Prevalence of Tendon Rupture and Tendinopathies Among Patients with Atherosclerotic Cardiovascular Disease Derived From United States Administrative Claims Data.

INTRODUCTION: The prevalence of tendon rupture and tendinopathies (TRT) has not been determined in a large population of patients with atherosclerotic cardiovascular disease (ASCVD). We investigated TRT prevalence among patients with ASCVD and in the general population, using data from the Symphony Health Integrated Dataverse, a large US medical and pharmacy claims database. METHODS: This retrospective, observational study included patients aged ≥ 19 years from the claims database during the identification period (January 2019 to December 2020) and 12 months of continuous enrollment. The primary outcome was evidence of TRT in the 12 months following the index date (first ASCVD diagnosis in the ASCVD cohort; first claim in the claims database in the overall population). Diagnostic codes (ICD-10 and/or CPT) were used to define ASCVD and TRT diagnosis. RESULTS: The ASCVD cohort and overall population included 5,589,273 and 61,715,843 patients, respectively. In the ASCVD cohort, use of medications with a potential or known association with TRT was identified in 67.9% (statins), 17.7% (corticosteroids), and 16.7% (fluoroquinolones) of patients. Bempedoic acid use was reported in 1556 (< 0.1%) patients. TRT prevalence during 12-month follow-up was 3.4% (ASCVD cohort) and 1.9% (overall population). Among patients with ASCVD, 83.5% experienced TRT in only one region of the body. Factors most associated with TRT in the ASCVD cohort were increasing age, most notably in those aged 45-|64 years (odds ratio [OR] 2.19; 95% confidence interval [CI] 2.07-2.32), obesity (OR 1.51; 95% CI 1.50-1.53), and rheumatoid arthritis (OR 1.47; 95% CI 1.45-1.79). Use of statins or bempedoic acid was not associated with increased TRT risk. CONCLUSION: Patients with ASCVD may have greater risk of TRT than the general population, which may be driven by an increased prevalence of comorbidities and use of medications with a potential or known association with TRT.

Patients with atherosclerosis, the main cause of heart attacks, strokes, and peripheral vascular disease, typically require several drugs to control the disease. Some of the drugs used to treat atherosclerosis have been linked to a higher occurrence of tendon tears (or ruptures) or swelling/inflammation of the tendons (tendinopathies). However, there may be other factors present in these patients that increase the risk of tendon injuries that are not related to these drugs. This study used the medical records of over 5.5 million patients with atherosclerosis and over 63 million patients reflecting the general population in the United States to determine the prevalence of tendon injury. Additionally, the researchers looked at other factors that might be related to a higher risk of tendon injury in each group. Over a 12-month period, tendon injuries occurred in 3.4% of patients with atherosclerosis and 1.8% of patients in the general population. In patients with atherosclerosis, factors such as being obese, older (45­64 years), or having rheumatoid arthritis were also linked to an increased risk of tendon injuries. There was no association seen between statin or bempedoic acid use and tendon injuries. These results may help healthcare providers to determine the underlying risk of tendon injuries and guide treatment of this patient population.

Early Onset Atherosclerotic Cardiovascular Disease.

Recent trends indicate a concerning increase in early-onset atherosclerotic cardiovascular disease (ASCVD) among younger individuals (age < 55 in men and <65 in women). These findings highlight the pathobiology of ASCVD as a disease process that begins early in life and underscores the need for more tailored screening methods and preventive strategies. Increasing attention has been placed on the growing burden of traditional cardiometabolic risk factors in young individuals while also recognizing unique factors that mediate risk of premature atherosclerosis in this demographic such as substance use, socioeconomic disparities, adverse pregnancy outcomes, and chronic inflammatory states that contribute to the increasing incidence of early ASCVD. Additionally, mounting evidence has pointed out significant disparities in the diagnosis and management of early ASCVD and cardiovascular outcomes based on sex and race. Moving toward a more personalized approach, emerging data and technological developments using diverse tools such as polygenic risk scores and coronary artery calcium scans have shown potential in earlier detection of ASCVD risk. Thus, we review current evidence on causal risk factors that drive the increase in early ASCVD and highlight emerging tools to improve ASCVD risk assessment in young individuals.

When Does Primary Prevention Encroach on Secondary Prevention?

PURPOSE OF REVIEW: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. RECENT FINDINGS: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

Emerging clinical role of proprotein convertase subtilisin/kexin type 9 inhibition-Part two: Current and emerging concepts in the clinical use of PCSK9 inhibition.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid-lowering effects. OBJECTIVE: This review aims to discuss existing and novel strategies of PCSK9 inhibition, providing an overview of established randomized controlled trials and ongoing outcome trials that assess the efficacy and long-term safety of PCSK9 inhibitors. It also explores the evolving role of PCSK9 beyond lipid metabolism and outlines the pleiotropic actions of PCSK9 inhibition in various disorders and future directions including novel strategies to target PCSK9. CONCLUSION: PCSK9 inhibition shows promise not only in lipid metabolism but also in other disease processes, including atherosclerotic plaque remodeling, acute coronary syndrome, stroke, inflammation, and immune response.

Cardiovascular disease risk: it is complicated, but race and ethnicity are key, a Bayesian network analysis.

Background: Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Despite the complexity of cardiovascular disease etiology, we do not fully comprehend the interactions between non-modifiable factors (e.g., age, sex, and race) and modifiable risk factors (e.g., health behaviors and occupational exposures). Objective: We examined proximal and distal drivers of cardiovascular disease and elucidated the interactions between modifiable and non-modifiable risk factors. Methods: We used a machine learning approach on four cohorts (2005-2012) of the National Health and Nutrition Examination Survey data to examine the effects of risk factors on cardiovascular risk quantified by the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). We estimated a network of risk factors, computed their strength centrality, closeness, and betweenness centrality, and computed a Bayesian network embodied in a directed acyclic graph. Results: In addition to traditional factors such as body mass index and physical activity, race and ethnicity and exposure to heavy metals are the most adjacent drivers of PCE. In addition to the factors directly affecting PCE, sleep complaints had an immediate adverse effect on FRS. Exposure to heavy metals is the link between race and ethnicity and FRS. Conclusion: Heavy metal exposures and race/ethnicity have similar proximal effects on cardiovascular disease risk as traditional clinical and lifestyle risk factors, such as physical activity and body mass. Our findings support the inclusion of diverse racial and ethnic groups in all cardiovascular research and the consideration of the social environment in clinical decision-making.

Establishment and validation of prediction model for atherosclerotic cardiovascular disease in patients with hyperuricemia.

OBJECTIVE: To construct a risk prediction model for atherosclerotic cardiovascular disease (ASCVD) in patients with hyperuricemia. METHODS: Data in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) (2007-2010). Participants from Huashan Hospital were included as an external validation. Logistic regression analysis was used to explore the relevant factors of ASCVD in patients with hyperuricemia. The discriminability of the model was evaluated using the area under the curve (AUC) statistic of the receiver operating characteristic curve. Hosmer-Lemeshow test, correction curve and decision curve analysis (DCA) were used to evaluate the model. RESULTS: A total of 389 patients collected from the NHANES were included in the final analysis. Logistic regression analysis showed that age, creatinine (Cr), glucose (Glu), serum uric acid (SUA), and history of gout were predictive factors for ASCVD in hyperuricemia (HUA) patients. These predictive factors were used to construct a nomogram. And 157 patients from NHANES were in the internal validation group and 136 patients from Huashan Hospital were in the external validation group. The AUC values of the three groups were 0.943, 0.735, and 0.664. The p values of the Hosmer-Lemeshow test were .568, .600, and .763. The calibration curve showed consistency between the nomogram and the actual observed values. The DCA curve indicated that the model has good clinical practicality. CONCLUSION: This study constructed the ASCVD risk prediction model for HUA patients, which is beneficial for medical staff to detect high-risk populations of ASCVD in the early stage.

Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

The Acute Coronary Syndrome Risk in Medically Managed Subjects with Type 2 Diabetes Mellitus - Is the ASCVD Risk Score Failing Here?

Objectives: Type 2 Diabetics have elevated risk for acute coronary syndrome (ACS). The current management algorithm focuses on atherosclerotic cardiovascular (ASCVD) risk score to stratify this risk. However, in medically managed subjects, this algorithm may not be accurate. This study compares the ASCVD risk score in an Indian population with T2DM under medical supervision and the actual incidence of ACS. It also compared the ASCVD risk scores in cases with T2DM who developed ACS to controls and tried to estimate whether the ASCVD risk score is different in the two subsets, evaluating the utility of the ASCVD risk score in predicting ACS. Methodology: This is an electronic medical record (EMR) based case-control study. Only records of subjects with T2DM where details of age, sex, body mass index, blood pressure, duration of diabetes, family history of ACS, lipid profile, renal and liver function tests were included. The incidence of ACS was calculated in the selected records, and the records of subjects with ACS were compared with age and sex-matched subjects without ACS. Data are summarized as median and interquartile range (IQR). Wilcoxon rank-sum test was used for checking differences in continuous variables and Pearson's Chi-squared test for categorical data. Univariate and multivariate logistic regression analyses were used to check the effect of ASCVD scores and other variables on the occurrence of ACS.Statistical data analyses were performed using JASP, version 0.16.4 (JASP Team [2022]) for MS Windows. Results: Of the 1226 EMRs included in the analysis, 207 had ACS. The actual incidence of ACS was 16.85% in 6 years, higher than the mean predicted 10-year incidence of 14.56 percent (p <0.05). The cases were age and sex-matched with controls and the ASCVD incidence was estimated in the two groups. The mean ASCVD score in the cases was 14.565 ± 8.709 (Min: 1.5, Max: 38.3) and controls 13.114 ± 8.247 (Min: 1.4, Max: 45). The chance of development of ACS increases with elevated systolic blood pressure (per mmHg rise OR: 1.04, 95% CI: 1.03, 1.06; p <0.001), positive family history (OR: 5.70, 95% CI: 3.41, 9.77; p <0.001), statin use (OR: 2.26, 95% CI: 1.46, 3.52; p <0.001), and longer duration of diabetes (for every year increase OR: 1.19, 95% CI: 1.13, 1.25; p <0.001). Conclusion: The ASCVD risk score underestimates the ACS risk in subjects with T2DM under medical supervision and may not differ in those who developed and did not develop ACS. We also conclude that factors like a negative family history (30% less risk), longer duration of diabetes, and higher SBP are relevant in those who developed ACS.

Association of triglyceride-glucose index and its related parameters with atherosclerotic cardiovascular disease: evidence from a 15-year follow-up of Kailuan cohort.

BACKGROUND: Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. METHOD: A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. RESULTS: During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged < 60 years (Pfor interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of 0.004 (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS. CONCLUSIONS: Both the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD.

Coronary artery calcium in 2023: Guidelines for LDL-C goals, non-statin therapies, and aspirin use.

Personalizing risk assessment and treatment decisions for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) rely on pooled cohort equations and increasingly coronary artery calcium (CAC) score. A growing body of evidence supports that elevated CAC scores correspond to progressively elevated ASCVD risk, and that scores of ≥100, ≥300, and ≥1000 denote risk that is equivalent to certain secondary prevention populations. This has led consensus guidelines to incorporate CAC score thresholds for guiding escalation of preventive therapy for lowering low-density lipoprotein cholesterol goals, initiation of non-statin lipid lowering medications, and use of low-dose daily aspirin. As data on CAC continues to grow, more decision pathways will incorporate CAC score cutoffs to guide management of blood pressure and cardiometabolic medications. CAC score is also being used to enrich clinical trial study populations for elevated ASCVD risk, and to screen for subclinical coronary atherosclerosis in patients who received chest imaging for other diagnostic purposes.

Inclisiran: the preclinical discovery and development of a novel therapy for the treatment of atherosclerosis.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality. Lipid lowering therapy (LLT) constitutes the cornerstone of ASCVD prevention and treatment. However, several patients fail to achieve therapeutic goals due to low treatment adherence or limitations of standard-of-care (SoC) LLTs. Inclisiran represents a pivotal low-density lipoprotein cholesterol (LDL-C) lowering agent aiming to address current unmet needs in LLT. It is the first available small interfering RNA (siRNA) LLT, specifically targeting PCSK9 mRNA and leading to post-transcriptional gene silencing (PTGS) of the PCSK9 gene. AREAS COVERED: Promising phase III trials revealed an ~ 50% reduction in LDL-C levels with subcutaneous inclisiran administration on days 1 and 90, followed by semiannual booster shots. Coupled with inclisiran's favorable safety profile, these findings led to its approval by both the EMA and FDA. Herein, the authors highlight the preclinical discovery and development of this agent and provide the reader with their expert perspectives. EXPERT OPINION: The evolution of gene-silencing treatments offers new perspectives in therapeutics. Inclisiran appears to have the potential to revolutionize ASCVD prevention and treatment, benefiting millions of patients. Ensuring widespread availability of Inclisiran, as well as managing additional healthcare costs that may arise, should be of paramount importance.

The Impact of an Educational Intervention on Enhancing Clinical Knowledge of Physicians and Pharmacists Regarding Statins and Monitoring Parameters: The Experience of a Tertiary Teaching Hospital.

Introduction: Understanding the latest guideline recommendations is crucial for healthcare professionals to apply statin therapy effectively. Thus, the purpose of this study was to evaluate the efficacy of an educational intervention in enhancing the awareness and understanding of physicians and pharmacists concerning risk assessment of Atherosclerotic cardiovascular disease (ASCVD) and the role of statin therapy. Methods: This pre- and post-intervention study was conducted in Sana'a, Yemen's capital city, at the University of Science and Technology Hospital. The study was done between 11/2021-12/2021, and two separate educational sessions were held. The McNemar's test and Wilcoxon signed-rank test were employed as necessary. Results: Participants' awareness of the Framingham CVD risk calculator improved significantly from 40.4% pre-intervention to 78.7% post-intervention. Similarly, understanding of the parameters used in the 10-year ASCVD Risk calculator rose from 46.8% pre-intervention to 76.6% post-intervention. The ability to identify high, moderate, and low-intensity statin therapy, for instance, increased from 34% to 63.8% post-intervention. Regarding statins' contraindications, safety, and efficacy monitoring parameters, pre-intervention knowledge was unsatisfactory, and the educational intervention improved it significantly (p <0.05). For physicians, the median ASCVD risk assessment knowledge score was significantly improved from 4 (IQR = 3-5) pre-intervention to 7 (6.25-8) immediately post-intervention, while the statin therapy clinical knowledge median score significantly improved from 3 (1.25-6.5) to 9 (7.25-14.75) post-education intervention, p-values were 0.002 and 0.003; respectively. For pharmacists, a similar significant improvement (p <0.05) in the overall knowledge scores for both ASCVD risk assessment and statin therapy was noted. Conclusion: The educational intervention improved participants' knowledge of statin therapy and ASCVD risk assessment. Therefore, further education lectures and training programs through continuing medical education on the up-to-date guidelines' recommendations should be regularly implemented to raise awareness and improve the clinical knowledge and appropriateness of statins use in clinical settings. .

The current landscape for diabetes treatment: Preventing diabetes-associated CV risk.

Despite the risk of atherosclerosis has progressively declined over the past few decades, subjects with type 2 diabetes mellitus (T2DM) continue to experience substantial excess of atherosclerotic cardiovascular disease (ASCVD)-related events. Therefore, there is urgent need to treat ASCVD disease in T2DM earlier, more intensively, and with greater precision. Many factors concur to increase the risk of atherosclerosis, and multifactorial intervention remains the basis for effective prevention or reduction of atherosclerotic events. The role of anti-hyperglycemic medications in reducing the risk of ASCVD in subjects with T2DM has evolved over the past few years. Multiple cardiovascular outcome trials (CVOTs) with new and emerging glucose-lowering agents, namely SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RA), have demonstrated significant reductions of major cardiovascular events and additional benefits. This robust evidence has changed the landscape for managing people with T2DM. In addition to glycemic and ancillary extra-glycemic properties, SGLT2i and GLP1-RA might exert favorable effects on subclinical and clinical atherosclerosis. Therefore, the objective of this review is to discuss the available evidence supporting anti-atherosclerotic properties of SGLT2i and GLP1-RA, with a quick nod to sotagliflozin and tirzepatide.

Temporal trends and racial/ethnic- and sex-differences in LDL cholesterol control among US adults with self-reported atherosclerotic cardiovascular disease.

Objective: Current guidelines for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend targeting a low-density lipoprotein cholesterol (LDL-C) of < 70 mg/dL. However, temporal trends and racial/ethnic- and sex-differences in achievement of LDL-C targets are not well described. We assessed trends and racial/ethnic- and sex-differences in achievement of LDL-C < 70 mg/dL using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008 to 2017-March 2020. Methods: We combined NHANES cycles into 4 periods: 2005-2008, 2009-2012, 2013-2016, and 2017-March 2020 and included participants ≥ 40 years with self-reported ASCVD. We estimated LDL-C < 70 mg/dL prevalence over time and further stratified by sex and race/ethnicity. We used multivariable logistic regression adjusted for social determinants of health and clinical covariates to model LDL-C target attainment. Results: Among 1,826 NHANES participants representing 7,161,221 US adults with self-reported ASCVD (59.6% ≥ 65 years, 56.4% male, 74.8% White), LDL-C target attainment increased from 19.0% (95% CI, 15.3%-23.3%) in 2005-2008 to 26.3% (95% CI, 20.4%-33.1%) in 2017-March 2020 (P = 0.012 for trend). Achievement of LDL-C < 70 mg/dL significantly rose among men from19.5% (95% CI, 15.1%-24.8%) to 29.4% (95% CI, 20.7%-29.9%) without significant change in women (from 18.3% [95% CI, 13.6%-24.2%] to 22.5% [95% CI, 13.0%-35.9%]; P = 0.241 for trend). Improvement in LDL-C target attainment was similar among White, Black, and Hispanic individuals (∼5-7% increase) and was greatest among individuals of other (non-White, Hispanic, or Black) race/ethnicity (23.1% increase). In our multivariable analysis, comorbid diabetes and ages 65-75 and > 75 years were associated with LDL-C target attainment. Conclusion: LDL-C control modestly improved between 2005 and 2008 and 2017-March 2020; however, only ∼1/4 of individuals met guideline-directed LDL-C treatment targets by 2017-March 2020. Women had lower LDL-C control and lesser magnitude of improvement in LDL-C control than men, highlighting a need for targeted interventions to improve lipid-lowering therapy utilization in this population.

Xanthohumol, a prenylated chalcone, regulates lipid metabolism by modulating the LXRα/RXR-ANGPTL3-LPL axis in hepatic cell lines and high-fat diet-fed zebrafish models.

Angiopoietin-like 3 (ANGPTL3) acts as an inhibitor of lipoprotein lipase (LPL), impeding the breakdown of triglyceride-rich lipoproteins (TGRLs) in circulation. Targeting ANGPTL3 is considered a novel strategy for improving dyslipidemia and atherosclerotic cardiovascular diseases (ASCVD). Hops (Humulus lupulus L.) contain several bioactive prenylflavonoids, including xanthohumol (Xan), isoxanthohumol (Isoxan), 6-prenylnaringenin (6-PN), and 8-prenylnaringenin (8-PN), with the potential to manage lipid metabolism. The aim of this study was to investigate the lipid-lowering effects of Xan, the effective prenylated chalcone in attenuating ANGPTL3 transcriptional activity, both in vitro using hepatic cells and in vivo using zebrafish models, along with exploring the underlying mechanisms. Xan (10 and 20 µM) significantly reduced ANGPTL3 mRNA and protein expression in HepG2 and Huh7 cells, leading to a marked decrease in secreted ANGPTL3 proteins via hepatic cells. In animal studies, orally administered Xan significantly alleviated plasma triglyceride (TG) and cholesterol levels in zebrafish fed a high-fat diet. Furthermore, it reduced hepatic ANGPTL3 protein levels and increased LPL activity in zebrafish models, indicating its potential to modulate lipid profiles in circulation. Furthermore, molecular docking results predicted that Xan exhibits a higher binding affinity to interact with liver X receptor α (LXRα) and retinoic acid X receptor (RXR) than their respective agonists, T0901317 and 9-Cis-retinoic acid (9-Cis-RA). We observed that Xan suppressed hepatic ANGPTL3 expression by antagonizing the LXRα/RXR-mediated transcription. These findings suggest that Xan ameliorates dyslipidemia by modulating the LXRα/RXR-ANGPTL3-LPL axis. Xan represents a novel potential inhibitor of ANGPTL3 for the prevention or treatment of ASCVD.

Atherosclerotic cardiovascular disease risk among Ghanaians: A comparison of the risk assessment tools.

Objectives: Risk stratification is a cornerstone for preventing atherosclerotic cardiovascular disease (ASCVD). Ghana has yet to develop a locally derived and validated ASCVD risk model. A critical first step towards this goal is assessing how the commonly available risk models perform in the Ghanaian population. This study compares the agreement and correlation between four ASCVD risk assessment models commonly used in Ghana. Methods: The Ghana Heart Study collected data from four regions in Ghana (Ashanti, Greater Accra, Northern, and Central regions) and excluded people with a self-declared history of ASCVD. The 10-year fatal/non-fatal ASCVD risk of participants aged 40-74 was calculated using mobile-based apps for Pooled Cohort Equation (PCE), laboratory-based WHO/ISH CVD risk, laboratory-based Framingham risk (FRS), and Globorisk, categorizing them as low, intermediate, or high risk. The risk categories were compared using the Kappa statistic and Spearman correlation. Results: A total of 615 participants were included in this analysis (median age 55 [Inter quartile range 46, 64]) years with 365 (59.3 %) females. The WHO/ISH risk score categorized 504 (82.0 %), 58 (9.4 %), and 53 (8.6 %) as low-, intermediate-, and high-risk, respectively. The PCE categorized 345 (56.1 %), 181 (29.4 %), and 89 (14.5 %) as low-, intermediate- and high-risk, respectively. The Globorisk categorized 236 (38.4 %), 273 (44.4 %), and 106 (17.2 %) as low-, intermediate-, and high-risk, respectively. Significant differences in the risk categorization by region of residence and age group were noted. There was substantial agreement between the PCE vs FRS (Kappa = 0.8, 95 % CI 0.7 - 0.8), PCE vs Globorisk (Kappa = 0.6; 95 % CI 0.6 - 0.7), and FRS vs Globorisk (Kappa = 0.6; 95 % CI 0.6 - 0.7). However, there was only fair agreement between the WHO vs Globorisk (Kappa = 0.3; 95 % CI 0.3-0.4) and moderate agreement between the WHO vs PCE and WHO vs FRS. Conclusion: There are significant differences in the ASCVD risk prediction tools in the Ghanaian population, posing a threat to primary prevention. Therefore, there is a need for locally derived and validated tools.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults.

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. Results: Compared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17-1.95); p<0.01], stroke [HR 1.47 (1.14-1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19-1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. Conclusion: Lack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

GLP-1RA may have varying effects on cardiac structure in patients with ASCVD depending on BMI.

Background: Glucagon-like peptide-1 receptor agonist(GLP-1RA) is commonly used in patients with cardiovascular disease due to its significant improvement in the prognosis of atherosclerotic cardiovascular disease (ASCVD). However, previous studies have primarily focused on obese patients, leaving uncertainty regarding whether GLP-1RA can yield similar cardiovascular benefits in individuals with normal or low body weight. Methods: In this study, we enrolled patients with ASCVD to establish a retrospective cohort. Patients receiving GLP-1RA treatment were assigned to the GLP-1RA group, while a control group was formed by matching age and body mass index (BMI) among patients not receiving GLP-1RA treatment. Each group was further divided into subgroups based on baseline BMI levels: normal weight, overweight, and obesity. A six-month follow-up was conducted to assess changes in patient weight, metabolic indicators, and cardiac structure and function. Results: Among the normal weight subgroup, no significant weight change was observed after six months of GLP-1RA treatment (57.4 ± 4.8 vs. 58.7 ± 9.2, p = 0.063). However, significant weight reduction was observed in the other two subgroups (Overweight group: 70.0 ± 9.1 vs. 73.1 ± 8.2, p = 0.003, Obesity group: 90.5 ± 14.3 vs. 95.5 ± 16.6, p<0.001). Regardless of baseline BMI levels, GLP-1RA demonstrated significant glucose-lowering effects in terms of metabolic indicators. However, GLP-1RA have a more significant effect on improving blood lipids in overweight and obese patients. The effects of GLP-1RA on cardiac structure exhibited variations among patients with different baseline BMI levels. Specifically, it was observed that the improvement in atrial structure was more prominent in patients with normal body weight(LAD: 33.0 (30.3, 35.5) vs. 35.0 (32.5, 37.1), p = 0.018, LAA (18.0 (16.0, 21.5) vs. 18.5 (16.5, 20.5), p = 0.008), while the enhancement in ventricular structure was more significant in obese subjects(LEVDD: 49.8 ± 5.8 vs. 50.2 ± 5.0, p < 0.001, LVMI: 65.1 (56.2, 71.4) vs. 65.8 (58.9, 80.4), p < 0.039). Conclusion: According to the study, it was found that the administration of GLP-1RA can have different effects on cardiac structure in patients with different baseline BMI, In obese patients, improvements in ventricular remodeling may be more associated with weight loss mechanisms, while in patients with normal or low BMI, GLP-1RA may directly improve atrial remodeling through GLP-1 receptors in atrial tissue.

Decoding Altered Consciousness: An Artery of Percheron Stroke.

The artery of Percheron (AOP) is a unique variant of the thalamic and midbrain perforating arteries. It originates from the P1 branch of the posterior cerebral artery (PCA) and supplies the bilateral paramedian thalami (BPT) along with variable contributions to the rostral midbrain. Four infarction patterns have been identified as a result of an AOP stroke, each associated with varying prognostic outcomes. We present an 89-year-old female with an AOP infarction and discuss the associated symptoms, implicated anatomy, and prognosis.