Changes In Low-density Lipoprotein Cholesterol Research Articles

Hypercholesterolemia treated with medicinal pad-separated moxibustion: A randomized clinical trial隔药饼灸治疗高胆固醇血症-随机临床试验

ObjectiveTo assess the effect of medicinal pad-separated moxibustion for reducing low-density lipoprotein cholesterol (LDL-C) in the patients with hypercholesterolemia. DesignClinical randomized controlled trial with blinding for outcome assessors and statisticians. SettingDepartment of Acupuncture-Moxibustion and Tuina, Department of Physical examination of the First Affiliated Hospital of Hunan University of Chinese Medicine and three community health centers adjacent to the Hospital and University, from July 2015 to December 2017. Patients60 patients with hypercholesterolemia (elevated LDL-C). InterventionsThe therapeutic lifestyle change (TLC) was provided in both groups.In the experiment group, medicinal pad-separated moxibustion was applied using two groups of acupoints (Group No.1: Jùquē [巨阙CV14], Tiānshū [天枢ST25] and Fēnglóng [丰隆ST40]). Group No.2: Xīnshū [心俞BL15], Gānshū [肝俞BL18] and Píshū [脾俞BL20]) alternatively for 3–5 times a week. In the control group, Simvastatin tablets were administered orally by the patients in accordance with instructions in the medication guides (10 mg/d). Main outcome measuresChange of LDL-C after 12 weeks of treatment compared with the baseline. ResultsAfter 12 weeks of treatment, LDL-C was reduced in both the medicinal pad-separated moxibustion group and the simvastatin group compared with that at baseline (both P < 0.05). The difference on change of LDL-C was not significant between groups (P > 0.05). At week 4 of follow-up, LDL-C was reduced compared with that at baseline in the medicinal pad-moxibustion group (P < 0.05), and the difference on change of LDL-C was significant between groups (P < 0.05). At week 12 of follow-up, the difference on change of LDL-C was not significant when compared with the baseline in each group (both P > 0.05) and between groups (P > 0.05). In comparison with values before treatment, the values of triglyceride (TC) and triacylglycerol(TG) were reduced in both groups (all P < 0.05), while value of high-density lipoprotein cholesterol (HDL-C) was increased in the medicinal pad-separated moxibustion group after 12 weeks of treatment (P < 0.05). The change of TG and HDL-C values were significantly different between groups (both P < 0.05). At week 4 of follow-up, values of TC and TG were lower (both P < 0.05) and HDL-C was higher (P < 0.05) when compared with that at baseline in the medicinal pad-separated moxibustion group; and value of TC was lower and HDL-C higher in the medicinal pad-separated moxibustion group compared with that in the simvastatin group (both P < 0.05). At week 12 of follow-up, compared with that at baseline, all blood lipid outcomes were not significantly different either within (P > 0.05) or between groups (P > 0.05). ConclusionMedicinal pad-separated moxibustion could reduce LDL-C and increase HDL-C in patients with hypercholesterolemia. However, these results need to be further verified by study with large sample size. Trial registrationClinicaltrials.gov NCT02269046.

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.

The effect of anti TNF alpha (certolizumab) treatment on insulin resistance, lipid parameters and cardiovascular risk in patients with axial spondyloarthritis (ankylosing spondylitis)

Objectives: To evaluate the effects of certolizumab treatment on insulin resistance (IR), lipid parameters, and cardiovascular (CV) risk in patients with ankylosing spondylitis (AS).&#x0D; Methods: This prospective study included 80 consecutive patients with AS (52 males, 28 females) and 74 control subjects (48 males, 26 feemales). The AS patients and control group were compared in respect of basal values. All AS patients with active disease were treated with certolizumab. Biochemical profiles were obtained before and after 24 weeks of certolizumab treatment. Homeostatic model assessment-insulin resistance (HOMA-IR) was used to measure IR and the quantitative insulin sensitivity control index (QUICKI) was used to measure insulin sensitivity. The Framingham equation was used to evaluate CV risk factors.&#x0D; Results: A statistically significant increase was determined in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) values after 24 weeks of certolizumab treatment. No statistically significant change was determined in the plasma atherogenic index (PAI) and low-density lipoprotein cholesterol (LDL-C) values. A statistically significant decrease was determined in HOMA-IR and an increase in QUICKI. When the Framingham risk scoring was compared with the baseline values, a statistically significant decrease in risk was found at week 24.&#x0D; Conclusions: Certolizumab therapy was associated with a significant increase in HDL-C, TC, and TG levels without any significant change in PAI and LDL-C, and was determined to increase insulin sensitivity and lower insulin resistance. There was also a significant reduction in SBP and 10-year Framingham risk scores at 24 weeks after the start of certolizumab therapy.

Importance of Dendrobium officinale in improving the adverse effects of high-fat diet on mice associated with intestinal contents microbiota.

A growing body of evidence suggests that the disturbance of intestinal microbiota induced by high-fat diet is the main factor causing many diseases. Dendrobium officinale (DO), a medicinal and edible homologous Chinese herbal medicine, plays essential role in regulating intestinal microbiota. However, the extent of DO on the intestinal contents microbiota in mice fed with a high-fat diet still remains unclear. Therefore, this study explored the role of intestinal contents microbiota in the regulation of adverse effects caused by high-fat diet by DO from the perspective of intestinal microecology. Twenty-four mice were randomly distributed into the normal saline-treated basal diet (bcn), normal saline-treated high-fat diet (bmn), 2.37 g kg−1 days−1 DO traditional decoction-treated high-fat diet (bdn) and 1.19 g kg−1 days−1 lipid-lowering decoction-treated high-fat diet (bjn) groups for 40 days. Subsequently, we assessed the changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) levels, and the characteristics of intestinal contents microbiota. Results demonstrated that DO exerted the modulating effect on the changes in body weight, TG, TC, LDL-C, and HDL-C levels. Besides, DO decreased the richness and diversity of intestinal contents microbiota, and altered the structure as a whole. Dominant bacteria, Ruminococcus and Oscillospira, varied significantly and statistically. Moreover, DO influenced the carbohydrate, amino acid, and energy metabolic functions. Furthermore, Ruminococcus and Oscillospira presented varying degrees of inhibition/promotion of TG, TC, LDL-C, and HDL-C. Consequently, we hypothesized that Ruminococcus and Oscillospira, as dominant bacteria, played key roles in the treatment of diseases associated with a high-fat diet DO.

Associations Between the Modified Food Standard Agency Nutrient Profiling System Dietary Index and Cardiovascular Risk Factors in an Elderly Population.

BackgroundHelping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure.Materials and MethodsDietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55–75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models.ResultsCompared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (β coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown.ConclusionThis prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure.

Metal mixtures with longitudinal changes in lipid profiles: findings from the manganese-exposed workers healthy cohort

The majority of epidemiological investigations on metal exposures and lipid metabolism employed cross-sectional designs and focused on individual metal. We explored the associations between metal mixture exposures and longitudinal changes in lipid profiles and potential sexual heterogeneity. We recruited 250 men and 73 women, aged 40years at baseline (2012), and followed them up in 2020, from the manganese-exposed workers healthy cohort. We detected metal concentrations of blood cells at baseline with inductively coupled plasma mass spectrometry. Lipid profiles were repeatedly measured over 8years of follow-up. We performed sparse partial least squares (sPLS) model to evaluate multi-pollutant associations. Bayesian kernel machine regression was utilized for metal mixtures as well as evaluating their joint impacts on lipid changes. In sPLS models, apositive association was found between manganese and change in total cholesterol (TC) (beta = 0.169), whilea negative association was observed between cobalt (beta = - 0.134) and change in low density lipoprotein cholesterol (LDL-C) (beta = - 0.178) among overall participants, which were consistent in men. Interestingly, rubidium was positively associated with change in LDL-C (beta = 0.273) in women, while copper was negatively associated with change in TC (beta = - 0.359) and LDL-C (beta = - 0.267). Magnesium was negatively associated with change in TC (beta = - 0.327). We did not observe the significantly cumulative effect of metal mixtures on lipid changes. In comparison to other metals, manganese had a more significant influence on lipid change [groupPIP (0.579) and conditionalPIP (0.556) for TC change in men]. Furthermore, male rats exposed to manganese (20mg/kg) had higher levels of LDL-C in plasma and more apparent inflammatory infiltration, vacuolation of liver cells, nuclear pyknosis, and fatty change than the controls. These findings highlight the potential role of metal mixtures in lipid metabolism with sex-dependent heterogeneity. More researches are needed to explore the underlying mechanisms.

Effect of empagliflozin on plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with type 2 diabetes

AimCardiovascular benefits of sodium-glucose cotrasporter-2 (SGLT2) inhibitors occur despite a modest increase in low-density lipoprotein cholesterol (LDL-c). We tested whether the effects of chronic SGLT2 inhibition on lipid profile composition are mediated by elevation in plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels inhibiting LDL clearance. Methods78 patients with type 2 diabetes (T2D) received empagliflozin 25 mg/d in an open-label design. At enrollment and after 4-week therapy, fasting blood samples were collected for the measurement of plasma PCSK9, glucose, total and fractional cholesterol, and triglycerides. ResultsPlasma PCSK9 was not significantly affected by empagliflozin (−10.7 [−24.1, 2.7] ng/mL). The treatment induced a mild increase in high-density lipoprotein cholesterol (+1.7 [0.5, 3.0] mg/dL), without significant LDL-c alterations (+1.0 [−4.1, 6.0] mg/dl). Changes in LDL-c were associated with changes in fasting glucose levels (β = 0.320, p = 0.017), but not with plasma PCSK9 (β = 0.010, p = 0.800), after adjustment for age, sex, baseline LDL-c, and body weight change. ConclusionIn patients with T2D, chronic SGLT2 inhibition with empagliflozin has no potentially harmful effects on circulating PCSK9 levels. This finding does not support a pathogenetic role of plasma PCSK9 in the mild plasma lipid alterations observed during SGLT2i treatment.

A Randomized Study to Evaluate the Effect of an Inclisiran First Implementation Strategy vs Usual Care in Patients with ASCVD and Elevated Low-density Lipoprotein Cholesterol: Rationale and Design of the VICTORION-INITIATE Trial

Lead Author's Financial Disclosures Nothing to disclose. Study Funding Novartis Pharmaceuticals Corporation, East Hanover, NJ. Background/Synopsis Most patients with atherosclerotic cardiovascular disease (ASCVD) have elevated low-density lipoprotein cholesterol (LDL-C). Compared to placebo, inclisiran has been shown to be safe, tolerable, and effective at reducing LDL-C in patients with ASCVD. It is unknown whether an inclisiran first strategy compared to usual care (allowing for changes in lipid-lowering therapy to mimic routine clinical decision-making) can improve LDL-C control in patients with ASCVD when inclisiran is added to statin therapy. Objective/Purpose Describe the rationale and design of the ongoing VICTORION-INITIATE (NCT04929249) trial. Methods VICTORION-INITIATE is a phase 3, randomized, 2-arm, parallel-group, open-label, U.S.-based trial assessing the efficacy of an inclisiran first strategy vs usual care to treat ASCVD. Patients in the inclisiran arm will receive both inclisiran and maximally tolerated statin therapy immediately upon failure to reach LDL-C less than 70 mg/dL with statins alone. Patients in the usual care arm will continue to receive maximally tolerated statin therapy and may receive other non-statin therapies per usual care. Sites were selected based on geography, population, and lipid management practices. The trial will enroll ∼444 patients (aged greater than or equal to 18 years) with established ASCVD and elevated LDL-C (greater than or equal to 70 mg/dL) or non-high-density lipoprotein cholesterol (greater than or equal to 100 mg/dL) despite receiving maximally tolerated statin therapy, fasting triglycerides less than 500 mg/dL, and an estimated glomerular filtration rate greater than 30 mL/min. The study has 6 planned visits over 330 days from screening to completion. Results Primary outcomes are percent change from baseline in LDL-C and proportion of patients discontinuing statins during the 330-day trial. Key secondary outcomes include the proportion of patients achieving prespecified LDL-C targets, proportion of patients achieving greater than or equal to 50% LDL-C reductions, absolute and time-averaged changes in LDL-C, changes in other lipids, changes in and adherence to ongoing lipid-lowering therapy, visit-to-visit variability in LDL-C, and inclisiran safety and tolerability. Conclusions VICTORION-INITIATE is ongoing and planned to complete in early 2023. This trial aims to determine the efficacy of adding inclisiran first when maximally tolerated statin therapy fails to achieve LDL-C less than 70 mg/dL in those with ASCVD. Nothing to disclose.

Associations of Two Common Polymorphisms in MTHFR Gene with Blood Lipids and Therapeutic Efficacy of Simvastatin.

Cardio-cerebrovascular disease is an important public health challenge worldwide, and its complex etiology has not been elucidated fully. The study investigated the relationship between two common polymorphisms, C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, baseline lipids and the lipid-lowering efficacy of simvastatin in a Chinese hyperlipidemic population. All participants were recruited from Anhui, China. By the extreme sampling method, we selected subjects with a low response (n=108) and high response (n=106) based on their adjusted lipid-lowering response to simvastatin administrated for 8 consecutive weeks. Both MTHFR C677T and A1298C loci were genotyped by the MALDI-TOF MS platform. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured at baseline and after 8 weeks of oral 20 mg/d tablets of simvastatin. Patients with the 677TT genotype had significantly higher baseline TC, HDL-C, and change in HDL-C (ΔHDL-C) levels after treatment than those with 677CC+CT genotypes (β = 0.207, P = 0.045; β = 0.182, P = 0.026; and β = 0.16, P = 0.002, respectively). Patients with 1298AC+CC genotypes had significantly higher baseline LDL-C and change in LDL-C (ΔLDL-C) levels (β = 0.276, P =0.043; β = 0.359, P = 0.025, respectively) than those with 1298AA genotype. We found statistical interactions between the two SNPs in association with baseline HDL-C (P for interaction = 0.034), TC (P for interaction = 0.069), and TG (P for interaction = 0.034). Baseline TC (P = 0.027) and HDL-C (P = 0.046) and change in HDL-C (P = 0.019) were different among those with the MTHFR A-T haplotype compared with A-C. Our major findings suggest that both MTHFR C677T and A1298C polymorphisms could be important genetic determinants of lipid traits and drug efficacy of simvastatin. This will contribute to a better understanding of strategies for personalized medication in Chinese patients with dyslipidemia.

Correlation between Vitamin D3 Supplementation and Lipidemia in Women of Maysan Province, Iraq with Uncontrolled Type 2 Diabetes

A total of 130 overweight Iraqi women with uncontrolled type 2 diabetes, the ages of the women ( 28 to 60) years, were divided into groups, group 5000 IU (65 women) as group A and control (65 women) as group B. were participants from The Specialized Center for Diabetes in Maysan Province and its related areas in the countryside and the city for this double-blind, randomized control trial (Maysan Province, Iraq). A placebo and 5000 IU of D3 daily were given to the participants for four months. Laboratory tests were conducted at baseline and four months to analyze serum levels. After four months of treatment, positive changes in total cholesterol, D3 levels, and LDL cholesterol. There was no statistically meaningful change in HDL and TG concentration, and there were no significant differences in age and place of residence. According to this study, vitamin D may help type 2 diabetics lower their total cholesterol and LDL concentrations.

Combined lipid goal attainment in patients with type 2 diabetes and dyslipidemia: A head-to-head comparative trial of statins.

This study compared the efficacy of two statin treatments (simvastatin vs rosuvastatin) in achieving the combined goal of low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/L and non-high-density lipoprotein cholesterol (non-HDL-C) <3.4 mmol/L in patients with type 2 diabetes and dyslipidemia. After a 5-week run-in, 89 patients with type 2 diabetes having fasting triglyceride (TG) levels of 1.7 to 5.7 mmol/L or non-HDL-C levels of 3.4 to 5.2 mmol/L were randomized to receive simvastatin 20 mg daily for 4 weeks followed by 40 mg for 8 weeks or rosuvastatin 10 mg for 4 weeks followed by 20 mg for 8 weeks. The primary end-point was the percentage of patients achieving the combined goal at week 12. Although significant between-group differences were observed in changes in LDL-C and non-HDL-C levels, both study treatments were sufficiently intensive for a 40% to 55% LDL-C reduction. At the end of the study, the two groups had similar percentages of patients who achieved the combined lipid goal (84% vs 89%, p = 0.66). All patients who attained the combined lipid goal also met the apolipoprotein B (Apo-B) target of <0.9 g/L. No between-group differences were noted in changes in HDL-C and TG levels at week 12. The patients tolerated both treatments well. In our study, ≈85% of patients with type 2 diabetes and dyslipidemia could achieve the combined lipid goal with statin monotherapy. The two statin treatments could sufficiently control diabetic dyslipidemia (NCT00506961).

The Efficacy of Ganoderma lucidum in Overweight Individuals: A Randomized Placebo-controlled trial

BACKGROUND: There are growing interests in the use of medicinal mushrooms in controlling overweight and obesity. OBJECTIVE: The aim of the present study was to assess the effect of Lingzhi on anthropometric indices, fasting blood sugar, lipid profile and blood pressure of overweight individuals METHODS: This randomized double-blind clinical trial was performed on seventy-two overweight individuals (Body Mass Index (BMI) = 25–29.9 kg/m2) received 3 capsule Ganoderma Lucidum (each capsule containing 220 mg of whole powder and 30 mg of pure aqueous extract) daily or matching placebo for 6 weeks. Anthropometric indices, metabolic tests (fasting blood sugar (FBS) and serum lipid profile) and blood pressure were measured before and after treatment. RESULTS: Data analyses indicated that body weight and BMI were decreased after 6-week intervention (P &lt; 0.05). The beneficial effect of supplementation was evident on some anthropometric indices. Changes in LDL-cholesterol were significantly different between two treatment and placebo groups (P &lt; 0.05). FBS, other components of lipid profile and blood pressure did not significantly change by Lingzi treatment. CONCLUSIONS: Results showed that Ganoderma Lucidum might have some potential benefits on anthropometric indices and mild effects on lipid profile, but and there is no claim for weight lose function. Hence, further long-term studies are recommended.

PCSK9 inhibitors safely and effectively lower LDL after heart transplantation: a systematic review and meta-analysis.

Coronary allograft vasculopathy (CAV) continues to afflict a high number of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT; however, data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. A total of six studies including 97 patients were included. Over a mean follow-up of 13months (range 3-21), PCSK9i use lowered LDL by 82.61mg/dL (95% CI - 119.15 to - 46.07; I2 = 82%) from baseline. Serious adverse drug reactions were rarely reported, and none was attributable to the PCSK9i therapy. Four studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. One study reported on immunologic safety, showing no DSA development within 1month of therapy. Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.

Safety and efficacy of inclisiran in South African patients at high cardiovascular risk: A subanalysis of the ORION phase III clinical trials

Background. Inclisiran significantly reduced low-density lipoprotein cholesterol (LDL-C) in individuals with heterozygous familial hypercholesterolaemia, established atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalents (type 2 diabetes, familial hypercholesterolaemia or a 10-year risk of a cardiovascular event ≥20%) in the ORION phase III clinical trials. Infrequent dosing at days 1, 90, 270 and 450 resulted in a mean LDL-C reduction of ~50%. A total of 298 participants from South Africa (SA) were enrolled. Local data are needed to support the use of inclisiran in the SA population, potentially addressing an unmet need for additional LDL-C-lowering therapies. Objectives. To analyse the ORION phase III trial data to assess the efficacy and safety of inclisiran in SA participants. Methods. ORION-9, 10 and 11 were randomised, double-blind, phase III trials. Participants were receiving maximally tolerated statins with or without other lipid-lowering therapies (excluding protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors). Participants were randomised 1:1 to inclisiran sodium 300 mg/284 mg (free acid) or placebo administered at days 1, 90, 270 and 450. The co-primary endpoints were the LDL-C percentage change from baseline to day 510 and the time-averaged percentage change in LDL-C from baseline after day 90 up to day 540. Key secondary endpoints included the absolute change in LDL-C from baseline to day 510, the time-averaged absolute change from baseline after day 90 up to day 540, and changes in other lipids and lipoproteins. Results. The mean age of the participants was 58.6 years (56% male). The mean LDL-C level at baseline was 3.6 mmol/L. At day 510, inclisiran reduced LDL-C levels by 54.2% compared with placebo (95% confidence interval (CI) –61.3 - –47.2; p&lt;0.0001). The corresponding time-averaged reduction in LDL-C was 52.8% (95% CI –57.9 - –47.8; p&lt;0.0001). Treatment-emergent adverse events at the injection site were more common with inclisiran compared with placebo (10.1% v. 0.7%); however, all were mild or moderate in nature and none were persistent. Conclusion. Inclisiran, given in addition to maximally tolerated standard lipid-lowering therapy, is effective and safe and results in robust reductions in LDL-C in SA patients at high cardiovascular risk.

The Effect of Different Vegetarian Diets on Cardiometabolic Profile in People With or At High Risk of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

ObjectivesThis systematic review and meta-analysis assesses the effect of various vegetarian diets on cardiometabolic risk factors (systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c)) in people with cardiovascular diseases (CVDs) or people with at least two risk factors of CVDs. MethodsWe performed systematic searches in EMBASE, MEDLINE, CINAHL and CENTRAL, from inception until 31st July 2021 for randomised controlled trials of vegetarian diet interventions in people with CVDs or people with at least two risk factors (e.g. being overweight, high blood pressure, high total cholesterol/LDL-C, high blood glucose) of CVDs. Trials had to use a non-vegetarian diet as the comparison diet and measure at least one of these outcomes: LDL-C, HbA1c and SBP. We extracted demographics, study design, sample size, and diet description of intervention and control group from included studies. We assessed the risk of bias of studies using the Cochrane Risk of Bias Assessment Tool 2.0. A random-effects model was used to assess mean changes in LDL-C, HbA1c, SBP and body weight. We evaluated the overall certainty of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) tool. ResultsOf the 7871 records screened, 29 (20 studies) met our inclusion criteria. Four studies targeted people with CVD, seven focused on people with type 2 diabetes mellitus and the remaining included people with at least two risk factors of CVDs. Meta-analyses showed that consuming vegetarian diets for at least 12 weeks significantly decreased LDL-C, HbA1c, and weight, by 6.8mg/dL (95%CI: –10.7, –3.0), 0.25% (95%CI: –0.43, –0.06), 3.4kg (95%CI: –4.6, –2.2), respectively, but the effect on SBP was not significant (–0.1 mmHg, 95%CI: –2.8, 2.6). The GRADE assessment showed a moderate level of evidence for LDL-C and HbA1c reduction. ConclusionsConsuming vegetarian diets causes a moderate improvement of LDL-C, HbA1c and body weight in people at high risk of CVD, highlighting the protective effects of vegetarian diets in the primary prevention of CVD. Additional high-quality clinical trials are warranted to further explore the effect of this diet in people with CVD. Funding SourcesAuthors are supported by the Australian NHMRC Investigator Grant, Australian Youth and Health Foundation and Philip Bushell Foundation.

Low-density lipoprotein cholesterol increased significantly after short-term discontinuation of atorvastatin, but did not correlate with plasma drug concentrations

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Dam foundation Introduction Statin non-adherence remains a prevalent challenge in cardiovascular disease prevention and robust methods to monitor adherence are needed. Large variations in low-density-lipoprotein cholesterol (LDL-C) response to a given type and dose of statin have been reported. The LDL-C response to short-term discontinuation of statins is not well defined. Moreover, the relationship between the blood concentrations of statin metabolites and LDL-C, and how clinical factors interact, are unknown. Purpose To determine changes in LDL-C at an individual and group level during four-day discontinuation of atorvastatin, and to investigate whether clinical factors and atorvastatin metabolites concentration correlate with changes in LDL-C. Methods This clinical pharmacokinetic adherence study conducted in 2021, included 60 adult participants treated with atorvastatin 20 mg (n=20), 40 mg (n=20) or 80 mg (n=20). The participants were instructed to take atorvastatin daily between 07 and 10 am the week before study start, to ensure steady state drug concentrations. The last dose of atorvastatin was taken 24 hours prior to the first blood sampling (day zero). Atorvastatin doses were omitted until after blood sampling on the fourth day. The concentrations of atorvastatin metabolites (acid and lactone forms, including 2-OH- and 4-OH metabolite) were measured by a liquid chromatography–tandem mass spectrometry assay. Paired-samples T-tests, Spearman rank correlations and linear regression analyses were performed with SPSS. Results Mean age was 65 (SD 11) years, 18 (30%) were female, 45 (75%) had cardiovascular disease and 11 (18%) had diabetes mellitus. Mean LDL-C at steady state on day zero was 1.9 (SD 0.6) mmol/L. LDL-C increased on average by 0.5 (SD 0.3) mmol/L (30%) from day zero to day four, during the period with atorvastatin discontinuation. The increase of LDL-C was significant already after the first omitted dose (day one) (Figure 1). LDL-C increased from day zero to day four in 78 out of the 80 patients (97.5%). Higher Body Mass Index was significantly associated with lager increase in LDL-C during the four-day discontinuation (B 0.02, 95% CI 0.01 to 0.04, p=0.028), whereas age, sex, kidney function, cardiovascular disease and diabetes were not. Changes in atorvastatin plus metabolites concentration from day zero to day four were not associated with changes in LDL-C during discontinuation (Figure 2). This also applied if we assessed the individual atorvastatin metabolites. Conclusion Atorvastatin discontinuation for only four days resulted in a statistically significant 30% increase of LDL-C. Atorvastatin pharmacokinetics did not correlate with change in LDL-C during the discontinuation. Even short-term non-adherence may have unfavourable consequences, and deserves further attention.

A COMPARATIVE STUDY OF HOMOCYSTEINE, CYANOCOBALAMINE, FOLATE, LIPID PROFILE AND SERUM CREATININE LEVEL IN HYPERTHYROID SUBJECTS BEFORE AND DURING TREATMENT

Introduction: Hyperthyroidism disorder results from over production of hormones secreted by thyroid gland itself. The present study plan to delineate influence of thyroxin on homocysteine, folate, cyanocobalamine, lipid profile and serum creatinine in hyperthyroid patients before and during treatment with antithyroid drugs. Material and Method: The present study was conducted on 75 pateints of hyperthyroidism of either sex in department of biochemistry, J.L.N. medical college and hospitals, Ajmer. Serum homocysteine, cyanocobalamine, folate level was measured by ELISA while thyroid function test were evaluated by RIA method. Result and discussion: There were significant change in homocysteine, folate, cyanocobalamine, total cholesterol, HDL-cholesterol and LDL-cholesterol in hyperthyroid subjects before and during treatment (P&lt;0.0001) and these emerging evidence suggest that these parameter are influenced by level of thyroxine hormone which were higher in hyperthyroid subjects before treatment with antithyroid drugs. Conclusion: It is concluded that treatment with antithyroid drug reduces the level of thyroxine hormone in hyperthyroid subject increases level of homocysteine and causes dyslipidemia which increases risk of coronary artery disease, angina pectoris in subclinical hyperthyroidism.

PCSK9 Inhibitors Safely and Effectively Lower LDL After Heart Transplantation: A Systematic Review and Meta-Analysis

<h3>Purpose</h3> Coronary allograft vasculopathy (CAV) continues to afflict a majority of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT, however data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. <h3>Methods</h3> We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15^th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. <h3>Results</h3> `A total of six studies including 97 patients were evaluated, most of which either had statin intolerance or refractory hyperlipidemia. Over a mean follow up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI -119.15 to -46.07; <i>I²</i>=82%) (<b>Figure 1</b>) from baseline. Serious adverse drug reactions were rarely reported, and none were attributable to the PCSK9i therapy. Three studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. No studies reported on immunologic safety (i.e. development of DSA), hence this endpoint cannot be assessed. <h3>Conclusion</h3> Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.

Effect of Pelacarsen on Lipoprotein(a) Cholesterol and Corrected Low-Density Lipoprotein Cholesterol

BackgroundLaboratory methods that report low-density lipoprotein cholesterol (LDL-C) include both LDL-C and lipoprotein(a) cholesterol [Lp(a)-C] content. ObjectivesThe purpose of this study was to assess the effect of pelacarsen on directly measured Lp(a)-C and LDL-C corrected for its Lp(a)-C content. MethodsThe authors evaluated subjects with a history of cardiovascular disease and elevated Lp(a) randomized to 5 groups of cumulative monthly doses of 20-80 mg pelacarsen vs placebo. Direct Lp(a)-C was measured on isolated Lp(a) using LPA4-magnetic beads directed to apolipoprotein(a). LDL-C was reported as: 1) LDL-C as reported by the clinical laboratory; 2) LDL-Ccorr = laboratory-reported LDL-C − direct Lp(a)-C; and 3) LDL-CcorrDahlén = laboratory LDL-C − [Lp(a) mass × 0.30] estimated by the Dahlén formula. ResultsThe baseline median Lp(a)-C values in the groups ranged from 11.9 to 15.6 mg/dL. Compared with placebo, pelacarsen resulted in dose-dependent decreases in Lp(a)-C (2% vs −29% to −67%; P = 0.001-<0.0001). Baseline laboratory-reported mean LDL-C ranged from 68.5 to 89.5 mg/dL, whereas LDL-Ccorr ranged from 55 to 74 mg/dL. Pelacarsen resulted in mean percent/absolute changes of −2% to −19%/−0.7 to −8.0 mg/dL (P = 0.95-0.05) in LDL-Ccorr, −7% to −26%/−5.4 to −9.4 mg/dL (P = 0.44-<0.0001) in laboratory-reported LDL-C, and 3.1% to 28.3%/0.1 to 9.5 mg/dL (P = 0.006-0.50) increases in LDL-CcorrDahlén. Total apoB declined by 3%-16% (P = 0.40-<0.0001), but non-Lp(a) apoB was not significantly changed. ConclusionsPelacarsen significantly lowers direct Lp(a)-C and has neutral to mild lowering of LDL-Ccorr. In patients with elevated Lp(a), LDL-Ccorr provides a more accurate reflection of changes in LDL-C than either laboratory-reported LDL-C or the Dahlén formula.

Rationale and design of two trials assessing the efficacy, safety, and tolerability of inclisiran in adolescents with homozygous and heterozygous familial hypercholesterolaemia.

Inclisiran is a small interfering RNA molecule that reduces low-density lipoprotein cholesterol (LDL-C) by inhibition of proprotein convertase subtilisin/kexin type 9. This subcutaneous, twice-yearly administered agent has been shown to effectively and safely lower LDL-C in adult patients with established atherosclerotic cardiovascular disease, adults at high risk for atherosclerotic cardiovascular disease, as well as in adults with heterozygous familial hypercholesterolaemia. With the current, limited treatment options available to reach treatment goals in children with severe heterozygous familial hypercholesterolaemia, homozygous familial hypercholesterolaemia, or statin intolerance, inclisiran could be a valuable new therapeutic option. The objective of these ongoing studies is to investigate the efficacy, safety, and tolerability of inclisiran in adolescents diagnosed with homozygous familial hypercholesterolaemia (ORION-13) or heterozygous familial hypercholesterolaemia (ORION-16). ORION-13 and ORION-16 are both two-part (1-year double-blind inclisiran vs. placebo/1 year open-label inclisiran) multicentre trials including adolescents aged 12 to &lt;18 years diagnosed with familial hypercholesterolaemia. ORION-13 will include ∼12 participants diagnosed with homozygous familial hypercholesterolaemia and ORION-16 will include ∼150 participants diagnosed with heterozygous familial hypercholesteroleamia. The primary endpoint is the percentage change in LDL-C from baseline to Day 330. Secondary efficacy and safety endpoints include changes in other lipid parameters and treatment-emergent adverse events as well as laboratory parameters and vital signs. Exploratory endpoints include individual responsiveness of the participants and change in LDL-C according to the type of underlying causal mutation. https://www.clinicaltrials.gov/. Unique identifier: NCT04659863 (ORION-13) and NCT04652726 (ORION-16).