Are Genetic Tests for Atherosclerosis Ready for Routine Clinical Use?

Paynter, Nina P.; Ridker, Paul M.; Chasman, Daniel I.

doi:10.1161/circresaha.115.306360

Cited by 30 publications

(20 citation statements)

References 144 publications

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“…Although it has been shown that genetic testing can potentially be used to guide treatment in patients with familial hypercholesterolemia, the use of genetic testing in other settings, such as primary prevention, is not currently recommended. 85 miRNAs are small noncoding RNAs that regulate gene expression (Table 4). In the general population, miRNA-126 is positively correlated with the risk of future coronary events (adjusted hazard ratio, 2.69), whereas miR-223 and miR-197 are inversely associated with the risk of future coronary events.…”

Section: Geneticsmentioning

confidence: 99%

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

2017

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Abstract:The use of risk markers has transformed cardiovascular medicine, exemplified by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, and imaging parameters offers further refinement. Identifying novel risk factors may allow greater risk stratification and a steady, but gradual progression toward precision medicine. Indeed, the generation of data in this area of research is explosive and when combined with new technologies and techniques provides the potential for more refined, targeted approaches to cardiovascular medicine. Although discussing the most recent developments in this field, this review article aims to strike a balance between novelty and validity by focusing on recent large samplesize studies that have been validated in a separate cohort in most cases. Risk markers related to atherosclerosis, thrombosis, inflammation, cardiac injury, and fibrosis are introduced in the context of their pathophysiology. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. Subsequently the prognostic ability of these risk markers in coronary artery disease, heart failure, and atrial fibrillation is discussed in detail. ( addition to these roles in the pathogenesis of coronary artery disease, lipid-related molecules have been identified to be markers of inflammation and oxidative stress (Table 1). Thrombosis-Related Risk MarkersAfter atherosclerotic plaque rupture, platelets adhere to exposed subendothelial components, such as collagen and von Willebrand factor, which promotes platelet activation and aggregation. 10 In addition, platelet activation is potentiated by exposure to released soluble agonists, such as thrombin and ADP.10 Activated platelets then further release ADP, which acts on platelet P2Y 12 ADP receptors and has a central role in amplifying the response of platelets to the initial stimulus. 10 Platelet reactivity to various agonists, including ADP, has been studied extensively in the context of acute coronary syndrome (ACS; Table 2). 11 The VerifyNow and Multiplate pointof-care tests allow for the measurement of platelet aggregation in response to stimulation, and it has been shown that high platelet reactivity is associated with adverse cardiovascular events. 26 Platelet microparticles are released on platelet activation, and their role in cardiovascular disease is an area of active investigation (Table 2). 15 Circulating microparticles are released from cells undergoing activation or apoptosis and are a type of small plasma membrane vesicle that retain defined properties from their original cell lineage. 15 Platelet activation and aggregation lead to the activation of the coagulation cascade and the formation of a stable crosslinked fibrin clot. The balance between prothrombotic factors and endogenous fibrinolysis determines whether the thrombus propagates or instead proceeds to dis...

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Section: Geneticsmentioning

confidence: 99%

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

2017

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“…Recent reviews have highlighted an additional potential use of predicting drug efficacy or toxicity based on human genetics, often termed ‘pharmacogenetics’. 98,99 …”

Section: Genomic Medicinementioning

confidence: 99%

Genetics of coronary artery disease: discovery, biology and clinical translation

2017

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Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked about 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forward, genetic testing could enable precision medicine approaches, by identifying subgroups of patients at increased risk of CAD or those with a specific driving pathophysiology in whom a therapeutic or preventive approach is most useful.

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“…Other methods may provide additional useful clinical information for dyslipidaemias. These techniques include: (1) proteomic methods, whereby protein expression is assessed at the cell or tissue level to indirectly evaluate gene expression; (2) metabolomics, which refers to the concurrent assessment of small molecule metabolites from serum or tissue samples to indirectly evaluate in a targeted manner variations in gene products involved in intermediate biochemical pathways or in drug metabolism; 20,21 and (3) genome-wide transcriptome analysis of RNA expression (e.g., RNASeq) that can be further used to assess gene expression and patterns of alternative RNA splicing within a cell or tissue. 22 Epigenetics is increasingly recognised as affecting genotype-phenotype relationships.…”

Section: Other Advanced Genetic Testsmentioning

confidence: 99%

The role of genetic testing in dyslipidaemia

Berberich

Hegele

2019

Pathology

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Dyslipidaemias encompass about two dozen relatively rare monogenic disorders and syndromes for which the genetic basis has largely been defined. In addition, the complex polygenic basis of disturbed lipids and lipoproteins has been characterised in many patients, and has been shown to result from accumulation of many common polymorphisms with small effects on lipids. Genetic technologies, including dedicated genotyping and sequencing methods can detect both rare and common DNA variants underlying dyslipidaemias. Some dyslipidaemias may be clinically silent for years, but early diagnosis, including genetic diagnosis, may permit early intervention to prevent or delay deleterious downstream clinical consequences, such as premature vascular disease or acute pancreatitis. The potential clinical utility of genetic testing for familial hypercholesterolaemia, familial chylomicronaemia syndrome, lysosomal acid lipase deficiency and some others will increase demand for reliable genetic diagnostic methods. We review some current technologies, such as targeted next-generation sequencing that seem to be helpful with DNA diagnosis of dyslipidaemias. We also address technical, biological and clinical limitations of genetic testing in dyslipidaemias. Finally, genetic counselling issues, the potential impact of results on patients and health care providers, current gaps and future directions will be discussed.

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Are Genetic Tests for Atherosclerosis Ready for Routine Clinical Use?

Cited by 30 publications

References 144 publications

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Genetics of coronary artery disease: discovery, biology and clinical translation

The role of genetic testing in dyslipidaemia

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