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CARDIOVASCULAR GENOMIC MEDICINE

Prospects for Personalized Cardiovascular Medicine

The Impact of Genomics

Geoffrey S. Ginsburg, MD, PhD, FACC^_*,,,_*, Mark P. Donahue, MD, MHS^_*, and L. Kristin Newby, MD, MHS, FACC^_*,

^_* Division of Cardiovascular Medicine, Department of Medicine, Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina.
Duke Clinical Research Institute, Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina.
Center for Genomic Medicine, Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina.

Manuscript received April 18, 2005; revised manuscript received June 23, 2005, accepted June 30, 2005.

^_* Reprint requests and correspondence: Dr. Geoffrey S. Ginsburg, Center for Genomic Medicine, Institute for Genome Sciences & Policy, CIEMAS, 101 Science Drive, Box 3382, Durham, North Carolina 27708. (Email: geoffrey.ginsburg{at}duke.edu).

Sequencing of the human genome has ushered in prospects for individualizing cardiovascular health care. There is growing evidence that the practice of cardiovascular medicine might soon have a new toolbox to predict and treat disease more effectively. The Human Genome Project has spawned several important "omic" technologies that allow "whole genome" interrogation of sequence variation (re-sequencing, genotyping, comparative genome hybridization), transcription (expression profiling, tissue arrays), proteins (gas or liquid chromatography and tandem mass spectroscopy [MS]), and metabolites (MS or nuclear magnetic resonance profiling); deoxyribonucleic acid, ribonucleic acid, protein, and metabolic approaches all provide more exacting detail of cardiovascular disease mechanisms and, in some cases, are redefining its taxonomy. Pharmacogenomic approaches are emerging across broad classes of cardiovascular therapeutics to assist practitioners in making more precise decisions about which drugs to give to which patients to optimize the benefit-to-risk ratio. Molecular imaging is developing chemical and biological probes that can sense molecular pathway mechanisms that will allow us to monitor health and disease. Together, these tools will enable a paradigm shift from genetic medicine—on the basis of the study of individual inherited characteristics, most often single genes—to genomic medicine, which by its nature is comprehensive and focuses on the functions and interactions of multiple genes and gene products, among themselves and with their environment. The information gained from such analyses, in combination with clinical data, is now allowing us to assess individual risks and guide clinical management and decision-making, all of which form the basis for cardiovascular genomic medicine.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ACS = acute coronary syndromes   BNP = brain natriuretic peptide   CAD = coronary artery disease   CI = confidence interval   CK = creatine kinase   CVD = cardiovascular disease   FLAP = 5-lipoxygenase accessory protein   hs-CRP = high-sensitivity C-reactive protein   LQT = long QT   MEF2A = member of the myocyte enhancer factor 2 transcription factor family   MI = myocardial infarction   MS = mass spectroscopy   NMR = nuclear magnetic resonance   PUFA = polyunsaturated fatty acid   RR = relative risk   SNP = single nucleotide polymorphism

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