Dataset Information

The Molecular Basis of Predicting Atherosclerotic Cardiovascular Disease Risk.

ABSTRACT: 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.

SUBMITTER: Nayor M

PROVIDER: S-EPMC7839236 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Molecular Basis of Predicting Atherosclerotic Cardiovascular Disease Risk.

Nayor Matthew M Brown Kemar J KJ Vasan Ramachandran S RS

Circulation research 20210121 2

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 ...[more]

PMID: 33476202

Similar Datasets

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.

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.).

Dataset Information

The Molecular Basis of Predicting Atherosclerotic Cardiovascular Disease Risk.

Publications

The Molecular Basis of Predicting Atherosclerotic Cardiovascular Disease Risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets