Interactions of serum copper, selenium, and low density lipoprotein cholesterol in atherogenesis.

OBJECTIVE: To investigate the interactions between serum copper, selenium, and low density lipoprotein cholesterol concentrations with regard to the progression of carotid atherosclerosis. DESIGN: Longitudinal study of a cohort of middle aged men followed up for 24 months. SETTING: Epidemiological survey of the population of seven communities in eastern Finland. SUBJECTS: 126 men aged 42, 48, 54, or 60 at examination randomly selected from a population based sample of 2682 men. MAIN OUTCOME MEASURES: Increase in maximal carotid intima media thickness. RESULTS: The mean increase in the maximal common carotid intima media thickness after two years was greater in men with high serum copper concentrations (0.16 mm compared with 0.08 mm in men with concentrations less than 17.6 mumol/l; p = 0.010), those with low serum selenium concentrations (0.15 mm compared with 0.09 mm in men with concentrations greater than or equal to 1.40 mumol/l; p = 0.035), and those with raised serum low density lipoprotein cholesterol concentrations (0.15 mm compared with 0.08 mm in men with concentrations less than 4.0 mmol/l; p = 0.032) after adjustment for age and cigarette pack years in a three way analysis of covariance. A raised serum low density lipoprotein concentration was associated with accelerated progression of atherosclerosis only in men with higher than median serum copper concentrations (net difference 0.22 mm; p less than 0.001 for two way interaction), and this synergism was even more pronounced in men with serum selenium concentrations below the median value (net difference 0.41 mm; p = 0.042 for three way interaction). CONCLUSION: These data provide evidence of a synergistic effect of copper (a pro-oxidant), a low serum concentration of selenium (a cofactor of an enzyme that scavenges free radicals), and low density lipoprotein cholesterol concentration in atherogenesis.