Lower Low-density Lipoprotein Cholesterol Research Articles

Clinical Efficacy of Ezetimibe Combined with Rosuvastatin in the Treatment of Patients with Primary Hypercholesterolemia Inadequately Controlled by Statin Therapy

Aims/Background Primary hypercholesterolemia (PHC) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Although the fact that statins effectively lower low-density lipoprotein cholesterol (LDL-C) levels, some patients fail to achieve target LDL-C levels and continue to have a high risk of cardiovascular disease. This study aims to evaluate the clinical efficacy and safety of ezetimibe combined with rosuvastatin in patients with PHC. Methods This study retrospectively examined 101 patients with PHC who received statins at the cardiology department of Jilin Province FAW General Hospital, between 2021 and 2024. Patients were divided into the observation (ezetimibe combined with rosuvastatin, n = 45) and control (rosuvastatin, n = 66) groups in accordance with their treatment regimens. Data were sourced from the hospital's electronic health records system, and statistical analysis was performed by using SPSS 25.0 software (IBM Corporation, Armonk, NY, USA). Results Baseline characteristics were similar between the two groups. After 12 weeks of treatment, the reduction in LDL-C levels in the observation group (–0.373 [–0.427, –0.348]) was greater than that in the control group (–0.240 [–0.318, –0.222], p < 0.001). The percentage changes in total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels were significantly better in the observation group (TC: –0.230 [–0.302, –0.144], TG: –0.292 [–0.333, –0.237], and HDL-C: 0.081 [0.067, 0.111]) than in the control group (TC: –0.127 [–0.158, –0.119], TG: –0.082 [–0.101, –0.067], and HDL-C: 0.000 [–0.163, 0.133] with p < 0.001, p < 0.001, and p = 0.011, respectively). Regarding drug safety, the incidence of adverse events was comparable between the two groups (11.10% vs. 12.10%, p = 0.871). Conclusion The combination of ezetimibe and rosuvastatin demonstrates superior lipid-lowering efficacy and good safety in patients with PHC inadequately controlled by statin therapy, providing an effective alternative treatment option. Further large-scale, multicenter randomized controlled trials are warranted to confirm its long-term efficacy and safety.

Association between low-density lipoprotein cholesterol levels and all-cause mortality in patients with coronary artery disease: a real-world analysis using data from an international network

The current cholesterol guidelines recommend maintaining low levels of low-density lipoprotein cholesterol (LDL-C) in patients with coronary artery disease (CAD). However, recent studies have suggested that both very low and very high LDL-C levels may be associated with increased mortality in the general population. We utilized data from TriNetX, a global health research network, to investigate the association between LDL-C levels and all-cause mortality in patients with CAD. CAD patients were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code and stratified into six LDL-C categories: <50 mg/dL (cohort 1), 50–69.9 mg/dL (cohort 2), 70–99.9 mg/dL (cohort 3), 100–129.9 mg/dL (cohort 4), 130–159.9 mg/dL (cohort 5), and ≥ 160 mg/dL (cohort 6). Mortality data were obtained by linking patient records to death registries spanning the 15 years prior to the analysis. Weighted Cox proportional hazards regression models were employed to estimate hazard ratios (HRs) for mortality outcomes along with their 95% confidence intervals (CIs). A total of 2,145,732 individuals with CAD (mean age 72 years, SD 13; mean LDL-C 87.7 mg/dL, SD 37.7) were included in the analysis. Over a 15-year follow-up period, 191,779 deaths (8.9%) were recorded. After propensity score matching, patients with LDL-C < 50 mg/dL (37.05% vs. 33.11%, HR 1.144, 95% CI 1.125–1.164, p < 0.0001), LDL-C 130–159.9 mg/dL (26.47% vs. 25.71%, HR 1.032, 95% CI 1.007–1.059, p = 0.0136), and LDL-C ≥ 160 mg/dL (26.29% vs. 24.38%, HR 1.121, 95% CI 1.082–1.163, p < 0.0001) demonstrated a higher risk of all-cause mortality compared to those with LDL-C 100–129.9 mg/dL. Conversely, patients with LDL-C 50–69.9 mg/dL (27.88% vs. 29.68%, HR 0.898, 95% CI 0.883–0.913, p = 0.0002) and LDL-C 70–99.9 mg/dL (26.21% vs. 27.84%, HR 0.908, 95% CI 0.893–0.923, p = 0.0057) exhibited a lower risk of all-cause mortality compared to the reference group (LDL-C 100–129.9 mg/dL). In conclusion, our findings suggest a U-shaped relationship between LDL-C levels and all-cause mortality in patients with CAD, where both very low (< 50 mg/dL) and high (≥ 130 mg/dL) LDL-C levels are associated with increased mortality risk. These results highlight the need for individualized LDL-C targets in managing patients with CAD.

Lowering low-density lipoprotein cholesterol targets to below 1.0 mmol/L in acute coronary syndrome patients: a potential new standard

Despite significant advancements in the diagnosis and treatment of ischemic heart disease primarily, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) plays a causal role in the development and progression of atherosclerosis. Randomized controlled trials have demonstrated that achieving lower LDL-C levels in patients with acute coronary syndrome (ACS) can stabilize or even reverse coronary plaque. This article examines existing evidence to explore whether further reducing LDL-C levels in all ACS patients (not just those with recurrent events) to below 1.0 mmol/L, lower than current guideline recommendations, could effectively reduce the incidence of adverse cardiovascular events.

Association between low density lipoprotein cholesterol levels and prostate cancer risk in non-hypertensive middle-aged and older American men

Often linked with the risk of various diseases, blood low-density lipoprotein cholesterol (LDL-C) levels are typically deemed more favorable when lower. The objective of this investigation is to elucidate the link between blood LDL-C levels and the risk of prostate cancer (PCa) in middle-aged and older men without hypertension in the United States. Utilizing continuous data from the National Health and Nutrition Examination Survey (NHANES) database spanning 2003–2010, a selection of 1,223 non-hypertensive men aged ≥ 40 years was made from a pool of 41,156 participants, ensuring no missing information. Regression analyses were employed to investigate the correlation between blood LDL-C levels and the PCa risk, while identifying potential inflection points indicative of threshold effects. Additionally, we scrutinized the linkage between cholesterol-lowering prescription drug usage and PCa. In our study of 2,224 participants, we found no significant correlation between blood LDL-C levels and the PCa risk after adjusting for confounding variables (Odds Ratio = 0.99; P-value > 0.05). However, upon conducting a subgroup analysis, we discovered a meaningful correlation between lower blood LDL-C levels and an increased PCa risk in the non-hypertensive population (Odds Ratio = 0.99; P-value < 0.05). Meanwhile, we identified a threshold effect and a tipping point at an LDL-C levels of 67 mg/dl. Furthermore, a significant correlation was identified between cholesterol-lowering prescription drug usage and a heightened PCa risk in the non-hypertensive population (Odds Ratio = 18.87; P-value < 0.05; P for interaction < 0.05). Our results indicate that in non-hypertensive middle-aged and older men residing in the United States, lower blood LDL-C levels are not necessarily better and the PCa risk escalates when blood LDL-C levels drop below 67 mg/dl, which may guide early screening and prognosis of PCa in specific populations. This finding calls for further validation via larger sample sizes and a more in-depth analysis of PCa history.

Long-Term Propolis Intake-Induced Liver Lipid Remodeling in Mice: Effects on Phospholipid-to-Glycerolipid Metabolism and Free Fatty Acid-Mediated Thermogenesis.

Research on the patterns and mechanisms of liver lipid remodeling regulated by propolis is limited. In the present study, the nine-month experimental duration has shed light on the positive influences of propolis on lipid metabolism and thermogenesis capacity in the livers of mice. Eight major compounds in propolis were characterized using UPLC-QTOF-MS technology. Propolis significantly lowered serum triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C), but it also led to increased insulin (INS) levels. Lipidomics change trend analysis of 1671 lipid components across 42 categories revealed that the level of glycerophospholipids (GPs) decreased while glycerolipids (GLs) and fatty acids (FAs) increased in the liver. The expression levels of eight key genes involved in the conversion of GP to GL pathways in the liver were enhanced in the propolis group. Molecular docking results elucidated the high binding affinities between the eight components of propolis and eight receptors involved in lipid metabolism, indicating that primary compounds of propolis possess potent capabilities for phospholipid remodeling and lipolysis. These results imply that propolis could facilitate the browning of the liver adipose tissue, promote the conversion of GPs to DGs and FFAs, enhance the consumption of FFAs through thermogenic pathways, and thereby exert lipolytic and hepatoprotective functions.

Differential statin intensity and outcomes in patients following myocardial infarction with very low low-density lipoprotein cholesterol.

Despite increasing evidence on the benefits of statin therapy for acute myocardial infarction (AMI), differential outcomes in accordance with statin intensity have not been evaluated in patients with AMI and low-density lipoprotein cholesterol (LDL-C) levels < 55 mg/dL. Therefore, this study aimed to compare the clinical outcomes of high- and moderate-intensity statin therapy in this population. A total of 752 participants with AMI and LDL-C levels < 55 mg/dL from a Korean nationwide multicenter observational cohort (2016-2020) were included and categorized into two groups: high-intensity statin group (n = 384) and moderate-intensity statin group (n = 368). The primary outcome was 1-year major adverse cardiac and cerebrovascular events (MACCEs). Propensity score matching (PSM) and Cox models were used to determine whether statin intensity independently influenced the primary outcome. Compared to the moderate-intensity statin group, the high-intensity statin group had a comparable risk of MACCE in all Cox models and PSM-adjusted analyses. The cumulative incidence of MACCE was comparable between the two groups. Statin intensity appeared to have no significant impact on clinical outcomes in AMI patients with LDL-C levels < 55 mg/dL. These results underscore the need for further investigations aimed at refining treatment strategies for this specific patient cohort, potentially reducing treatment-related burdens without compromising clinical effectiveness.

Alternative LDL Cholesterol–Lowering Strategy vs High-Intensity Statins in Atherosclerotic Cardiovascular Disease

In patients with atherosclerotic cardiovascular disease (ASCVD), intensive lowering of low-density lipoprotein (LDL) cholesterol levels with high-intensity statins is generally recommended. However, alternative approaches considering statin-related adverse effects and intolerance are needed. To compare the long-term efficacy and safety of an alternative LDL cholesterol-lowering strategy vs high-intensity statin strategy in patients with ASCVD in randomized clinical trials. PubMed, Embase, and other websites (ClinicalTrials.gov, European Society of Cardiology, tctMD) were systematically searched from inception to April 19, 2024. Randomized clinical trials comparing an alternative LDL cholesterol-lowering strategy vs a high-intensity statin strategy in patients with ASCVD, with presence of cardiovascular events as end points. Individual patient data were obtained from randomized clinical trials that met the prespecified eligibility criteria: RACING (Randomized Comparison of Efficacy and Safety of Lipid-Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease) and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy vs Intensity-Based Statin Therapy in Patients With Coronary Artery Disease). The moderate-intensity statin with ezetimibe combination therapy in the RACING trial and the treat-to-target strategy in the LODESTAR trial were classified as alternative LDL cholesterol-lowering strategies. The primary analysis was based on a 1-stage approach. The primary end point was a 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. The secondary end points comprised clinical efficacy and safety end points. Individual patient data from 2 trials including 8180 patients with ASCVD (mean [SD] age, 64.5 [9.8] years; 2182 [26.7%] female; 5998 male [73.3%]) were analyzed. The rate of the primary end point did not differ between the alternative strategy and high-intensity statin strategy groups (7.5% [304 of 4094] vs 7.7% [310 of 4086]; hazard ratio, 0.98; 95% CI, 0.84-1.15; P = .82). The mean (SD) LDL cholesterol level during treatment was 64.8 (19.0) mg/dL in the alternative strategy group and 68.5 (20.7) mg/dL in the high-intensity statin strategy group (P < .001). The alternative strategy group had a lower rate of new-onset diabetes (10.2% [271 of 2658] vs 11.9% [316 of 2656]; P = .047), initiation of antidiabetic medication for new-onset diabetes (6.5% [173 of 2658] vs 8.2% [217 of 2656]; P = .02), and intolerance-related discontinuation or dose reduction of assigned therapy (4.0% [163 of 4094] vs 6.7% [273 of 4086]; P < .001). Results of this systematic review and individual patient data meta-analysis suggest that compared with a high-intensity statin strategy, the alternative LDL cholesterol-lowering strategy demonstrated comparable efficacy regarding 3-year death or cardiovascular events in patients with ASCVD, with an associated reduction in LDL cholesterol levels and risk for new-onset diabetes and intolerance. PROSPERO CRD42024532550.

High low-density lipoprotein cholesterol levels in people with HIV by individual cardiovascular risk: A retrospective observational study

BackgroundPeople with HIV (PWH) are at increased risk of atherosclerotic cardiovascular disease (ASCVD). Lowering low-density lipoprotein cholesterol (LDL-C) is central of cardiovascular disease prevention. The aim of this study was to assess the prevalence, treatment, and control of high LDL-C levels as assessed on the basis of the ASCVD risk profiles indicated by European Society of Cardiology (ESC) guidelines of a cohort of PWH in order to evaluate the state of LDL-C management in current clinical practice. MethodsWe retrospectively assessed the prevalence, treatment, and control of high LDL-C levels in a cohort of PWH aged ≥40 years who accessed our HIV outpatient clinic between 1 March 2022 and 31 March 2023. Their 10-year ASCVD risk was calculated on the basis of their age and co-morbidities as recommended by guidelines. High LDL-C levels were defined as those above the “step two” target of their specific ASCVD risk category. ResultsAmong the 1404 assessed PWH, who were prevalently male (74.5 %) and Caucasian (85.6 %), and had a median age of 56 years (interquartile range [IQR] 49–61), 295 (21 %) were at very high risk (VHR), 634 (45.2 %) at high-risk (HR), and 348 (24.8 %) not at HR. The overall median LDL-C level was 116 mg/dL (IQR 96–141). Five hundred and sixteen (37 %) were undergoing lipid lowering treatment (LLT), and 650 (46.3 %) failed to achieve any step of their target LDL-C levels. ConclusionsDespite the high prevalence of PWH at VHR/HR for ASCVD, LDL-C levels were poorly controlled and LLT was greatly under used.

Myostatin as a plausible biomarker for early stage of sarcopenic obesity

Since sarcopenic obesity (SO) impacts negatively on our health, early detection of SO is essential. However, prevalence of SO in an apparently healthy population has not been well examined. This study aimed to elucidate the prevalence and related factors of SO in middle-aged women, and to investigate useful diagnostic criteria for SO. Body component analyses were conducted on 432 female Osaka University employees aged 30–59 during their health checkups. Healthy (H) and SO groups were defined using cutoff values of 5.7 kg/m2 for skeletal muscle mass index and 30% for percent body fat. Serum myostatin and insulin levels were additionally measured. Among 432 participants, the prevalence of SO was 6.3%. Grip strength (P < 0.0001) was lower and triglyceride (P = 0.0004) and low-density lipoprotein cholesterol (P = 0.0105) levels, and Homeostatic Model Assessment of Insulin Resistance (P = 0.0262) were higher in the SO group than in the H group. Serum myostatin levels in the SO group were lower than in the H group (3,107 pg/mL vs. 3,957 pg/mL, P = 0.0003). Myostatin levels may be suppressed in individuals with SO without any pre-existing conditions. Our diagnostic criteria for SO could reveal the risks for metabolic-related diseases and may be useful for the early detection of SO.

L-shaped association of plasma low-density lipoprotein cholesterol with atrial fibrillation recurrence after catheter ablation: a prospective cohort study

The association between plasma low-density lipoprotein cholesterol (LDL-C) and atrial fibrillation (AF) recurrence after catheter ablation remains unclear. We aimed to assess the relationship between preprocedural LDL-C and the AF recurrence in patients undergoing catheter ablation. The cohort study consecutively included AF patients who underwent de novo catheter ablation between April 2021 and January 2023 in the Second Affiliated Hospital of Nanchang University in Jiangxi Province, China. Patients were divided into quartiles based on their baseline fasting LDL-C level (Q1-Q4). Multivariable Cox proportional hazards models were used to evaluate the relationship between LDL-C and AF recurrence. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and two-piecewise Cox proportional hazards models, to address the nonlinearity between preprocedural LDL-C and AF recurrence. A total of 482 AF patients with de novo catheter ablation were enrolled, with a median follow-up period of 15.00 months, AF recurrence occurred in 96 (19.92%) patients. The relationship between preprocedural LDL-C and AF recurrence after ablation presented as an L-shape, and the inflection point for the curve was found at the LDL-C level of 3.20 mmol/L (Log likelihood ratio P = 0.031). The hazard ratios (HR) [(95% confidence intervals (CI)] for AF recurrence were 0.50 (0.33–0.74) and 2.11 (0.76–5.89) to the left and right of the inflection point, respectively. Lower LDL-C level is associated with increased AF recurrence risk after catheter ablation were consistent across all subgroups.

Abstract 4129733: Glucagon-like Peptide 1 Receptor Agonists Effect on 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 impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on lipid components is unclear. The objective of this study was to measure the lipid-lowering effect of GLP-1RAs. Methods: A thorough database search was performed to identify placebo-controlled randomized controlled trials (RCTs) on GLP-1RA therapy through January 2023. From these trials, data was extracted and a robust statistical analysis was performed using a random effects model to determine outcomes with weighted mean difference (MD) in milligrams per deciliter (mg/dL) and 95% confidence intervals (CIs). The primary outcome was the mean difference in low-density lipoprotein cholesterol (LDL-C). Secondary outcomes were mean differences in total cholesterol (TC), triglycerides, high-density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). To account for covariates, subgroup analyses and meta-regression were performed. Results: A total of 33 studies were included in the final meta-analysis carried out between 2008 and 2023, which were conducted in 26 countries. Of the 5,918 participants, the study population comprised 2,603 (44%) males and 3,315 (56%) females, aged between 33.7 and 65.9 years. GLP-1RAs significantly reduced LDL-C compared to placebo (MD -2.93, 95% CI (-5.01, -0.85), P=0.01). Treatment effect was consistent regardless of duration of treatment;12 weeks or less MD: -5.39, 95% CI (-10.36, -0.42), P=0.03 vs &gt;12 weeks MD: -2.39, 95% CI (-4.70, -0.007), P=0.04, P interaction 0.28). In our analysis, 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) and VLDL-C ~4 mg/dl (MD = -3.99, 95%, CI (-8.73, 0.75), P=0.10). Furthermore, GLP-1RA did not increase HDL-C (MD = -0.12, 95% CI (-0.73, 0.49], P=0.69. Regression analysis determined that weight loss did not affect the treatment effect on LDL-C (tau2=28.38, I2=99.83, R2=0.0, p=0.67), and total cholesterol (tau2=93.6, I2=99.86, R2=0.0, p=0.92). Conclusion: Patients on GLP-1RA experienced modest LDL-C and TC lowering compared to placebo. GLP-1RA did not decrease triglycerides and VLDL-C. GLP-1RA did not increase HDL-C.

Abstract 4131775: Effectiveness of Lipid-lowering therapy with Bempedoic Acid plus Ezetimibe in a Real-world Cohort

Introduction: Bempedoic acid and the combination with ezetimibe (BA+EZE) have demonstrated low-density lipoprotein cholesterol (LDL-C) lowering in clinical trials of adults with primary hyperlipidemia at high risk for or with cardiovascular disease. The impact of BA+EZE on LDL-C outcomes in a real-world cohort has not been studied. Aim: To evaluate the effectiveness of BA+EZE on LDL-C reduction and goal achievement using real-world data. Methods: This was a retrospective cohort study using deidentified electronic health records and linked claims data. Adult patients were included if they had a pharmacy claim for BA+EZE from March 1, 2020 to March 15, 2024 (date of first pharmacy claim = index date ), had ≥1 baseline LDL-C lab result on or within 6 months prior to the index date, and ≥2 LDL-C lab results post-index, including 1 lab result 12 months post-index (±60 days). Patients with documented use of ezetimibe on or within 6 weeks prior to index were excluded. For all patients with available valid lab results, LDL-C was determined at baseline (the value closest to but not after the index date), 3 months (±30 days), 6 months (±60 days) and 12 months (±60 days). Results: A total of 615 BA+EZE patients were identified (mean age 62±11 years, 52% women). At baseline, 64% had evidence of statin use in the prior 12 months and the mean LDL-C was 131±52 mg/dl. Figure 1 shows the change in the proportion of patients achieving LDL-C control at index, 3-, 6-, and 12-months post-index. The proportion of patients achieving LDL-C &lt;100 mg/dL more than doubled from index (30%) to 3 months (67%), and was sustained through 12 months (55%). At 12 months, there were fewer patients with LDL-C ≥130 mg/dL (24% vs 47% at index). The mean LDL-C reduction was 28% at 3 months (to 94±47 mg/dL), 27% at 6 months (96±44 mg/dL), and 22% at 12 months (102±47 mg/dL) (p&lt;0.0001 for all vs index). Conclusion: Patients who initiated BA+EZE showed early and sustained improvements in LDL-C. Future research should consider the impact of time on therapy and adherence on LDL-C control.

Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis.

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined. A participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD). The multivariable-adjusted association between baseline Lp(a) level and ASCVD risk was modeled continuously using generalized additive models, and the association between baseline LDL-C level and ASCVD risk by baseline Lp(a) level by Cox proportional hazards models with random effects. The joint association between Lp(a) level and statin-achieved LDL-C level with ASCVD risk was evaluated using Cox proportional hazards models. Compared with an Lp(a) level of 5 mg/dL, increasing levels of Lp(a) were log-linearly associated with ASCVD risk in statin- and placebo-treated patients. Among statin-treated individuals, those with Lp(a) level >50 mg/dL (≈125 nmol/L) had increased risk across all quartiles of achieved LDL-C level and absolute change in LDL-C level. Even among those with the lowest quartile of achieved LDL-C level (3.1-77.0 mg/dL), those with Lp(a) level >50 mg/dL had greater ASCVD risk (hazard ratio, 1.38 [95% CI, 1.06-1.79]) than those with Lp(a) level ≤50 mg/dL. The greatest risk was observed with both Lp(a) level >50 mg/dL and LDL-C level in the fourth quartile (hazard ratio, 1.90 [95% CI, 1.46-2.48]). These findings demonstrate the independent and additive nature of Lp(a) and LDL-C levels for ASCVD risk, and that LDL-C lowering does not fully offset Lp(a)-mediated risk.

Adolescent urinary concentrations of phthalate metabolites and indices of overweight and cardiovascular risk in Dutch adolescents

Phthalates have been linked to cardiovascular risk factors. Exposure to chemicals with endocrine disrupting properties during the pubertal period can interfere with normal endocrine processes. This study aims to determine whether adolescent urinary concentrations of phthalate metabolites are associated with indices of overweight and cardiovascular risk in 13–15-year-old children. In this Dutch observational cross-sectional cohort study, 101 adolescents were included (mean age 14.4 ± 0.8 years), 55 were boys. The concentrations of 13 phthalate metabolites were measured in morning urine samples. Levels of cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, fasting insulin, fasting glucose, leptin, and adiponectin were measured. The children’s height, weight, waist circumference, hip circumference, and blood pressure were measured. Higher urinary mono-ethyl phthalate concentrations were associated with higher BMI and a larger hip circumference. In girls, higher urinary mono-hydroxy-iso-nonyl phthalate concentrations were associated with higher levels of lipids and obesogenic traits. In boys, higher concentrations of urinary phthalate metabolites were associated with lower LDL-C. The results of this explorative study suggest that higher levels of phthalate metabolites are associated with higher levels of lipids and obesogenic traits in 13–15-year-old girls.

Effect of evolocumab in patients with chronic limb threatening ischemia (Evol-CLI study)

BackgroundChronic limb-threatening ischemia (CLTI) is associated with increased risk of major adverse cardiac and limb events (MACLE). In patients with peripheral arterial disease (PAD), evolocumab is associated with decreased MACLE, improved maximal walking time, increased vascular flow-mediated dilation (FMD), and decreased carotid intima-media thickness (IMT). We investigated the additive effect of evolocumab in patients with CLTI on maximally tolerated lipid lowering therapy after an index revascularization for non-healing wounds. MethodsThis double-blind, prospective, randomized, single-center, placebo-controlled study investigated the effect of monthly evolocumab for 6 months compared to placebo in patients with CLTI, with recent revascularization, and on maximally tolerated statin therapy. The primary endpoint was the reduction of low-density lipoprotein cholesterol (LDL-C) at 6 months of therapy. Secondary endpoints included evaluation of FMD and carotid IMT. ResultsN = 13 in the evolocumab arm and N = 14 in the placebo arm. The evolocumab arm had a lower mean LDL-C level at 3 months and 6 months compared to baseline (mean 82 mg/dL at baseline, 26 mg/dL at 3 months, and 34 mg/dL at 6 months, p = 0.017). The placebo arm had no significant difference in LDL-C at 3 and 6 months compared to baseline. Treatment with evolocumab resulted in increased FMD of the brachial artery and decrease in carotid IMT at 6 months. There was no deleterious effect on wound healing. ConclusionEvolocumab was associated with a decrease in LDL-C, decreased carotid IMT, and improved FMD in CLTI patients who were on evolocumab therapy in addition to maximally tolerated statin. There was no adverse effect on wound healing with further reduction in LDL-C.

Serum Low-Density Lipoprotein Cholesterol Levels are Associated with Relapse in Neuromyelitis Optica Spectrum Disorder.

The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients. We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan-Meier Plot. Over a mean disease course of 100±87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (p<0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (p< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76-4.04, p<0.001), and 2.38 (1.48-3.83, p<0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795mmol/L with potential benefits to prevent relapse in NMOSD. In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD.

Association between the rs12654778 SNP of the β-2 adrenergic receptor and LDL cholesterol levels in the Chilean adult population

IntroductionVarious polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene have been associated with cardiometabolic risk factors, such as hypertension, dyslipidemia, type 2 diabetes mellitus and obesity contributing to the physiopathology of these chronic conditions. However, the association of the single nucleotide polymorphism (SNP) rs12654778 at the ADRB2 gene with metabolic changes has been poorly studied and there is no information on the Chilean adult population. ObjectiveTo investigate the association between the rs12654778 SNP at the ADRB2 gene with cardiometabolic risk markers in a Chilean adult population. MethodsWe conducted a cross-sectional study including 404 participants from the GENADIO study whom were genotyped for rs12654778 and categorized into GG, AG, and AA genotypes. Associations with cardiometabolic risk markers, such as blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood glucose and insulin were examined using multivariate regression analysis, while statistical models were adjusted for sociodemographic and lifestyle variables. ResultsOur findings indicate a significant association between the presence of the protective genotype (AA) of the rs12654778 polymorphism and lower low-density lipoprotein cholesterol levels corresponding to 8.75mg/dL per each copy of the protective allele (maximally adjusted model). No significant associations were seen for the remaining variables. ConclusionThe AA genotype of the rs12654778 SNP at the ADRB2 gene had a protective effect specifically against low-density lipoprotein cholesterol levels. This is the first study ever conducted in Chile on this SNP of ADRB2 and one of the few conducted worldwide to establish an association between the rs12654778 SNP at the ADRB2 gene and LDL cholesterol.

Clinical pharmacokinetics and pharmacodynamics of ongericimab: A potential long-acting PCSK9 monoclonal antibody in healthy subjects and patients with hypercholesterolemia: Randomized, double-blind, placebo-controlled phase Ia and Ib/II studies.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein-cholesterol (LDL-C) by decreasing the expression of the LDL-receptor on hepatic cells. Ongericimab (JS002) is a novel PCSK9 monoclonal antibody that exhibits a long-acting LDL-C lowering effect by exclusively inhibiting PCSK9 in pre-clinical studies. Two randomized, double-blind, placebo-controlled trials were conducted to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic profiles of ongericimab in healthy subjects and patients with hypercholesterolemia. Eighty-four healthy subjects in the phase Ia study received a single dose of placebo or ongericimab (15-450 mg). Ninety patients with hypercholesterolemia in the phase Ib/II study received placebo or ongericimab 150 mg Q2W, 300 mg Q4W, or 450 mg Q4W for 12 weeks. Ongericimab exhibited non-linear kinetics. The apparent clearance decreased as the dosage increased, with terminal elimination half-life (t1/2) values of 4.5-6.5 days. Overall, ongericimab was well tolerated in both studies. A single dose of ongericimab reduced LDL-C levels by 30%-73% in healthy subjects, and repeated doses of ongericimab reduced LDL-C levels by 67%-80% in patients with hypercholesterolemia. At the end of the dosing interval in the phase Ib/II study, over 70% of patients' LDL-C levels decreased by more than 50% from baseline. The results showed that ongericimab had a significant long-acting LDL-C lowering effect with good safety and potential for clinical application.

Safety and Effectiveness of Low-Density Lipoprotein Cholesterol-Lowering Therapy With Evolocumab for Familial Hypercholesterolemia/Hypercholesterolemia in Japan: A Real-World, Postmarketing, Single-Arm Study.

Evolocumab is the first monoclonal antibody against proprotein convertase subtilisin/kexin type 9 approved in Japan for familial hypercholesterolemia (FH) and hypercholesterolemia; however, data on its safety and effectiveness in the real-world setting in Japan are limited. This real-world, postmarketing, single-arm study assessed the safety and effectiveness of low-density lipoprotein cholesterol lowering with evolocumab in patients with homozygous/heterozygous familial hypercholesterolemia and hypercholesterolemia with high risk in Japan (668 sites). The primary safety end point was the incidence (percentage) and number of patients with adverse drug reactions and serious adverse events during the 104-week follow-up. Primary effectiveness end points included the percentage change in low-density lipoprotein cholesterol levels from baseline to week 12, assessed using 2-sided paired t tests. The safety and effectiveness sets comprised 3724 (homozygous FH, n=108; heterozygous FH, n=2009; hypercholesterolemia with high risk, n=1607) and 2797 (homozygous FH, n=91; heterozygous FH, n=1615; hypercholesterolemia with high risk, n=1091) patients, respectively. Overall, mean age and disease duration were 63.2 and 12.3 years, respectively. Serious adverse drug reactions and serious adverse events were experienced by 0.5% and 10.3% of patients; the incidence rates of myocardial infarction and stroke were 0.7% and 0.3%, respectively. A significant mean±SD percentage change in low-density lipoprotein cholesterol levels was observed at week 12 among patients with homozygous FH (-45.7%±28.2; P<0.001), heterozygous FH (-55.9%±28.8; P<0.001), and hypercholesterolemia with high risk (-63.3%±23.7; P<0.001). Evolocumab was well tolerated, and real-world patients with familial hypercholesterolemia and hypercholesterolemia with high risk in Japan had sustained low-density lipoprotein cholesterol reduction. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02808403.

Efficacy of combination therapy with statin and ezetimibe versus high dose statin monotherapy in secondary prevention in high-risk patients

Abstract Background Secondary prevention in patients with acute coronary syndrome focuses on lowering low-density lipoprotein (LDL) cholesterol below 55 mg/dL. In all statin-naïve patients at high risk (LDL-cholesterol target &amp;lt;55 mg/dL), initiation of high-intensity statin monotherapy is recommended by ESC guidelines. Nonetheless, at one month, a significant proportion of patients do not reach their LDL-cholesterol target. Purpose The aim of this study was to compare lipid-lowering therapy with statin monotherapy versus statin with ezetimibe in secondary prevention in patients at high risk. Methods The current prospective study included 264 consecutive patients admitted with acute ST elevation myocardial infarction who underwent percutaneous coronary intervention. None of the patients had taken lipid-lowering drugs in the previous 12 months. Patients were randomly assigned to one of two treatment groups: Group 1 - rosuvastatin 40 mg (n= 144) and Group 2 - rosuvastatin 40 mg and ezetimibe 10 mg (n= 120). All patients' lipid profiles were assessed upon admission and after one month of lipid-lowering treatment. Results At baseline, no patient had LDL cholesterol level lower than 55 mg/dL. There was no significant difference in lipid profile at baseline between the two groups (all p &amp;gt; 0.05). No differences were observed between the two groups in terms of baseline LDL-cholesterol deviation from the target (103.4% versus 99.70%; p= 0.66). As expected, the combination therapy reduced LDL-cholesterol at one month significantly higher compared to high-dose statin monotherapy (-59.65% versus -37.54%; p&amp;lt; 0.0001). After one month of treatment, only 47.92% of patients in Group 1 reached the LDL-cholesterol target (&amp;lt;55 mg/dL) compared to 90.00% of the patients in Group 2 (p&amp;lt;0.0001; R.R.= 0.53). Conclusion(s) Our findings show that statin and ezetimibe combination therapy is more effective in reduction in LDL-cholesterol levels and reaching targets compared to statin monotherapy alone. In statin-naïve patients at high risk, early initiation of the statin and ezetimibe combination instead of statin monotherapy should be taken into account in secondary prevention, for an earlier reach of the LDL-cholesterol target and to reduce the overall cardiovascular risk.