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

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.