Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events. METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed. RESULTS: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin. CONCLUSIONS: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02546323.

Measuring effects on intima-media thickness: an evaluation of rosuvastatin in Chinese subjects with subclinical atherosclerosis-design, rationale, and methodology of the METEOR-China study.

BACKGROUND: The beneficial effect of statins on atherosclerosis and cardiovascular outcomes has been well established. The Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) global study demonstrated that a 2-year orally administered treatment with rosuvastatin 40 mg daily significantly slowed the progression of carotid intima-media thickness (CIMT) compared to placebo. The current METEOR-China study is designed to evaluate the effect of rosuvastatin 20 mg daily versus placebo on the progression of atherosclerosis measured by CIMT in asymptomatic Chinese subjects. METHODS: This is a phase 3, randomised, double-blind, placebo-controlled, multicentre parallel-group study. Asymptomatic Chinese subjects with a 10-year ischaemic cardiovascular disease (ICVD) risk < 10% will be recruited at 25 study sites. They will be treated with rosuvastatin 20 mg or placebo for 104 weeks. The primary endpoint is the annualised rate of change in CIMT measured by B-mode ultrasonography. Secondary endpoints include the annualised rate of change in CIMT at three different sections of the carotid artery and changes in the serum lipid profile. Safety parameters will also be assessed. CONCLUSION: The study will evaluate whether rosuvastatin 20 mg slows the progression of CIMT in asymptomatic Chinese subjects at low risk of ICVD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02546323 . Registered on September 10, 2015.

The role of von Willebrand factor and ADAMTS13 in the no-reflow phenomenon: after primary percutaneous coronary intervention.

We prospectively studied the correlations between plasma levels of von Willebrand factor and its cleaving protease--a disintegrin and metalloproteinase with thrombospondin type I motif, member 13 (ADAMTS13)--in 126 patients who did or did not develop no-reflow phenomenon after primary percutaneous intervention for acute ST-segment-elevation myocardial infarction. Quantitative plasma levels of von Willebrand factor and ADAMTS13 were measured by immunoturbidometric assay.Angiographic no-reflow was observed in 46 (37%) of the 126 patients. At admission, plasma levels of von Willebrand factor were significantly higher in the no-reflow group (P < 0.001), but levels of ADAMTS13 at admission were similar in the 2 groups (P = 0.143). At logistic regression, after adjustment for serum creatinine, left ventricular ejection fraction, high-sensitivity C-reactive protein, and N-terminal pro B-type natriuretic peptide, plasma von Willebrand factor level at admission (≥ 5,531 mU/mL) was still the predictive factor for the no-reflow phenomenon. The area under the receiver operating characteristics curve was 0.785.Our results suggest that high von Willebrand factor level is related to the no-reflow phenomenon in such a way that it might be a predictor of the phenomenon.

[Relationship between post-stenting coronary thrombolysis in myocardial infarction flow and plasma von Willebrand factor and ADAMTS-13 levels in patients with ST segment elevation myocardial infarction].

OBJECTIVE: To investigate the relationship between post-stenting coronary thrombolysis in myocardial infarction (TIMI) flow and plasma von Willebrand factor (vWF) and its cleaving protease (ADAMTS-13) levels in patients with ST segment elevation myocardial infarction (STEMI). METHODS: STEMI patients who underwent primary percutaneous coronary intervention (PCI) and stenting between September, 2007 and December, 2009 were enrolled. According to the post-stenting TIMI flow, patients were divided to TIMI ≤ 2 group (n = 43) and TIMI 3 group (n = 43). Patients with chest pain or dyspnea and normal coronary angiographic results served as control group (n = 43). The levels of vWF and ADAMTS-13 were measured by ELISA at three time points: immediately after admission, beginning of PCI and 1 week after PCI. RESULTS: Levels of vWF in STEMI patients at all 3 time points were significantly higher than in control patients, and the level of vWF was significantly higher in TIMI ≤ 2 group than in TIMI 3 group [at admission: (6721.83 ± 1380.58) U/L vs. (4786.12 ± 2362.01) U/L, P < 0.05; at the beginning of PCI: (5744.65 ± 1240.71) U/L vs. (3011.33 ± 2270.40) U/L, P < 0.05 and at 1 week after PCI: (2001.48 ± 931.70) U/L vs. (1365.17 ± 724.12) U/L, P < 0.05]. ADAMTS-13 levels were similar among groups at admission and at beginning of PCI, however, the level of ADAMTS-13 at 1 week after PCI was significantly higher in TIMI ≤ 2 group than that in TIMI 3 group [(406.93 ± 101.44) mg/L vs. (270.34 ± 115.12) mg/L, P < 0.001]. Logistic regression analysis showed that both vWF at admission (OR = 1.917, P < 0.01) and vWF at the beginning of PCI (OR = 2.016, P < 0.01) were risk factors of TIMI ≤ 2. CONCLUSION: Increased vWF during peri-PCI periods was associated with post-stenting coronary TIMI ≤ 2 after primary PCI in STEMI patients, and the imbalance between vWF and ADAMTS-13 may thus play an important role in the development of slow flow post PCI.

Tissue factor pathway inhibitor-2 is downregulated by ox-LDL and inhibits ox-LDL induced vascular smooth muscle cells proliferation and migration.

INTRODUCTION: Tissue factor pathway inhibitor-2 (TFPI-2) is a member of the Kunitz-type family of serine protease inhibitors, which inhibits several matrix metalloproteinases activity involved in extracellular matrix degradation. Studies have shown low TFPI-2 expression in the shoulder regions of atherosclerotic plaques. But studies evaluating its role in the progression of atherosclerotic plaque are scarce. Vascular smooth muscle cells (VSMCs) are important components of atherosclerotic plaques and oxidized low density lipoprotein (ox-LDL) is an important detrimental factor of atherosclerosis. The aim of this study is to elucidate the effect of TFPI-2 on smooth muscle cell proliferation and migration induced by ox-LDL. METHODS: Retroviruses expressing human TFPI-2 were constructed. Cell proliferation was determined by CCK-8 assay. Cell apoptosis was analyzed by double staining of FITC-Annexin V and propidium iodide. Cell migration was studied through a Transwell chamber and with a scratch-wound assay. The matrix metalloproteinase-2 and -9 activities were analyzed by gelatin zymography. Phosphorylation of FAK was analyzed by western blot. RESULTS: TFPI-2 over-expression of mRNA and protein was confirmed in infected cells. CCK-8 assay showed that TFPI-2 inhibit VSMCs proliferation induced by ox-LDL while without cytotoxicity to VSMCs. Transwell and scratch wound assay confirmed TFPI-2 over-expression can inhibit VSMC migration. Zymography assay showed that TFPI-2 can inhibit MMP-2, 9 activity induced by ox-LDL. Western blot assay showed TFPI-2 can inhibit cyclinD1 expression and FAK phosphorylation. CONCLUSION: TFPI-2 over-expression may strongly inhibit the proliferation and migration of VSMCs and suppresses MMP-2, 9 activity induced by ox-LDL, making it a promising candidate for treatment of atherosclerotic process.