Low density lipoprotein (LDL) physical-chemical characteristics were studied as nontraditional risk factors of coronary artery disease (CAD) in a well-characterized population of 98 men aged < or = 50 and 100 women aged < or = 60 who underwent elective diagnostic coronary arteriography. The average LDL diameter was determined by gradient gel electrophoresis, chemical composition (%w/w) was measured, and the density of the major LDL peak was determined by equilibrium density gradient ultracentrifugation. Logistic regression was used to examine the association of various LDL characteristics with CAD before and after adjustment for other covariates. Smaller, cholesterol-poor LDL particles were associated with CAD independently of traditional risk factors (age, sex, smoking, diabetes, LDL and HDL cholesterol concentrations), other than the plasma triglyceride concentration. These characteristics were generally more strongly associated with CAD when measured on the major LDL subfraction (defined as the density gradient ultracentrifugation fraction with the highest LDL concentration) than the average characteristics of the more heterogeneous parent LDL (d 1.019-1.063 g/ml). The associations with CAD among men and women were generally similar. These data show that a broad range of LDL characteristics are associated with CAD before, but not after, adjustment for the plasma triglyceride concentration. These data further indicate the importance of hypertriglyceridemia and LDL heterogeneity in premature CAD.