LDL-C Levels Research Articles

The Association between Serum Lipid Profile Levels and Hypertension Grades: A Cross-Sectional Study at a Health Examination Center.

Hypertension and dyslipidemia are major cardiovascular risk factors that often coexist. Hyperlipidemia is a crucial modifiable risk factor in preventing cardiovascular disease. We aimed to explore the relationship between lipid levels and the grading of hypertension in a community-based adult population. A total of 63,091 non-employed individuals were included in this study. Measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting plasma glucose (FPG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (STB), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c). Chi-square and t-tests were used to obtain basic population characteristics. Multivariate logistic regression was used to evaluate the association between the prevalence of hypertension and lipid profiles, as well as to identify influencing factors. A P-value < 0.05 was considered statistically significant. Statistical charts were utilized to analyze the relationship between lipid parameters and hypertension grades. A total of 30,588 men and 32,503 women with an average age of 64.57 ± 12.5 years participated in this study. After adjusting STB and TC, every 1 mmol/L increase in TG and LDL-c was associated with a 6.0% and 6.5% increase in the prevalence of hypertension, respectively. Conversely, for every 1 mmol/L increase in HDL-c, the prevalence of hypertension decreased by 4.1%. Increases in TG and LDL-c levels were observed across all grades of hypertension, while very high HDL-c was significantly associated in grade III hypertension (1.54→1.66 mmol/L). Additionally, age, BMI, FPG, ALT, AST, SCr, and BUN significantly influenced the association between hypertension and lipid levels. Hyperlipidemia and hypertension often coexist in health examination populations. Elevated levels of TG and LDL-C are associated with all grades of hypertension, while extremely high HDL-C level is linked to more severe hypertension.

Relationship between metabolomics of T2DM patients and the anti-diabetic effects of Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma herb pair in mice

Ethnopharmacological relevanceType 2 diabetes mellitus (T2DM) poses significant threats to public health. In Traditional Chinese Medicine (TCM), the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma (PCC/AR) herb pair has long been used for T2DM treatment, although its specific anti-diabetic mechanisms remain unclear. Aim of the studyThis study aimed to elucidate the relationship between metabolomics of T2DM patients and the anti-diabetic effects of PCC/AR herb pair in mice through clinical metabolomics and both in vitro and in vivo experiments. Materials and methodsIn this study, a T2DM mouse model was established via high-fat feeding (HFD) and streptozotocin (STZ) injection. The effects of PCC/AR on blood glucose, lipid metabolism, and inflammatory markers were evaluated. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed for metabolomics analysis of T2DM patients. ResultsSerum metabolomics analysis identified significant alterations in metabolites linked to the biosynthesis of unsaturated fatty acids and purine metabolism in T2DM patients, with elevated 2-hydroxyvaleric acid (2HB) levels. In T2DM mice, PCC/AR intervention normalized FBG, GHbA1c, TC, TG, LDL-C, HDL-C, TNF-α and IL-1β levels, while improving insulin sensitivity and pancreatic β-cell function in T2DM mice. Notably, PCC/AR reduced key enzymes in gluconeogenesis and fatty acid synthesis, PEPCK and ACC1. ConclusionPCC/AR herb pair exerts an anti-diabetes effect in T2DM mice by regulating 2HB through ACC1 inhibition, thereby reducing FFA and TG synthesis. Additionally, PCC/AR may also exert its effects by modulating glucose and lipid metabolism and reducing inflammation. These results support further investigation into the PCC/AR herb pair as a complementary therapy for T2DM.

PCSK9 inhibitors in the research progress of atherosclerotic cardiovascular diseases

Abstract. Atherosclerosis is a major global health issue, with cardiovascular diseases leading to over 4 million deaths in China in 2019. Effective management of atherosclerosis is crucial for reducing its incidence and mortality, with LDL-C reduction being a key strategy. This study examines the role of PCSK9 in atherosclerosis and the therapeutic potential of PCSK9 inhibitors, focusing on their ability to lower LDL-C levels and prevent cardiovascular events A literature review was conducted, analyzing the mechanisms of PCSK9 in lipid metabolism and the efficacy of various PCSK9 inhibitors, including monoclonal antibodies, antisense oligonucleotides, and small interfering RNA. PCSK9 inhibitors, such as Alirocumab, evolocumab, and Inlisiran, have demonstrated effectiveness in reducing LDL-C levels. Inlisiran, in particular, offers a long-lasting effect and has shown significant potential in clinical trials. Nucleic acid-based treatments are emerging as promising options with advantages such as sustained efficacy and a broad application scope, despite the need for further research to address delivery and off-target effects.

Detailed Lipid Profiles and Lipid-related Residual Risk after 12-week 10 mg Rosuvastatin Treatment for Acute Myocardial Infarction.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods and Results Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

The outcomes of electronic personal health records in patients with heart failure or coronary artery disease.

There are limited data on the efficacy of smartphone-based personal health records (PHRs) in patients with cardiovascular disease. This study aimed to examine the processes, outcomes and challenges associated with the implementation of integrated PHRs in patients with heart failure (HF) or coronary artery disease (CAD). This prospective single-group study evaluated the effects of a PHR system with the capability to capture electronic health records and vital signs in patients with HF or CAD. The outcomes measured were the 6-month changes in blood pressure (BP), body weight (BW), brain natriuretic peptide (BNP) levels, lipid profiles and haemoglobin (Hb) A1c levels. Between June 2021 and March 2022, we enrolled 111 patients (median age: 61years and 47% women) with CAD and/or HF. Over 6months, the PHR review count distribution was skewed: median 749 times (lowest 2, highest 5724)/180days, suggesting both low and excessive PHR users. After 3days, 23% of the patients discontinued inputting their vital signs and medication status. At 6months, compared with patients who discontinued, those who continued to input their vital signs (N=86) showed a significant decrease in their systolic BP and LDL-C levels but not in the diastolic BP, BW, BNP, HDL-C, triglyceride or HbA1c levels. The implementation of smartphone-based PHRs in daily practice is challenging for patients with HF or CAD. However, we observed positive indications of the benefits of PHR in these patients. UMIN000044369.

Lipid variability in drug-naïve individuals affected with Major Depressive Disorder: a systematic review and meta-analysis

Background This study aimed to provide a comprehensive synthesis of the evidence examining lipid profiles in drug-naïve MDD patients. Materials and methods We searched PubMed, Scopus, and ISI Web of Science up to August 2023 for total cholesterol, HDL-C, LDL-C, and triglyceride levels in drug-naïve MDD patients. Results A total of 17 articles comprising 2174 individuals including drug-naïve MDD subjects and controls were included. Our results showed that concentrations of total cholesterol were lower in drug-naïve MDD patients compared with healthy controls (SMD −0.49, 95% CI −0.881 to −0.105; p = 0.015; I2 = 90.6%). However, comparison of other lipid levels between MDD patients and healthy controls demonstrated no significant difference. The results revealed that the association of total cholesterol levels with MDD is more prominent in male-dominant studies (SMD −1.20, 95% CI −2.23 to −0.18, I2 = 87.9%) than in female-dominant studies (SMD −0.25, 95% CI −0.63–0.13, I2 = 89.0%). In meta-regression, none of the factors including year of publication, Newcastle-Ottawa Scale score, sample size, BMI, and mean age of participants had a significant influence on the association between cholesterol levels and MDD. Conclusions Lower levels of total cholesterol, especially in males, are associated with MDD, so early lipid monitoring and targeted interventions are necessary.

PCSK9 and its relationship with HMGB1, TLR4, and TNFα in non-statin and statin-treated coronary artery disease patients.

Despite statin use in coronary artery disease (CAD), significant risk remains, potentially due to increased proprotein convertase subtilisin/kexin-type 9 (PCSK9) production, which raises LDL-C levels and induces inflammation. The exact relationship between PCSK9, inflammatory markers like TNFα, TLR4, CRP, and HMGB1, and monocyte subsets is poorly understood. This study aimed to explore these relationships in non-statin and statin-taking CAD patients. This case-control study included 91 controls and 91 stable CAD patients, divided into no-statin (NS, n = 25), low-dose statin (LDS, n = 25), and high-dose statin (HDS, n = 41) groups. Serum levels of LDL-C, CRP, PCSK9, TLR4, HMGB1, and TNFα were measured. Monocyte subsets were classified using flow cytometry into classical monocytes (CM), intermediate monocytes (IM), and non-classical monocytes (NCM). CAD patients showed elevated PCSK9, LDL-C, and inflammatory markers compared to controls. Statin groups (LDS, HDS) had lower LDL-C and inflammatory markers but higher PCSK9 than the NS group, with the HDS group showing the lowest LDL-C and inflammatory markers but the highest PCSK9. In the NS group, PCSK9 positively correlated with inflammatory markers (HMGB1, TNFα, TLR4, CRP) and monocyte subsets (IM%, NCM%). In the total statin group (LDS + HDS), PCSK9 negatively correlated with HMGB1, TLR4, and NCM%, for each, respectively, and positively with CM%. Multivariable linear regression showed significant associations between PCSK9 and HMGB1, NCM%, and IM% in the NS group, and HMGB1, NCM%, and TLR4 in the total statin group. In conclusion, we recommend combining PCSK9 inhibitors with statins in high-risk CAD patients. This may enhance statin efficacy, reduce LDL-C, and inhibit the TLR4/NF-кB inflammatory pathway, decreasing atherosclerotic inflammation.

2-Acetamidophenol (2-AAP) Suppresses the Progression of Atherosclerosis by Alleviating Hyperlipidemia and Attenuating the Ferroptosis Pathway.

Hyperlipidemia and consequent endothelial inflammation, along with foam cell generation, promote the progression of atherosclerosis (AS). Here, we aimed to investigate the effects of 2-acetamidophenol (2-AAP), which was selected by zebrafish phenotypic screening, in alleviating AS by relieving hyperlipidemia and inhibiting foam cell formation, as well as the underlying mechanisms. In a zebrafish hyperlipidemia model, 2-AAP increased lipid-lowering efficacy; alleviated TC, TG, LDL-C, and MDA levels; elevated HDL-C and T-SOD levels; significantly improved intravascular macrophage aggregation; and improved blood flow. In an ox-LDL-induced RAW264.7 model, 2-AAP inhibited lipid phagocytosis in RAW264.7 cells; reduced the intracellular TC, TG, FC, and CE contents; and decreased the CE/TC ratio, thus slowing foam cell generation. In addition, 2-AAP alleviated intracellular ROS and ferrous ion accumulation in RAW264.7 cells, reduced the MDA content, and increased GPX4 viability. Furthermore, transcriptome analyses and gene expression validation showed 2-AAP treatment upregulates genes related to GSH synthesis and transport, such as gclc, gclm, gss, and gpx4a, and enhanced the expression levels of genes involved in the storage and transportation of iron ions, such as fpn1, fth, and g6pd, indicating that 2-AAP dramatically regulated the ferroptosis and glutathione metabolic pathways. Overall, our study demonstrated that 2-AAP demonstrated potential in AS by alleviating hyperlipidemia and attenuating the ferroptosis pathway and provided evidence supporting the future application of 2-AAP in AS treatment.

Abstract 4138704: Safety and Efficacy of Generic Atorvastatin in Korean Dyslipidemia Patients: A Non-Interventional Observational Study

Background: Statins are widely used for controlling dyslipidemia. However, most evidences for dyslipidemia prevention and treatment with statins are based on studies involving Caucasian populations, resulting in limited data on Korean patients. This study was conducted to evaluate the efficacy lipid profile and safety of generic atorvastatin in a real-world clinical setting among Korean dyslipidemia patients. Methods: This study was conducted as a non-interventional, multi-center observational study. It was carried out across 264 institutions and clinics from October 2017 to July 2021. Total 16,992 participants were enrolled. The safety and efficacy evaluation cohorts consisted of 16,803 and 11,035 subjects, respectively. The liver function evaluation cohort included 13,889 subjects. The main eligibility criteria were dyslipidemia patients prescribed generic atorvastatin according to approved indications. Adverse event rates were collected for safety evaluation, and lipid profiles, including LDL-C, were collected for efficacy evaluation. Results: In the safety endpoint evaluation, 1,612 adverse events were reported in 1,027 subjects (6.11%). Common adverse events such as dizziness, headache, and constipation, which were frequently observed in this study, were within the approved labels. Muscle pain occurred in 0.14% of subjects, and myopathy, myositis, rhabdomyolysis, and CK abnormalities or increases were reported in 0.01% of subjects, respectively. Most of the adverse events were confirmed to be mild or resolved, and the study was completed without changing the dose. All abnormal liver function test results were reported in less than 1% of subjects (AST increase: 0.14%, ALT increase: 0.1%, ALP increase: 0.01%, γ-GT increase: 0.01%). The mean LDL-C decreased from 117.31 mg/dL to 89.97 mg/dL, showing a statistically significant improvement in LDL-C levels (p &lt; 0.0001). Conclusions: Generic atorvastatin demonstrated tolerable safety as well as significant efficacy on lipid profile. Generic atorvastatin might be safe and effective for Korean patients with dyslipidemia.

Abstract 4136978: Six-month Changes in Lipid Management in the Veterans Affairs Lipid Optimization Reimagined Quality Improvement (VALOR-QI) Program

Background: US Veterans have a high burden of cardiovascular disease (CVD). While cholesterol management is one of the most effective approaches for reducing CVD burden, over two-thirds of Veterans with atherosclerotic cardiovascular disease (ASCVD) are not optimally managed. Aims: To evaluate LDL-C monitoring, lipid lowering therapy (LLT) use, and LDL-C levels at baseline and six-months for Veterans in the Veterans Affairs Lipid Optimization Reimagined Quality Improvement (VALOR-QI) Program. Methods: VALOR-QI is a national quality improvement collaboration between the US Department of Veterans Affairs and the American Heart Association (AHA) with the goal of improving lipid management among Veterans with ASCVD. To assess and address barriers to achieving optimal lipid levels, Clinical Champions, Health Care Coaches, and participating providers from 50 VA sites work with AHA QI Consultants. Eligible Veterans (those with an ASCVD diagnosis at two outpatient or one inpatient visit or one ASCVD procedure) were considered engaged in VALOR-QI if they had a qualifying appointment with a participating provider during the program. We examined rates of LDL-C monitoring and LLT use at baseline (start of site monitoring) and 6 months after. Among Veterans who were in the program ≥6 months and had &gt;1 LDL-C measure, we investigated percent meeting an LDL-C goal of &lt;70 mg/dL at their first LDL-C (closest to their first visit with priority given to labs within 365 days before their first visit) and follow-up LDL-C (closest to 6 months after entering the program) and mean LDL-C change (paired t-test). Results: Six months after starting VALOR-QI, sites had a 41% increase in LDL-C monitoring and a 6% increase in LLT use. Among 29,610 Veterans engaged in the program ≥6 months with at least two lipid labs [mean (SD) age 71.0 (9.3) years, 95% men, 72% white race], the proportion who met the LDL-C goal &lt;70 mg/dL increased from 44% at their first measure to 51% at 6-month follow-up. Among these Veterans, we observed a mean LDL-C decrease of 5.1 mg/dL (95% CI: -5.50, -4.78). Conclusion: We observed an increase in lipid monitoring and LLT use and improved LDL-C at 6-month follow-up among US Veterans engaged in VALOR-QI.

Abstract 4138757: Lipid-Lowering Therapy Intensification and Low-Density Lipoprotein Cholesterol Testing Following a Major Cardiovascular Event or Procedure in Adult Patients in the United States

Background: Optimizing lipid-lowering therapy (LLT) use is foundational to reduce atherosclerotic cardiovascular disease (ASCVD) risk, especially among patients who have already experienced an ASCVD event. This study aimed to evaluate the patterns of LLT intensification and LDL-C testing within 12 months following an ASCVD event in US patients. Methods: Adults who experienced an ASCVD event (acute coronary syndrome, coronary revascularization, stable angina, ischemic stroke, transient ischemic attack, or peripheral arterial disease) between January 1, 2016 and December 31, 2022 in the IQVIA Longitudinal Access and Adjudication Data were included. The first instance of LLT intensification after the event was defined as an increase from a low-moderate to high intensity statin, or the initiation of statins, ezetimibe, PCSK9i, or bempedoic acid in addition to a baseline LLT regimen that did not include these medications. Baseline medication use was defined during 6 months before the ASCVD event. Results: Among 6,028,573 patients who had an eligible ASCVD event (mean age: 63.6 years, 51.5% male), 53.9% were not taking any LLT and 43.2% were taking statins only (low-moderate intensity: 26.7%; high intensity: 16.4%) during baseline. Within 1, 3, and 12 months after the event, 16.3%, 21.3%, and 30.0% of patients intensified LLT, respectively. Among patients who intensified LLT within 12 months (n= 1,820,246), the most commonly observed intensification was from no LLT use at baseline to low-moderate (29.0%) or high-intensity statins (43.5%), followed by intensification from low-moderate to high-intensity statins (20.3%). LDL-C values at baseline were available in a subset of 10.7% of patients, with the median being 95 mg/dL (78.9% ≥70 mg/dL). LDL-C values were observed in 17.7% of patients within 12 months after the ASCVD event, with the median being 84 mg/dL (68.3% ≥70 mg/dL). Conclusions: Within 12 months after an ASCVD event, only about one-third of patients intensified LLT and two-thirds did not achieve guideline-recommended LDL-C levels. The results highlight a missed opportunity to reduce recurrent ASCVD events. Future effort is warranted to address the clinical inertia that may be contributing to this unmet need.

Abstract 4137928: Race-Dependent Association of Inflammation and Cholesterol with Cardiovascular Mortality in US Population

Background: Inflammation and cholesterol jointly contribute to cardiovascular disease and mortality. The relative contributions of inflammation and cholesterol to the risk of future cardiovascular events might shift according to pre-existing traits of each individual. Whether the association of inflammation and cholesterol with cardiovascular mortality differ by race remains unclear. Method: We sampled 12,726 participants from NHAENS III who were categorized as non-Hispanic White, non-Hispanic Black or Mexican Americans. In all race groups, we used the Cox proportional hazard regression model to relate log-transformed CRP and LDL-C levels to CVD deaths. All models simultaneously included CRP and LDL-C, and were adjusted for age, current smoking, hypertension, diabetes mellitus, body mass index, lipid-lowering medications, total cholesterol and family income. Results: 12,726 participants (53.4% female, mean age 46.8 ± 19.7 years) including 5648 non-Hispanic White (44.4%), 3484 non-Hispanic Black (27.4%) and 3594 Mexican-American (28.2%) were followed up for a median 26.3 years , and 1905 cardiovascular deaths were documented. After adjusting for cardiometabolic risk factors, per 1 SD increase in log-transformed CRP was associated with 14% (HR 1.14 [95% CI, 1.08-1.21], P &lt; 0.001) and 13% (HR 1.13 [95% CI, 1.04-1.23], P = 0.001) higher risk of CVD mortality in non-Hispanic White and non-Hispanic Black respectively, while the association was neutral in Mexican American. Notably, per 1 SD increase in LDL-C was not associated with CVD mortality in all race groups (P &gt; 0.05 for all). Conclusion: After a follow up of median 26.3 years, we found that, in non-Hispanic White and Black individuals, but not in Mexican American, inflammatory was a stronger predictor of cardiovascular mortality, compared to cholesterol.

Abstract 4139141: Predicted efficacy of inclisiran on cardiovascular outcomes in lower extremity peripheral artery disease: results of the In Silico Sirius study

Introduction: Symptomatic lower extremity peripheral artery disease (PAD) patients have the highest risk of cardiovascular (CV) outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Inclisiran, an siRNA targeting PCSK9 mRNA, reduces LDL-C levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower CV events in ASCVD patients. Research question/Hypothesis: SIRIUS in silico study aims to predict the efficacy of inclisiran on CV outcomes in subgroups of patients with or without PAD. Methods: The SIRIUS in silico trial was conducted using a knowledge-based mechanistic computational model of ASCVD applied to a virtual ASCVD population with LDL-C ≥ 70 mg/dL. Each virtual patient is its own control. This model was previously calibrated and validated before running the trial. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statins with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal ischemic stroke (IS) over 5 years. Occurrence of major acute limb events (MALE) was also individually assessed in time-to-first-event analyses. Results: Among 204, 691 virtual SIRIUS ASCVD patients, 28,072 (13.7%) had PAD. At 5 years, the mean predicted percentage reduction in LDL-C with inclisiran as compared to placebo was -49.3% and -49.8% in patients with or without PAD, respectively. The predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm in patients with PAD (17.62% vs 22.88%; Hazard Ratio (HR): 0.75 medium uncertainty) and in patients without PAD (10.33% vs 13.64%; HR: 0.75 low uncertainty). Compared to placebo, inclisiran was also predicted to consistently reduce MALE in patients with or without PAD (2.71% vs 4.11%; HR: 0.65 medium uncertainty and 0.19% vs 0.29%; HR: 0.66 high uncertainty respectively). Conclusion: Pending the results of ORION-4 and VICTORION-2-P, this first In Silico trial in virtual PAD patients predicted a potential effect of inclisiran on 3P-MACE and MALE reductions over 5 years follow-up.

Abstract 4134364: Predicted Low-Density Lipoprotein Cholesterol and Cardiovascular Outcomes Lowering With Inclisiran in Patients With or Without stroke: Insights from SIRIUS in silico trial.

Introduction: Inclisiran, an siRNA, targeting PCSK9 mRNA, reduces LDL-c levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower cardiovascular (CV) events in virtual patients with atherosclerotic cardiovascular disease (ASCVD). Research question: This analysis predicted the potential efficacy of inclisiran on CV outcomes in virtual patients with or without prior ischemic stroke (IS). Methods: The SIRIUS trial was conducted using a calibrated and validated knowledge-based mechanistic computational model of ASCVD applied to a virtual population with LDL-C ≥ 70 mg/dL. Each virtual patient was its own control. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statin with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal IS over 5 years in patients with or without prior IS. Occurrence of fatal and non-fatal (IS) was also individually assessed in time-to-first-event analyses. Results: Among 204,691 virtual SIRIUS ASCVD patients, 39 371 (19%) had prior IS. At 5 years, the predicted mean percentage reduction in LDL-C with inclisiran as compared to placebo was –49.17% and –49.88% in patients with or without prior IS respectively. Patients with prior IS were at higher risk of 3P-MACE than patients without IS both with placebo and inclisiran (17.01% vs 14.41% with placebo and 13.44% vs 10.83% with inclisiran). However, the predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm for both prior IS and no prior IS (HR 0.78 medium uncertainty and 0.74 low uncertainty respectively). Compared to placebo, inclisiran was also predicted to consistently reduce fatal and non-fatal IS in patients with or without prior IS (5.45% vs 7.22%; HR: 0.75 medium uncertainty and 1.87% vs 2.54%; HR: 0.73 medium uncertainty respectively). Conclusion: SIRIUS provides insights into the potential efficacy of inclisiran on CV events suggesting a substantial 3P-MACE and fatal and non-fatal IS reduction in ASCVD patients including those with prior IS, several years before the availability of results from ongoing outcomes trials (ORION-4, VICTORION-2P).

Euthyroid sick syndrome predicts the risk of ischemic stroke-associated pneumonia in the acute stage of ischemic stroke: a nested case-control study.

Ischemic stroke-associated pneumonia (iSAP) affects about 10% of acute ischemic stroke patients during hospitalization. Current prediction scales for iSAP are insufficient. Identifying early biomarkers for stroke-associated pneumonia is crucial for improving patient outcomes. This study aimed to investigate the predictive value of euthyroid sick syndrome (ESS) for iSAP in acute-stage of ischemic stroke patients. We studied 1767 acute ischemic stroke patients within one week of symptom onset, categorizing them into an infection group (iSAP, n=376) and control group (control, n=1391). COX regression analysis was used to identify the potential risk and protected factors. Kaplan-Meier time-event curves and Log-Rank tests were performed to differentiate infection time in patients with ESS or normal T3 group. The iSAP group had higher rates of risk factors like older age, atrial fibrillation, COPD, and ESS, along with elevated levels of WBC, CRP,and FT4 levels (all P < 0.001). Conversely, iSAP patients had lower GCS scores, eGFR, TSH, T3, FT3 (all P < 0.001) and T4 levels (P = 0.005) upon admission. No significant differences were observed in sex, smoking history, hypertension, diabetes, or LDL-C levels (P > 0.05). COX regression analysis identified age, KWST scores, leukocyte count, CRP, and ESS (all P < 0.001) as significantly correlated with iSAP. ROC analysis revealed ESS as a predictor with sensitivity of 35.64% and specificity of 87.92% for SAP prediction, like atrial fibrillation and higher than COPD and eGFR. ESS at admission predicts a higher risk of stroke-associated pneumonia in acute-stage of ischemic stroke.

Antidiabetic activity of Inonotus obliquus water extract in alloxan-induced diabetic mice.

The Inonotus obliquus is a medicinal mushroom that grows on mature birch trees and is commonly used in traditional medicine for various ailments. The current study aimed to explore the hypoglycemic, hypolipidemic, and pancreatic protective effects of the water extract of Mongolian natural Inonotus obliquus on alloxan-induced diabetic mice. Alloxan monohydrate (200 mg/kg) was intraperitoneally single injected into C57BL/6 mice to induce diabetes. Alloxan-induced diabetic mice were orally given the water extract of inonotus obliquus (WEIO) at doses of 500 mg/kg and subcutaneously administered with insulatard 0.6 IU for 4weeks. Subsequently, the levels of factors related to blood glucose, insulin and lipids were assessed. WEIO significantly restored body weight, reduced fasting blood glucose levels, improved glucose tolerance ability, and increased insulin levels compared to the control diabetic mice. WEIO also enhanced cholesterol transportation in the liver, correlated with increased HDL-C levels and decreased TC, TG and LDL-C levels. Histologic examinations revealed that WEIO alleviated alloxan-induced pancreatic tissue damage. Natural Mongolian I. Obliquus water extracts have an antihyperglycemic effect and enhance islet cell function in alloxan-induced diabetic mice. It is a good candidate for a hypoglycemic functional food or medicine.

Homozygous familial hypercholesterolemia in Spain. Data from Registry of the Spanish Atherosclerosis Society.

Subjects with HoFH, confirmed by the presence of two pathogenic variants in the genes mentioned above, included in the registry from 2013 to June 2023 with an updated review were analyzed. 71 HoFH subjects were included. 40.8% were women, aged 52 [24-62] years, 57 adults and 13 children. The median follow-up was 7 [4-13] years. Age of diagnosis was 14 [2-26] years, with 10% of ASCVD at diagnosis and 27% of current ASCVD at 40.6 (13.4) years of age. 38% were on PCSK9i, 9 patients on lomitapide, 9 on LDL apheresis and 1 patient on evinacumab. Subjects with more than 4 therapies achieved >80% reduction in LDLc. In the last visit, the median LDLc was 139.3 [89.4-204.2] mg/dL. ASCVD was strongly associated with male sex and family history of ASCVD, relative risk 5.26 (1.53-18.10) and 2.53 (1.03-6.26), p<0.05, respectively. Only 18% and 10% meet the recommended LDLc goal in primary and secondary prevention respectively. The current situation of HoFH in Spain is better than expected, with marked reductions in LDLc levels with new treatments. In this population, recommended LDLc goals are difficult to achieve despite maximum lipid-lowering therapy. ASCVD has been reduced and delayed by two decades.

OTUD7B inhibited hepatic injury from NAFLD by inhibiting K48-linked ubiquitination and degradation of β-catenin

Non-alcoholic fatty liver disease (NAFLD) is the prevalent liver disease. Ovarian tumor domain-containing 7B (OTUD7B) is a deubiquitinating enzyme and its role in NAFLD remains unclear. In high-fat diet (HFD)-induced NAFLD mouse model and palmitic acid (PA)-treated HepG2 cells, OTUD7B expression was decreased. Adenoviral overexpression of OTUD7B in mice resulted in reduced body weight and liver injury, with decreased serum aminotransferase (ALT) and aspartate aminotransferase (AST) levels. OTUD7B overexpression attenuated hepatic lipid deposition (serum TG, TC, LDL-C, HDLC, and FFA levels), which might be through the suppression of lipogenesis and β-oxidation-related genes. The contents of hepatic inflammatory factors (TNF-α, IL-6, and IL-1β) were decreased following OTUD7B overexpression in NAFLD mice. A mechanism study indicated that the protective effect of OTUD7B overexpression might be associated with β-catenin signal activation. OTUD7B overexpression promoted PA-induced β-catenin activity in TopFlash assay, and increased total β-catenin and c-myc levels in cells. The increase in β-catenin levels was contributed to the stabilization via inhibiting K48-linked ubiquitination and proteasomal degradation by OTUD7B. NR4A2 role in NASH has been proved. NR4A2 ChIP-seq and RNA-seq data excluded transcriptional regulation of NR4A2 to OTUD7B, and it was experimentally evidenced that NR4A2 bound to OTUD7B promoter region and positively transcriptionally regulate OTUD7B expression. In summary, OTUD7B overexpression ameliorated hepatic inflammation and steatosis in NAFLD. The possible mechanism of OTUD7B might be through the inhibition of β-catenin degradation by removing K48-linked ubiquitination, which might be regulated by NR4A2.

Clinical and angiographic characteristics of patients with familial hypercholesterolemia presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Familial hypercholesterolemia (FH) is a world public health problem that enhances the risk of premature coronary artery disease (CAD) with a high incidence of acute coronary syndrome. This study aimed to evaluate the clinical and angiographic characteristics of the patients with and without FH who had ST-elevation myocardial infarction (STEMI). It included 690 patients who presented with the first attack of STEMI and underwent primary percutaneous coronary interventions (PPCI). The patients were analyzed to diagnose FH according to the Dutch Lipid Clinic Network (DLCN) criteria. All angiograms were analyzed for the number of diseased vessels, Syntax score, thrombus burden grade, and final Thrombolysis in Myocardial Infarction (TIMI) flow grade. The majority of patients were male (72.6%) with a mean age of 54 ± 12 years. Based on DLCN criteria, they were classified into unlikely/possible FH (86.1%) and probable/definite FH (13.9%) groups. Probable/definite FH patients were significantly younger, and higher incidence of males < 55 years compared with unlikely/possible FH patients (p < 0.001 for each). Moreover, probable/definite FH patients had a higher frequency of three-vessel disease (p = 0.007) and Syntax score (p < 0.001) with a moderate positive correlation with the DLCN score (r = 0.592, p < 0.001). Furthermore, probable/definite FH patients showed a higher thrombus burden and final TIMI slow/no-reflow when compared to the unlikely/possible FH patients (p = 0.006 and p = 0.027, respectively). Patients with probable/definite FH and LDL-C level were independent predictors of high thrombus burden besides males < 55 years, and the number of diseased vessels. In conclusion, STEMI patients with FH were younger males and associated with severe CAD with frequent multivessel CAD, high anatomical complexity of CAD, and frequent high thrombus burden. Furthermore, FH was one of the predictors of high thrombus burden.

Iterative random forest-based identification of a novel population with high risk of complications post non-cardiac surgery

Assessing the risk of postoperative cardiovascular events before performing non-cardiac surgery is clinically important. The current risk score systems for preoperative evaluation may not adequately represent a small subset of high-risk populations. Accordingly, this study aimed at applying iterative random forest to analyze combinations of factors that could potentially be clinically valuable in identifying these high-risk populations. To this end, we used the Japan Medical Data Center database, which includes claims data from Japan between January 2005 and April 2021, and employed iterative random forests to extract factor combinations that influence outcomes. The analysis demonstrated that a combination of a prior history of stroke and extremely low LDL-C levels was associated with a high non-cardiac postoperative risk. The incidence of major adverse cardiovascular events in the population characterized by the incidence of previous stroke and extremely low LDL-C levels was 15.43 events per 100 person-30 days [95% confidence interval, 6.66–30.41] in the test data. At this stage, the results only show correlation rather than causation; however, these findings may offer valuable insights for preoperative risk assessment in non-cardiac surgery.