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Epigenetics and precision medicine in cardiovascular patients: from basic concepts to the clinical arena.

ABSTRACT: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and also inflict major burdens on morbidity, quality of life, and societal costs. Considering that CVD preventive medications improve vascular outcomes in less than half of patients (often relative risk reductions range from 12% to 20% compared with placebo), precision medicine offers an attractive approach to refine the targeting of CVD medications to responsive individuals in a population and thus allocate resources more wisely and effectively. New tools furnished by advances in basic science and translational medicine could help achieve this goal. This approach could reach beyond the practitioners 'eyeball' assessment or venerable markers derived from the physical examination and standard laboratory evaluation. Advances in genetics have identified novel pathways and targets that operate in numerous diseases, paving the way for 'precision medicine'. Yet the inherited genome determines only part of an individual's risk profile. Indeed, standard genomic approaches do not take into account the world of regulation of gene expression by modifications of the 'epi'genome. Epigenetic modifications defined as 'heritable changes to the genome that do not involve changes in DNA sequence' have emerged as a new layer of biological regulation in CVD and could advance individualized risk assessment as well as devising and deploying tailored therapies. This review, therefore, aims to acquaint the cardiovascular community with the rapidly advancing and evolving field of epigenetics and its implications in cardiovascular precision medicine.

SUBMITTER: Costantino S

PROVIDER: S-EPMC6293269 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Epigenetics and precision medicine in cardiovascular patients: from basic concepts to the clinical arena.

Costantino Sarah S Libby Peter P Kishore Raj R Tardif Jean-Claude JC El-Osta Assam A El-Osta Assam A Paneni Francesco F

European heart journal 20181201 47

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and also inflict major burdens on morbidity, quality of life, and societal costs. Considering that CVD preventive medications improve vascular outcomes in less than half of patients (often relative risk reductions range from 12% to 20% compared with placebo), precision medicine offers an attractive approach to refine the targeting of CVD medications to responsive individuals in a population and thus allocate resources ...[more]

PMID: 29069341

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Project description:Cardiovascular diseases remain the leading cause of mortality and a major contributor to preventable deaths worldwide. The dominant modifiable risk factors and the social and environmental determinants that increase cardiovascular risk are known, and collectively, are as important in racial and ethnic minority populations as they are in majority populations. Their prevention and treatment remain the foundation for cardiovascular health promotion and disease prevention. Genetic and epigenetic factors are increasingly recognized as important contributors to cardiovascular risk and provide an opportunity for advancing precision cardiovascular medicine. In this review, we explore emerging concepts at the interface of precision medicine and cardiovascular disease in racial and ethnic minority populations. Important among these are the lack of racial and ethnic diversity in genomics studies and biorepositories; the resulting misclassification of benign variants as pathogenic in minorities; and the importance of ensuring ancestry-matched controls in variant interpretation. We address the relevance of epigenetics, pharmacogenomics, genetic testing and counseling, and their social and cultural implications. We also examine the potential impact of precision medicine on racial and ethnic disparities. The National Institutes of Health's All of Us Research Program and the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine Initiative are presented as examples of research programs at the forefront of precision medicine and diversity to explore research implications in minorities. We conclude with an overview of implementation research challenges in precision medicine and the ethical implications in minority populations. Successful implementation of precision medicine in cardiovascular disease in minority populations will benefit from strategies that directly address diversity and inclusion in genomics research and go beyond race and ethnicity to explore ancestry-matched controls, as well as geographic, cultural, social, and environmental determinants of health.

Dataset Information

Epigenetics and precision medicine in cardiovascular patients: from basic concepts to the clinical arena.

Publications

Epigenetics and precision medicine in cardiovascular patients: from basic concepts to the clinical arena.

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