Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease: Update

Ganesh, Santhi K.; Arnett, Donna K.; Assimes, Themistocles L.; Basson, Craig T.; Chakravarti, Aravinda; Ellinor, Patrick T.; Engler, Mary B.; Goldmuntz, Elizabeth; Herrington, David M.; Hershberger, Ray E.; Hong, Yuling; Johnson, Julie A.; Kittner, Steven J.; McDermott, Deborah A.; Meschia, James F.; Mestroni, Luisa; O’Donnell, Christopher J.; Psaty, Bruce M.; Vasan, Ramachandran S.; Ruel, Marc; Shen, Win Kuang; Terzic, André; Waldman, Scott A.

doi:10.1161/01.cir.0000437913.98912.1d

Cited by 99 publications

(68 citation statements)

References 398 publications

(344 reference statements)

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“…38 Family history and a number of genetic markers are associated with risk of coronary heart disease, but the role of hereditary factors in disease prevention is largely open. 39 Genetic background of the population has not changed during the past 40 years and cannot explain the substantial decrease in coronary heart disease mortality.…”

Section: Population Based Primary Preventionmentioning

confidence: 99%

Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: population based observational study

Jousilahti

Laatikainen

Peltonen

et al. 2016

BMJ

108

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Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: population based observational study interventiOns Change in main cardiovascular risk factors through population based primary prevention. Main OutCOMe MeasuresPredicted and observed age standardised mortality due to coronary heart disease. Predicted change was estimated with a logistic regression model using risk factor data collected in nine consecutive, population based, risk factor surveys conducted every five years since 1972. Data on observed mortality were obtained from the National Causes of Death Register.results During the 40 year study period, levels of the three major cardiovascular risk factors decreased except for a small increase in serum cholesterol levels between . From years 1969 -1972to 2012, coronary heart disease mortality decreased by 82% (from 643 to 118 deaths per 100 000 people) and 84% (114 to 17) among men and women aged 35-64 years, respectively. During the first 10 years of the study, changes in these three target risk factors contributed to nearly all of the observed mortality reduction. Since the mid-1980s, the observed reduction in mortality has been larger than predicted. In the last 10 years of the study, about two thirds (69% in men and 66% in women) of the reduction could be explained by changes in the three main risk factors, and the remaining third by other factors. COnClusiOnReductions in disease burden and mortality due to coronary heart disease can be achieved through the use of population based primary prevention programmes. Secondary prevention among high risk individuals and treatment of acute events of coronary heart disease could confer additional benefit.

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Section: Population Based Primary Preventionmentioning

confidence: 99%

Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: population based observational study

Jousilahti

Laatikainen

Peltonen

et al. 2016

BMJ

108

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“…A 2013 American Heart Association statement 26 supports the notion that for rare and familial forms of CVD, we are identifying single-gene mutations that impart relatively large effects on individual phenotype. For these cases, progress has led to several clinically useful diagnostic tests.…”

Section: Genetic Variationmentioning

confidence: 99%

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Ferguson¹,

Allayee²,

Gerszten³

et al. 2016

Circ Cardiovasc Genet

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Abstract-Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies investigating the relationship between genetic variants and diet in modulating cardiometabolic risk, as well as the effects of dietary components on multiple "omic" measures, including transcriptomics, metabolomics, proteomics, lipidomics, epigenetic modifications, and the microbiome. Here, we describe the current state of the field of nutrigenomics with respect to cardiometabolic disease research and outline a direction for the integration of multiple omics techniques in future nutrigenomic studies aimed at understanding mechanisms and developing new therapeutic options for cardiometabolic disease treatment and prevention. The interpretation and scope of nutrigenomics may vary, but it can be thought to encompass the spectrum of nutritional genomics research, including classic nutrigenetics studies of gene-diet interactions and molecular nutrition, in vitro and in vivo models, human nutrition studies, and the application of largescale, unbiased studies using high-throughput "omics" techniques to study the effects of nutrients on the body. 6 As the Figure shows, diet and the genome may influence cardiometabolic health through a variety of interconnected intermediates, perturbations in which can be measured through omics technologies, including RNA expression (transcriptome), epigenetic modifications (epigenome), metabolites (metabolome), lipids (lipidome), proteins (proteome), and resident microbial communities (microbiome). Although it is clear that both nutrients and genes play a distinct role in determining health, the complex interactions among genes, diet, and downstream networks are not well understood. The application of nutrigenomics approaches to questions of human health and disease is an important component in understanding the complexities of the interplay between basic metabolic processes and externalThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 22, 2016, and the American Heart Association Executive Committee on February 23, 2016. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The...

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“…Moreover, genetic association studies have discovered that variants in numerous genes impact cardiovascular disease risk. 42 Functional evaluation of these genetic loci to characterize their impact on disease pathology at the individual patient level may reveal opportunities for the development of targeted therapies. Current and future clinical trials will determine whether or not these findings will translate into successful therapeutic strategies for cardiovascular disease and increased implementation of personalized medicine approaches.…”

Section: Discussion and Future Perspectivementioning

confidence: 99%

Personalized Cardiovascular Medicine Today

et al. 2015

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Abstract-Over the past decade, personalized medicine has received considerable attention from researchers, drug developers, and regulatory agencies. Personalized medicine includes identifying patients most likely to benefit and those most likely to experience adverse reactions in response to a drug, and tailoring therapy based on pharmacokinetics or pharmacodynamic response, as well. Perhaps most exciting is finding ways to identify likely responders through genetic, proteomic, or other tests, so that only likely responders will be treated. However, less precise methods such as identifying historical, demographic, or other indicators of increased or reduced responsiveness are also important aspects of personalized medicine. The cardiovascular field has not used many genetic or proteomic markers, but has regularly used prognostic variables to identify likely responders. The development of biomarker-based approaches to personalized medicine in cardiovascular disease has been challenging, in part, because most cardiovascular therapies treat acquired syndromes, such as acute coronary syndrome and heart failure, which develop over many decades and represent the end result of several pathophysiological mechanisms. More precise disease classification and greater understanding of individual variations in disease pathology could drive the development of targeted therapeutics. Success in designing clinical trials for personalized medicine will require the selection of patient populations with attributes that can be targeted or that predict outcome, and the use of appropriate enrichment strategies once such attributes are identified. Here, we describe examples of personalized medicine in cardiovascular disease, discuss its impact on clinical trial design, and provide insight into the future of personalized cardiovascular medicine from a regulatory perspective.

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Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease: Update

Cited by 99 publications

References 398 publications

Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: population based observational study

Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: population based observational study

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Personalized Cardiovascular Medicine Today

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