Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase Comparison with unfractionated heparin

AbstractObjectivesWe examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment–elevated acute myocardial infarction (AMl).BackgroundActivated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro.MethodsAfter successful thrombolysis with alteplase, study patients were assigned to receive one of the two conjunctive therapies for 48 h intravenously: human plasma-derived APC at 0.06 mg/kg per day (APC group, n = 9) or unfractionated heparin at 100 to 400 U/kg per day, adjusted to maintain an activated partial thromboplastin time at 1.5 to 2 times of the control level (heparin group, n = 10).ResultsAdverse events, including reocclusion of the recanalized infarct-related coronary artery and major or minor hemorrhagic complications, occurred more frequently in the heparin group (4 of 10 cases) than in the APC group (none of 9 cases) (p = 0.033). In the heparin group, plasma PAI activity (IU/ml, median value [range]) was increased continuously from 8 to 24 h after thrombolysis and peaked at 24 h (30.9 [11.3 to 38.5]); on the other hand, it was not increased in the APC group at 24 h after thrombolysis (11.3 [0.0 to 31.0], p < 0.01 vs. heparin group).ConclusionsAdministration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients

Elevated Levels of VE-Cadherin-Positive Endothelial Microparticles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

ObjectivesThe purpose of this study was to examine whether CD144-EMP (endothelium-derived microparticles) is useful as a specific marker of endothelial cell (EC) dysfunction and to determine whether plasma levels of circulating CD144-EMP predicted coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM).BackgroundEndothelial cell dysfunction is involved in atherogenesis; however, the quantitative assessment of EC dysfunction has yet to be established clinically. Endothelium-derived microparticles are small, membrane-shed vesicles that are generated from the EC surface in response to cellular dysfunction and/or injury. Diabetes mellitus is known to be associated with EC dysfunction and accelerated atherosclerosis.MethodsWe characterized EMP using anti-CD144 (VE-Cadherin) antibody in various atherosclerosis-related cells and investigated the association between the levels of CD144-positive microparticles and hydrogen-peroxide-induced EC injury and acetylcholine-induced coronary vasomotion. Furthermore, we evaluated plasma CD144-EMP levels in patients with and without DM.ResultsWe demonstrated that CD144-positive microparticles were derived selectively from human EC. The levels of CD144-EMP reflected the degree of in vitro hydrogen-peroxide-induced EC injury and impairment of in vivo endothelium-dependent coronary vasodilation (p < 0.01). Plasma CD144-EMP levels were increased significantly in DM patients compared with patients without DM (p < 0.001). In DM patients, the elevated levels of CD144-EMP were the most significant risk factor for CAD relative to all other traditional risk factors (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8 to 6.9, p < 0.001). Notably, plasma CD144-EMP identified a subpopulation of established CAD patients in DM subjects without typical anginal symptoms (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001).ConclusionsThe CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD

Retrospective comparison of clinical and angiographic outcomes after primary stenting using sirolimus-eluting and bare-metal stents in nonrandomized consecutive 568 patients with first ST-segment elevated myocardial infarctions

SummaryBackground and purposeThe long-term safety and efficacy of primary stenting using drug-eluting stents (DES) in patients with ST-segment elevation myocardial infarction (STEMI) are not fully understood in Japan. Therefore, we retrospectively examined the midterm clinical and angiographic outcomes in STEMI patients after primary stenting using sirolimus-eluting stents (SES) in a clinical setting through a historical comparison with those of bare-metal stents (BMS).Methods and resultsThe study design was a retrospective, nonrandomized, and single-center study. The clinical outcomes for 568 consecutive patients who presented within 12h of their first STEMI and who were treated with BMS (n=198; 184 STEMIs from June 2003 to August 2004 and 14 STEMIs from September 2004 to May 2007) or SES (n=370; from August 2004 to May 2007) at our medical center in Japan were retrospectively investigated in February 2010. The incidence of post-discharge events (comprising cardiac death and nonfatal recurrent MI) after SES placement (3.9%) was not significantly different from that after BMS placement (6.7%). SES was not related to the risk of post-discharge events (mean follow-up for SES, 1327±415 days; BMS, 1818±681 days) (hazard ratio of 0.369 at 95% CI, 0.119–1.147, p=0.085). The incidence of definite stent thromboses after SES placement (0.54%) was not significantly higher than that after BMS placement (0%). The incidence of binary in-stent restenosis (% diameter stenosis of more than 50% at secondary angiography) after SES placement (8.3%) was significantly lower than that after BMS placement (25.7%; p<0.001).ConclusionsFrom the present historical comparison of SES and BMS, we conclude that primary stenting using SES in a clinical setting has favorable clinical and angiographic outcomes in Japanese STEMI patients

Urinary biopyrrins levels are elevated in relation to severity of heart failure

AbstractObjectivesWe investigated the relationship between the urinary levels of biopyrrins and the severity of heart failure (HF).BackgroundOxidative stress is evident in heart disease and contributes to the development of ventricular dysfunction in patients with HF. Biopyrrins, oxidative metabolites of bilirubin, have been discovered as potential markers of oxidative stress.MethodsWe measured the levels of urinary biopyrrins and plasma B-type natriuretic peptide (BNP) in 94 patients with HF (59 men; mean age 65 years) and 47 control subjects (30 men; mean age 65 years). Urine and blood samples were taken after admission in all subjects. Further urine samples were obtained from 40 patients after treatment of HF.ResultsThe urinary biopyrrins/creatinine levels (μmol/g creatinine) were the highest in patients in New York Heart Association (NYHA) class III/IV (n = 26; 17.05 [range 7.85 to 42.91]). The urinary biopyrrins/creatinine levels in patients in NYHA class I (n = 35; 3.46 [range 2.60 to 5.42]) or II (n = 33; 5.39 [range 3.37 to 9.36]) were significantly higher than those in controls (2.38 [range 1.57 to 3.15]). There were significant differences in urinary biopyrrins/creatinine levels among each group. The treatment of HF significantly decreased both urinary biopyrrins/creatinine levels (from 7.43 [range 3.84 to 17.05] to 3.07 [range 2.21 to 5.71]) and NYHA class (from 2.5 ± 0.1 to 1.7 ± 0.1). Log biopyrrins/creatinine levels were positively correlated with log BNP levels (r = 0.650, p < 0.001).ConclusionsThese results indicate that urinary biopyrrins levels are increased in patients with HF and are elevated in proportion to its severity

Standards of Practice in Acute Ischemic Stroke Intervention: International Recommendations

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Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study

Aims To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol = 2.59 to = 100 to = 2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy

Increased Levels of Cardiac Troponin I in Subjects with Extremely Low B-type Natriuretic Peptide Levels

Abstract Because of the lack of studies focused on the biological implications of extremely low B-type natriuretic peptide (BNP) levels, we investigated whether extremely low BNP levels could be harmful to the cardiovascular system due to compromised cardio-protection. By using cardiac troponin I (cTnI) as an indicator of cardiovascular disorder, we assessed whether cTnI was inversely associated with BNP in populations with low BNP levels. A total of 2,001 apparently healthy subjects older than 38 years were included in this study. We defined subgroups from this population by limiting the maximum BNP level with cut-off values ranging from 1 through 20 pg/mL and performed covariance structure analyses by comparing log(BNP) with log(cTnI) in each subgroup. The beta values between log(BNP) and log(cTnI) sharply decreased as the BNP cut-off was reduced from 20 pg/mL (beta = 0.04) to 1 pg/mL (beta = −0.29) and became significant when the BNP cut-off levels were lower than 4 pg/mL (p < 0.005). In subgroups with BNP levels lower than 4 pg/mL, elevation in cTnI level was inversely associated with BNP (p < 0.005), which suggests that insufficient BNP may play a pathogenic role in the occurrence of cardiovascular abnormalities