Decreased longevity in Japanese men, associated with low-molecular-weight apolipoprotein(a) phenotypes

Lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerosis. H igh plasma Lp(a) concentrations are associated with low-molecular-weight (L MW) apolipoprotein(a) (apo a) phenotypes, which raises the question of whet her LMW apo a phenotypes occur less frequently in the elderly. To assess th is possibility, we studied apo A phenotype and allele frequencies in Japane se subjects greater than or equal to 80 years old (men:women=40:34) in comp arison with those <80 years old (men:women= 221:296). Significantly fewer L MW phenotypes and LMW alleles were observed in <greater than or equal to> 8 0 year old men compared with those < 80 years old: 2.5% versus 16.1% for th e 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 f ound in the women. Consistent with this, plasma Lp(a) concentrations were s ignificantly lower in the men greater than or equal to 80 years old than in the younger group. These results indicate that LMW apo a phenotypes are as sociated with a shorter lifespan in men but not in women, possibly reflecti ng the higher susceptibility of men to atherosclerosis.