Statin-ezetimibe versus statin lipid-lowering therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Studies comparing the clinical efficacy and safety of intensive statin therapy with ezetimibe-statin combination therapy are still rare at present, especially in Asian population. METHODS: We enrolled 202 patients who suffered acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) between May and July in 2016. Patients were allocated into three groups based on the lipid lowering strategy: moderate-intensity statin group (n=118), ezetimibe combined with moderate-intensity statin group (ezetimibe-statin combination, n=55) and intensive statin group (n=29). The lipid profiles and side effects were analyzed and compared among the patients in three groups at admission, 1 month and 3 months after PCI. The clinical outcomes of the patients were observed through 6-month follow-up. RESULTS: One month after PCI, the level of non-high density lipoprotein-cholesterol (non-HDL-C) was decreased by 41.9%, 21.6% and 29.8% by ezetimibe-statin combination therapy, moderate-intensity statin therapy and intensive statin therapy, respectively (P<0.05). The reduction percentages of TC and LDL-C were significantly higher in ezetimibe-statin combination group than in moderate-intensity statin group (P<0.001). The proportion of patients reaching LDL-C goal was higher in ezetimibe-statin combination group (69.1%, P=0.007) and intensive statin group (67.9%, P=0.047) compared with moderate-intensity statin group (46.9%) at 1 month after PCI. There was no significant difference among the three groups with respect to hepatic enzymes level, creatine kinase (CK) level and incidence of muscle symptoms. CONCLUSIONS: The reduction percentage of non-HDL-C was larger in ezetimibe-statin combination group than intensive statin group. This finding suggested that statin/ezetimibe combination therapy could be an alternative to intensive statin therapy in Chinese patients with atherosclerotic cardiovascular disease.

Efficacy and safety of ticagrelor versus clopidogrel with different dosage in high-risk patients with acute coronary syndrome.

BACKGROUND: Dual antiplatelet therapy is recommended as a standard antiplatelet strategy in acute coronary syndrome. For those with reduced pharmacologic response to clopidogrel, strengthening antiplatelet therapy (clopidogrel 150mg daily) may reduce adverse clinical events. Ticagrelor is a direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and offset than clopidogrel. METHODS: In this retrospective study, we compared ticagrelor (180mg loading dose 90mg twice daily thereafter), clopidogrel (300mg loading dose, 75mg or 150mg daily thereafter) for the prevention of cardiovascular events in 273 high-risk patients admitted to coronary care unit with acute coronary syndrome. RESULTS: The rate of IST in hospital was significantly reduced in patients of ticagrelor group comparing with those receiving clopidogrel 75mg (0.69% vs 8.2%, p=0.009). Moreover, the TVR rate was less in the ticagrelor group than clopidogrel 75mg group (2.7% vs 13.1%, p=0.007) 6months follow-up. The incidence of MACCE has no difference between the two clopidogrel groups. Kaplan-Meier analysis of MACCE-free indicated that there was no difference between the three groups. Ticagrelor significantly increased the rate of minor bleeding compared with clopidogrel 75mg daily during hospital (45.5% vs 26.2%,p=0.012) and 6-month follow-up (66.9% vs 45.9%,p=0.004).Bleeding-free prognosis was significantly better in the clopidogrel 75mg daily group. CONCLUSIONS: In patients with acute coronary syndrome undergoing PCI, the rate of in-stent thrombosis and TVR were significantly reduced treated with ticagrelor compared with clopidogrel 75mg daily, without an increase of overall major bleeding, but with an increase of minor bleeding.

Effect of orthodontic force on inflammatory periodontal tissue remodeling and expression of IL-6 and IL-8 in rats.

OBJECTIVE: To investigate effect of orthodontic force on inflammatory periodontal tissue remodeling and expression of IL-6 and IL-8 in rats. METHODS: Eighty SD rats were randomly divided into 4 groups, blank control group (group A) with 5 rats, treatment normal group (group B) with 25 rats, inflammation control group (group (group C) with 25 rats, inflammation treatment group (group D) with 25 rats. Immunohistochemistry and histomorphometric analysis was performed to measure the expression of IL-6, IL-8 and the first molar to the recent movement in the distance. RESULTS: The expression of IL-8 reached a maximum on day 5 and declined thereafter in group B; the expression of IL-6 reached a maximum on day 5 in group B. The expression of IL-6 and IL-8 was gradually weakened with time in group C. The expression of IL-6 and IL-8 were high, and reached a maximum on day 5 and declined thereafter in group D. AD of positive cells in group D were higher than group B at each time point (P<0.05). The time which 0.49 N orthodontic force was loaded was longer, orthodontic tooth movement distance was greater. Movement distance in group D were longer than group B (P<0.05). CONCLUSIONS: Orthodontic force as well as inflammatory stimulus can evoke the expression of IL-6 and IL-8. Under the combined effects of inflammation and orthodontic force, the expression of IL-6, IL-8 will increase.

[Pitavastatin enhances angiogenesis and perfusion in a murine mode of limb ischemia].

OBJECTIVE: We investigated the effects of pitavastatin on angiogenesis and perfusion in C3H/He mice with unilateral hind limb ischemia. METHODS: C3H/He mice treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per gavage for 1 week underwent unilateral hind limb ischemia surgery and were treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme histochemical technique, vascular endothelial growth factors (VEGFs) expression in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by chrome dioxide Griess method. RESULTS: Lower extremity perfusion was significantly improved in pitavastatin treated mice vs. controls as measured by LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment was associated with significantly increased capillary count [(47 +/- 11) vs. (26 +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho-Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P < 0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P < 0.05) and VEGF protein expression in ischemic limbs were also significantly increased in pitavastatin group than those in control group. CONCLUSIONS: Pitavastatin enhances angiogenesis and perfusion in CsH/He mice with limb ischemia.

[The pro-angiogenesis effect of Pitavastatin in the Klotho gene-knockout mice].

AIM: To discuss the effect of Pitavastatin on angiogenesis in vivo and its mechanism in Klotho heterozygous deficient mice. METHODS: The heterozygous deficient Klotho mice (kl +/-) and wild mice (kl +/+) from the same litter were used to establish the animal model of hind-limb ischemia and grouped into control and Pitavastatin group, respectively. Hind-limb blood flow was evaluated using Laser Doppler perfusion imager (LDPI) before treatment and after operation of hind-limbs. The capillaries in muscle of limbs were counted by means of CD-31 labeled immuno-fluorescence. The phosphorylation of Akt (Protein kinase B) in cells was measured by direct immunohistochemical technique. The expression of vascular endothelial growth factors (VEGFs) in muscle of limbs was assessed using Western blotting. RESULTS: After treatment of Pitavastatin, the blood flow in ischemic limbs of the Kl +/- and wild mice improved obviously, the ratio of blood flow area in ischemic limb to that in non-ischemic limb increased and the density of capillaries increased in ischemic limbs of the Kl +/- and wild mice. Pitavastatin enhanced the phosphorylation of Akt and the expression of VEGF in ischemic limbs of the Kl +/- and wild mice. CONCLUSION: Pitavastatin has the pro-angiogenesis effect in vivo and the VEGF-p-Akt-NO pathway may be involved in the mechanism of the effect of Pitavastatin.

[Effect of changes in pH on intracellular Ca2+ and cell length of myocytes].

AIM: To examine the effects of pHi on [Ca2+]i, cell length and Ca2+ sensitivity of myofilaments in rat myocyte. METHODS: We used microscopic spectral imaging approach to monitor simultaneously [Ca2+]i, pHi and cell length with fluorescent indicator indo-1 and SNARF-1 in isolated single rat myocyte. RESULTS: Exposure of cell to 20 mmol/L Sodium Propionate induced an intracellular acidosis which increased slightly systolic and diastolic [Ca2+]i, decreased the cell shortening (CS) and Ca2+ sensitivity of myofilament (P < 0.01). Exposure of cell to 15 mmol/L NH4Cl induced an intracellular alkalosis which decreased systolic and diastolic [Ca2+]i, increased the cell shortening and Ca2+ sensitivity of myofilament (P < 0.01). CONCLUSIONS: In the early time of acidosis, [Ca2+]i, as well as cell length increases respectively. While alkalosis, [Ca2+]i and cell length decreases respectively. The effect of acidosis and alkalosis on Ca2+ sensitivity presents non-linear relationship, i.e. the effect of acidosis on sensitivity, caused by pHi change, is less than that of alkalosis.