Effects of short-term atorvastatin treatment on global fibrinolytic capacity, and sL-selectin and sFas levels in hyperlipidemic patients with coronary artery disease.
BACKGROUND
The beneficial effects of HMG-CoA reductase inhibitors (statins) in patients with coronary artery disease (CAD) appear to be attributable not only to their lipid-lowering properties, but also to their therapeutic effects on the coagulation system, and anti-inflammatory effect. Furthermore, statins mitigate the apoptosis of vascular smooth muscle cells (VSMC) and macrophages in atherosclerotic plaques.


OBJECTIVE
The purpose of this study was to evaluate the effects of short-term atorvastatin treatment on the fibrinolytic system and systemic inflammatory status, and on apoptosis in hyperlipidemic patients with CAD.


METHODS
The study population consisted of 36 hyperlipidemic patients (14 women and 22 men, mean age 53+/-9 years) with stable CAD, untreated with lipid-lowering medications. Serum lipoproteins, fibrinogen levels, sFas and sL-selectin, and global fibrinolytic capacity (GFC) were measured at baseline and after 12 weeks of treatment with atorvastatin, 10 mg/day.


RESULTS
Atorvastatin treatment decreased serum low-density lipoprotein (-39%, P=0.0001), total cholesterol (-32%, P=0.0001), and triglycerides (-22%, P=0.0001), and increased high-density lipoprotein (+13%, P=0.0001) at 12 weeks compared to baseline. These effects were associated with a decrease in plasma fibrinogen from 331+/-73 to 298+/-58 mg/dl (P=0.0001), and sL-selectin levels from 666+/-201 to 584+/-162 ng/ml (P=0.0001). sFas levels and GFC increased from 3754+/-1264 to 4873+/-1835 pg/ml and from 3.5+/-2.4 to 5.6+/-2.9 microg/ml, respectively (both P=0.0001).


CONCLUSIONS
These results suggest that lipid lowering with atorvastatin therapy significantly increases GFC, decreases fibrinogen levels, and causes leukocyte deactivation. Our findings also suggest that atorvastatin treatment mitigates apoptosis of VSMC in the atherosclerotic plaque. These effects of atorvastatin may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.
Atalar
Enver
E
Department of Cardiology, Hacettepe University School of Medicine, Ankara, Turkey. eatalar@lycos.com
Ozmen
Ferhan
F
Haznedaroglu
Ibrahim
I
Açil
Tayfun
T
Ozer
Necla
N
Ovünç
Kenan
K
Aksöyek
Serdar
S
Kes
Sirri
S
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000150:complications* / Q000188:drug therapy*; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000150:complications* / Q000188:drug therapy*; D019041:L-Selectin / Q000097:blood* / Q000187:drug effects*; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D005227:Fatty Acids; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011758:Pyrroles; D014280:Triglycerides; D019041:L-Selectin; D002784:Cholesterol; D000069059:Atorvastatin