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(Circulation. 2000;101:2777.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Cardiovascular Disease Mortality in Familial Forms of Hypertriglyceridemia: A 20-Year Prospective Study

Melissa A. Austin, PhD; Barbara McKnight, PhD; Karen L. Edwards, PhD; Cynthia M. Bradley, MPH; Marguerite J. McNeely, MD, MPH; Bruce M. Psaty, MD, PhD; John D. Brunzell, MD; Arno G. Motulsky, MD

From the Department of Epidemiology (M.A.A, K.L.E., C.M.B.) and the Department of Biostatistics, School of Public Health and Community Medicine (B.M.); the Division of General Internal Medicine, Department of Medicine, School of Medicine, (M.J.M.); the Departments of Medicine, Epidemiology, and Health Services, Cardiovascular Health Research Unit, Schools of Medicine and Public Health and Community Medicine (B.M.P.); the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, School of Medicine (J.D.B.); and the Division of Medical Genetics, Department of Medicine and Department of Genetics (A.G.M.); University of Washington, Seattle.

Correspondence to Melissa A. Austin, PhD, Department of Epidemiology, Box 357236, University of Washington, Seattle, WA 98195-7236. E-mail maustin{at}u.washington.edu

Background—Familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG) are 2 of the most common familial forms of hyperlipidemia. There is a paucity of prospective data concerning the risk of cardiovascular disease (CVD) in such families. The purposes of this study were to estimate 20-year total and CVD mortality risk among relatives in these families and to evaluate plasma triglyceride as a predictor of death.

Methods and Results—The study was based on lipid and medical history data from 101 families ascertained in 2 studies conducted in the early 1970s. Vital status and cause of death was determined during 1993 to 1997 for 685 family members, including first-degree relatives of the probands and spouse control subjects. Compared with spouse control subjects, 20-year CVD mortality risk was increased among siblings and offspring in FCHL (relative risk 1.7, P=0.02) after adjustment for baseline covariates. In FHTG families, the relative risk was also 1.7 but was not statistically significant (P=0.39). Baseline triglyceride was associated with increased CVD mortality risk independent of total cholesterol among relatives in FHTG families (relative risk 2.7, P=0.02) but not in FCHL families (relative risk 1.5, P=0.16) after adjustment for baseline covariates.

Conclusions—This prospective study establishes that relatives in FCHL families are at increased risk for CVD mortality and illustrates the need for effective prevention strategies in this group. Baseline triglyceride level predicted subsequent CVD mortality among relatives in FHTG families, adding to the growing evidence for the importance of hypertriglyceridemia as a risk factor for CVD.

Key Words: cardiovascular diseases • follow-up studies • hyperlipoproteinemia • lipids • mortality

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