Apolipoprotein A-1 predicts coronary heart disease only at low concentrations of high-density lipoprotein cholesterol: an epidemiological study of Japanese-Americans

Conventional epidemiological and clinical studies of apolipoprotein A-1 and high-density lipoprotein-cholesterol have demonstrated, when examined join tly, that high-density lipoprotein is a better predictor of coronary heart disease. This strategy does not take into account known lipid metabolic rel ationships. A statistical approach that takes into account apoliprotein A-1 being a constituent of the high-density lipoprotein particle is more appro priate. Among 1,177 Japanese-American men of the Honolulu Heart Program coh ort free of disease at baseline (1980-1982), 182 new coronary heart disease cases developed over a 12-year follow-up period. After removing the linear relationship with high-density lipoprotein-cholesterol, a relative measure of apoliprotein A-1 concentration was derived. Based on joint conditions o f "low" and "high" relative apoliprotein h-l concentration and less than or equal to 40 and >40 mg/dl for the high-density lipoprotein-cholesterol dis tribution, four groupings were created. Among relative joint groupings of h igh/less than or equal to 40, low/less than or equal to 40, high/>40, and l ow/>40, respectively, the 12-year coronary heart disease incidence varied f rom 28.6, 18.2, 8.3, to 11.7 cases per 1,000 person-years. A test of statis tical interaction was significant (P=0.028). Additional analyses revealed c oronary heart disease cases were more likely among men with triglycerides > 190 mg/dl. Observed patterns of relationships among relative apoliprotein A -1 level, high-density lipoprotein cholesterol, and triglycerides with inci dent coronary heart disease are consistent with patterns noted in clinical, laboratory, and transgenic animal research more capable of elucidating mec hanisms of disease causation. This epidemiological study suggests similar m echanisms may be operating at a population level, and may contribute to the public health burden of coronary heart disease.