Stressing the Endothelium to Assess Localized Inflammatory Potential and the Risk for Atherosclerotic Cardiovascular Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Rohatgi A
PROVIDER: S-EPMC8162315 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Stressing the Endothelium to Assess Localized Inflammatory Potential and the Risk for Atherosclerotic Cardiovascular Disease.
Circulation 20210517 20
Similar Datasets
Project description: Not available
| S-EPMC10774583 | biostudies-literature
Project description:Elevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies with statins and ezetimibe are highly effective for reducing LDL-C levels, over half of high-risk patients do not achieve guideline-recommended LDL-C goals. Thus, there is a significant gap between treatment guidelines and their implementation in daily clinical practice. The major causes are individual variability in the response to lipid-lowering therapies and variation in treatment adherence. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies combined with statins provide marked and consistent reduction in LDL-C levels; however, poor adherence due to the need for subcutaneous injections every 2 or 4 weeks and high cost are major obstacles to their use in real-world clinical settings. Inclisiran, a recently approved novel small interfering ribonucleic acid (siRNA) molecule that inhibits PCSK9 synthesis, provides robust and long-term reduction in LDL-C levels with a low inter-individual variability in the LDL-C-lowering response. Moreover, its administration by biannual injection is expected to greatly improve treatment adherence. Clinical trials of this drug lasting for up to 4 years showed acceptable safety profiles, and ongoing studies accumulate evidence of its longer-term safety. This narrative review summarizes the available evidence on the efficacy and safety of inclisiran and analyzes its potential to overcome the gap between guideline recommendations and real-world clinical practice in current LDL-C-lowering therapies, with a focus on reduced LDL-C level variability and improved treatment adherence.
| S-EPMC9887852 | biostudies-literature
Project description:Introduction: Age is a major risk factor that affects the likelihood of developing atherosclerotic cardiovascular disease (ASCVD). The anticipated 10-year ASCVD risk for nearly all individuals aged 70 years and older surpasses conventional risk thresholds. When considering treatment for risk factors, it is important to take into account ASCVD risk modifiers, such as malnutrition, polypharmacy, and comorbidities. Objectives: The aim of this study was to estimate ASCVD risk in apparently healthy (without established ASCVD) elderly persons. We also evaluated several biochemical and clinical indicators to better characterize the studied population. Patients and methods: A total of 253 elderly individuals aged 70 years and older, who were apparently healthy and did not have established atherosclerotic cardiovascular disease (ASCVD), were enrolled in the study. The Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) model was utilized to assess their 10-year risk of developing ASCVD. Results: Among the 253 participants, 41 (16.2%) were classified as high risk, while 212 (83.8%) were categorized as very high risk. No individuals had a low ASCVD risk (defined as less than 7.5%). The median 10-year risk of developing ASCVD for the study group was 23% (ranging from 17% to 32%). The number of individuals identified as very high risk increased significantly with age, with nearly all participants aged 75 years and older being considered very high risk. An age of 75 years or older is associated with a very high risk for ASCVD, supported by a C-statistic of 0.92, which reflects a positive predictive value (PPV) of 99% and a negative predictive value (NPV) of 52% (p < 0.001). Conclusions: Elderly individuals without established ASCVD constitute a varied group. The majority were identified as being at very high risk for ASCVD. Age and hypertension were the primary factors contributing to this risk. Furthermore, modifiers of ASCVD risk, including malnutrition, polypharmacy, and multimorbidity, were commonly observed.
| S-EPMC11641976 | biostudies-literature
Project description:BackgroundClonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear.MethodsWe used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls. To assess causality, we perturbed the function of Tet2, the second most commonly mutated gene linked to clonal hematopoiesis, in the hematopoietic cells of atherosclerosis-prone mice.ResultsIn nested case-control analyses from two prospective cohorts, carriers of CHIP had a risk of coronary heart disease that was 1.9 times as great as in noncarriers (95% confidence interval [CI], 1.4 to 2.7). In two retrospective case-control cohorts for the evaluation of early-onset myocardial infarction, participants with CHIP had a risk of myocardial infarction that was 4.0 times as great as in noncarriers (95% CI, 2.4 to 6.7). Mutations in DNMT3A, TET2, ASXL1, and JAK2 were each individually associated with coronary heart disease. CHIP carriers with these mutations also had increased coronary-artery calcification, a marker of coronary atherosclerosis burden. Hypercholesterolemia-prone mice that were engrafted with bone marrow obtained from homozygous or heterozygous Tet2 knockout mice had larger atherosclerotic lesions in the aortic root and aorta than did mice that had received control bone marrow. Analyses of macrophages from Tet2 knockout mice showed elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis.ConclusionsThe presence of CHIP in peripheral-blood cells was associated with nearly a doubling in the risk of coronary heart disease in humans and with accelerated atherosclerosis in mice. (Funded by the National Institutes of Health and others.).
| S-EPMC6717509 | biostudies-literature
Project description:Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual's susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction. More than a dozen of large-scale retrospective studies using different sets of biomarkers and different statistical methods have consistently demonstrated the additive prognostic value of these panels over traditionally used clinical risk scores. Prospective studies are needed to determine the clinical utility of a biomarker panel in clinical ASCVD risk stratification. When combined with the genetic predisposition captured with polygenic risk scores and the actual ASCVD phenotype observed with coronary artery imaging, proteomics and lipidomics can advance understanding of the complex multifactorial causes underlying an individual's ASCVD risk.
| S-EPMC10163980 | biostudies-literature
Project description:ObjectiveThis study aims to determine the distribution of observed atherosclerotic cardiovascular disease (ASCVD) incidence in contemporary cohorts in China, and to identify cut-off points for ASCVD risk classification based on traditional criteria and new equations developed by Prediction for ASCVD Risk in China (China-PAR).MethodsThe study populations included cohorts in the China-PAR project, with 34,757 participants eligible for the current analysis. Traditional risk stratification was assessed by using Chinese guidelines on prevention of CVD and hypertension, and 5 risk groups were classified based on these guidelines after slight modification for available risk factors. Kaplan-Meier analysis was conducted to obtain the cumulative incidence of observed ASCVD events for all subjects and sub-groups. The predicted 10-year ASCVD risk was obtained using the China-PAR equations.ResultsA total of 1922 ASCVD events were identified during an average follow-up of 14.1 years. According to the group classification based on traditional risk stratification, the observed 10-year risks for ASCVD were 4.61% (95% confidence interval [CI]: 4.11-5.10%) in the moderate-risk group and 8.74% (95% CI: 7.82-9.66%) in the high-risk group. Based on the China-PAR equations for risk assessment of ASCVD, those with predicted risks of <5%, 5-10%, and ≥10% could be classified into categories of low-, moderate-, and high-risk for ASCVD, respectively.ConclusionThe findings enable development of a simple method for classification of individuals into low-, moderate-, and high-risk groups, based on the China-PAR equations. The method will be useful for self-management and prevention of ASCVD in Chinese adults.
| S-EPMC5643596 | biostudies-literature
Project description:Despite enormous advances in both surgical and pharmacological treatment, cardiovascular diseases are still the most common cause of morbidity and disability in the western world [...].
| S-EPMC9781134 | biostudies-literature
Project description:Atherosclerotic cardiovascular disease (ASCVD) proceeds through a series of stages: initiation, progression (or regression), and complications. By integrating known biology regarding molecular signatures of each stage with recent advances in high-dimensional molecular data acquisition platforms (to assay the genome, epigenome, transcriptome, proteome, metabolome, and gut microbiome), snapshots of each phase of atherosclerotic cardiovascular disease development can be captured. In this review, we will summarize emerging approaches for assessment of atherosclerotic cardiovascular disease risk in humans using peripheral blood molecular signatures and molecular imaging approaches. We will then discuss the potential (and challenges) for these snapshots to be integrated into a personalized movie providing dynamic readouts of an individual's atherosclerotic cardiovascular disease risk status throughout the life course.
| S-EPMC7839236 | biostudies-literature
Project description:BackgroundThe improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested.ObjectivesThis study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis).MethodsThe PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell's C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease-related death, or fatal or nonfatal stroke.ResultsOf 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell's C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell's C statistic when added to the cPCE.ConclusionsCAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers.
| S-EPMC4724058 | biostudies-literature
Project description:BackgroundMicroRNA-10a (miR-10a) inhibits transcriptional factor GATA6 to repress inflammatory GATA6/VCAM-1 signaling, which is regulated by blood flow to affect endothelial function/dysfunction. This study aimed to identify the expression patterns of miR-10a/GATA6/VCAM-1 in vivo and study their implications in the pathophysiology of human coronary artery disease (CAD), i.e., atherosclerosis.MethodsHuman atherosclerotic coronary arteries and nondiseased arteries were used to detect the expressions of miR-10a/GATA6/VCAM-1 in pathogenic vs. normal conditions. In addition, sera from CAD patients and healthy subjects were collected to detect the level of circulating miR-10a.ResultsThe comparison of human atherosclerotic coronary arteries with nondiseased arteries demonstrated that lower levels of endothelial miR-10a are related to human atherogenesis. Moreover, GATA6/VCAM-1 (a downstream target of miR-10a) was highly expressed in the endothelium, accompanied by the reduced levels of miR-10a during the development of human atherosclerosis. In addition, CAD patients had a significantly lower concentration of miR-10a in their serum compared to healthy subjects.ConclusionsOur findings suggest that low miR-10a and high GATA6/VCAM-1 in the cardiovascular endothelium correlates to the development of human atherosclerotic lesions, suggesting that miR-10a signaling has the potential to be developed as a biomarker for human atherosclerosis.
| S-EPMC8298183 | biostudies-literature