BACKGROUND: Increased serum lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. We previously reported that aspirin reduced Lp(a) production by cultured hepatocytes via the reduction of apolipoprotein(a) [apo(a)] gene transcription. METHODS: We evaluated both the effect of aspirin treatment (81 mg/day) on serum Lp(a) concentrations and the correlation between the degree of reduction in serum Lp(a) and the type of apo(a) isoform in 70 patients with coronary artery disease or cerebral infarction. RESULTS: Aspirin lowered serum Lp(a) concentrations to approximately 80% of the baseline values in patients with high Lp(a) concentrations (>300 mg/L). The percentage of decrease in serum Lp(a) was larger in patients with high Lp(a) than in patients with low Lp(a) (<300 mg/L), irrespective of apo(a) isoform size. The decreases in serum Lp(a) in high Lp(a) patients with both the high-molecular-weight and the low-molecular-weight isoforms were positively correlated with the baseline Lp(a) concentrations. CONCLUSIONS: Because the secretory efficiencies of apo(a) in the same isoform are likely to be similar, the difference in serum Lp(a) concentrations in patients having the same apo(a) isoform depends on the transcriptional activity of the apo(a) gene. These findings suggest that aspirin decreases serum Lp(a) concentrations via a decrease in apo(a) gene transcription more effectively in patients with high transcriptional activity of this gene.
BACKGROUND: Increased serum lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. We previously reported that aspirin reduced Lp(a) production by cultured hepatocytes via the reduction of apolipoprotein(a) [apo(a)] gene transcription. METHODS: We evaluated both the effect of aspirin treatment (81 mg/day) on serum Lp(a) concentrations and the correlation between the degree of reduction in serum Lp(a) and the type of apo(a) isoform in 70 patients with coronary artery disease or cerebral infarction. RESULTS:Aspirin lowered serum Lp(a) concentrations to approximately 80% of the baseline values in patients with high Lp(a) concentrations (>300 mg/L). The percentage of decrease in serum Lp(a) was larger in patients with high Lp(a) than in patients with low Lp(a) (<300 mg/L), irrespective of apo(a) isoform size. The decreases in serum Lp(a) in high Lp(a)patients with both the high-molecular-weight and the low-molecular-weight isoforms were positively correlated with the baseline Lp(a) concentrations. CONCLUSIONS: Because the secretory efficiencies of apo(a) in the same isoform are likely to be similar, the difference in serum Lp(a) concentrations in patients having the same apo(a) isoform depends on the transcriptional activity of the apo(a) gene. These findings suggest that aspirin decreases serum Lp(a) concentrations via a decrease in apo(a) gene transcription more effectively in patients with high transcriptional activity of this gene.
Authors: Daniel I Chasman; Dov Shiffman; Robert Y L Zee; Judy Z Louie; May M Luke; Charles M Rowland; Joseph J Catanese; Julie E Buring; James J Devlin; Paul M Ridker Journal: Atherosclerosis Date: 2008-07-26 Impact factor: 5.162