 mg/dl) reaching the desirable target. Conclusions: Inclisiran is a valid therapeutic strategy for reaching the desiderable cholesterol target in patient at high cardiovascular risk. In our first patients inclisiran, added to statin and ezetimibe therapy, successfully lowered LDL to the desirable target. Surprinsigly, it lowered LDL up to 85%, much more than expected. Further studies will be needed to identify which patients may be super responders to Inclisiran.

Acute coronary syndromes: hospital management of dyslipidaemia with proprotein convertase subtilisin/kexin 9 inhibitors: time to act.

Atherosclerotic cardiovascular disease (ASCVD) in its countless clinical presentations is, in industrialized countries, the most frequent cause of death and, in recent years, a leading role in the prevention of ASCVD has been attributed to the treatment of dyslipidaemias. If statins and ezetimibe remain the cornerstone of pharmacological treatment, an increasingly relevant role is attributed to the inhibitors of the proprotein convertase subtilisin/kexin 9 (PCSK9i), as a result of the excellent results obtained in their respective trials, not only on the reduction of low-density lipoprotein (LDL) or LDL cholesterol (LDL-C) but also on plaque stabilization and regression. The addition of PCSK9 inhibitors leads to a further reduction in LDL levels and a consequent improvement in prognosis and it is recommended in 'fast-track' administration (intrahospital/discharge) in patients with acute coronary syndromes (ACSs) or multiple cardiovascular events already on statin therapy and LDL >70 mg/dL and in statin-naïve ACS patients and LDL >140 mg/dL. By applying guidelines and fast-track, ∼25% of patients with ACS should receive PCSK9i at discharge but unfortunately patients are currently undertreated.

Abstract 60: Impact of a Multisite, Protocol-Driven, Nurse Practitioner-Led, Cardiovascular Prevention Program in a Hispanic Medicare Advantage Population at High Risk for ASCVD: Healthy Heart Program at Cano Health.

Introduction: Despite availability of effective and inexpensive pharmacologic therapies for hypercholesterolemia and hypertension, many patients at high risk for atherosclerotic cardiovascular disease (ASCVD) do not achieve optimal low-density lipoprotein (LDL) and systolic blood pressure (SBP) levels. We hypothesized that risk factor control could be improved by using nurse practitioners and a guideline-directed protocol in a Medicare Advantage (MA) population. Methods: We designed and implemented an ongoing 18 site, multistate (FL, TX, NV), ASCVD risk assessment and management program (Healthy Heart) in a large national MA primary care clinic (Cano Health). The cardiometabolic risk assessment and management program was designed by a team of preventive cardiologists, with the plan of being Nurse Practitioner (NP)-led, with remote support by a cardiologist. Protocols provided details on initiation and titration of drug therapy to achieve LDL-C and SBP goals. Patients with organ transplants, advanced cancer, an ejection fraction &lt;35%, and on hemodialysis were excluded. Results: From October 2021-October 2022, 5430 patients were enrolled in the program. A total of 1858 (34.2%) had established ASCVD, 1033 (19.0%) had diabetes mellitus (DM). A total of 713 (13.1%) had both ASCVD and DM. In patients who had ASCVD and diabetes together, high intensity statin use increased from 39.4% to 68.3% after enrollment; 52.66% achieved an LDL-C &lt;70 mg/dl after enrollment compared to 31.0% at baseline. Antihypertensive medications were intensified in 408/1041 (39.2%) of ASCVD and 276/558 (49.5%) of DM patients, with a higher proportion achieving a SBP &lt;130 mm Hg after enrollment. Conclusions: Implementing a novel cardiovascular prevention program in a population of mostly Hispanic MA patients at high risk for ASCVD, using NPs, with strict adherence to a step-by-step evidence-based protocol supervised by cardiologists, is associated with reduction in LDL levels and SBP and with improvement in reaching LDL and SBP targets.

Magnitude of low-density lipoprotein reduction and impact on major cardiovascular outcomes.

Less is more (?) Ludwig Mies van der Rohe Atherosclerotic cardiovascular (CV) disease is a primary worldwide cause of morbidity and mortality.1 Its association with elevated levels of low-density lipoprotein (LDL) cholesterol (LDL-C) has been broadly established. Therefore, cholesterol-lowering drugs (eg, statins, ezetimibe, and proprotein convertase subtilisin/kexin 9 [PCSK9]-inhibiting monoclonal antibodies) are massively used in primary and secondary prevention of cardiovascular events.2 Systematic reviews and metanalysis on LDL-C–lowering therapies have found an association between the absolute reduction of LDL levels and the reduction of major vascular events (composite of CV death, acute coronary syndromes, revascularization, and stroke). In particular, the 5-year incidence of major coronary events, revascularization, and stroke is reduced by one-fifth per mmol/L of LDL-C reduction. However, achieved LDL level seems to be associated with a reduction of the risk of coronary death and myocardial infarction (MI).3,4 Accordingly, the latest European guidelines recommend reaching low levels of LDL-C, especially for very high-risk (LDL-C <55 mg/dL) and high-risk (LDL-C <70 mg/dL) patients, together with a reduction of at least 50% of LDL-C from the baseline.5,6 Absolute reduction of LDL levels and achieved LDL level may not be the only variables to consider when LDL-C–lowering therapies are used because other parameters may help in predicting the clinical benefit of the treatment. Notably, Navarese et al7 recently published a meta-analysis suggesting that the greatest benefit from LDL-C–lowering therapy may occur in patients with baseline LDL-C levels of 100 mg/dL or greater. In the current issue of the Journal, Ennezat et al8 aimed at appraising, in an interesting and extensive meta-analysis, the association between changes in LDL with lipid-lowering agents and clinical outcomes, using refined meta-regression methods (Fig. 1). The authors tried to appraise whether the percentage of LDL reduction is associated with the effect size of all cause and CV mortality (primary endpoints). The effect size on MI, stroke, and non-CV death (secondary endpoints) were also assessed. The impact of other variables such as absolute LDL reduction, baseline LDL levels, achieved LDL levels, and CV mortality rate of the population studies on the aforementioned endpoints was also assessed. The analysis was performed on 60 selected randomized controlled trials with a mean follow-up of at least 52 weeks. A total of 323,950 subjects were included. Patients enrolled in the studies presented unknown or known atherosclerotic CV disease. Furthermore, some of them showed other comorbidities that were not consistently represented in all the trials (ie, left ventricular dysfunction, kidney disease or aortic stenosis, rheumatoid arthritis, or chronic obstructive pulmonary disease). Hence, those variables were not included in the analysis, representing a potential limitation. The comparison focused on lipid-modifying agents (statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies) versus placebo/standard/usual care and between intensive versus less intensive LDL-C–lowering therapies. The effect of hypolipemic therapy on the endpoints has been assessed in absolute rate differences (ARD), number needed to treat (NNT), and rate ratios as secondary analyses. NNT and ARD allow a better appreciation of the clinical relevance of the treatment benefit, as the greater the absolute benefit, the smaller the NNT. Rate ratios, like hazard ratios, however, may overstate the benefit of the treatment in low event rates population while NNT increases. In general, all the analyses showed a high annual NNT. Mortality (all-cause and CV mortality) was overall reduced by lipid-lowering therapy, although it seems like it was neither related to the relative (expressed in percentage) or absolute LDL reduction nor to baseline and achieved LDL-C levels. The effect on mortality was not evident in trials where more than 50% reduction of LDL-C occurred and in the ones with low baseline LDL-C levels. MI risk was overall reduced, mainly in trials with high baseline LDL levels and with an important magnitude of LDL-C reduction (relative: 50%; absolute: 65 mg/dL). Indeed, those were the characteristics present in the studies that presented the lowest NNT. Conversely, the benefit on stroke risk was not evident with such important reduction in LDL. Interestingly, it was found that achieving LDL <55 mg/dL was not associated with further significant reduction in the primary endpoints. However, a prespecified secondary analysis of 25,982 patients from the randomized FOURIER trial reported a monotonic relationship between LDL levels and major CV outcomes.9 It should be considered that the heterogeneity of the clinical setting of the trials, as the unknown presence or absence of other comorbidities in all the studies, represents a noteworthy limitation: these confounding factors may affect the outcomes. Moreover, this systematic review and meta-analysis used studies where hypolipemic drugs were used for primary and secondary prevention, gathering 2 populations with different baseline risk. It is difficult to establish only one parameter (baseline LDL, achieved LDL, percentage reduction, absolute reduction, or CV mortality rate of the population studies) for predicting the reduction of all major events, and it must be borne in mind that residual individual risk still plays an important role in causing future events, even under hypolipemic treatment.4 In this regard, beside the burden of non-LDL atherogenic lipoproteins (eg, apoB-containing particles, triglyceride rich lipoproteins, and lipoprotein (a)), inflammation has been demonstrated, with the CANTOS trial, to play a key role in this context.10,11 Indeed, this phase III study, proved that canakinumab (an anti-interleukin-1β antibody) was effective for the secondary prevention of CV events in subjects who had a previous MI and who had persistent pro-inflammatory response (ie, high-sensitivity C-reactive protein levels of ≥2 mg/L) despite the use of other aggressive secondary preventive strategies, without affecting LDL levels.11 Nevertheless, it seems to be not a universally cost-effective solution.12 On top of that, other trials investigating the benefit of colchicine for secondary prevention confirmed the hypothesis of an inflammatory-related CV risk burden.13,14 Differently from canakinumab, its use has been included in the latest guidelines of cardiovascular prevention.15FIGURE 1.: Impact of LDL cholesterol (LDL-C) lowering on CV outcomes. Pt, patients; RCTs, randomized controlled trials.Interestingly, the reduction of MI seems to be associated with a more intensive treatment, hence with a lower achieved LDL and a greater magnitude of the reduction. It may be a consequence of plaque stabilization induced by these drugs, which, by reducing the lipidic content and increasing the thickness of the fibrous cap, reduce the risk of plaque rupture and subsequent thrombosis.16,17 In an era of precision medicine, the need to identify which subgroup of patients would benefit the most from LDL-C levels reduction is clinically and economically relevant. Indeed, we could design an intensive and strict therapeutical path for these patients and spear the administration of costly drugs to subjects who would not be aided by them.18

Abstract 11354: Role of PCSK9 Inhibitors in Acute Coronary Syndromes - A Pilot Study

Introduction: The proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have been guideline-approved for intolerant patients to statin therapy or unable to achieve target LDL levels with maximally tolerated therapies. The study aimed to determine whether early initiation of PCSK9 inhibitor with statin therapy in acute coronary syndromes (ACS) patients is beneficial in relation to low-density lipoprotein (LDL) reduction and short-term cardiovascular outcomes. Methods This pilot study included eighty ACS patients randomized to receive either PCSK9 inhibitor (Evolocumab) with statin therapy (n=40) or statin monotherapy (n=40). Patients were followed up for 6 months to assess for LDL levels, left ventricular ejection fraction (LVEF), and major adverse cardiovascular events (MACE) (a composite of myocardial infarction, heart failure, and cardiovascular death). Results Eighty patients with ACS (mean age 59±11 years, 66.3% male) had LDL and LVEF measured at baseline, 3 months, and 6 months. There was no difference between baseline LDL levels (153.1±39.5 vs 146.1±32, p=0.39). LDL levels in PCSK9 inhibitor/statin group were significantly lower at 3 months and 6 months compared to statin monotherapy (76.2±27.7 vs 118.6±31, p&lt;0.0001 and 78.2±22.1 vs 103.7±22.5, p&lt;0.0001, respectively). There was no significant difference between incidences of cardiovascular death (1 vs 3, p=0.31) and MACCE (4 vs 6, p=0.5) between both groups at 6-month follow-up. Conclusion The early initiation of PCSK9 inhibitors/statin combination therapy in ACS patients was associated with a significant reduction of LDL levels at 3 and 6 months yet there was no significant difference in relation to short-term cardiovascular outcomes at a 6-month follow-up. Further research is required to determine whether early initiation of PCSK9 inhibitors in combination with statins or as monotherapy in ACS patients can be associated with improved short or long-term cardiovascular outcomes.

Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk.

Statins lower low-density lipoprotein cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced low-density lipoprotein reduction increases risk of intracerebral haemorrhage has been debated for almost two decades. Here, we explored whether genetically predicted on-statin low-density lipoprotein response is associated with intracerebral haemorrhage risk using Mendelian randomization. Using genomic data from randomized trials, we derived a polygenic score from 35 single nucleotide polymorphisms of on-statin low-density lipoprotein response and tested it in the population-based UK Biobank. We extracted statin drug and dose information from primary care data on a subset of 225 195 UK Biobank participants covering a period of 29 years. We validated the effects of the genetic score on longitudinal low-density lipoprotein measurements with generalized mixed models and explored associations with incident intracerebral haemorrhage using Cox regression analysis. Statins were prescribed at least once to 75 973 (31%) of the study participants (mean 57 years, 55% females). Among statin users, mean low-density lipoprotein decreased by 3.45 mg/dl per year [95% confidence interval (CI): (-3.47, -3.42)] over follow-up. A higher genetic score of statin response [1 standard deviation (SD) increment] was associated with significant additional reductions in low-density lipoprotein levels [-0.05 mg/dl per year, (-0.07, -0.02)], showed concordant lipidomic effects on other lipid traits as statin use and was associated with a lower risk for incident myocardial infarction [hazard ratio per SD increment 0.98 95% CI (0.96, 0.99)] and peripheral artery disease [hazard ratio per SD increment 0.93 95% CI (0.87, 0.99)]. Over a 11-year follow-up period, a higher genetically predicted statin response among statin users was associated with higher intracerebral haemorrhage risk in a model adjusting for statin dose [hazard ratio per SD increment 1.16, 95% CI (1.05, 1.28)]. On the contrary, there was no association with intracerebral haemorrhage risk among statin non-users (P = 0.89). These results provide further support for the hypothesis that statin-induced low-density lipoprotein reduction may be causally associated with intracerebral haemorrhage risk. While the net benefit of statins for preventing vascular disease is well-established, these results provide insights about the personalized response to statin intake and the role of pharmacological low-density lipoprotein lowering in the pathogenesis of intracerebral haemorrhage.

Effect of Metformin Therapy on Low Density Lipoprotein (LDL) Levels in Type 2 Diabetes Mellitus Patients at Undata Hospital in Palu City Central Sulawesi

Background: Metformin, which can control blood glucose levels, can reduce LDL levels in type 2 DM patients. Objectives: To determine the mean value of pre and post LDL in type 2 DM patients after receiving metformin therapy for three months. Methods: This study used a cross-sectional study with a prospective approach, It was done by conducting pre and post examination of LDL levels using metformin. This study was analyzed using the SPSS Wilcoxon statistical test. The total sample that met the inclusion and exclusion criteria was 18 respondents. Results: This study used a single metformin value (sig = 0.000 &lt;0.05) with a baseline mean value of 148.22 mg / dL and an evaluation of 133.56 mg / dL where the difference in reduction was 14.66 mg / dL. Conclusion: There was a decrease in LDL levels in type 2 DM patients after using metformin for three months.

Involvement of LDL and ox-LDL in Cancer Development and Its Therapeutical Potential.

Lipid metabolism disorder is related to an increased risk of tumorigenesis and is involved in the rapid growth of cancer cells as well as the formation of metastatic lesions. Epidemiological studies have demonstrated that low-density lipoprotein (LDL) and oxidized low-density lipoprotein (ox-LDL) are closely associated with breast cancer, colorectal cancer, pancreatic cancer, and other malignancies, suggesting that LDL and ox-LDL play important roles during the occurrence and development of cancers. LDL can deliver cholesterol into cancer cells after binding to LDL receptor (LDLR). Activation of PI3K/Akt/mTOR signaling pathway induces transcription of the sterol regulatory element-binding proteins (SREBPs), which subsequently promotes cholesterol uptake and synthesis to meet the demand of cancer cells. Ox-LDL binds to the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cluster of differentiation 36 (CD36) to induce mutations, resulting in inflammation, cell proliferation, and metastasis of cancer. Classic lipid-lowering drugs, statins, have been shown to reduce LDL levels in certain types of cancer. As LDL and ox-LDL play complicated roles in cancers, the potential therapeutic effect of targeting lipid metabolism in cancer therapy warrants more investigation.

Ezetimibe- A Novel Add on Treatment Strategy to Achieve Targeted LDL in Patients with Uncontrolled LDL Levels on High Dose Statin Alone

Background: The lowering of low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy in the primary and secondary prevention of cardiovascular events. Statins are the most prescribed lipid-lowering drugs, but many patients fail to achieve the target low-density lipoprotein (LDL) level with statin alone or at higher doses. The add-on therapy of 'Ezetimibe' to statin monotherapy has resulted in a synergistic effect in reducing LDL levels and achievements of lipid targets. Cholesterol comes from two sources. endogenous and exogenous. Rather than inhibiting one source, it is better to inhibit two sources. While statins inhibit endogenous production, Ezetimibe decreases absorption of cholesterol. Indian patients are also observed to have low HDL which is another risk factor for heart diseases. We aimed to assess the efficacy of the combination of atorvastatin plus ezetimibe in Indian patients with dyslipidemia and to see whether it can reduce LDL levels and Improve HDL and triglyceride levels. Objective: (1) To find out LDL reduction by addition of ezetimibe in combination with statin in Indian patients. (2) To find out increase in HDL levels by adding ezetimibe in combination with statin along with the reduction in triglyceride levels in Indian patients. Methods: The retrospective data from EMR of the patients diagnosed with a high level of LDL and satisfying the study's inclusion criteria were collected. The patients at the baseline were given monotherapy. Those who did not achieve the desired LDL were given treatment with Atorvastatin high dose (40 mg and 80 daily) and were allocated to the add-on therapy with Ezetimibe at 10 mg/day after 3 months. The groups (monotherapy and combined therapy) were compared at baseline and subsequent follow-up visits. Data were analyzed using R studio 1.2.1335 and Microsoft Excel. Statistical significance was considered at p&lt;0.05. Results: The LDL level showed a significant decrease after 18 months from baseline till the subsequent follow-up visits. The reduction observed in the serum concentration of LDL was from 167.95 ± 12.85 mg/dL to 91.9 ± 10.39 mg/dL (p &lt; 0.001) in 40 mg group and from 164.76 ± 9.9 mg/dL to 106.71 ± 17.17 mg/dL (p &lt; 0.001) in 80 mg group. Furthermore, the rate of achieving an LDL level &lt;100 mg/dL increased from 0% to 45.28% in the 40 mg group and from 0% to 35.24% in 80 mg group and showed significantly greater improvement (p = 0.001). Conclusion: Compared with high doses of statin, the combination of statin with Ezetimibe not only achieves targeted serum lipid levels, suggesting that combination therapy should be a priority when statin resistance or poor efficacy occurs with the higher dose of statin monotherapy. Keyword: LDL; HDL; Triglycerides; Atorvastatin; Ezetimibe

The effects of liraglutide on liver enzymes and metabolic factors in patients with nonalcoholic steatohepatitis: a meta-analysis of randomized controlled trials.

Nonalcoholic steatohepatitis (NASH) is the most common cause of chronic liver disease, but no drug therapies have been approved to date. While glucagon-like peptide-1 (GLP-1) analogues may help in the management, the existing evidence remains conflicting. This meta-analysis aims to elucidate the efficacy of liraglutide in patients with NASH. We searched 4 databases for randomized controlled trials assessing the efficacy of liraglutide in patients with NASH. We analysed continuous outcomes using the mean difference (MD) and relative 95% confidence interval (CI), while dichotomous outcomes were analysed using the risk ratio (RR) and relative 95% CI. Primary endpoints included alanine aminotransferase (ALT) (IU/l), aspartate aminotransferase (AST) (IU/l), alkaline phosphatase (ALP) (IU/l), and γ-glutamyl transferase (GGT) (IU/l). Secondary outcomes were body mass index (BMI) (kg/m2), waist circumference (cm), total cholesterol (TC) (mmol/l), triglyceride (TG) (mmoll), high-density lipoprotein (HDL) (mmol/l), low-density lipoprotein (LDL) (mmol/l), and glycated hemoglobin (HbA1c) (%). A total of 5 clinical trials were included. The analysis showed that liraglutide is effective in increasing HDL (MD = +0.10 (-0.18, -0.02), p = 0.02) and reducing LDL levels in blood (MD = -0.29 (-0.56, -0.02), p = 0.04). No significant difference was noted in levels of ALT (MD = 2.66 (-1.56, 6.87), p = 0.22), AST (MD = -1.99 (-5.70, 1.72), p = 0.29), GGT (MD = 5.02 (-0.86, 10.90), p = 0.09), ALP (MD = -5.16 (-11.90, 1.59), p = 0.13), TC (MD = -0.31 (-0.65, 0.03), p = 0.07), or TG (MD = -0.14 (-0.53, 0.25), p = 0.48). The HbA1c (%) level was found to be significantly reduced in the liraglutide arm (MD = -0.62 (-0.88, -0.36), p < 0.01). Liraglutide effectively improves the lipid profile in patients with NASH.

Soybean-Derived Peptides Attenuate Hyperlipidemia by Regulating Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis.

Increased triglyceride, cholesterol, and low-density lipoprotein (LDL) levels cause hyperlipidemia. Despite the availability of statin-based drugs to reduce LDL levels, additional effective treatments for reducing blood lipid concentrations are required. Herein, soybean hydrolysate prepared via peptic and tryptic hydrolysis promoted trans-intestinal cholesterol excretion (TICE) by increasing ATP-binding cassette subfamily G member 5 (ABCG5) and ABCG8 expression. The peptide sequence capable of promoting TICE was determined via HPLC and LC-MS/MS. Based on this, pure artificial peptides were synthesized, and the efficacy of the selected peptides was verified using cellular and hyperlipidemic mouse models. Soybean hydrolysates, including two bioactive peptides (ALEPDHRVESEGGL and SLVNNDDRDSYRLQSGDAL), promoted TICE via the expression of ABCG5 and ABCG8 in enterocytes. They downregulated expression of hepatic cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1 via expression of fibroblast growth factor 19 (FGF19) in a liver X receptor α (LXRa)-dependent pathway. Administration of bioactive peptides to hyperlipidemic mouse models by oral gavage reduced cholesterol levels in serum via upregulation of ABCG5 and ABCG8 expression in the proximal intestine and through fecal cholesterol excretion, upregulated FGF 15/19 expression, and suppressed hepatic bile acid synthesis. Oral administration of soybean-derived bioactive peptides elicited hypolipidemic effects by increasing TICE and decreasing hepatic cholesterol synthesis.

Engineered red blood cells carrying PCSK9 inhibitors persistently lower LDL and prevent obesity.

Low plasma levels of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) are associated with decreased low-density lipoprotein (LDL) cholesterol and a reduced risk of cardiovascular disease. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of LDL receptors (LDLR), very low-density lipoprotein receptors (VLDLR), apolipoprotein E receptor 2 (ApoER2), and lipoprotein receptor–related protein 1 (LRP1) and accelerates their degradation, thus acting as a key regulator of lipid metabolism. Antibody and RNAi—based PCSK9 inhibitor treatments lower cholesterol and prevent cardiovascular incidents in patients, but their high-cost hampers market penetration. We sought to develop a safe, long-term and one-time solution to treat hyperlipidemia. We created a cDNA encoding a chimeric protein in which the extracellular N- terminus of red blood cells (RBCs) specific glycophorin A was fused to the LDLR EGFA domain and introduced this gene into mouse bone marrow hematopoietic stem and progenitor cells (HSPCs). Following transplantation into irradiated mice, the animals produced RBCs with the EGFA domain (EGFA-GPA RBCs) displayed on their surface. These animals showed significantly reduced plasma PCSK9 (66.5% decrease) and reduced LDL levels (40% decrease) for as long as 12 months post-transplantation. Furthermore, the EGFA- GPA mice remained lean for life and maintained normal body weight under a high-fat diet. Hematopoietic stem cell gene therapy can generate red blood cells expressing an EGFA—glycophorin A chimeric protein as a practical and long-term strategy for treating chronic hyperlipidemia and obesity.

Isomers of guggulsterone in hyperlipidemia

Hyperlipidemia is one of the major issues which results in serious cardiovascular complications. Plant-based medicinal products have been commonly used for several chronic disorders. Guggulsterone isomers is proven to be cholesterol lowering activity which is a major bioactive compound present in Commiphora mukul and Commiphora wighti . On the basis of existing clinical evidence, it seems that guggulsterone is much helpful in reduction of Low-density lipoprotein levels. On the other hand, it is important to consider clinical pharmacokinetics of Guggulsterone isomers to create a definitive decision in this context. • Guggulsterone isomer is one of the major bioactive compounds present in Commiphora species. • Guggulsterone antagonizes the Farnesoid X Receptor, which involves the conversion of cholesterol into bile acids. • Long term administration of Guggulsterone isomers shows a significant reduction of LDL-C.

The Effect of Turmeric and Ginger Powder on Japanese Quail (Coturnix coturnix) Serum Lipid Profile

Lipids are essential fatty acids. Lipids function as a source of energy and structural constituent components of Japanese quails. Japanese quail (Coturnix coturnix japonica) is one of the livestock sectors that is efficient in providing nutrients, both from eggs and meat. However, this animal has high cholesterol levels. This study aimed to determine the effect of organic feed on the cholesterol, triglyceride, HDL (High Density Lipoprotein), and LDL (Low Density Lipoprotein) level of Japanese quail. This study used an experimental method with a completely randomized design (CRD). The test animals were 30 females Japanese quail which were divided into 3 groups (2 individuals each) with different treatments i.e. P0: control (commercial feed); P1: standard organic feed (corn, soybean, bran and fish meal); P2: special organic feed (corn, soybean, bran, fish meal, cassava leaves, turmeric and ginger powder). Each treatment consisted of 5 replications. Feed was given for 2 months and at the end of the treatment, the blood was collected for analysis. Data obtained were analyzed using analysis of variance (ANOVA) and continued with Duncan test with a confidence of 95% (α=0.05). Analysis was performed using SPSS software 16.0 for windows. The results showed that the effect of organic feed containing cassava leaves, turmeric and ginger powder is significantly different on live weight, and not significantly different on feed consumption and drinking consumption. Moreover, the provision of that special organic feed was able to stabilize the cholesterol and HDL levels, and reduce LDL levels in Japanese quail (Coturnix coturnix japonica).

Impact of different dietary approaches on blood lipid control in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis.

The aim of this study was to assess the effects of different dietary approaches on low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride (TG) levels in patients with type 2 diabetes (T2D) by applying network meta-analysis (NMA). Systematic electronic and hand searches were conducted until January 2018. Randomized controlled trials (RCTs) with an intervention period of ≥ 12weeks, focussing on adults with T2D, and comparing dietary approaches regarding LDL, HDL or TGs, were included. For each outcome measure, random effects NMA was performed in order to determine the effect of each dietary approach compared to every other dietary intervention. Mean differences (MDs) and 95% confidence intervals (95% CIs) were calculated, and for the ranking, the surface under the cumulative ranking curves (SUCRA) was determined. Additionally, the credibility of evidence was evaluated. 52 RCTs (44 for LDL, 48 for HDL and 52 for TGs) comparing nine dietary approaches (low fat, vegetarian, Mediterranean, high protein, moderate carbohydrate, low carbohydrate, control, low glycaemic index/glycaemic load and Palaeolithic diet) enrolling 5360 T2D patients were included. The vegetarian diet most effectively reduced LDL levels [MD (95% CI): - 0.33 (- 0.55, - 0.12) mmol/L; compared to the control diet]. The Mediterranean diet beneficially raised HDL [MD (95% CI): 0.09 (0.04, 0.15) mmol/L] and decreased TG levels [MD (95% CI): - 0.41 (- 0.72, - 0.10) mmol/L] compared to the control diet. The Mediterranean diet was the most effective dietary approach to manage diabetic dyslipidaemia altogether (SUCRA: 79%). The overall findings are mainly limited by low credibility of evidence.

Improved endothelial function after short-term therapy with evolocumab

The reduction of cholesterol levels with cholesterol-lowering therapy may improve endothelial function. Lipid-lowering therapy has been greatly enhanced by the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies. Less is known of the effect of PCSK9 inhibitors on endothelial function of subjects with hypercholesterolemia. To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test. Brachial artery vasoreactivity test was performed in 14 consecutive patients with previous myocardial infarction before and after 2months of therapy with evolocumab 140mg twice in a month. Mean brachial artery diameter, velocity time integral, flow-mediated dilation (FMD) and low-density lipoprotein (LDL) cholesterol levels were also evaluated. After 2months of treatment with evolocumab, mean total cholesterol levels decreased from 245±41 to 128±30mg/dL (P<.001, -48%), and LDL levels from 176±43 to 71±26mg/dL (P=.001, -59%); FMD conversely increased from 6.3±4.1% to 8.8±6.3% (P=.004,+40%). Improvement in FMD was proportional to reduction of LDL levels (r=0.69, P=.006). Therapy with evolocumab increased brachial artery diameter during vasoreactivity test (peak values 0.39±0.09 vs 0.36±0.11cm, P=.010; final values 0.36±0.10 vs 0.34±0.10cm, P=.001), and velocity time integral (peak levels 96±1 vs 85±9cm, P=.045). Two months of treatment with evolocumab 140mg may improve endothelial function in subjects with increased cardiovascular risk. The improvement in endothelial function is proportional to LDL reduction.

Adiponectin promoter polymorphisms are predictors of lipid profile improvement after bariatric surgery.

Our aim was to investigate if single nucleotide polymorphisms (SNPs) located in the 5′ regions of leptin (LEP, -2548 G > A, rs7799039), resistin (RETN, -420 C > G, rs1862513) and adiponectin (ADIPOQ, -11391 G > A, rs17300539 and -11377 C > G, rs266729) genes were related to changes in body mass index (BMI) and metabolic variables after bariatric surgery in 60 extremely obese individuals. At baseline, ADIPOQ -11391 A-allele carriers showed higher plasma adiponectin and lower total cholesterol levels when compared to G/G homozygotes. Approximately 32 months post-surgery, a mean reduction of 35% in BMI and an important improvement in metabolic profiles were observed. In addition, for the ADIPOQ -11377 polymorphism, a higher decrease in lipid profile was associated to the C/C genotype. Moreover, individuals bearing the A-C haplotype for the two ADIPOQ SNPs were more prone to show a reduction in low-density lipoprotein levels after bariatric surgery (-43.0% A-C carriers vs. -18.1% G-G carriers, p = 0.019). We did not find any association of leptin and resistin SNPs with the clinical parameters analyzed. In summary, our results indicate that the A-C haplotype is a predictor of better lipid profile post-surgery and the studied SNPs in ADIPOQ gene are associated to changes in metabolic variables in obese individuals.