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(Circulation. 2003;108:519.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Coronary Artery Disease Risk in Familial Combined Hyperlipidemia and Familial Hypertriglyceridemia

A Case-Control Comparison From the National Heart, Lung, and Blood Institute Family Heart Study

Paul N. Hopkins, MD, MSPH; Gerardo Heiss, MD, PhD; R. Curtis Ellison, MD; Michael A. Province, PhD; James S. Pankow, PhD; John H. Eckfeldt, MD, PhD; Steven C. Hunt, PhD

From Cardiovascular Genetics Research, University of Utah, Salt Lake City, UT (P.N.H., S.C.H.); Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC (G.H.); Boston University School of Medicine, Boston, MA (R.C.E.); Division of Biostatistics, Washington University, St Louis, Mo (M.A.P.); Division of Epidemiology, School of Public Health (J.S.P.), and Department of Laboratory Medicine and Pathology (J.H.E.), University of Minnesota, Minneapolis, Minn.

Correspondence to Paul N. Hopkins, MD, MSPH, Cardiovascular Genetics, 410 Chipeta Way, Room 167, Salt Lake City, UT 84108. E-mail paul{at}ucvg.med.utah.edu

Received December 17, 2002; de novo received March 3, 2003; revision received May 9, 2003; accepted May 12, 2003.

Background— Conventional wisdom suggests that a diagnosis of familial combined hyperlipidemia (FCHL) carries a substantially greater risk of premature coronary artery disease (CAD) than a diagnosis of familial hypertriglyceridemia (FHTG). However, no population-based studies have critically addressed this issue.

Methods and Results— FCHL and FHTG were diagnosed in 10.2% and 12.3% of 334 random control families and in 16.7% and 20.5% of 293 families with at least one case of premature CAD. The diagnosis of either FCHL or FHTG in an individual was associated with an odds ratio for CAD of 2.0 (P=0.003 and 0.002, respectively). However, odds ratios for premature CAD associated with both lipid disorders decreased substantially and identically with further adjustment for hypertension, diabetes, and especially HDL cholesterol, triglycerides, or apolipoprotein B. Similar results were found for differences in carotid intima-medial thickness and ankle-brachial index. Metabolic syndrome was identified in 65% of FCHL and 71% of FHTG patients compared with 19% in controls without FCHL or FHTG and was associated with an odds ratio of 3.3 (P<0.0001). The increased prevalence of the metabolic syndrome alone could account for the elevated CAD risk associated with both FCHL and FHTG.

Conclusions— FCHL and FHTG appear more alike than dissimilar. Further, the risk of CAD in FCHL and FHTG was strongly related to features of the metabolic syndrome. These findings suggest that the hypertriglyceridemia in FHTG is not benign and may warrant a change in epidemiological, genetic, and clinical approaches to these lipid disorders.

Key Words: coronary disease • genetics • lipoproteins • epidemiology

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