Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in hypercholesterolemic subjects at high cardiovascular risk.
The effect of statins on Lp(a) levels is controversial; furthermore, the potential action of statins on apo(a) fragmentation is indeterminate. We therefore determined the circulating levels of Lp(a) and of apo(a) fragments in hypercholesterolemic patients before and after treatment (6 weeks) with Atorvastatin 10 mg/day (A10) or Simvastatin 20 mg/day (S20). In a double blind study, hypercholesterolemic patients (n=391) at high cardiovascular risk (LDL-C>=4.13 mmol/l; TG<2.24 mmol/l; 34% with documented CHD; 45% hypertensive; and 29% current smokers) were assigned to treatment with A10 (n=199) or S20 (n=192). Plasma Lp(a) and apo(a) fragment levels (n=206) were measured prior to and after treatment. At baseline, A10 and S20 groups did not differ in plasma levels of lipids, Lp(a) (A10: 0.45+/-0.48 mg/ml, S20: 0.46+/-0.5), and apo(a) fragments (A10: 3.88+/-5.22 microg/ml; S20: 3.25+/-3), and equally in apo(a) isoform size (A10: 26+/-5 kr, S20: 25.5+/-5.3). After treatment, both statins significantly reduced Lp(a) levels (A10: 0.42+/-0.47 mg/ml, 6% variation, P<0.001; S20: 0.45+/-0.53 mg/ml, 0.02% variation, P=0.046). A10 and S20 did not significantly differ in their efficacy to lower Lp(a) levels. In a multivariate logistic regression analysis, the reduction of Lp(a) levels was independently associated with Lp(a) baseline concentration, but not to other variables, including LDL-C reduction. Plasma levels of apo(a) fragments were not modified by either statin. In conclusion, both A10 and S20 significantly lowered Lp(a), although this effect was of greater magnitude in atorvastatin-treated patients.
Institut National de la Santé et de la Recherche Medicale, Unité 551, Dyslipoproteinemies et Athérosclerose, Hôpital de la Pitié, 83 Boulevard de l'Hôpital, 75651 Cedex 13, Paris, France.
Sophie
S
Gonbert
Sophie
S
Malinsky
Andrei C
AC
Sposito
Hervé
H
Laouenan
Chantal
C
Doucet
M John
MJ
Chapman
Joëlle
J
Thillet
D000328:Adult; D000368:Aged; D001054:Apolipoproteins A / Q000097:blood* / Q000187:drug effects*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000097:blood* / Q000187:drug effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011336:Probability; D011758:Pyrroles / Q000008:administration & dosage*; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019821:Simvastatin / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D001054:Apolipoproteins A; D006538:Heptanoic Acids; D017270:Lipoprotein(a); D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin