Cholesterol metabolism in familial hypertriglyceridemia: Effects of obesity versus triglyceride level

Excessive production of cholesterol has been associated with type IV hyperlipidemia, but the influence of the confounding variable of obesity has been difficult to ascertain. Moreover, cholesterol metabolism has not been systematically evaluated in patients with familial hypertriglyceridemia (FHT), one of the two major subsets of type IV patients. We used isotope dilution to measure cholesterol production, pools, and kinetic constants in 8 hypertriglyceridemic subjects, 6 of whom could be confidently classified as FHT. These were compared with measurements in 9 control subjects matched for sex, age, serum cholesterol, and body mass index (BMI). By t test, hypertriglyceridemic subjects did not differ from controls with respect to cholesterol production, size of readily or slowly miscible pools, or kinetic transfer coefficients. Results were the same whether controls were compared with all hypertriglyceridemic patients or only the 6 with definite FHT. By analysis of covariance (ANCOVA), serum triglyceride level was not a significant determinant of any parameter of cholesterol metabolism. However, BMI was a highly significant determinant of cholesterol production (p = 0.0001) and size of both readily and slowly miscible pools (p = 0.001 to 0.008). These data suggest that FHT per se is not associated with abnormalities of cholesterol metabolism but that an apparent association could result from the confounding variable of obesity.