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Sudden Cardiac Death, Genes, and Arrhythmogenesis  Consideration of New Population and Mechanistic Approaches From a National Heart, Lung, and Blood Institute Workshop, Part I*

(Circulation. 2001;103:2361.) © 2001 American Heart Association, Inc.
Peter M. Spooner, PhD; Christine Albert, MD; Emelia J. Benjamin, MD, ScM; Robin Boineau, MD; Robert C. Elston, PhD; Alfred L. George, Jr, MD; Xavier Jouven, MD; Lewis H. Kuller, MD, PhD; Jean W. MacCluer, PhD; Eduardo Marbán, MD, PhD; James E. Muller, MD; Peter J. Schwartz, MD; David S. Siscovick, MD; Russell P. Tracy, MD, PhD; Wojciech Zareba, MD, PhD; Douglas P. Zipes, MD 2

From the National Heart, Lung, and Blood Institute (P.M.S., R.B.), Bethesda, Md; Brigham and Women’s Hospital (C.A.), Boston, Mass; Boston University (E.J.B.), Boston, Mass; Case Western Reserve University (R.C.E.), Cleveland, Ohio; Vanderbilt University (A.L.G.), Nashville, Tenn; Hospital Boucicaut, Paris, France (X.J.); University of Pittsburgh (L.H.K.), Pittsburgh, Pa; Southwest Foundation for Biomedical Research (J.W.M.), San Antonio, Texas; Johns Hopkins Medical School (E.M.), Baltimore, Md; Harvard Medical School (J.E.M.), Boston, Mass; University of Pavia (P.J.S.) Pavia, Italy; University of Washington (D.S.S.), Seattle; University of Vermont (R.P.T.), Colchester; University of Rochester (W.Z.), Rochester, NY; and Indiana University (D.P.Z.), Indianapolis.

Abstract—Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation, in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality.

quote from part II
"Parental history of SCD increased the relative risk of SCD to 1.8 after adjustment for conventional CAD risk factors.."   "In a small subset in which there was a history of both maternal and paternal SCD events, the relative risk for SCD in offspring was a remarkable 9.4." 

This was based on >7,000 men followed for an average of 23 years in a Paris Prospective Study, which included 118 SCDs and 192 myocardial infarction deaths "that occurred in previous healthy participants who had not history of cardiac disease on enrollment."