The influence of statin therapy on platelet activity markers in hyperlipidemic patients after ischemic stroke

Abstract

IntroductionLow-density lipoprotein cholesterol (LDL-C) has been reported to increase platelet activation. Reducing the level of LDL-C with statins induces important pleiotropic effects such as platelet inhibition. This association between platelet activity and statin therapy may be clinically important in reducing the risk of ischemic stroke. We investigated the effect of simvastatin therapy on platelet activation markers (platelet CD62P, sP-selectin, and platelet-derived microparticles (PDMPs)) in hyperlipidemic patients after ischemic stroke.Material and methodsThe study group consisted of 21 hyperlipidemic patients after ischemic stroke confirmed by CT, and 20 healthy subjects served as controls. We assessed the CD62P expression on resting and thrombin-activated blood platelets. CD62P and PDMPs were analyzed by the use of monoclonal antibodies anti-CD61 and anti-CD62 on a flow cytometer. The level of sP-selectin in serum was measured by the ELISA (enzyme-linked immunosorbent assay) method. All markers were re-analyzed after 6 months of treatment with simvastatin (20 mg/day).ResultsHyperlipidemic patients presented a significantly higher percentage of CD62+ platelets and higher reactivity to thrombin compared to control subjects. After simvastatin therapy hyperlipidemic patients showed a reduction of the percentage of resting CD62P(+) platelets (p = 0.005) and a reduction of expression and percentage of CD62P(+) platelets after activation by thrombin (median p < 0.05; percentage: p = 0.001). A decrease of sP-selectin levels (p = 0.001) and percentage of PDMPs (p < 0.05) in this group was also observed.ConclusionsHMG-CoA reductase inhibitor therapy in stroke patients with hyperlipidemia may be useful not only due to the lipid-lowering effect but also because of a significant role in reduction of platelet activation and reactivity.

Cross-Talk between Lipoproteins and Inflammation: The Role of Microvesicles

“…Other researchers have also observed that statins decrease MV release from several cell origins [90][91][92], and modify their molecular fingerprint by decreasing their cargo of cell activation markers [93,94]. In stroke patients with hyperlipidemia, simvastatin treatment for 6 months reduced the percentage of CD61 + platelet-derived MV to similar levels to those of age-and sex-matched controls [95].…”

Gender Differences in Cardiovascular Drugs

“…Statins directly inhibit 3-hydroxy-3-methyl-glutarylCoA (HMG-CoA) reductase, a key enzyme for cholesterol synthesis in the liver, and thereby reduce circulating LDL-C levels [17]. Statins also exhibit beneficial pleiotropic effects associated with decreased inflammation, improved endothelial function, and enhanced atherosclerotic plaque stability [17][18][19][20][21]. Cardiovascular benefits derived from statin use are attributed to a combination of these effects [17][18][19][20][21].…”

“…However, health providers are advised to avoid overemphasizing these adverse effects and determine individual risk versus benefit for the use of statins in primary prevention of cardiovascular events in women. Meanwhile, the use of intensive statin therapy for secondary prevention of cardiovascular events in women is routinely recommended, since it has demonstrated significant decreases in myocardial infarction, unstable angina, heart failure and death [16][17][18][19][20][21][22][23][24]. Absorption ↓ gastric acid secretion ↑ GI transit time [6][7][8][9][10][11] Distribution ↓ body weight ↓ intravascular volume ↓ organ volume ↓ muscle volume ↑ adipose tissue…”

Immune-mediated and lipid-mediated platelet function in atherosclerosis

“…Prior to simvastatin therapy hyperlipidemic patients show a significantly higher percentage of P-selectin-positive platelets and higher reactivity to thrombin compared with healthy control individuals. Simvastatin therapy reduces P-selectin expression on platelets and soluble P-selectin (sP-selectin) levels [117]. The ARMYDA-ACS (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) clinical trial showed that atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes (ACS) undergoing early percutaneous coronary intervention [118].…”