Use Of Lipid-lowering Medications Research Articles

Characterizing Lipid Changes and Use of Lipid-Lowering Medications in Patients With Alopecia Areata Treated With Baricitinib: Integrated Results From the BRAVE-AA1 and -AA2 Clinical Trials

Introduction. Elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) can occur with baricitinib treatment, consistent with a class effect of JAK inhibitors. In this analysis, we characterized changes in lipid levels and use of lipid-lowering medication among patients with severe alopecia areata (AA) treated with baricitinib through 152-weeks of treatment. Methods. Two integrated datasets from the BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) trials were analyzed: 1. Extended BARI AA includes patients treated with continuous baricitinib 2 mg (N=383) and 4 mg (N=565) from baseline and censored at dose change: 2. ALL BARI AA (N=1303) includes data for patients who received ≥1 dose of baricitinib at any time. Outcomes included abnormal changes in lipid parameters, mean change from baseline in lipids, and concomitant use of lipid-lowering medications. Results. At time of enrollment, 43% of patients had hypercholesterolemia. Incidence rates for categorical increases in total cholesterol (TC; ≥240mg/dL), LDL-C (≥130 mg/dL), and HDL-C (>60 mg/dL) were 11.8, 13.3, and 12.9 per 100 patients-years of exposure, respectively in the ALL BARI AA dataset. In the Extended BARI AA the mean maximal increase in lipids (mg/dL) for baricitinib 4 mg was 20.9 for TC, 12.4 for LDL-C, and 8.5 for HDL-C. Changes occurred early and stabilized by one year for TC and LDL-C and by 12 weeks for HDL-C. 6.1% (n=79) of patients in the ALL BARI AA dataset used lipid-lowering medication at baseline; post-baseline, 3.9% (n=51) discontinued this medication and 4.7% (n=61) initiated lipid lowering medication. No patients discontinued baricitinib treatment due to treatment-emergent adverse events related to hyperlipidemia. Conclusions. Elevations in TC, LDL-C, and HDL-C, but not triglycerides were associated with baricitinib treatment in patients with AA, consistent with a class effect of JAK inhibitors. The relatively low use of lipid-lowering medications at baseline despite the prevalence of hypercholesterolemia may reflect undermanagement of this condition in the population. Notably, the mean maximal magnitude of increase in lipid levels on baricitinib was modest. Initiation of lipid-lowering medication was infrequent, and no patients discontinued due to lipid abnormalities.

Abstract 4140140: Cardiology Follow-Up as a Determinant of LDL-C Management Success in Secondary Cardiovascular Prevention

Managing low-density lipoprotein (LDL) cholesterol is crucial for secondary cardiovascular prevention. Despite ACC/AHA recommendations for maintaining LDL below 70 mg/dL, achieving this target remains suboptimal. This study investigates the impact of consistent cardiologist involvement on LDL cholesterol management. Methods: We conducted a multicenter, cross-sectional cohort study within the Steward Healthcare System in Massachusetts, analyzing data from 10,211 patients hospitalized from January 2019 to March 2024. This study offers a detailed snapshot of data across the study period, capturing both recent and long-standing cases identified through ICD codes for conditions like NSTEMI, CAD, STEMI, or CABG, specifically as markers for secondary cardiovascular prevention. We utilized the most recent LDL cholesterol measurements for our analysis and compared the distribution of lipid-lowering medications across groups. Notably, follow-ups with cardiologists outside our network were not tracked, potentially omitting relevant data. Statistical analysis employed the Chi-square test for categorical variables and binary logistic regression to adjust for confounders. Results: showed that patients with regular cardiology visits more often achieved LDL levels below 70 mg/dL (57.45% vs. 46.67%; OR 1.54, 95% CI: 1.42-1.68; P<0.0001). These patients also had lower mean LDL levels (68.72 ± 27.02) compared to those without cardiology follow-up (75.82 ± 30.27; P<0.0001). Higher usage of PCSK9 inhibitors and non-statin medications was noted among the visiting group, with an adjusted OR of 1.43 (95% CI: 1.29-1.59; P<0.0001). Conclusion: Our study shows that cardiologist involvement significantly enhances cholesterol management in CAD patients, as evidenced by a higher proportion achieving optimal LDL levels and more aggressive use of lipid-lowering medications. Despite these benefits, some patients discontinue their follow-ups with cardiologists after coronary events, shifting cholesterol management to primary care providers (PCPs). This transition often results in less aggressive treatment strategies, evidenced by elevated LDL levels in patients lacking recent cardiology care. To sustain effective cholesterol management and stringent LDL targets, long-term follow-up with a cardiologist is crucial. Furthermore, equipping PCPs with the necessary tools and protocols to adopt more aggressive treatment approaches could bridge the care gap when specialist visits are infrequent.

Modifying effect of obesity status on the association between low-density lipoprotein cholesterol with incident hemorrhagic stroke: evidence from a community-based longitudinal cohort study in China

Abstract Background Previous results on the association between lipids and hemorrhagic stroke were controversial. Modifying effect of obesity on the association between low-density lipoprotein cholesterol (LDL-C) and hemorrhagic stroke risk in the Chinese community-based population remains unclear. Objectives We aimed to investigate the association between LDL-C and hemorrhagic stroke risk in the Chinese community-based population. In addition, we aimed to explore the potential modifying effect of obesity status, particularly abdominal obesity, on this relationship. Methods A total of 7899 eligible subjects, without history of stroke and myocardial infarction, and any use of lipid-lowering medication at baseline, were enrolled in this study. Levels of LDL-C, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were assessed at baseline. The primary endpoint was the hemorrhagic stroke. Abdominal obesity was defined as waist circumference > 90 cm in men and > 85 cm in women. Results Of all participants, the mean age was 56.13 ± 8.87 years, 2848 (36.1%) were male. During a mean 9.71-year follow-up, 66 hemorrhagic strokes occurred. After multivariable adjustment (Figure 1), compared to participants with LDL-C levels 2.6 – 3.4 mmol/L, those with LDL-C levels < 1.8 mmol/L had 3.32 times the risk (hazard ratio [HR]: 3.32; 95% confidence interval [CI]: 1.24, 8.84) of incident hemorrhagic stroke. Compared with participants with TC levels 3.1 – 5.2 mmol/L, HR (95% CI) was 7.82 (2.36, 25.90) for hemorrhagic stroke in those with TC < 3.1 mmol/L. We observed no significant associations between TG or HDL-C levels and hemorrhagic stroke risk. Interaction effects were found between obesity and LDL-C for incident hemorrhagic stroke. Accordingly, significant associations between low LDL-C level (< 1.8 mmol/L) and the risk of incident hemorrhagic stroke were found only among abdominal obesity participants (HR: 3.76; 95% CI: 1.01, 13.97), or those with body mass index (BMI) > = 24 kg/m2 (HR: 3.74; 95% CI: 1.24, 11.34) (Figure 2). Conclusions LDL-C levels < 1.8mmol/L and TC levels < 3.1mmol/L were associated with increased risk of hemorrhagic stroke. Modifying effect of obesity status on the association between low LDL-C level and hemorrhagic stroke was observed in our study.

Advanced Applications of Nanomaterials in Atherosclerosis Diagnosis and Treatment: Challenges and Future Prospects.

Atherosclerosis-induced coronary artery disease is a major cause of cardiovascular mortality. Clinically, conservative treatment strategies for atherosclerosis still focus on lifestyle interventions and the use of lipid-lowering and anticoagulant medications. Despite achieving some therapeutic effects, these approaches are limited by low bioavailability, long intervention periods, and significant side effects. With the advancement of nanotechnology, nanomaterials have demonstrated extraordinary potential in the biomedical field. Their excellent biocompatibility, surface modifiability, and high targeting capability not only enable efficient diagnosis of plaque progression but also allow precise drug delivery within atherosclerotic plaques, significantly enhancing drug bioavailability and reducing systemic side effects. Here, we systematically review the current research progress of nanomaterials in the field of atherosclerosis to summarize not only the types of nanomaterials but also their applications in both the diagnosis and treatment of atherosclerosis. Notably, in the context of plaque therapy, we provide a comprehensive overview of current nanomaterial applications based on their targeted therapeutic systems for different cell types within plaques. Additionally, we address the persistent challenge of clinical translation of nanomaterials by summarizing current issues and providing directions for innovation and improvement in nanomaterial design. Overall, we believe that this review systematically summarizes the applications and challenges of biomedical nanomaterials in atherosclerosis diagnosis and therapy, thereby offering insights and references for the development of therapeutic materials for atherosclerosis.

Predicting the risk of coronary artery calcium progression in the general population: insights from the MESA and CARDIA studies

AIMCoronary artery calcium (CAC) progression is a strong predictor of cardiovascular disease. This study aims to develop and validate a practical tool for predicting individual CAC progression in the general population. METHODSData were utilized from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, comprising 5486 participants (47.3% male, mean ± SD age: 61.9 ± 10.2 years), who were randomly assigned to either a training set or an internal validation set at a 7:3 ratio. Additionally, a separate cohort of 2447 participants (44.6% male, mean ± SD age: 40.4 ± 3.5 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) study served as the external validation set. A nomogram was developed based on a Cox regression model incorporating 10 variables selected by the least absolute shrinkage and selection operator (LASSO) method to predict CAC progression. RESULTSFrom the 61 features considered, 10 key variables were identified: age, male sex, smoking status, waist circumference, systolic blood pressure, fasting glucose, lipid abnormalities, and the use of antihypertensive, glucose-lowering, and lipid-lowering medications. The nomogram demonstrated good discrimination, with a C-statistic of 0.682 (95% CI, 0.665–0.699) in the training set and 0.750 (95% CI, 0.729–0.771) in the external validation set. Decision curve analysis further confirmed the nomogram’s clinical utility in predicting the risk of CAC progression. CONCLUSIONOur nomogram offers a practical tool for individualized prediction of CAC progression, potentially aiding in the primary prevention of cardiovascular disease in clinical practice. Registration URLhttps://www.clinicaltrials.gov; Unique identifier: NCT00005130 (CARDIA), NCT00005487 (MESA)

Optimal blood pressure control with fewer antihypertensive medications: Achieved mostly in low-risk hypertensive patients.

Recent studies indicate that intensive blood pressure (BP) targets can be reached with less than two medications. This cross-sectional study, involving 4991 individuals from the Majiapu community, assessed the correlation between BP control and the burden of antihypertensive drugs. Participants on medication were categorized into controlled (BP<140/90mm Hg) and uncontrolled (BP≥140/90mm Hg) groups, with the former further divided into optimal (BP<130/80mm Hg) and good control (BP<140/90 but >130/80mm Hg) subgroups. Multivariate logistic regression analyzed factors affecting hypertension control across these BP categories. The study found that, 54% of participants had hypertension. Of those treated (62.5%), 55.7% achieved BP control, including 23.15% maintaining BP below 130/80mm Hg. The average number of antihypertensive medications was 1.61 for the controlled group (with an average BP of 126.6/76mm Hg) and 1.75 for the uncontrolled group (with an average BP of 150.6/84.0mm Hg). Additionally, the average number of antihypertensive medications was 1.66 in the good control group and 1.55 in the optimal control group. The uncontrolled group had a higher mean systematic coronary risk estimation (SCORE) of 5.59, against 3.97 and 2.5 in the good and optimal control groups, respectively. Key factors linked to poor BP control included age over 65, male sex, obesity, and former smoking, whereas lipid-lowering medication use was associated with better control. In conclusions, patients needing fewer antihypertensive drugs to achieve stricter targets may have a lower risk profile. Notably, only a small proportion of treated patients are low-risk individuals who can easily achieve BP levels below 130/80mm Hg.

Novel insights into the association between genetically proxied inhibition of proprotein convertase subtilisin/kexin type 9 and risk of sarcopenia.

The effects of lipid-lowering drugs [including statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors] on hyperlipidaemia have been established. Some may have treatment effects beyond their reported properties, offering potential opportunities for drug repurposing. Epidemiological studies have reported conflicting findings on the relationship between lipid-lowering medication use and sarcopenia risk. We performed a two-sample Mendelian randomization (MR) study to investigate the causal association between the use of genetically proxied lipid-lowering drugs (including statins, ezetimibe, and PCSK9 inhibitors, which use low-density lipoprotein as a biomarker), and sarcopenia risk. The inverse-variance weighting method was used with pleiotropy-robust methods (MR-Egger regression and weighted median) and colocalization as sensitivity analyses. According to the positive control analysis, genetically proxied inhibition in lipid-lowering drug targets was associated with a lower risk of coronary heart disease [PCSK9 (OR, 0.67; 95% CI, 0.61 to 0.72; P=7.7E-21); 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR; OR, 0.68; 95% CI, 0.57 to 0.82; P=4.6E-05), and Niemann-Pick C1-like 1 (NPC1L1; OR, 0.53; 95% CI, 0.40 to 0.69; P=3.3E-06)], consistent with drug mechanistic actions and previous trial evidence. Genetically proxied inhibition of PCSK9 (beta, -0.040; 95% CI, -0.068 to -0.012; P=0.005) and circulating PCSK9 levels (beta, -0.019; 95% CI, -0.033 to -0.005; P=0.006) were associated with reduced appendicular lean mass (ALM) with concordant estimates in terms of direction and magnitude. Validation analyses using a second instrument for PCSK9 yielded consistent results in terms of direction and magnitude [(PCSK9 to ALM; beta, -0.052; 95% CI, -0.074 to -0.032; P=7.1E-7); (PCSK9 protein to ALM; beta, -0.060; 95% CI, -0.106 to -0.014; P=0.010)]. Genetically proxied inhibition of PCSK9 gene expression in the liver may be associated with reduced ALM (beta, -0.013; 95% CI, -0.035 to 0.009; P=0.25), consistent with the results of PCSK9 drug-target and PCSK9 protein MR analyses, but the magnitude was less precise. No robust association was found between HMGCR inhibition (beta, 0.048; 95% CI, -0.015 to 0.110; P=0.14) or NPC1L1 (beta, 0.035; 95% CI, -0.074 to 0.144; P=0.53) inhibition and ALM, and validation and sensitivity MR analyses showed consistent estimates. This MR study suggested that PCSK9 is involved in sarcopenia pathogenesis and that its inhibition is associated with reduced ALM. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of sarcopenia.

Lipid-Lowering Medication and Outcomes After Anatomical and Functional Imaging in Suspected Coronary Artery Disease.

Anatomical and functional imaging identify different phenotypes of coronary artery disease (CAD) that may have implications for lipid-lowering medication (LLM). The aim of this study was to assess the associations between LLM and long-term outcomes after combined anatomical and functional imaging in patients with suspected obstructive CAD. Consecutive patients (n=1,973; 41% men; median age: 63 years) underwent coronary computed tomography angiography (CTA) because of suspected CAD. Patients in whom obstructive CAD was not ruled out by CTA underwent ischemia testing by positron emission tomography. Data on LLM purchases were collected until 2 years, and the combined endpoints of death, myocardial infarction, and unstable angina pectoris were assessed at a median of 6.7 years. After imaging, LLM was used by 24% of patients with no CAD, 51% of patients with nonobstructive CAD, 72% of patients with obstructive CAD on CTA without myocardial ischemia, and 91% of patients with myocardial ischemia. The use of LLM decreased during follow-up, with 77% of patients with myocardial ischemia using LLM for 2 years. The use ofLLM was associated with a lower annual rate of adverse events in patients with myocardial ischemia (6.1% vs 2.8%; P= 0.032) or obstructive CAD without myocardial ischemia (2.9% vs 1.4%; P = 0.004) but not in patients with nonobstructive CAD (1.5% vs 1.4%; P = 0.89) or no CAD (0.3% vs 0.3%; P = 0.68). The CAD phenotype defined by anatomical and functional imaging guides the use of LLM. The presence of myocardial ischemia and anatomical obstructive coronary lesions were associated with a long-term outcome benefit from LLM.

Scoping Review on Associations Between Dietary Intake and Lipid-Lowering Medication Use

Scoping Review on Associations Between Dietary Intake and Lipid-Lowering Medication Use

Repurposing lipid-lowering drugs as potential treatment for acne vulgaris: a Mendelian randomization study.

Acne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for acne vulgaris remains underexplored. This study seeks to investigate the impact of lipid-lowering therapies on the risk of developing acne vulgaris using two-sample Mendelian randomization (MR) analysis. The two-sample MR method was employed for analysis, and information on lipid-lowering drugs was obtained from the DrugBank and ChEMBL databases. The summary data for blood low-density lipoprotein (LDL) and triglycerides were sourced from the Global Lipids Genetics Consortium, while genome-wide association studies (GWAS) summary data for acne vulgaris were obtained from the FinnGen database. Heterogeneity was examined using the Q-test, horizontal pleiotropy was assessed using MR-Presso, and the robustness of analysis results was evaluated using leave-one-out analysis. The MR analysis provided robust evidence for an association between lowering LDL cholesterol through two drug targets and acne vulgaris, with PCSK9 showing an odds ratio (OR) of 1.782 (95%CI: 1.129-2.812, p = 0.013) and LDL receptor (LDLR) with an OR of 1.581 (95%CI: 1.071-2.334, p = 0.021). Similarly, targeting the lowering of triglycerides through lipoprotein lipase (LPL) was significantly associated with an increased risk of acne vulgaris, indicated by an OR of 1.607 (95%CI: 1.124-2.299, p = 0.009). The current MR study presented suggestive evidence of a positive association between drugs targeting three genes (PCSK9, LDLR, and LPL) to lower lipids and a reduced risk of acne vulgaris.

Epigenetic age acceleration is associated with blood lipid levels in a multi-ancestry sample of older U.S. adults.

Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia. We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids. After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment. Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages.

Trends in the Use of Medications for Secondary Ischemic Stroke Prevention in Denmark, 2005-2021.

Understanding trends in the use of medications for secondary stroke prevention is crucial for identifying areas for improvement in stroke care. We examined the use of lipid-lowering, antihypertensive, glucose-lowering, oral anticoagulant, and antiplatelet medications after ischemic stroke hospitalization, from 2005 to 2021. Using nationwide registries in Denmark, we identified a cohort of patients discharged from hospital with a first-time or recurrent ischemic stroke (N = 150,744). Stratified by calendar year, we ascertained the 180-day probability of filling a prescription for the abovementioned medications after discharge. We further assessed factors associated with medication use. From 2005 to 2021, lipid-lowering medication use increased from 58.3% to 82.0%; atorvastatin use rose from 2.1% to 64.8% and simvastatin use decreased from 55.7% to 8.6%. Antihypertensive medication use remained stable, at approximately 89%, and various antihypertensive classes were used comparably. Glucose-lowering medication use increased from 71.5% in 2005 to 84.1% in 2021, driven primarily by an increase in metformin use (from 28.0% to 59.5%). Use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors continually increased (from 1.7% to 17.5% and from 0.5% to 17.3%, respectively) between 2015 and 2021. Anticoagulant medication use rose from 45.9% in 2005 to 87.0% in 2021, primarily because of increased use of direct oral anticoagulant medications starting around 2010 and a decline in warfarin use. Antiplatelet use remained consistently high, at approximately 95%. Trends were consistent across subgroups of interest; however, overall medication use was lower in older patients (65 years and older), patients with severe stroke, and patients with neurologic and psychiatric comorbidities. Despite increasing trends in the use of 3 of 5 medication classes, the overall use of lipid-lowering, glucose-lowering, and oral anticoagulant medications was somewhat lower than expected according to clinical guidelines, particularly among older patients with more severe stroke and other comorbidities. The relatively low use in these subgroups may signify appropriate clinical decision making in consideration of frequent contraindications and reduced life expectancy or highlight potential areas of improvement for the care of patients with recent ischemic stroke.

Longitudinal blood glucose level and increased silent myocardial infarction: a pooled analysis of four cohort studies

BackgroundFasting glucose (FG) demonstrates dynamic fluctuations over time and is associated with cardiovascular outcomes, yet current research is limited by small sample sizes and relies solely on baseline glycemic levels. Our research aims to investigate the longitudinal association between FG and silent myocardial infarction (SMI) and also delves into the nuanced aspect of dose response in a large pooled dataset of four cohort studies.MethodsWe analyzed data from 24,732 individuals from four prospective cohort studies who were free of myocardial infarction history at baseline. We calculated average FG and intra-individual FG variability (coefficient of variation), while SMI cases were identified using 12-lead ECG exams with the Minnesota codes and medical history. FG was measured for each subject during the study’s follow-up period. We applied a Cox regression model with time-dependent variables to assess the association between FG and SMI with adjustment for age, gender, race, Study, smoking, longitudinal BMI, low-density lipoprotein level, blood pressure, and serum creatinine.ResultsThe average mean age of the study population was 60.5 (sd: 10.3) years with median fasting glucose of 97.3 mg/dL at baseline. During an average of 9 years of follow-up, 357 SMI events were observed (incidence rate, 1.3 per 1000 person-years). The association between FG and SMI was linear and each 25 mg/dL increment in FG was associated with a 15% increase in the risk of SMI. This association remained significant after adjusting for the use of lipid-lowering medication, antihypertensive medication, antidiabetic medication, and insulin treatment (HR 1.08, 95% CI 1.01–1.16). Higher average FG (HR per 25 mg/dL increase: 1.17, 95% CI 1.08–1.26) and variability of FG (HR per 1 sd increase: 1.23, 95% CI 1.12–1.34) over visits were also correlated with increased SMI risk.ConclusionsHigher longitudinal FG and larger intra-individual variability in FG over time were associated in a dose–response manner with a higher SMI risk. These findings support the significance of routine cardiac screening for subjects with elevated FG, with and without diabetes.

Abstract MP22: Age-Varying Implications of Recalibration of Cardiovascular Disease Risk Prediction in a New England-Based Healthcare System

Introduction: Atherosclerotic cardiovascular disease (ASCVD) risk estimation via the 2013 Pooled Cohort Equations (PCE) overestimates risk in population-based cohorts. We evaluated its recalibration performance in a contemporary healthcare cohort. Methods: We identified 160,926 patients in the Mass General Brigham healthcare system aged 40-79 years and without prior ASCVD or lipid-lowering medication use between 2010 and 2012. Recalibration was achieved using sex- and race-specific baseline survival and risk factor distributions of the derivation (80%) set. Internal validation compared Kaplan-Meier-adjusted observed and predicted risk based on original versus recalibrated PCE. Changes in sensitivity and specificity were calculated across various treatment thresholds for each age decile. Results: Of the 160,926 patients (mean [SD] age: 54.6 [8.6] years; 61.4% female; 82.7% non-Hispanic White), 20,373 (12.7%) underwent ASCVD over 10 years. The original PCE underestimated ASCVD risk (observed vs. predicted incidence rate: 0.13 vs. 0.05) globally and across all sex, race, and risk categories. After recalibration (observed vs. predicted incidence rate: 0.13 vs. 0.18), the prediction closely mirrored the actual ASCVD incidence in low-to-borderline risk but overestimated risk in the high risk. At ≥7.5% treatment threshold, patients aged 40-49 years derived the greatest net relative benefit (sensitivity: +42.9%; specificity: -26.6%) whereas the extent of specificity loss surpassed that of sensitivity gain beyond age 50 years with minimal reclassification by seventh decade in life. Treatment threshold yielding the greatest net benefit was incrementally higher with older age from ≥7.4% in age 40-49 years to ≥24.1% in 60-69 years. Conclusion: In healthcare setting, PCE significantly underestimated risk. Recalibration recovered sensitivity at the expense of reduced specificity in age-differential manner, highlighting the need for individualized prediction and clinical decision-making.

Omentin associates with serum metabolite profiles indicating lower diabetes risk: KORA F4 Study

IntroductionCirculating omentin levels have been positively associated with insulin sensitivity. Although a role for adiponectin in this relationship has been suggested, underlying mechanisms remain elusive. In order to reveal the...

Low Handgrip Strength (Possible Sarcopenia) With Insulin Resistance Is Associated With Type 2 Diabetes Mellitus.

Older adults with sarcopenic obesity are at high risk for type 2 diabetes mellitus (T2DM). However, few East Asians have sarcopenic obesity. Since many East Asians have insulin resistance (IR) without obesity, it is possible that older East Asians with sarcopenia and IR might be at high risk for T2DM. However, this relationship has not been studied. This cross-sectional study included 1629 older adults aged 65 to 84 years registered in the Bunkyo Health Study. All underwent a 75-g oral glucose tolerance test and handgrip strength measurement. Participants were classified into 4 groups by possible sarcopenia (handgrip strength <28 kg in men and <18 kg in women) and IR status (triglyceride glucose [TyG] index ≥8.79 for men and ≥8.62 for women [third quartile]). Modified Poisson regression was used to estimate relative risk (RR) and 95%CIs for T2DM with adjustment for confounding factors. The mean age was 73.1 ± 5.4 years. T2DM was diagnosed in 212 (13.0%) participants. After adjusting for age, sex, body mass index, use of lipid-lowering medications, hypertension, and cardiovascular disease, possible sarcopenia and IR were associated with T2DM, with their coexistence showing a notably stronger association (control: RR, 1.00 [Reference]; possible sarcopenia: RR, 1.55 [95% CI, 1.04-2.30]; IR: RR, 2.69 [95% CI, 1.99-3.65]; and IR possible sarcopenia: RR, 4.76 [95% CI, 3.34-6.79]). Possible sarcopenia based on low handgrip strength and IR based on the TyG index are independently associated with T2DM in older Japanese individuals. Their coexistence shows a particularly strong association with T2DM.

PCSK-9 inhibitors: a new direction for the future treatment of ischemic stroke.

Ischemic stroke, the most prevalent and serious manifestation of cerebrovascular disease, is the main cause of neurological problems that require hospitalization, resulting in disability and death worldwide. Currently, clinical practice focuses on the effective management of blood lipids as a crucial approach to preventing and treating ischemic stroke. In recent years, a great breakthrough in ischemic stroke treatment has been witnessed with the emergence and use of a novel lipid-lowering medication, Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor. And its remarkable potential for reducing the occurrence of ischemic stroke is being acknowledged. This article aims to provide a comprehensive review, encompassing the association between PCSK9 and the heightened risk of ischemic stroke, the mechanisms, and the extensive evidence supporting the proven efficacy of PCSK9 inhibitors in clinical practice. Through this present study, we can gain deeper insights into the utilization and impact of PCSK9 inhibitors in treating ischemic stroke.

Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: a longitudinal registry-based cohort study

BackgroundDisturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms.ObjectiveTo explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment.MethodsA longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users.ResultsOur cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent.ConclusionsSome patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses.

The analysis of serum lipids profile in Guillain-Barre syndrome.

Guillain-Barre syndrome (GBS) is an immune-mediated inflammatory peripheral neuropathy. This study aimed to conduct a systematic analysis of the serum lipids profile in GBS. We measured the serum lipids profile in 85 GBS patients and compared it with that of 85 healthy controls matched for age and sex. Additionally, we analyzed the correlation between lipids and the severity, subtypes, precursor infections, clinical outcomes, clinical symptoms, immunotherapy, and other laboratory markers of GBS. Compared to the healthy controls, GBS exhibited significantly elevated levels of Apolipoprotein B (APOB), Apolipoprotein C2 (APOC2), Apolipoprotein C3 (APOC3), Apolipoprotein E (APOE), triglycerides (TG), and residual cholesterol (RC). Conversely, Apolipoprotein A1 (APOA1), Apolipoprotein A2 (APOA2), and high-density lipoprotein (HDL) were substantially lower in GBS. Severe GBS displayed noticeably higher levels of APOC3 and total cholesterol (TC) compared to those with mild disease. Regarding different clinical outcomes, readmitted GBS demonstrated higher RC expression than those who were not readmitted. Moreover, GBS who tested positive for neuro-virus antibody IGG in cerebrospinal fluid (CSF) exhibited heightened expression of APOC3 in comparison to those who tested negative. GBS with cranial nerve damage showed significantly reduced expression of HDL and APOA1 than those without such damage. Additionally, GBS experiencing limb pain demonstrated markedly decreased HDL expression. Patients showed a significant reduction in TC after intravenous immunoglobulin therapy. We observed a significant positive correlation between lipids and inflammatory markers, including TNF-α, IL-1β, erythrocyte sedimentation rate (ESR), white blood cells, monocytes, and neutrophils in GBS. Notably, APOA1 exhibited a negative correlation with ESR. Furthermore, our findings suggest a potential association between lipids and the immune status of GBS. The research demonstrated a strong connection between lipids and the severity, subtypes, clinical outcomes, precursor infections, clinical symptoms, immunotherapy, inflammation, and immune status of GBS. This implies that a low-fat diet or the use of lipid-lowering medications may potentially serve as an approach for managing GBS, offering a fresh viewpoint for clinical treatment of this condition.

Prevalence, awareness, treatment and control of dyslipidaemia and their determinants: results from a population-based survey of 60 283 residents in eastern China

ObjectivesTo investigate the prevalence, awareness, treatment and control of dyslipidaemia and its associated factors in eastern China.DesignCross-sectional study.SettingData were collected from the 2017 Nanjing Chronic Disease and Risk Factor Surveillance.ParticipantsThis...