Changes In Low-density Lipoprotein Cholesterol Research Articles

Nutritional management, skipping breakfast, glycemic control, and cardiovascular risk on type 2 diabetes mellitus

Abstract Background Meal timing is an emerging field that investigates the influence of eating patterns on circadian rhythm and general health. There is still disagreement in the literature as to whether eating windows could impact weight gain and biochemical markers. Purpose 1- Evaluate the impact of nutritional interventions on weight, body mass index (BMI), waist circumference (WC), fasting blood glucose (FG), glycated hemoglobin (HbA1c), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides, systolic blood pressure (SBP), and diastolic blood pressure (DBP), between 0th and 12th month in Type 2 Diabetes Mellitus (T2D); 2-Observe breakfast skipping and sleep disorders, and also analyze the influence of these data with possible changes in anthropometric and biochemical markers. Methods This experimental and observational study recruited 44 participants with T2D. The assessments were carried out in October 2022 and 2023. The nutritional assessment consisted of prescribing a personalized eating plan (Mediterranean diet and DASH). Statistical analysis: For the variables "breakfast habits", "nocturnal awakenings", and "sleep duration", the numbers of participants were converted into percentages of the total number of individuals. Parametric variables were compared using the paired t-test and non-parametric variables were compared by the Wilcoxon test. To evaluate the influence of the habit of eating breakfast and sleep disorders on quantitative variables, variations were calculated between the 0th and 12th month between participants who had or did not have the habit of eating breakfast and had or did not have sleep disorders. Parametric variables were compared using the unpaired t test and non-parametric variables using the Mann-Whitney test. Parametric data were presented as mean ± standard deviation and non-parametric data as median ± interquartile range, both accompanied by the dispersion of all repetitions. α<0.05 and P<0.05 were adopted. Results Significant reductions were found between the 0th and 12th month of FG, HbA1c, LDL-C, triglycerides, SBP, DBP, BMI, WC, and weight (p<0.0001). Regarding breakfast habits, in the 1st month, 77.3% of participants skipped this meal, reducing to 13.6% in the 12th month. For sleep duration, in the 1st month, 90.9% of participants slept less than 6 hours, reducing to 40.9% in the 12th month. For nocturnal awakenings, 70.5% of participants had at least 1 awakening in the 1st month, reducing to 54.5% in the 12th month. For influence analysis, no significant differences were found between changes in FG, HbA1c, LDL-C, triglycerides, SBP, DBP, BMI, WC, and weight on breakfast habit or sleep disorders, except for HDL-C and sleep disorders (p<0.005). Conclusion Nutritional management improved biochemical markers, reduced anthropometric data, regulated the eating window, reduced nocturnal awakenings, and optimized sleep duration in patients with T2D.

Asia-Pacific Real-World Evolocumab Use, LDL-C Reduction, Physician Goals, and Patient Perceptions: HALES Observational Study.

Real-world data are needed to understand the effectiveness of new therapeutic options for low-density lipoprotein cholesterol (LDL-C) reduction in Asia-Pacific clinical practice. Description of evolocumab use among adults with establisHed Atherosclerotic cardiovascuLar diseasE or hypercholesterolemia in ASia-Pacific region (HALES) was performed to better understand characteristics of and clinical decision-making for adults with established atherosclerotic cardiovascular disease/hypercholesterolemia after local evolocumab approval. The HALES observational study, conducted at 33 sites (Hong Kong, Thailand, South Korea, Singapore, Taiwan, and Australia) comprised (1) chart review of patients who received evolocumab, a proprotein convertase subtilisin/kexin type9 inhibitor (PCSK9i), and (2) physician/patient survey and one-time data collection of patients with high cardiovascular risk initiating evolocumab or initiating/continuing non-PCSK9i lipid-lowering therapy. Patients could only enroll in (1) or (2). Chart review included 724 very high-risk patients initiating evolocumab from regulatory approval to 2021. From median baseline LDL-C of 3.2mmol/L (123.7mg/dL), patients had a median percent change in LDL-C of - 60.8% at 1-6months. Goal achievement increased from 7.9% to 69.8% for < 1.8mmol/L (< 70mg/dL) and 4.4% to 57.8% for < 1.4mmol/L (< 55mg/dL) from baseline to 12months. In the one-time data collection, more patients had ≥ 1.8mmol/L (≥ 70mg/dL) baseline LDL-C in the evolocumab vs non-PCSK9i group (95.2% and 48.5%, respectively). Surveys found that physicians applied guideline-recommended treatment targets, and patients demonstrated gaps in understanding cardiovascular risk. Real-world, Asia-Pacific data showed that LDL-C reduction after initiating evolocumab was consistent with that observed in other clinical trials and patient populations. Graphical abstract available for this article.·.

A register-based cohort study on the effectiveness and Safety of anti-PCSK9 treatment in persons with hyperlipidemia.

Dyslipidemia is a known risk factor for cardiovascular disease. While statins are the primary treatment, some individuals require additional lipid-lowering therapies, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Alirocumab and evolocumab have shown efficacy in reducing low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major cardiovascular events (MACE) but have not been directly compared in clinical trials. This study aims to assess the effects of PCSK9 inhibitors on LDL-C levels and evaluate the impact of a mandated switch from alirocumab to evolocumab. Taking advantage of the mandated switch in PCSK9 treatment in Denmark, we conducted a register-based cohort study of 907 individuals with dyslipidemia treated with PCSK9 inhibitors in the Capital Region of Denmark from 2016 to 2022. We analyzed LDL-C levels, treatment retention, and MACE, adjusting for variables such as age, sex, dose, and concurrent lipid-lowering medications. We show that PCSK9 inhibitors treatment resulted in a 49% reduction in LDL-C levels. Following a mandated switch from alirocumab to evolocumab, no significant difference was observed in LDL-C levels or adverse clinical outcomes, including MACE. Treatment discontinuation was most likely within the first 100 days, and no significant difference in discontinuation rates was found between the two drugs. Our study demonstrates that both alirocumab and evolocumab are effective in significantly reducing LDL-C levels in individuals with dyslipidemia. The mandated switch from alirocumab to evolocumab did not result in significant changes in LDL-C or clinical outcomes, suggesting that these treatments can be used interchangeably. These findings support the clinical equivalence of the two PCSK9 inhibitors and may guide therapeutic decisions in lipid management.

Hypercholesterolemia and inflammation-Cooperative cardiovascular risk factors.

Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events.In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation. Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering. Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.

8073 Association Between Serum GDF15 Level And Metabolic Parameters in Severely Obese Men Undergoing Weight Loss From Lifestyle Intervention

Abstract Disclosure: S. Bathina: None. V. Fuenmayor Lopez: None. M. Prado: None. G. Colleluori: None. D.T. Villareal: None. R.C. Villareal: None. Background: Growth Differentiation factor (GDF-15), member of TGF-β superfamily was identified as marker of aging, frailty, and metabolic disorders. Several clinical studies demonstrated an association between GDF15 with obesity and cardiovascular disease. However, information on the changes in GDF15 and its relationship to changes in metabolic and body composition parameters in the population of severely obese subjects undergoing weight loss (WL) remains lacking. Objective: The objective of this study is to evaluate the influence of WL on serum GDF15 level and its relationship to glucometabolic parameters in severely obese hypogonadal men. Method: Data from 116 severely obese (BMI ≥35 kg/m2) hypogonadal men participating in an ongoing clinical trial of WL from lifestyle intervention±anastrozole, aged 35-65 years old (NCT03490513) were analyzed. Hemoglobin A1C (A1C) was measured by HPLC, lipid profile by colorimetric method (except LDL was calculated), testosterone (T) and estradiol (E2) LC-MS and GDF-15 by ELISA. Body composition was measured by DXA. Results: The mean age of the participants was 51.4±7.6 years with mean BMI 41.8 ±5.4 kg/m2. At baseline, serum GDF15 positively correlated with age (r=0.25, p=0.01), fasting blood glucose (r=0.29, p=0.004) and A1C (r=0.39, p&amp;lt;0.001) but no correlation was found for lipid parameters and with T and E2. GDF15 was negatively correlated with total lean mass (r= -0.23, p=0.03), appendicular lean mass (r= -0.30, p=0.02), and fat-free mass (r= -0.22, p=0.03), but positively correlated with visceral adipose tissue volume (r=0.22, p=0.03). Average WL was 4.2±4.7% and 5.8±8.5% at 6months (6M) and 12 months (12M), respectively. Overall GDF15 levels increased by 9.4±84.7% at 6M and 18.4±128.0% at 12M. At 12M, changes in GDF15 levels positively correlated with changes in A1C (r= 0.26, p&amp;lt;0.05), and negatively with changes in total cholesterol ( r= -0.30, p=0.05), Triglycerides (r= -0.35, p=0.02) and E2 (r=-0.31, p=0.028). For LDL cholesterol changes, a negative correlation with GDF15 changes was observed at 6M (r= -0.27, p=0.047). There was no correlation between changes in GDF15 with changes in body weight and changes in body composition parameters. A comparison for those with significant WL (≥5%) vs. those with less WL showed that at 6M, GFD15 levels were reduced among those with WL of ≥5% (-19.5±42.3%) vs &amp;lt;5% (+19.8±93.9%), p=0.07, and at 12M (≥5% (-29.5±38.7) vs &amp;lt;5% (+0.61±69%), p&amp;lt;0.1). Conclusion: We demonstrated that changes in serum GDF15 in severely obese men undergoing WL was associated with alteration in cardiometabolic parameters. Our results show a new perspective on the potential role of GDF15 in cardiometabolic disorders associated with severe obesity. Aside from GDF15 used as a biomarker for health, it may also be used as target for drug development in modifying potential cardiometabolic complications in severe obesity. Presentation: 6/1/2024

Recaticimab Monotherapy for NonfamilialHypercholesterolemia andMixed Hyperlipemia: ThePhase 3 REMAIN-1 Randomized Trial.

Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have been used to reduce the level of low-density lipoprotein cholesterol (LDL-C), but require either biweekly or monthly dosing frequency. Recaticimab is a new humanized monoclonal antibody selectively targeting PCSK9, with long-acting characteristic. The purpose of this study was to assess the efficacy and safety of recaticimab monotherapy in patientswith nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk, and to explore different dosing strategies to provide patients with flexible administration options. This was a randomized, double-blind, placebo-controlled, phase 3 study conducted at 59 sites in China. Patients with fasting LDL-C≥2.6 to<4.9mmol/L, fasting triglyceride≤5.6mmol/L, and 10-year ASCVD risk score<10% were randomly assigned (2:2:2:1:1:1) to receive subcutaneous injections of recaticimab at 150mg every 4weeks (Q4W), 300mg every 8weeks (Q8W), or 450mg every 12weeks (Q12W), or matching placebo, on background lipid-lowering diet. Primary endpoint was percentage change in LDL-C from baseline to week 12 for 150mg Q4W and 450mg Q12W and to week 16 for 300mg Q8W. A total of 703 patients underwent randomization and received recaticimab (n=157, 156, and 155 for 150mg Q4W, 300mg Q8W, and 450mg Q12W, respectively) or placebo (n=78, 79, and 78, respectively). Compared with placebo, recaticimab further reduced LDL-C by 49.6% (95%CI: 44.2%-54.9%) at 150mg Q4W, 52.8% (95%CI: 48.3%-57.2%) at 300mg Q8W, and 45.0% (95%CI: 41.0%-49.0%) at 450mg Q12W (P< 0.0001 for all comparisons). Safety with recaticimab was comparable to placebo. After 12 or 16weeks of treatment, patients who received recaticimab continued treatment until week 24, whereas those allocated to placebo were switched to recaticimab treatment with the same dosing strategy. Both 24-week recaticimab and 12- or 8-week recaticimab switched from placebo were effective. With 24weeks of recaticimab treatment, the most common treatment-related adverse event was injection site reaction (n = 23 [4.9%]). Recaticimab monotherapy yielded significant LDL-C reductions and showed comparable safety vs placebo in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate ASCVD risk, even with an infrequent dosing interval up to Q12W.

6956 Changes in LDL-Cholesterol from 6 Weeks to 12 Months Postpartum in Women with Recent Gestational Diabetes

6956 Changes in LDL-Cholesterol from 6 Weeks to 12 Months Postpartum in Women with Recent Gestational Diabetes

The therapeutic effect of PCSK9 inhibitors on dyslipidemia: one-year follow up.

Despite the availability of statins and lifestyle modifications, many patients with Dyslipidemia struggle to achieve optimal low-density lipoprotein cholesterol (LDL-C) control. PCSK9 inhibitors offer a promising new therapeutic option with superior LDL-C lowering efficacy compared to statins. However, data on their real-world use, particularly in Iran, is limited. This study aims to address this gap by investigating the one-year effects of evolocumab on lipid profiles and potential cardiovascular outcomes in Iranian patients with Familial Hypercholesterolemia (FH).This single-center, prospective study evaluated evolocumab effectiveness in lowering LDL-C in 50 Iranian adults with FH. Participants with a documented LDL-C > 190 mg/dL on existing cholesterol medications (excluding PCSK9 inhibitors) and a clinical FH diagnosis was included. After baseline assessments (medical history, demographics, lipid profile), evolocumab was administered subcutaneously every two weeks for one year. Follow-up assessments at year one measured changes in LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. The study enrolled 50 participants with an average age of 55 years old (range 35-80 years).Treatment with evolocumab led to significant improvements in lipid profiles at all follow-up points compared to baseline. On average, LDL-C levels decreased by 105.24 mg/dL, triglycerides decreased by 59.20 mg/dL, and HDL-C levels increased by a modest but significant 4.5 mg/dL after one year(p<0.001). Subgroup analysis revealed no statistically significant interactions between baseline demographics (age, sex, BMI) or lifestyle habits (smoking, alcohol) and changes in lipid levels(p>0.05). However, a significant interaction emerged between baseline lipid levels and their corresponding reductions, suggesting greater improvement in patients with higher baseline values(p<0.05). It is noteworthy that no new cardiovascular events were reported during the study period. This study demonstrates the effectiveness of evolocumab in improving lipid profiles in Iranian patients with FH. The observed reductions in LDL-C and triglycerides, along with a modest increase in HDL-C, suggest potential benefits for cardiovascular risk reduction. The absence of new cardiovascular events during the study is encouraging, but further research with larger and longer-term follow-up is needed to confirm these findings and assess the long-term safety and impact on quality of life.

Remnant cholesterol, LDL cholesterol, and APOB absolute mass changes explain results of prominent and other fibrate trials

Remnant cholesterol, LDL cholesterol, and APOB absolute mass changes explain results of prominent and other fibrate trials

A UK multicentre audit of the management of patients with primary hypercholesterolaemia or mixed dyslipidaemia with bempedoic acid against published lipid-lowering treatment targets.

Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC) <5 mmol/L and low-density lipoprotein cholesterol (LDL-C) <3 mmol/L or ≥25% reduction in TC and ≥30% reduction in LDL-C) at 12 weeks post-initiation. At week 12, the mean absolute change in LDL-C was -1.0 mmol/L; the mean percentage reduction from baseline was 22.0%. Additionally, 52% (96/185) of patients had an LDL-C of <3 mmol/L and 10% (18/185) an LDL-C of <1.8 mmol/L at 12 weeks (as per JBS3). This audit highlights the role of bempedoic acid as part of combination therapy for a population with previously limited treatment options.

Influence of Dapagliflozin Dosing on Low-Density Lipoprotein Cholesterol in Type 2 Diabetes Mellitus: A Systematic Literature Review and Meta-Analysis.

A systematic literature review and meta-analysis was performed to evaluate the effects of dapagliflozin on low-density lipoprotein (LDL) cholesterol in type 2 diabetes mellitus. Data on changes in LDL cholesterol, adverse cardiac events (ACEs), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were pooled in a meta-analysis. Data from dose comparison trials were separately pooled, and meta-analysis was conducted by using RevMan (5.4.1) and R (4.1.2). Dapagliflozin increased LDL cholesterol by 2.33 mg/dL (95% CI, 1.46 to 3.19; I2 = 0%; P <.00001), increased risk of ACEs by 1.56 (95% CI, 1.02 to 2.39; I2 = 0%; P <.04), decreased HbA1c by -0.41% (95% CI, -0.44 to -0.39; I2 = 85%; P <.00001), and decreased FBG by -13.51 mg/dL (95% CI, -14.43 to -12.59; I2 = 92%; P <.00001) versus any placebo or active comparator. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 1.71 mg/dL (95% CI, -1.20 to 4.62; I2 = 53%; P =.25) versus a 5 mg dose and by 1.04 mg/dL (95% CI, -1.17 to 3.26; I2 = 62%; P =.36) versus a 2.5 mg dose. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 3.13 mg/dL (95% CI, 1.31 to 4.95; I2 = 0%; P =.0008), increased the risk of ACEs by 1.26 (95% CI, 0.56 to 2.87; I2 = 0%; P =.58), decreased HbA1c by -0.4% (95% CI, -0.45 to -0.35; I2 = 89%; P <.00001), and decreased FBG by -8.39 mg/dL (95% CI, -10 to -6.77; I2 = 96%; P <.00001) versus a placebo or active comparator. Dapagliflozin monotherapy resulted in a minimal but statistically significantly (P =.0002) increase in LDL cholesterol. However, this minor change does not increase the risk of ACEs (P =.17) when compared with placebo or active comparator.

Rationale, Design and Baseline Characteristics of a Randomized Controlled Trial of a Cardiovascular Quality Improvement Strategy in India: The C-QIP Trial

BackgroundQuality of chronic care for cardiovascular disease (CVD) remains suboptimal worldwide. The Collaborative Quality ImProvement (C-QIP) trial aims to develop and test the feasibility and clinical effect of a multicomponent strategy among patients with prevalent CVD in India. MethodsThe C-QIP is a clinic-based, open randomized trial of a multicomponent intervention versus usual care that was locally developed and adapted for use in Indian settings through rigorous formative research guided by Consolidated Framework for Implementation Research (CFIR). The C-QIP intervention consisted of 5 components: 1) electronic health records and decision support system for clinicians, 2) trained non-physician health workers (NPHW), 3) text-message based lifestyle reminders, 4) patient education materials, 5) quarterly audit and feedback reports. Patients with CVD (ischemic heart disease, ischemic stroke, or heart failure) attending outpatient CVD clinics were recruited from September 2022 to September 2023 and were randomized to the intervention or usual care arm for at least 12 months follow-up. The co-primary outcomes are implementation feasibility, fidelity (i.e., dose delivered and dose received), acceptability, adoption and appropriateness, measured at multiple levels: patient, provider and clinic site-level, The secondary outcomes include prescription of guideline directed medical therapy (GDMT) (provider-level), and adherence to prescribed therapy, change in mean blood pressure (BP) and LDL-cholesterol between the intervention and control groups (patient-level). In addition, a trial-based process and economic evaluations will be performed using standard guidelines. ResultsWe recruited 410 socio-demographically diverse patients with CVD from four hospitals in India. Mean (SD) age was 57.5 (11.7) years, and 73.0% were males. Self-reported history of hypertension (48.5%) and diabetes (41.5%) was common. At baseline, mean (SD) BP was 127.9 (18.2) /76.2 (11.6) mm Hg, mean (SD) LDLc: 80.3 (37.3) mg/dl and mean (SD) HbA1c: 6.8% (1.6%). At baseline, the GDMT varied from 62.4% for patients with ischemic heart disease, 48.6% for ischemic stroke and 36.1% for heart failure. ConclusionThis study will establish the feasibility of delivering contextually relevant, and evidence-based C-QIP strategy and assess whether it is acceptable to the target populations. The study results will inform a larger scale confirmatory trial of a comprehensive CVD care model in low-resource settings. Trial registrationClinical Trials Registry India: CTRI/2022/04/041847; Clinicaltrials.gov number: NCT05196659

Dyslipidaemia in women with polycystic ovary syndrome referred to a teaching hospital in Cape Town, South Africa.

The polycystic ovary syndrome (PCOS) imparts health risks including dyslipidaemia, diabetes and cardiovascular disease that are amenable to lifestyle adjustment and/or medication. We describe dyslipidaemia in women referred to a gynaecological endocrine clinic. Clinical data and endocrine and lipoprotein investigations comprising fasting triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and calculated low density lipoprotein cholesterol (LDLC) were studied along with electrophoresis patterns of apolipoprotein B-containing lipoproteins. The 1721 participants comprised black, mixed ancestry, white and Indian individuals (9.8%, 83.2%, 5.8% and 1.2%, respectively). The mean ± standard deviation of the age, body mass index (BMI) and waist/hip ratio were 26.0 ± 5.9 years, 32.3 ± 8.3 kg/m2 and waist/hip ratio 0.88 ± 0.11, respectively. Overweight status (BMI 26-30 kg/m2) and obesity (BMI >30 kg/m2) involved 272 (15.8%) and 1010 (58.7%) individuals, respectively. Morbid obesity (BMI >40 kg/m2) was present in 309 (17.9%) individuals. The TG, TC, HDLC and LDLC concentrations were 1.22 ± 0.86, 4.77 ± 1.02, 1.3 ± 0.36, 2.94 ± 0.94 mmol/L, respectively. LDL hypercholesterolaemia occurred in 753 (43.7%) and exceeded 5 mmol/L in 39 (2.3%) women. Low HDLC (<0.9 mmol/L) affected 122 (7%), hypertriglyceridaemia (>1.7 mmol/L) affected 265 (15.4%) and exceeded 2.5 mmol/L in 91 (5.3%) women. Mixed hyperlipidaemia (TG >1.7, TC >5.0 mmol/L) occurred in 176 (10.2%). Electrophoresis revealed small LDL particles in 79 (4.6%) and dysbetalipoproteinaemia in 13 (0.76%) of the cohort. Small LDL associated with obesity, blood pressure, TG and glucose concentration and higher androgenic state. Many women with PCOS had unfavourable lipoprotein results: mostly moderate changes in TG, HDLC and LDLC. Small LDL is not rare, may aid risk assessment and is best determined directly. Incidental monogenic disorders of lipoprotein metabolism included dysbetalipoproteinaemia, familial hypercholesterolaemia and severe hypertriglyceridaemia. Dyslipidaemia in PCOS requires more careful diagnosis, individualised management and research.

Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia.

A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia. A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; P<0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; P<0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups. Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.

Randomized Trial of a Vascular Care Team vs Education for Patients With Peripheral Artery Disease

BackgroundUnderutilization of therapies to reduce ischemic risk in peripheral artery disease (PAD) persists. ObjectivesThe purpose was to conduct an implementation trial of lipid management in vascular disease. MethodsThe OPTIMIZE PAD-1 (Implementation of Vascular Care Team to Improve Medical Management of PAD Patients) trial randomized patients with peripheral artery disease with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL to management via a vascular care team including a clinical pharmacist and an algorithm of intensive lipid management to achieve goal LDL-C in 1 step vs usual care plus provider education. Medications were obtained using commercial insurance. The primary endpoint was percent change in LDL-C at 12 months. ResultsOf 166 enrolled patients, 74.2% did not have an LDL-C level at goal. Among 114 randomized patients (mean age 66 years, 36.0% women, and 15.8% Black), 50.9% received high-intensity statin, and 7.9% received ezetimibe at baseline. The mean 12-month LDL-C change was −49.1% (95% CI: −58.7% to −39.5%) with vascular care team management and −5.4% (95% CI: −15.3% to 4.6%) with usual care; the between-group least-squares mean difference was −43.7% (95% CI: −57.6% to −29.9%; P < 0.0001). Mean LDL-C was reduced in vascular care team patients from 100.6 mg/dL at baseline to 54.8 and 50.1 mg/dL by week 4 and month 12, respectively. At 12 months, vascular care team patients were >3 times as likely to achieve LDL-C <70 mg/dL and 8 times as likely to achieve LDL-C <55 mg/dL (P < 0.0001) than usual care. ConclusionsOPTIMIZE PAD-1 showed that an interprofessional, algorithm-based program can achieve rapid LDL-C lowering in vascular patients using available insurance and therapies, and LDL-C targets can be met in most patients if enabled by optimized systems of care.

Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials.

To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata. Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3-month doses up to 18 months, with background oral lipid-lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m2). Co-primary endpoints were percentage and time-adjusted percentage change in low-density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed. Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo-corrected) with inclisiran from baseline to Day 510 ranged from -47.6% to -51.9% and from -48.8% to -54.4% across glycaemic/BMI strata, respectively. Similarly, time-adjusted percentage changes after Day 90 and up to Day 540 ranged from -46.8% to -52.0% and from -48.6% to -53.3% across glycaemic/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of <1.8 mmol/L and <1.4 mmol/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic/BMI strata, a higher proportion of individuals had mild/moderate treatment-emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%-7.7%) versus placebo (0.2%-2.1%). Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic/BMI strata, with a modest excess of transient mild-to-moderate TEAEs at the injection site.

Obicetrapib on top of maximally tolerated lipid‐modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a) and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

Degree of serum LDL cholesterol reduction by simvastatin and ezetimibe is dependent on baseline LDL cholesterol concentration but not on baseline values and changes in cholesterol synthesis and absorption parameters.

We questioned whether the baseline status of low-density lipoprotein cholesterol (LDL-C), cholesterol synthesis and absorption, and the changes in these parameters determine the change in serum LDL-C under statin or ezetimibe treatment or under combination treatment. 37 mildly hypercholesterolemic healthy male subjects were studied under placebo, simvastatin (20mg/d), ezetimibe (10mg/d), and combination treatment. We correlated the change of LDL-C (ΔLDL-C) under treatment with the placebo end values of LDL-C (baseline), whole-body cholesterol synthesis, and hepatic cholesterol synthesis (serum lathosterol to cholesterol ratio) as well as fractional absorption rate (FAR) of cholesterol and serum campesterol to cholesterol ratio. The change in serum LDL-C was also correlated with the changes in synthesis and absorption parameters. ΔLDL-C was highly negatively related to baseline LDL-C under ezetimibe (p<0.0001), simvastatin (p<0.0001), and combination treatment (p<0.0001). Under combination treatment, LDL-C lowering appears possible from baseline values of 10 mg/dL upwards, while ΔLDL-C was independent of the baseline value (-50 to -60%). ΔLDL-C was positively associated with placebo FAR under ezetimibe (p=0.0106) and combination treatment (p=0.0457). No associations were found between ΔLDL-C and baseline values for synthesis nor between ΔLDL-C and changes in synthesis and absorption surrogate markers. Under ezetimibe, simvastatin, and combination treatment, ΔLDL-C is predominantly dependent on the baseline LDL-C concentration. We hypothesize that the concentration gradient between serum LDL-C and hepatic cellular cholesterol determines the efficiency of serum LDL-C lowering. Combination treatment is the preferred treatment.

Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial

Background and aimsThe PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial. MethodsAmong 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT. ResultsIn the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (−0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94–0.99) for a -7 mg/dL (−0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01–1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01–1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96–1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91–1.15) in the PROMINENT trial. ConclusionsAbsolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm.

The Effect of Whole-Body Electromyostimulation on Inflammatory Biomarkers and Adipokines in Overweight to Obese Adults with Knee Osteoarthritis: a Randomized Controlled Study

Evidence of an anti-inflammatory effect of WB-EMS is growing. However, applying comparable impulse-protocols, studies reporting positive effects on inflammatory markers, possibly including adipokines, used high volume, superimposed WB-EMS protocols that differ from the time-efficient, non-superimposed concepts mainly used in scientific and commercial settings. The aim of the present trial was to determine the effect of “standard WB-EMS” on inflammatory markers and adipokines in overweight to obese adults. Seventy-two overweight to obese adults 40-70 years old with osteoarthritis (OA) of the knee, were randomly allocated to a 29-week standard WB-EMS application 1.5x20min/week (WB-EMS) or to a usual care control groups (CG) with six sessions of physiotherapy. Study outcomes were changes of ultra-sensitive CRP, IL-1b, adiponectin, leptin, total and LDL-cholesterol. Intention to treat analyses with multiple imputation with an ANCOVA adjusted for baseline group difference was applied. Six participants (WB-EMS=5) were lost to follow-up. Attendance rate averaged 88±10% in the WB-EMS group and &gt;90% in the CG. After the intervention, we did not observe any significant change of usCRP, IL-1b, adiponectin, leptin, total and LDL-cholesterol levels or significant between group differences (i.e. “effects”). Adverse effects related to the intervention were not observed or reported. The present low-volume, non-superimposed WB-EMS (standard) approach does not seem to have a significant effect on the analyzed inflammatory biomarkers and adipokines in overweight to obese adults with knee OA.