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A family history of coronary heart disease (CHD) is a known risk factor for CHD. To investigate the possible role of lipoprotein particles in the relationship between family history of CHD and risk of CHD, we performed a case-control study in a sample of adolescents. The case group consisted of 97 adolescents whose parents had suffered a verified myocardial infarction before the age of 55 years. The control group was composed of 194 subjects without any family history of CHD. One case patient was matched to two control subjects for gender, age, and body mass index. In both groups, plasma lipid variables were measured, including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), lowdensity lipoprotein cholesterol, apolipoprotein (apo)AI, apoB, apoAI-containing lipoprotein particles without apoAII (LpAI) and with apoAII, and apoB-containing lipoprotein particles with apoE and with apoCIII. Adolescents with a family history of early myocardial infarction had lower plasma levels of HDL-C (/ » <.0001), apoAI (P<.01), and LpAI (P<.0001) than control subjects (adjusted for gender, age, body mass index, smoking habits, and oral contraceptive use). No other differences were statistically significant between case and control subjects. The analysis was repeated separately for male and female subjects. In young men, the best predictor of family history of early myocardial infarction was the LpAI plasma level, whereas in young women it was the HDL-C plasma level. Decreased levels of HDL-C and LpAI lipoprotein particles explain part of the relationship between parental history of early myocardial infarction and CHD risk. (Arterioscler Thromb. 1993;13:1640-1644 KEY WORDS • lipoproteins • LpAI • family history • coronary heart disease • adolescents • risk factors A family history of coronary heart disease (CHD) predicts CHD in adults, 1 which suggests that k. family history may be a useful tool for identifying high-risk subjects at a young age. This increased CHD risk in those with a positive family history is partly related to the familial clustering of known risk factors such as cigarette smoking, obesity, and plasma lipid levels.2 Among these risk factors, abnormalities in lipid metabolism have been extensively studied. Alterations in plasma lipoprotein and apolipoprotein (apo) levels are variously associated with parental history of CHD in children, adolescents, young adults, and adults: plasma low-density lipoprotein cholesterol (LDL-C) and apoB levels are higher 3 ' 4 and high-density lipoprotein cholesterol (HDL-C) and apoAI levels 5 7 are lower in subjects with a family history of CHD.Biochemical and immunological analyses show that these lipoprotein subfractions are heterogeneous and include subpopulations with different lipid and apolipoprotein compositions.8 By using combinations of mono- clonal and polyclonal antibodies directed against apolipoproteins, it is possible to identify HDL subpopulations of apoAI-containing lipoparticles without apoAII (LpAI) or with apoAII (LpAILAI); LDL subp...