ANTIATHEROGENIC AND PLEIOTROPIC ACTIVITY OF VARIOUS DOSES OF ATORVASTATIN IN PATIENTS WITH ISCHEMIC STROKE

Aim. To study the effects of various atorvastatin doses on blood lipids, hemostatic parameters, endothelial function, renin-angiotensin￾aldosterone (RAAS) system, and circadian profile of blood pressure (BP) in patients with ischemic stroke (IS).

Material and methods. The study included 34 IS patients (mean age 58,0±6,6 years) with serum levels of low-density lipoprotein cholesterol (LDL-CH) >2,5 mmol/l, arterial hypertension (AH), and BP levels <160/100 mm Hg. All participants were randomised into Groups I and II, which received atorvastatin in daily doses of 10 and 40 mg, respectively, for 12 weeks. The atorvastatin effects on lipid profile, hemostatic parameters, nitric oxide (NO) end products, endothelin-1 (ET-1), angiotensin (AT) II, blood serotonin, and BP dynamics were assessed.

Results. After 12 weeks, the patients receiving 10 and 40 mg/d of atorvastatin demonstrated a significant reduction in total CH (by 26,6% (p<0,001) and 33% (p<0,001), respectively), LDL-CH (by 32% (p<0,001) and 44% (p<0,001), respectively), and triglycerides (TG) (by 14% (p<0,001) and 24% (p<0,001), respectively). In both groups, there was no marked dynamics in the initially elevated levels of fibrinogen. In Group I, spontaneous platelet aggregation (PA) reduced by 22,6% (p<0,05). Moreover, in Group I, ADP-induced PA decreased by 16,7% (p<0,05) and 67,2% (p<0,01) for 0,5 and 2 μM of ADP, respectively. In Group II, the respective figures were 30,1% (p<0,05) and 31,6% (p<0,01). The concentration of NO end products increased in both Group I (+15% (p<0,05) after 12 weeks) and Group II (+7,7% (p<0,05) after 6 weeks; +15,5% (p<0,01) after 12 weeks). In all participants (Groups I and II; n=34), atorvastatin therapy was associated with a reduction in ET-1 levels by 4,8% (p<0,05). In Group II, there was a significant reduction in the levels of AT II (-7,1%; p<0,05; n=17) and serotonin (-28,6%; p<0,05; n=11). These changes were accompanied by reduced BP variability, time BP index, and area BP index.

Conclusion. In IS patients with hyperlipidemia and AH, atorvastatin demonstrated a dose-dependent lipid-lowering effect on LDL-CH and TG, as well as a dose-dependent pleiotropic activity.

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