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(Circulation. 2008;118:1854-1863.)
© 2008 American Heart Association, Inc.

Contemporary Reviews in Cardiovascular Medicine

Genetic Determinants of Sudden Cardiac Death

Peter A. Noseworthy, MD; Christopher Newton-Cheh, MD, MPH

From the Cardiology Division (P.A.N., C.N.-C.), the Center for Human Genetic Research (C.N.-C.), and Cardiovascular Research Center (C.N.-C.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass; and the Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Mass (C.N.-C.).

Correspondence to Christopher Newton-Cheh, MD, MPH, Center for Human Genetic Research, Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge St, CPZN 5.242, Boston, MA 02114. E-mail cnewtoncheh@chgr.mgh.harvard.edu

Key Words: death, sudden • epidemiology • genetics • heart arrest • tachyarrhythmias

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Sudden cardiac death (SCD) is the final common end point of multiple disease processes. It results from a complex interplay of structural, metabolic, and genetic determinants. Although epidemiological risk factors such as age, prior myocardial infarction, and low ejection fraction are well established, this syndrome also has a strong genetic component. An understanding of the genetic contributions to risk could add substantially to the prediction and prevention of SCD. In this review, we explore the epidemiology, heritability, and allelic architecture of SCD and provide a detailed overview of the genetics of inherited electrophysiological and structural heart diseases that are potent risk factors for SCD.

	Epidemiology of SCD

 
Each year, SCD claims >300 000 lives in the United States.¹ Most cases, 80%, are related to underlying coronary artery disease. Fewer cases, 10% to 15%, are associated with an underlying nonischemic myopathic process such as hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). Approximately 5% are estimated to have a primary defect of cardiac electrophysiology (eg, long-QT syndrome [LQTS] or Brugada syndrome [BS]).²

At the population level, the conventional cardiac risk factors are powerful risk factors for SCD. For example, diabetes mellitus is associated with a marked increase in risk of SCD (odds ratio=1.7 without microvascular disease; odds ratio=2.7 with microvascular disease).³ Among subjects with known coronary artery disease, smoking is linked to an increase in risk of SCD (hazard ratio=2.5).⁴ In a multivariate analysis from the Paris Prospective Study, a 42-mg/dL increase in total cholesterol (1 SD of the sample variation) was associated with a . . . [Full Text of this Article]

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