Lower Low-density Lipoprotein Cholesterol Research Articles

Efficacy of an avocado-based Mediterranean diet on serum lipids for secondary prevention after ischemic stroke: a randomized phase 2 controlled pilot trial

BackgroundThe impact of a healthy diet on the secondary prevention of ischemic stroke (IS) remains uncertain. Levels of low-density lipoprotein cholesterol (LDL-C) are inversely associated with the risk of IS recurrence. A Mediterranean diet (MeDi), consisting of a preference for fish/poultry, monosaturated fats from olive oil, fruit, vegetables, whole grains, legumes/nuts and limited red meats, animal fats and sweetened beverages, reduces metabolic syndrome, LDL-C levels and stroke risk. Avocados also reduce metabolic syndrome and LDL-C levels but are not part of the traditional MeDi diet. The effects of an avocado-based Mediterranean diet on LDL-C were investigated and compared to those of a low-fat diet in patients with previous IS.MethodsThe Avocado-Based Mediterranean Diet on Serum Lipids for Secondary Prevention after Ischemic Stroke (ADD-SPISE) was a prospective, randomized, open-label, blinded outcome assessment, phase 2, clinical trial. The participants were adults with an IS in the previous month who were randomly assigned at a 1:1 ratio to a MeDi or a low-fat diet for three months. Outcome assessors of laboratory results and data analysts were masked. The primary outcome was the mean difference in LDL-C between groups at 90 days, adjusted by statin use. Safety, feasibility and acceptability (assessed through a 14-item questionnaire administered to all patients who completed the follow-up) were also evaluated.ResultsFrom August 2018 to October 2022, 200 participants were enrolled (97 randomized to the low-fat diet and 103 to the MeDi), with 189 (94.5%) completing the study. There were no significant differences in LDL-C levels between the MeDi group and the low-fat group at 90 days: 66.5 mg/dL (95% confidence interval [CI] 59.6, 73.4) in the MeDi group and 69.9 mg/dL (62.6, 77.2) in the low-fat group at the end of follow-up. The adjusted difference was − 3.4 mg/dL (-13.4, -6.62); P = 0.50. The intervention group showed significant improvements in Mediterranean diet adherence (P < 0.01). Moreover, no significant differences in adverse events were observed between the groups.ConclusionCompared with a low-fat diet, the avocado-based MeDi did not significantly lower LDL-C in IS patients after three months. The intervention was safe, feasible, and well accepted. Larger trials should establish whether longer dietary interventions could yield clinically significant benefits in these patients. The study is registered under ADD-SPISE at www.clinicaltrials.gov. Identifier: NCT03524742.

Low LDL cholesterol and risk of bacterial and viral infections – observational and Mendelian randomisation studies

Abstract Aims Low levels of low-density-lipoprotein(LDL) cholesterol may be associated with risk of infectious disease. We tested the hypothesis that low LDL cholesterol due to genetic variation in the LDLR, PCSK9, and HMGCR genes, and a polygenic LDL cholesterol score is associated with risk of infectious diseases in the general population. Methods and results Using observational and Mendelian randomisation designs, we examined associations of low plasma LDL cholesterol with risk of bacterial and viral infections in 119,805 individuals from the Copenhagen General Population Study/Copenhagen City Heart Study, 468,701 from the UK Biobank, and up to 376,773 from the FinnGen Research Project. Observationally, low LDL cholesterol concentrations were associated with risk of hospitalisation for both bacterial and viral infections. In genetic analyses, a 1 mmol/L lower LDL cholesterol was associated with lower plasma PCSK9(-0.55 nmol/L[95%CI: -1.06–-0.05], p=0.03), leucocyte count(-0.42 x109/L[-0.61–-0,24]; p&amp;lt;0.001), and high-sensitivity C-reactive protein(-0.44 mg/L[-0.79–-0.09]; p=0.014). Using an LDLR, HMGCR, and PCSK9 score, a 1 mmol/L lower LDL cholesterol was associated with risk ratios of 0.91(95%CI: 0.86–0.97; p=0.002) for unspecified bacterial infection, of 0.92(0.87–0.97; p=0.004) for diarrhoeal disease, and of 1.15(1.03-1.29; p=0.012) for unspecified viral infections and 1.64(1.13-2.39; p=0.009) for HIV/AIDS. Using a polygenic LDL cholesterol score largely showed similar results and in addition a lower risk of 0.85(0.76-0.96; p=0.006) for bacterial pneumonia and 0.91(0.82-0.99; p=0.035) for sepsis. Conclusion Genetically low LDL cholesterol concentrations were associated with lower concentration of markers of inflammation, and lower risk of hospitalisation for unspecified bacterial infections, infectious diarrhoeal diseases, bacterial pneumonia, and sepsis; and higher risk of viral infections and HIV/AIDS.

Concurrent exercise training during pregnancy is related to more favourable maternal lipid levels when IL-8 increases

ABSTRACT It is unclear how exercise-induced stimuli affect and translate into immunometabolic adaptations during pregnancy. We previously found that exercise influences maternal-foetal circulating cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α). This study investigated i) the influence of an exercise training programme during pregnancy on metabolic markers (glycaemic and lipid markers, and C-reactive protein) in maternal, and cord arterial and venous serum; and ii) whether these cytokines mediated the effects of exercise on metabolic markers. Eighty-eight pregnant women, divided into exercise (n = 44) and control (n = 44) groups, participated in this quasi-experimental study. The exercise group followed a 60-min 3 days/week concurrent (aerobic+resistance) exercise training. Glycaemic and lipid markers and C-reactive protein concentrations, and cytokines levels, were measured at weeks 17 and 34 and birth with standard biochemical methods and Luminex xMAP technology. Overall, exercise did not induce detectable changes in maternal metabolic markers during pregnancy, except for those exercisers whose IL-8 levels increased, where it was related to lower maternal total cholesterol (indirect effect= −9.1; 95% CI= −24.6, −1.1) and low-density lipoprotein-cholesterol gains (−8.9; −21.9, −1.1). This suggests a mechanism by which exercise may optimise lipid metabolism regulation. Moreover, exercise was related to lower cord arterial serum glucose levels. Further research, especially concerning foetal metabolism, is necessary.

Long-Term Lipid Lowering With Evolocumab in Older Individuals.

Concerns about the efficacy and safety of intensive low-density lipoprotein cholesterol lowering in older patients have led to weaker recommendations in the U.S. guidelines for patients≥75 years of age compared to younger patients. Data are sparse on long-term benefits of proprotein convertase subtilisin/kexin type 9 inhibition in older patients. This study aims to assess the long-term benefit of evolocumab among patients aged≥75 years. The FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial randomized 27,564 patients who were 18 to 85 years of age with atherosclerotic cardiovascular disease to evolocumab vs placebo with 2.2 years of median follow-up. In the open-label extension (FOURIER-OLE), 6,635 participants were transitioned to open-label evolocumab for an additional 5-year median follow-up. The primary endpoint (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) was compared based on the original allocation to evolocumab vs placebo stratified by age (<75 vs≥75 years). Analyses were underpowered for individual components of the composite endpoint. The annualized incidence rates for adverse events of interest were calculated for the OLE population across age groups during the parent FOURIER trial by randomized treatment arm and during the combined parent and FOURIER-OLE studies for patients originally allocated to evolocumab. Of 27,564 patients, 2,526 (9%) were≥75 years of age at entry into FOURIER (median age: 77 years [Q1-Q3: 76-79 years]). The median follow-up in FOURIER and FOURIER-OLE was 7.1 years (Q1-Q3: 6.7-7.6 years), with a maximum of 8.7 years. Earlier initiation of evolocumab reduced the rate of the primary endpoint at least as well in older (HR: 0.79; 95%CI: 0.64-0.97) as in younger patients (HR: 0.86; 95%CI: 0.80-0.92; P interaction=0.43). The absolute risk reductions were 5.4% (95%CI: -2.0% to 12.8%) in older and 2.3% (95%CI: 0.1%-4.5%) in younger patients, leading to numbers needed to treat of 19 and 44, respectively. The annualized incidence rates of safety events generally appeared similar across treatment arms in both age groups. Early initiation of long-term evolocumab provides older patients with atherosclerotic cardiovascular disease cardiovascular benefits at least as good as those observed in younger patients, with a more favorable number needed to treat in older patients for reducing a composite endpoint and no significant safety concerns. These findings may be helpful in guiding future recommendations.

Monacolin K as a Natural Alternative for Synthetic Statins

Introduction: This review paper aims to verify the safety of monacolin K, examine the effect on blood cholesterol levels, discuss the contribution to the reduction of cardiovascular risk and indicate examples of pleiotropic effects of this substance. Materials and methods: A review of chosen literature in the PubMed database was conducted, using the following key words: ,,Monacolin K”, ,,Hypercholesterolemia’’, ,,Red yeast rice’’, ,,Supplementation’’. Summary: Monacolin K is considered to be natural statin contained in fermented red rice or oyster mushroom. The use of monacolin K may contribute to the development of mild muscle pain or rhabdomyolysis, but it is noticed less frequently than in treatment with synthetic statins. In addition, there are also concerns about liver and/or kidney damage, headaches and/or dizziness, musculoskeletal symptoms and gastrointestinal disturbances in some people, especially when high doses of monacolin K are used. Monacolin K lowers the level of cholesterol in the blood and contributes to reducing the risk of cardiovascular diseases. Furthermore, monacolin K has anti-inflammatory effects and anti-cancer mechanisms. Conclusions: Monacolin K improves the lipid profile by lowering low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and total cholesterol (TC) levels which indirectly reduces the cardiovascular risk with less frequently observed side effects. Monacolin K has many pleiotropic effects like anti-inflammatory and anti-cancer mechanisms by inhibiting cancer cell proliferation and stimulating apoptosis. It should be emphasized that the long-term safety of regular use of these preparations has not been fully documented. Some people taking these supplements experience side effects similar to those seen with statins. Both health benefits and side effects should be further investigated in future studies.

Interaction Between Lipoprotein(a) and Other Lipid Molecules: A Review of the Current Literature

Lipoprotein(a) [Lp(a)] is a well-established causal risk factor for cardiovascular diseases (CVDs), as reported by multiple Mendelian randomization studies and large epidemiological studies. When elevated Lp(a) is combined with other risk factors, most notably elevated low-density lipoprotein cholesterol (LDL-C), a synergistic atherogenic effect has been reported. However, the current literature is conflicting regarding how Lp(a) interacts in the context of controlled LDL-C levels (e.g., &lt;70 mg/dL) and whether reducing LDL-C can modify the atherogenic effect of Lp(a). In some studies, elevated Lp(a) was still significantly associated with a higher risk of cardiovascular events, despite controlled levels of LDL-C. In contrast, multiple studies have reported attenuation of the cardiovascular risk mediated by elevated Lp(a) with lower LDL-C levels. Moreover, the relationship between Lp(a) and triglycerides, high-density lipoprotein, and very low-density lipoprotein remains unclear. In this literature review, we summarize and discuss the current evidence regarding the interactions between Lp(a) and other lipid molecules, how they contribute to the pathogenesis of CVD, and future perspectives, particularly in the current era where promising targeted Lp(a)-lowering therapies are under development.

Beyond LDL cholesterol: remnant cholesterol is associated with cardiometabolic risk factors in children

BackgroundRecent evidence from both randomized controlled trials and cohort studies in adults suggests that plasma remnant cholesterol (RC) levels predict cardiovascular disease. In children, studies are scarce, although high levels of RC might represent a marker of early atherosclerotic damage. Thus, the aim of this study was to explore the cardiometabolic risk associated with RC, which extends beyond low-density lipoprotein cholesterol (LDL-c) in children.MethodsCardiometabolic risk factors (plasma insulin levels, homeostatic model assessment for insulin resistance, mean arterial blood pressure (MAP), waist circumference (WC), and cardiorespiratory fitness (CRF)) were examined in 3417 Spanish schoolchildren aged 8–11 years. The children were categorized into four subgroups (low vs. high) based on the cutoff of ≥ 110 mg/dL for LDL-c and of ≥ 15 mg/dL for RC to define higher levels, and ANCOVA models were applied to assess the role of both lipid parameters in cardiometabolic risk. Additionally, multilevel mixed-effects generalized linear regression models were used to assess the associations of RC or LDL-c with cardiometabolic risk factors and to examine whether the associations between RC and these factors varied in children with low or high LDL-c levels.ResultsChildren in the high-RC subgroups, specifically those with low LDL-c/high RC and high LDL-c/high RC, presented significantly greater insulin levels and WC than did their peers in the low-RC subgroups. RC was more strongly associated with cardiometabolic risk factors than LDL-c (insulin β = 2.073/ − 0.026; HOMA-IR β = 0.451/ − 0.002; MAP β = 1.214/0.300; WC β = 2.842/1.058; and CRF β = − 0.316/ − 0.194 for RC and LDL-c, respectively). Furthermore, RC exhibited associations even in children with low LDL-c levels: insulin (β = 2.305; p < 0.001), HOMA-IR (β = 0.499; p < 0.001), MAP (β = 1.397, p < 0.001), WC (β = 2.842; p < 0.001), and CRF (β = − 0.367; p < 0.001).ConclusionsThe associations between RC and cardiometabolic risk factors were stronger than those between LDL-c and cardiometabolic risk, extending its significance even in children with low LDL-c levels. These findings may be clinically useful for cardiovascular risk stratification and for guiding future interventions in children, although they should be confirmed by longitudinal studies.

Clinical significance of small dense low-density lipoprotein cholesterol measurement in type 2 diabetes.

Low-density lipoprotein cholesterol (LDL-C) is known to be a causal substance of atherosclerosis, but its usefulness as a predictive biomarker for atherosclerotic cardiovascular disease (ASCVD) is limited. In patients with type 2 diabetes (T2D), LDL-C concentrations do not markedly increase, while triglycerides (TG) concentrations are usually elevated. Although TG is associated with ASCVD risk, they do not play a direct role in the formation of atheromatous plaques. TG changes the risk of ASCVD in a way that is dependent on LDL-C, and TG is the primary factor in reducing LDL particle size. Small dense (sd)LDL, a potent atherogenic LDL subfraction, best explains the "Atherogenic Duo" of TG and LDL-C. Although hypertriglyceridemia is associated with small-sized LDL, patients with severe hypertriglyceridemia and low LDL-C rarely develop ASCVD. This suggests that quantifying sdLDL is more clinically relevant than measuring LDL size. We developed a full-automated direct sdLDL-C assay, and it was proven that sdLDL-C is a better predictor of ASCVD than LDL-C. The sdLDL-C level is specifically elevated in patients with metabolic syndrome and T2D who have insulin resistance. Due to its clear link to metabolic dysfunction, sdLDL-C could be named "metabolic LDL-C." Insulin resistance/hyperinsulinemia promotes TG production in the liver, causing steatosis and overproduction of VLDL1, a precursor of sdLDL. sdLDL-C is closely associated with steatotic liver disease and chronic kidney disease, which are common complications in T2D. This review focuses on T2D and discusses the clinical significance of sdLDL-C including its composition, pathophysiology, measurements, association with ASCVD, and treatments.

Adjunctive PCSK9 Inhibitor Evolocumab in the Prevention of Early Neurological Deterioration in Non-cardiogenic Acute Ischemic Stroke: A Multicenter, Prospective, Randomized, Open-Label, Clinical Trial.

Early neurological deterioration (END) is associated with a poor prognosis in acute ischemic stroke (AIS). Effectively lowering low-density lipoprotein cholesterol (LDL-C) can improve the stability of atherosclerotic plaque and reduce post-stroke inflammation, which may be an effective means to lower the incidence of END. The objective of this study was to determine the preventive effects of evolocumab on END in patients with non-cardiogenic AIS. This was a multicenter, prospective, open-label, blinded-endpoint clinical trial. Participants with AIS within 24 h were randomly assigned to either the group receiving combination therapy of evolocumab and atorvastatin, which is a 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, i.e., a "statin" (PI group), or the group receiving atorvastatin monotherapy (AT group). The primary outcome was END within 7 days, defined as a 2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or a 1-point increase in motor function within 24 h-7 days from the onset of AIS. Secondary outcomes included LDL-C target achievement rate on day 7 (≤ 1.8 mmol/L with a reduction exceeding 50% from baseline), inflammatory factors (interleukin [IL]-6, IL-8, and tumor necrosis factor [TNF]-α) before and after 7 days of treatment, and stroke-related death with 7 days. Safety endpoints included any adverse events. Patients with AIS (n = 272) were randomly assigned to the PI (n = 136) or AT (n = 136) groups. Within 7 days, 18 (13.2%) and 33 (24.3%) patients experienced END in the PI and AT groups, respectively (relative risk [RR] -0.90; 95% confidence interval [CI]: -1.59 to -0.22; p = 0.010). On the seventh day, LDL-C target achievement rate in the PI and AT groups was 74.3% and 14.7%, respectively (RR 3.27; 95% CI: 2.40-4.15; p = 0.001). Changes in IL-6 over 7 days were significantly lower in the PI group compared with the AT group, respectively (median 1.02 [range -1.91, 5.47] versus 2.54 [-0.83, 15.20]; p = 0.033). On the 90th day of follow-up, 83.1% and 65.4% of patients had a modified Rankin Scale score ≤ 2 in the PI and AT groups, respectively (RR 0.51; 95% CI: 0.66-2.66; p = 0.001). There was no significant difference in stroke recurrence between the two groups within 90 days (RR -1.72; 95% CI: -4.57 to 1.13; p = 0.237). Regarding adverse events, 15 and 22 patients in the PI and AT groups, respectively, experienced slight abnormalities in liver and kidney function laboratory values during the 7-day treatment period (odds ratio 0.62; 95% CI: 0.30-1.29; p = 0.203), but no serious adverse events were observed in either group. These results suggest that the combination therapy of evolocumab and atorvastatin within 24 h of AIS onset may effectively reduce the incidence of END compared with atorvastatin monotherapy. Additionally, in the early stages of AIS, this combination therapy can reduce blood LDL-C levels, and inhibit IL-6 elevation, potentially improving the prognosis of patients with AIS within 90 days. China Clinical Trials Registry (No: ChicTR2200059445, 29 April 2022, https://www.chictr.org.cn/ ).

Meat Quality, Intestinal Microbiology and Serum Biochemical Parameters of Broilers Fed Different Levels of Green Tea (Camellia sinensis) and Mulberry (Morus alba) Leaves Powder.

Today, customers pay more attention to the feed composition and carcasses of poultry, and the interest in using natural and safe compounds such as medicinal plants and their extracts in animal feed is increasing. The present experiment was conducted to assess the effect of green tea (Camellia sinensis) and mulberry (Morus alba) leaves powder on the meat quality, intestinal microbiology and serum biochemical parameters in broilers. The experiment was conducted with 648 one-day-old Ross 308 broiler male chicks with a factorial arrangement including three levels of green tea powder (GTP) and three levels of mulberry leaf powder (MLP), with nine treatments and six replications in a completely randomized design for 42 days. Treatments included: (1) no GTP + no MLP (control), (2) 1% GTP + no MLP, (3) 2% GTP + no MLP, (4) no GTP + 1% MLP, (5) 1% GTP + 1% MLP, (6) 2% GTP + 1% MLP, (7) no GTP + 2% MLP, (8) 1% GTP + 2% MLP and (9) 2% GTP + 2% MLP. The results showed that the lowest lightness (L*), drip loss and total cholesterol levels, and the highest Lactobacillus population were observed in treatments: 1% GTP + no MLP, 2% GTP + no MLP, 1% GTP + 1% MLP, 2% GTP + 1% MLP, no GTP + 2% MLP, 1% GTP + 2% MLP and 2% GTP + 2% MLP (p <0.05). The groups receiving 1% GTP + 1% MLP, 2% GTP + 1% MLP, no GTP + 2% MLP, 1% GTP + 2% MLP and 2% GTP + 2% MLP had the highest pH 24h (p <0.05). The chickens fed with 1% and 2% GTP showed lower low-density lipoprotein cholesterol (LDL) and malondialdehyde (MAD) levels (p <0.05). The results showed that using the GTP and MLP in the diet of broilers could improve meat quality traits and beneficial ileal bacteria populations and reduce serum lipid and MDA levels.

Prevalence, genetic variants, and clinical implications of hypocholesterolemia in children.

In contrast to extensively studied hypercholesterolemia, knowledge of hypocholesterolemia is limited. This study aims to assess the prevalence, clinical characteristics, and genetics of children and adolescents with hypocholesterolemia. This national prospective cross-sectional cohort study was part of Slovenia's universal opt-out cholesterol screening program. The first part assessed hypocholesterolemia prevalence among 3538 children aged 5 years, randomly selected at the mandatory check-up. The second part included analysis of demographic and clinical data and genetic testing of 71 individuals with suspected hypocholesterolemia (total cholesterol [TC]<3.0mmol/L [116.0mg/dL]) referred to the Lipid Clinic of University Children's Hospital Ljubljana. The prevalence of hypocholesterolemia among 3538 children was 2.66% (95% CI: 2.13-3.19%). Among the 71 genetically tested individuals with suspected hypocholesterolemia, those with pathogenic variants had lower TC (2.58±0.44mmol/L vs. 2.85±0.42mmol/L [99.77±17.02mg/dL vs. 110.20±16.24mg/dL]; p=0.037) and low-density lipoprotein cholesterol (1.00±0.40mmol/L vs. 1.33±0.40mmol/L [38.67±15.47mg/dL vs. 51.43±15.47mg/dL]; p=0.014) compared to those without such variants. Genetic testing identified pathogenic alterations in 15 subjects, including 4 novel loss-of-function variants in the APOB gene. All but one subject were asymptomatic. This study provides new clinical and genetic insights into hypocholesterolemia. Asymptomatic patients with hypocholesterolemia may not require further evaluation, but additional research is needed to understand hypocholesterolemia better.

Effects of Cinnamomum zeylanicum (Ceylon cinnamon) extract on lipid profile, glucose levels and its safety in adults: A randomized, double-blind, controlled trial.

Cinnamon has been studied as a possible way to control blood glucose and serum cholesterol levels. However, there are no well-conducted randomized controlled trials that can accurately measure the lipid and glucose-lowering effects of Cinnamomum zeylanicum (C. zeylanicum) extract. This study primarily aimed to evaluate the effect of a standardized C. zeylanicum extract on serum low-density lipoprotein cholesterol (LDL-C) levels and secondarily on other lipid parameters (high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglycerides), glucose levels, anthropometric measures, blood pressure, and safety outcomes in individuals with an LDL level between 100-190mg/dL. This was a randomized, double-blinded, placebo-controlled clinical trial. Participants were allocated to either C. zeylanicum extract or placebo group (1:1 allocation ratio). They were advised to take two capsules per day (1000 mg/day, a dose based on prior clinical studies suggesting potential efficacy and safety). Reduction in LDL-C at 12 weeks (from the baseline value) was compared between the two groups using ANCOVA. A complete-case analysis was adhered to in analyzing the outcome data. The mean age (SD) of the 150 participants was 50.4 (10.52) years, and 66% were females. Among the 127 participants assessed at 12 weeks, those in the C. zeylanicum extract arm had a lower LDL-C value than the placebo arm but the difference was not significant (the baseline adjusted mean difference was 6.05mg/dL; 95% CI: -2.43 to 14.52; p = 0.161). However, participants in the C. zeylanicum extract group showed significantly greater reductions in fasting blood sugar (FBS) levels (the baseline adjusted mean difference was 8.59mg/dL; 95% CI: 0.59 to 16.59; p = 0.036). There was a significant interaction effect between the supplement and participants' glycemic status, with individuals with type 2 diabetes mellitus (T2DM) who received C. zeylanicum extract experiencing a notable reduction in FBS levels (standardized coefficient: -63, 95% CI: -102 to -25; p = 0.002). C. zeylanicum extract did not have significantly reduce LDL-C but demonstrated a significant FBS-lowering effect, particularly in individuals with T2DM, with a favorable safety profile. The trial was registered with the Sri Lanka Clinical Trials Registry: SLCTR/2021/011.

Systematic Review on Efficacy, Effectiveness, and Safety of Pitavastatin in Dyslipidemia in Asia.

Objectives: Dyslipidemia, a significant risk factor for cardiovascular disease (CVD), is marked by abnormal lipid levels, such as the elevated lowering of low-density lipoprotein cholesterol (LDL-C). Statins are the first-line treatment for LDL-C reduction. Pitavastatin (PIT) has shown potential in lowering LDL-C and improving high-density lipoprotein cholesterol (HDL-C). This review assesses pitavastatin's efficacy, effectiveness, and safety in dyslipidemia management in Asia. Methods: A systematic review was conducted using PubMed, Cochrane, and Embase databases up to November 2024, adhering to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies (12 RCTs and 5 non-RCTs) were analyzed, focusing on LDL-C reduction, safety profiles, and adverse events. The quality of the studies was assessed using checklists to ensure the selection of the best studies and to limit bias. Results: Pitavastatin doses (1-4 mg) reduced LDL-C by 28-47%, comparable to atorvastatin, rosuvastatin, and simvastatin. The 2 mg dose matched atorvastatin's 10 mg dose in efficacy for both short-term (35-42%) and long-term (28-36%) use. LDL-C target achievement rates were 75-95%. Adverse events, including mild myalgia and elevated liver enzymes, were rare, and discontinuation rates were low. Conclusions: Pitavastatin is an effective and safe alternative to traditional statins for dyslipidemia management in Asia. Further research on long-term outcomes and high-risk groups is warranted.

Inclisiran as a siRNA Inhibitor of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); Past, Present, and Future.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C. In 2021, inclisiran, a small interfering ribonucleic acid (siRNA) molecule targeting PCSK9 was approved by the Food and Drug Administration (FDA). Inclisiran has demonstrated effective reductions of LDL-C, such as in the large phase-3 ORION-9, ORION-10, and ORION-11 trials in which it achieved LDL-C reductions of 39.7%, 52.3%, and 49.9%, respectively. This review discusses the current clinical evidence and ongoing clinical studies of inclisiran as well as analyzes other areas of PCSK9 inhibition development.

Effect of Statins on the Prognosis After Thoracic Endovascular Aortic Repair for Patients With Acute Type B Aortic Dissection.

To analyze the clinical efficacy of long-term statin therapy following thoracic endovascular aortic repair (TEVAR) in patients with acute type B aortic dissection (ATBAD). We retrospectively analyzed data from 645 patients treated between January 2005 and June 2022, dividing them into Statin Group (n=330) and Non-statin Group (n=315) based on whether they received long-term postoperative statin therapy. Patients were further categorized based on median admission low-density lipoprotein cholesterol (LDL-C) levels into High and Low LDL-C Groups to assess the effect of statins on the prognosis of ATBAD patients after TEVAR. The cohort had an average age of 53.44±11.42 years old, and 81.71% were male. Statin therapy significantly reduced occurrences of all-cause death (3.03% vs 8.57%, p=0.002) and aorta-related death (0.91% vs 3.81%, p=0.015), particularly in patients with high admission LDL-C levels. In addition, patients with statin therapy had a lower incidence of aorta-related adverse events (ARAE) (4.24% vs 11.11%, p=0.001). Kaplan-Meier analysis indicated statins reduced 5-year cumulative incidence rates of all-cause death and ARAE (all Log-rank p<0.05). These trends were sustained after adjustment. Multivariate Cox analysis confirmed that statin therapy was associated with reduced risks of all-cause and aorta-related deaths, as well as ARAE. Long-term statin therapy appears to decrease the risk of all-cause and aorta-related death in ATBAD patients after TEVAR, particularly patients with high admission LDL-C levels. Patients with lower LDL-C levels at admission have a reduction of aorta-related death in the follow-up period. Statin therapy also was associated with a lower incidence of ARAE in follow-up. These findings suggest that statins might be crucial in improving long-term outcomes in this patient population. Long-term statin therapy administered to patients with acute type B aortic dissection (ATBAD) following thoracic endovascular aortic repair (TEVAR) demonstrates a substantial reduction in both all-cause and aorta-related mortality. Notably, this therapeutic benefit is most evident in patients presenting with elevated low-density lipoprotein cholesterol (LDL-C) levels at admission. Furthermore, statin therapy is associated with a decreased incidence of aorta-related adverse events during follow-up. These findings underscore the pivotal role of statin therapy in enhancing long-term clinical outcomes for ATBAD patients undergoing TEVAR, thereby contributing to improved patient care and prognosis.

Glucagon-like peptide 1 receptor agonists modestly reduced low-density lipoprotein cholesterol and total cholesterol levels independent of weight reduction: a meta-analysis and meta-regression of placebo controlled randomized controlled trials

Background The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on lipid components are unclear. We aim to quantify the lipid lowering effects of GLP1-RAs. Methods A comprehensive database search for placebo-controlled randomized controlled trials (RCTs) on GLP-1RA treatment was conducted until January 2023. Data extraction and quality assessment were performed, and outcomes were analyzed using a random-effects model to calculate weighted mean differences (MDs) in milligrams per deciliter (mg/dl) and 95% confidence intervals (CIs). The primary endpoint was the mean difference in low-density lipoprotein cholesterol (LDL-C). Secondary endpoints included total cholesterol (TC), triglycerides, high density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). Subgroup analyses and meta-regression accounted for covariates. Results GLP-1RAs modestly reduced LDL-C (MD −2.93, 95% CI (-5.01, −0.85), p = 0.01), consistent across treatment durations: ≤12 weeks (MD: −5.39, 95% CI (-10.36, −0.42), p = 0.03) and >12 weeks (MD: −2.39, 95% CI (-4.70, −0.007), p = 0.04). GLP-1RA reduced TC by ∼7 mg/dl. There was no significant reduction in triglycerides (MD = −7.19, 95% CI (-15.01, 0.62), p = 0.07) or VLDL-C (MD = −3.99, 95%, CI (-8.73, 0.75), p = 0.10). GLP-1RA did not increase HDL-C (MD = −0.12, 95% CI (-0.73, 0.49), p = 0.69). Weight change did not influence LDL-C (tau2 = 28.38, I2 = 99.83, R2 = 0.0, p = 0.67) or TC (tau2 = 93.6, I2 = 99.86, R2 = 0.0, p = 0.92). Conclusion GLP-1RA treatment modestly decreased LDL-C and TC but did not significantly affect triglycerides, VLDL-C, or HDL-C.

On-Target Low-Density Lipoprotein Cholesterol in Adults with Diabetes Not at High Cardiovascular Disease Risk Predicts Greater Mortality, Independent of Early Deaths or Frailty.

Background/Objectives: Lowering low-density lipoprotein cholesterol (LDL-C) to <70 mg/dL is recommended for most patients with diabetes. However, clinical trials investigating subjects with diabetes who are not at high cardiovascular risk are inconclusive regarding the all-cause mortality benefit of the current target, and real-world studies suggest greater mortality. We aimed to assess the all-cause mortality at different LDL-C levels among subjects with diabetes not at high risk and to examine the potential roles of early deaths and frailty for this greater mortality. Methods: We followed 2098 such participants of the ELSA-Brasil cohort between 2008 and 2019. Results: Over 10.3 (1.4) years of follow-up, 204 (9.7%) individuals died. In the proportional hazards models, participants with LDL-C values < 100 mg/dL and <70 mg/dL had greater adjusted mortality compared to those with LDL-C 100-129 mg/dL (HR = 1.67; 95%CI 1.21-2.30 and HR = 2.27; 95%CI 1.51-3.41, respectively). Increased risk when LDL-C was <100 mg/dL was higher in those >60 years (HR = 2.12; 95%CI 1.35-3.34) and greatest for deaths due to cancer (HR = 2.55; 95%CI 1.10-5.91). Further analyses for those with LDL-C < 100 mg/dL that excluded early deaths and adjusted for the frailty phenotype (HR = 2.01; 1.19-3.41) or frailty index (HR = 1.92; 1.17-3.16) did not materially alter the results. The risk of death across the spectrum of LDL-C was U-shaped, with a nadir at 112.2 mg/dL. Conclusions: The higher risk of all-cause mortality in these subjects with LDL-C within currently recommended levels was not explained by early deaths or frailty. Given the recent decline in cardiovascular mortality and the increased risk of cancer and infections in persons with diabetes, the clinical significance of low LDL-C in diabetes requires reconsideration and the definition of LDL-C treatment targets in diabetes warrants further trial evaluation.

Current and emerging PCSK9-directed therapies to reduce LDL-C and ASCVD risk: A state-of-the-art review.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Lowering low-density lipoprotein cholesterol (LDL-C) levels is a primary strategy to reduce ASCVD risk. Although statin therapy remains the initial therapy of choice to reduce LDL-C and ASCVD risk, statin intolerance and suboptimal LDL-C lowering response prompts the need for additional non-statin therapies. Ezetimibe and bempedoic acid are reasonable options but they modestly reduce LDL-C levels (15% to 25%). Therapies directed at the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, however, reduce LDL-C levels by 50%-60% when added to background statin therapy. PCSK9 is an enzyme synthesized by the liver that facilitates the degradation of LDL receptors and prevents their recycling to the hepatocyte surface to remove LDL-C from circulation. Approaches to inhibit this effect have centered on monoclonal antibodies (mAbs) (alirocumab, evolocumab) targeting PCSK9 functionality and small interfering RNA (siRNA) therapies (inclisiran) targeting the hepatic synthesis of PCSK9. Randomized controlled trials have demonstrated beneficial cardiovascular outcomes of PCSK9 mAbs, but such evidence is not yet available for inclisiran. Current clinical practice guidelines generally recommend PCSK9-directed therapies for higher-risk patients with established ASCVD and those with familial hypercholesterolemia. This approach is, in part, due to their cost and uncertain economic value, but also because these therapies require subcutaneous administration, which is not preferred by some patients. Oral therapies targeting PCSK9 are, however, in development. This scoping review covers the development of current and emerging PCSK9-directed therapies, their efficacy, safety, and role in clinical practice.

Dyslipidemia in severe fever with thrombocytopenia syndrome patients: A retrospective cohort study.

Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressive infectious disease triggered by a novel bunyavirus (SFTSV). Despite the critical role of host lipid metabolism in viral infections, research on dyslipidemia in SFTS remains limited. This retrospective study included 433 SFTS patients, who were stratified into survival group (n = 365) and death group (n = 68) and who were treated at the Shandong Public Health Clinical Center from September 2021 to December 2023. Additionally, 96 healthy controls with matching baseline characteristics were included from Shandong Provincial Hospital. Cross-sectional analysis based on admission data and longitudinal analysis over time were employed to survey the correlation between serum lipid profiles and mortality in SFTS patients. SFTS patients exhibited elevated triglyceride (TG) levels and reduced total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels compared to healthy individuals. Cross-sectional analysis demonstrated that lower LDL-C and apolipoprotein-B (ApoB) levels were related to elevated mortality risk in SFTS patients. Longitudinal analysis demonstrated that LDL-C and ApoB levels remained consistently lower in the death group, while TG levels gradually declined, and HDL-C levels gradually increased as the disease progressed. SFTS patients exhibit significant dyslipidemia compared to healthy individuals. Lower LDL-C and ApoB levels may independently influence mortality in SFTS patients. Elevated TG and reduced HDL-C levels may associate with disease progression.

Evolocumab (Repatha)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform nonbinding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses Evolocumab (Repatha) 140 mg/mL, prefilled syringea and autoinjector, subcutaneous injection 120 mg/mL, automated mini-doser with prefilled cartridge, subcutaneous injection. Indication: Evolocumab is indicated for the reduction of elevated low-density-lipoprotein cholesterol (LDL-C) in adult patients with primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH] and atherosclerotic cardiovascular disease [ASCVD]): as an adjunct to diet and statin therapy, with or without other lipid-lowering therapies, in patients who require additional lowering of LDL-C as an adjunct to diet, alone or in combination with nonstatin lipid-lowering therapies, in patients for whom a statin is contraindicated