BackgroundIn vitro, animal and epidemiological studies suggest that lipoprotein oxidation may play an important role in atherosclerosis. Antioxidants may protect against lipoprotein oxidation and in that way inhibit atherosclerosis and its clinical sequelae. To investigate this possibility, we examined the association between levels of several antioxidants and myocardial infarction using serum specimens collected 7 to 14 years before the onset of myocardial infarction.Methods and ResultsA nested case-control design was used. Cases and control subjects were selected from the 25 802 persons who had donated 15 mL of blood in 1974 for a serum bank. Cases comprised 123 persons with a subsequent first diagnosis of myocardial infarction who ranged from 23 through 58 years of age in 1974 and who had had their first diagnosis of myocardial infarction during 1981 to 1988. Two groups of control subjects matched to the cases for sex and age were selected from donors to the serum bank, one from those with hospital admissions during the same period and the other from the total group of donors. Sera were assayed for four carot-A enoids (β-carotene, lycopene, lutein, and zeaxanthin), α-to-copherol, and cholesterol. Because associations with these serum nutrients showed similar trends whether based on hospital or community controls, the two control groups were combined. There was a significantly increasing risk for subse-quent myocardial infarction with decreasing levels of (β-caro-tene in 1974 (Pvalue for trend,.02) and a suggestive trend with decreasing levels of lutein (P=.09). When the results were stratified by smoking status, the excess risk of myocardial infarction associated with low serum levels of carotenoids was limited to smokers. A protective association with higher levels of α-tocopherol was suggested only among persons with high levels of serum cholesterol.ConclusionsLow serum levels of carotenoids were associ-ated with an increased risk of subsequent myocardial infarc-tion among smokers.