Lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerosis. High plasma Lp(a) concentrations are associated with low-molecular-weight (LMW) apolipoprotein(a) (apo a) phenotypes, which raises the question of whether LMW apo a phenotypes occur less frequently in the elderly. To assess this possibility, we studied apo A phenotype and allele frequencies in Japanese subjects > or = 80 years old (men:women = 40:34) in comparison with those <80 years old (men:women = 221:296). Significantly fewer LMW phenotypes and LMW alleles were observed in > or = 80 year old men compared with those < 80 years old: 2.5% versus 16.1% for the LMW phenotype frequency and 1.3% versus 9.7% for the LMW allele frequency (P<0.05, Fisher's exact probability test). Similar differences were not found in the women. Consistent with this, plasma Lp(a) concentrations were significantly lower in the men > or = 80 years old than in the younger group. These results indicate that LMW apo a phenotypes are associated with a shorter lifespan in men but not in women, possibly reflecting the higher susceptibility of men to atherosclerosis.