BackgroundTo discern whether hypertriglyceridemia (hyper-TG, TG >95th percentile) and hypoalphalipoproteinemia (hypoalpha, high-density lipoprotein [HDL-C] 10th percentile) are jointly transmitted in families, we studied 385 probands with marked elevations in TG or cholesterol levels (TG or cholesterol >99th percentile in a previous visit) and their 2072 first-degree relatives in the Lipid Research Clinics' Family Study. Repeat TG measurement, with exclusion criterion of TG ≤95th percentile, resulted in 162 probands with hyper-TG.Methods and ResultsWhen the proband demonstrated the conjoint trait (CT; ie, TG >95th percentile, HDL-C 10th percentile, n=82), an average of 10.6% of first-degree relatives conjointly expressed hyper-TG and hypoalpha in contrast to only 4.1% of first-degree relatives of a proband who expressed high TG levels with normal HDL-C levels (TG >95th percentile, HDL-C >10th percentile, n=80). Hyper-TG was expressed in 24.2% of first-degree relatives of probands with CT. However, hyper-TG was expressed in only 14.4% of first-degree relatives of probands with hyper-TG alone. CT probands and their family members tended to have more reported cardiac events and symptoms (P=.02 and.09, respectively) than those subjects associated with hyper-TG alone.ConclusionsThe differences in HDL-C-TG abnormalities between families related to hyper-TG probands with or without hypoalpha indicate that bottom decile HDL-C is not simply secondary to hyper-TG. A familial interaction is suggested between HDL-C and TG levels consistent with the transmission of hyper-TG and hypoalpha among first-degree relatives. Among subjects and their families with hyper-TG, those who in addition have low HDL-C demonstrate a tendency for more coronary artery disease than do those with normal HDL-C levels.