BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )
Effects of Huoxue Bushen Mixture on skin blood vessel neogenesis and vascular endothelial growth factor expression in hair follicle of C57BL/6 mice Objective : To investigate the possible stimulat ing mechanism of Huoxue Bushen Mixtu re (HXBSM) , a tradi tional Chinese compound medicine , on hair growth of mice via measuring the variance of skin blood vessel neogenesis and vascular endothelial growth factor (VEGF) expression in the hair follicle . Methods : Hot rosin and paraffin mixture depilation were used to induce C57BL/6 mice hair follicle to enter from telogen into anagen . Ninety C57BL/6 mice were divided into 3 groups randomly : HXBSM group , Yang xue Shengfa Capsule (YXSFC , another traditional Chinese compound medicine) group and untreated group . The mice were fed wi th corresponding drugs after modeling . The hair growth of the mice was observed every day . Every ten mice out of each group were executed respectively at day 4 , 11 and day 17 . Skin blood vessel neogenesis was counted through pathological section and VEGF expression in the hair follicle was measured via immunohistochemical method . Results : The number of local blood vessel neogenisis in the HXBSM group observed was larger than that in the untreated group at day 4 ( P < 0 .05) ; and evidently larger than that in the YXSFC group and the untreated group at day 11 ( P < 0 .05) .The expression of VEGF in the hair follicle was distinctively higher than that in the YXSFC group and the untreated group at day 11 and day 17 ( P < 0 . 05) . Conclusion : HXBSM upregulates VEGF expression to accelerate blood vessel neogenesis and hair growth . · 0 7 1 · 中西医 结合 学报 2007 年 3 月 第 5 卷 第 2 期 Jo urn al o f C hinese In t eg ra tiv e M edicin e , M arch 2007 ; V ol .5 , N o .2
The purpose of the present study was to determine if the acute alterations in uterine prostanoid levels at the end of pregnancy are influenced locally by the fetoplacental unit (FPU). Unilaterally pregnant rats were killed on Days 20 and 21 of pregnancy (delivery = Day 21.5) and uterine tissue was removed and analyzed for prostaglandin (PG) E, PGF, thromboxane B2 (TxB2), and 6-keto-PGF1 alpha (6KF) by radioimmunoassay. A significant (P less than 0.05) main effect of Day (20 vs. 21) and Uterine Horn (nonpregnant vs. pregnant), but no interaction for PGE, PGF, and TxB2 was detected. In contrast, a significant interaction (P less than 0.05) of Day with Uterine Horn was found for uterine 6KF levels. Examination of the simple main effects indicated an enhanced level (P less than 0.05) of 6KF in uterine tissue adjacent compared to opposite the FPU at Days 20 and 21. However, uterine 6KF levels in the nonpregnant, but not pregnant, uterine horn were greater at Day 21 compared to Day 20 of pregnancy. The lack of a significant interaction of the main effects for PGE, PGF, and TxB2 suggests that the increased levels of these PGs between Days 20 and 21 were proportional in the nonpregnant and pregnant uterine horn. Therefore, the factor(s) responsible for the augmentation in these uterine PG levels between Days 20 and 21 is(are) most likely arriving via systemic circulation. In addition, the proportionate increases in uterine PGs imply that the FPU is not conferring upon adjacent uterine tissue any unique ability to respond to systemic factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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