Nine-year trend of oral anticoagulant use in patients with embolic stroke due to nonvalvular atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly used as an alternative to warfarin in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is sufficient prescription of oral anticoagulants (OACs) to decrease the incidence of embolic stroke remains unclear. METHODS AND RESULTS: We conducted a retrospective observational study of patients hospitalized with ischemic stroke between January 1, 2010 and December 31, 2018. During the 8 years, the annual incidence ratio of embolic stroke to all ischemic strokes did not decrease over time (21-33%) except for that in 2018. The proportion of OAC users did not also change over time (from 23% to 45% [overall 31%], P = .78). Among the OAC users, 19% patients were warfarin users, and 12% patients were DOAC users. In 73% of warfarin users, prothrombin time was subtherapeutic, whereas in 60% of DOAC users, the dose was adequately prescribed. OACs were prescribed more often in patients with high CHADS2 score than in those with low score (P = .01). The number of patients who had no medical history of a doctor visit before admission increased significantly in the recent period of 2015-2018 (22% vs 8% in the previous period of 2010-2014) (P = .01). CONCLUSIONS: The incidence of embolic stroke patients without OACs did not decrease over time, and OACs in patients with NVAF have not been sufficient, even in DOAC era. In recent years, the incidence of undiagnosed AF has increased. To prevent embolic stroke, a correct AF diagnosis beforehand is important.

Glycemic variability is associated with myocardial damage in nondiabetic patients with ST-elevation myocardial infarction.

BACKGROUND: Glycemic variability (GV) induces coronary microcirculatory disturbance and myocardial damage in diabetic patients with acute myocardial infarction. However, in nondiabetic acute myocardial infarction patients, the relationship between GV and myocardial damage remains unclear. PATIENTS AND METHODS: We investigated GV with a continuous glucose monitoring system in nondiabetic ST-segment elevation myocardial infarction patients treated with emergent percutaneous coronary intervention. GV was expressed as the mean amplitude of glycemic excursions (MAGE). Myocardial damage was estimated by myocardial blush grade and ST-segment resolution (STRes). STRes was defined as complete (>70%), partial (30-70%), or none (<30%). RESULTS: Consecutive patients (n=73) were enrolled and classified into a lower or higher MAGE group on the basis of the median MAGE. The higher MAGE group showed lower levels of myocardial blush grade (2.41±0.76 vs. 1.72±0.85, P=0.001) and STRes (complete: 56.8 vs. 33.3%, P=0.044; partial: 32.4 vs. 36.1%, P=0.741; none: 10.8 vs. 30.6%, P=0.037). CONCLUSION: GV was associated with myocardial damage after percutaneous coronary intervention in nondiabetic ST-segment elevation myocardial infarction patients.

Acute myocardial infarction due to simultaneous spasm of 3 coronary arteries that worsened over time.

Coronary artery spasm (CAS) rarely worsens from single-vessel to simultaneous multivessel CAS naturally, and simultaneous multivessel CAS leads to serious conditions such as cardiopulmonary arrest (CPA). A 77-year-old Japanese man who took medications for CAS was transferred to our hospital due to persistent chest pain. On arrival, his vital signs were stable, but his electrocardiogram (ECG) showed ST-segment elevation in leads II, III and aVF. Ventricular fibrillation developed suddenly. Although routine cardiopulmonary resuscitation (CPR) including intravenous administration of epinephrine was performed immediately, he could not be resuscitated. After initiation of percutaneous cardiopulmonary support (PCPS), there was a return of spontaneous circulation. His ECG showed exacerbation of myocardial ischemia with ST-segment elevation in leads I, II, III, aVL, aVF and V3-V6. Emergency coronary angiography revealed severe CAS of the right and left coronary arteries, which was relieved completely by intracoronary administration of nitrates. He was diagnosed with acute myocardial infarction due to simultaneous 3-vessel CAS that progressed over time. About 6h after arrival, he developed hemodynamic instability and died. CAS worsened from single-vessel to simultaneous 3-vessel spasm, and intracoronary administration of nitrates was effective in relieving CAS, which was documented by the ECG and coronary angiogram. Since CAS can progress over time, nitrates must be administered immediately. When CAS leads to CPA, epinephrine may be ineffective in CPR because of its vasoconstrictive effect on coronary arteries; therefore, PCPS should be initiated, and intracoronary nitrates should be administered.

Cardiac Sarcoidosis Presenting as Acute Progressive Heart Failure with Abdominal Lymphadenopathy.

A 77-year-old Japanese woman presented with asymptomatic abdominal lymphadenopathy. Soluble interleukin-2 receptor (sIL2R) and angiotensin-converting enzyme (ACE) levels were elevated, and a pathological examination of lymph-node biopsies revealed non-caseating granulomas, which was consistent with sarcoidosis. Fluorodeoxyglucose-positron emission tomography did not show a clear accumulation in the mediastinal lymph-nodes or heart. Five months later, she presented with acute progressive heart failure that was refractory to conventional treatment. Her sIL2R and ACE levels decreased spontaneously over time, without steroid treatment. Autopsy findings revealed non-caseating granulomas. Cardiac sarcoidosis presenting as acute, progressive, treatment-refractory heart failure is rare. Steroid therapy after the resolution of inflammation did not affect the clinical outcome.

In-stent restenosis is inhibited in a bare metal stent implanted distal to a sirolimus-eluting stent to treat a long de novo coronary lesion with small distal vessel diameter.

OBJECTIVES: This study examined whether sirolimus-eluting stent (SES) implantation exerts an antiproliferative action on a bare metal stent (BMS) placed distally in the same coronary artery. BACKGROUND: Diffusion of sirolimus into flowing coronary blood may cause accumulation of this drug in the coronary bed beyond the distal edge of an SES. METHODS: We analyzed data from 115 consecutive patients with ischemic heart disease who were treated with two overlapping stents without a gap in the same coronary artery for a long de novo lesion. The distal stent was a 2.25 mm BMS in all patients, and the proximal stent was an SES in 73 patients (SES-BMS group) and a BMS in 42 patients (BMS-BMS group). Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) were performed at stent implantation and 8 months later. RESULTS: Clinical and procedural variables were comparable between the two groups. QCA and IVUS showed that the SES-BMS group had less luminal late loss and a lower percent of in-stent volume obstruction in the distal BMS compared with the BMS-BMS group. Furthermore, compared with the BMS-BMS group, the SES-BMS group had less in-stent restenosis (23.3 vs. 54.8%, P < 0.0005) and target lesion revascularization (21.9 vs. 50.0%, P < 0.005). CONCLUSIONS: SES implantation just proximal to a BMS inhibits neointimal proliferation in the BMS, when both stents are implanted in the same coronary artery to treat a de novo lesion.

Ultrasound assessment of brachial endothelial vasomotor function in addition to carotid plaque echolucency for predicting cardiovascular events in patients with coronary artery disease.

BACKGROUND: Single assessment of either flow-mediated vasodilatation of the brachial artery (FMD) or carotid plaque echolucency provides prognostic information for both cerebrovascular and coronary events. OBJECTIVES: This study tested the hypothesis that combined assessment using carotid plaque echolucency and FMD may have an additive effect when predicting cardiovascular events in patients with coronary artery disease (CAD). METHODS: Ultrasound assessment of carotid plaque echolucency with integrated backscatter (IBS) analysis (calibrated IBS=intima-media IBS value-adventitia IBS) and FMD was performed in 547 consecutive patients with CAD. All the study patients were followed up prospectively for a period of ≤ 60 months until the occurrence of one of the following cardiovascular events: cardiac death, non-fatal myocardial infarction, unstable angina requiring coronary revascularization, or ischemic stroke. RESULTS: During a mean follow-up period of 52 ± 10 months, 69 cardiovascular events occurred. A multivariate Cox proportional hazard model after 1000 bootstrapped resampling demonstrated that calibrated IBS and FMD were significant, independent predictors of future cardiovascular events after adjustment for known risk factors (calibrated IBS, HR 0.88, 95% CI 0.83-0.93; FMD, HR 0.76, 95% CI 0.68-0.85). The c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses showed that the combination of calibrated IBS and FMD values had a greater incremental effect on the predictive value of known risk factors for cardiovascular events. CONCLUSIONS: Combined assessment of brachial endothelial function and carotid plaque echolucency is an independent predictor of cardiovascular events and improves risk prediction when added to known risks.

Usefulness of a collateral channel dilator for antegrade treatment of chronic total occlusion of a coronary artery.

OBJECTIVES: The aim of this study was to clarify the effectiveness of a collateral channel dilator microcatheter in antegrade percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) of a coronary artery. BACKGROUND: The Corsair microcatheter, which was originally developed as a collateral channel dilator, has been reported to be useful for retrograde CTO-PCI. METHODS: We compared the success rate of the Corsair microcatheter collateral channel dilator for antegrade CTO-PCI with a previously available microcatheter. We analyzed the data from 27 patients (32 CTOs) using the FinecrossMG (Finecross group) and the data from 31 patients (34 CTOs) using the Corsair (Corsair group). RESULTS: There were no significant differences in the clinical or lesion characteristics between the 2 groups. The success rate for crossing the CTO by the microcatheter was 62.5% in the Finecross group and 85.3% in the Corsair group (P < 0.05). After the Corsair crossed the CTO, a 2-mm diameter balloon catheter crossed the lesion in all the cases, but it crossed the lesion in only 17 of 20 cases in the Finecross group (85.0%, P < 0.05). The number of balloon catheters used for predilation was significantly less in the Corsair group compared with the Finecross group (P < 0.05). CONCLUSIONS: The success rate for crossing of the microcatheters and the balloon catheters through the occlusion in antegrade CTO-PCI was better with the Corsair than with the FinecrossMG. In addition, the use of the Corsair reduced the number of balloon catheters used for predilation in antegrade CTO-PCI.

Endothelial vasomotor dysfunction in the brachial artery predicts the short-term development of early stage renal dysfunction in patients with coronary artery disease.

BACKGROUND: This study examined whether endothelial vasomotor dysfunction in the brachial artery predicted early renal dysfunction in patients with coronary artery disease (CAD). Endothelial function in the renal vasculature plays an important role in the regulation of renal hemodynamics. As endothelial dysfunction is a systemic disorder, there may be a relationship between endothelial function in the brachial artery and renal vasculature. METHODS: Flow-mediated endothelium-dependent dilation (FMD) in brachial artery and renal functional parameters were measured in 757 patients with CAD without macroalbuminuria. RESULTS: In a cross-sectional data, an impaired FMD was associated with higher serum creatinine levels and urinary albumin excretion (UAE), lower creatinine clearance rate and estimated glomerular filtration rate (eGFR) at baseline in multiple linear regression analysis. In a follow-up study including a subgroup of 448 patients with normal renal function (serum creatinine level <1.0mg/dL, UAE <25mg/day and eGFR ≥ 60 mL/min/1.73 m(2) at baseline), 96 patients had an endpoint of early stage renal dysfunction (serum creatinine levels ≥ 1.2mg/dL, UAE ≥ 30 mg/day and/or eGFR <60 mL/min/1.73 m(2)) during 12 month follow-up. Multivariate logistic regression analysis showed that impaired FMD was significantly associated with progression to the early stage renal dysfunction after adjustment with age, diabetes mellitus, hypertension and C-reactive protein levels. CONCLUSIONS: Endothelial vasomotor dysfunction in the brachial artery is independently associated with progression from normal renal function to early stage renal dysfunction in patients with CAD. Measurement of FMD may therefore be useful for assessing risk of future renal dysfunction.

High plasma levels of macrophage migration inhibitory factor are associated with adverse long-term outcome in patients with stable coronary artery disease and impaired glucose tolerance or type 2 diabetes mellitus.

OBJECTIVES: MIF is proatherogenic and is highly expressed in unstable atherosclerotic plaques. Circulating levels of MIF are increased in patients with impaired glucose tolerance or type 2 diabetes mellitus (IGT/T2DM). We examined whether high circulating levels of macrophage migration inhibitory factor (MIF) are related to increased risk of future coronary events in patients with coronary artery disease (CAD) and IGT/T2DM. METHODS: Plasma MIF levels after overnight fast were measured by ELISA in 617 patients with stable CAD including 79 patients with IGT and 215 patients with T2DM. All patients were prospectively followed for 60 months or until occurrence of one of the coronary events: cardiac death, nonfatal myocardial infarction, unstable angina pectoris requiring coronary revascularization. RESULTS: During the follow-up period, an event occurred in 77 (26%) patients with IGT/T2DM and 50 (15%) patients without IGT/T2DM. In patients with IGT/T2DM, higher MIF levels were a significant predictor of coronary events in a multivariate Cox proportional hazards analysis that included the known risk factors, C-reactive protein levels and medication as covariates (HR 3.3, 95% CI 1.6-8.3, p=0.006). The c-statistic showed that the predictive value of MIF levels was incremental over that of the conventional predictors for coronary events (area under ROC curve; 0.70 and 0.61, respectively, p=0.001). In contrast, MIF levels were not significantly related to future coronary events in patients without IGT/T2DM. CONCLUSIONS: High MIF levels are an independent risk factor for future coronary events in CAD patients with IGT/T2DM.

Comparative study of bezafibrate and pravastatin in patients with coronary artery disease and high levels of remnant lipoprotein.

BACKGROUND: Remnant lipoproteinemia is a strong risk factor for cardiovascular (CV) diseases. This study examined which of 2 common lipid-lowering drugs (fibrates and statins) is more effective in patients with remnant lipoproteinemia and if lowering remnant lipoprotein levels can reduce CV risk. METHODS AND RESULTS: Remnant lipoprotein levels were measured by an immunoseparation method (remnant-like lipoprotein particles cholesterol: RLP-C) in 274 patients with coronary artery disease and high RLP-C levels (>or=5.0 mg/dl). They were randomly assigned to receive bezafibrate (200-400 mg/day) or pravastatin (10-20 mg/day), and were prospectively followed-up for 1 year or until the occurrence of CV events. Complete follow-up data were obtained in 180 patients. RLP-C levels at 1 year of treatment were reduced more by bezafibrate than pravastatin (37% and 25% from baseline, respectively). During follow-up, bezafibrate-treated patients had 3 CV events, compared with 12 events in pravastatin-treated patients (P<0.01). In multivariate logistic regression analysis, a decrease in RLP-C level was significantly associated with a reduction in CV events after adjustment for treatment group and changes in levels of other lipids. CONCLUSIONS: Bezafibrate therapy decreased RLP-C levels to a greater extent than pravastatin and a decrease in RLP-C level may be associated with a reduction in CV events in patients with high RLP-C levels.

Assessment of carotid plaque echolucency in addition to plaque size increases the predictive value of carotid ultrasound for coronary events in patients with coronary artery disease and mild carotid atherosclerosis.

OBJECTIVES: This study examined whether combined ultrasound assessment of plaque size and echolucency in the carotid artery had an additive effect for predicting coronary events in patients with coronary artery disease (CAD). Ultrasound assessment of either plaque size or echolucency of carotid artery provides prognostic information on coronary events. Combined assessment of plaque size and echolucency of carotid artery has the advantage of obtaining both structural and compositional information in the same artery in a single session. METHODS AND RESULTS: Ultrasound assessment of carotid plaque maximum intima-media thickness (plaque-IMTmax) and echolucency with integrated backscatter analysis was performed in 413 patients with CAD and carotid plaque. All study patients were followed up prospectively for 54 months or until the occurrence of a coronary event. During the follow-up period, 49 coronary events occurred including 2 cardiac deaths, 10 non-fatal acute myocardial infarctions and 37 recurrent and refractory unstable angina. Multivariate Cox hazards analysis showed plaque-IMTmax alone (HR 2.01, 95%CI 1.30-3.10), plaque echogenicity alone (HR 0.86, 95%CI 0.80-0.91) and combination of high plaque-IMTmax and low echogenicity on categorical data (HR 2.56, 95%CI 1.39-4.74) were independent predictors of coronary events. Analysis using c-statistics showed that plaque-IMTmax and plaque echolucency in combination had a significant incremental effect on the predictive value of the conventional risk factors for coronary events. CONCLUSIONS: Combined ultrasound assessment of carotid plaque size and echolucency has an additive value for prediction of coronary events. Further studies need to evaluate the clinical utility of both ultrasound measurements for risk stratification in CAD.

Treatment of acute myocardial infarction with sirolimus-eluting stents results in chronic endothelial dysfunction in the infarct-related coronary artery.

BACKGROUND: Sirolimus-eluting stent (SES) implantation aggravated endothelial vasomotor dysfunction in infarct-related coronary arteries. METHODS AND RESULTS: This study examined the effect of SES implantation on the duration of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and on postinfarct left ventricular dysfunction in acute myocardial infarction (AMI). Patients with a first AMI due to occlusion of the left anterior descending coronary artery and successful reperfusion using SES (n=15) or bare metal stents (BMS; n=18) were examined. The vasomotor response of the left anterior descending coronary artery to acetylcholine and left ventriculography were examined 2 weeks and 6 months after AMI. At 6 months after AMI, the impairment of epicardial coronary artery dilation and coronary blood flow increase in response to acetylcholine was recovered from 2 weeks after AMI in BMS-treated patients, whereas the responses of SES-treated patients improved but remained impaired compared with BMS-treated patients (% increase in blood flow, 77+/-12% in SES versus 116+/-15% in BMS at 10 microg/min of acetylcholine, P<0.01). Left ventricular regional wall dysfunction in the left anterior descending coronary artery territory improved from 2 weeks to 6 months after AMI in BMS-treated patients but not in SES-treated patients (% improvement of average SD/chord, 6% in SES versus 19% in BMS, P<0.05), although left ventricular global ejection fraction was similar between the groups at any time points. CONCLUSIONS: SES implantation may delay recovery of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and left ventricular regional dysfunction for at least 6 months after AMI.

Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease.

OBJECTIVES: We assessed the hypothesis that changes in endothelial vasomotor function in response to optimized therapy for atherosclerotic coronary artery disease predict future cardiovascular events. BACKGROUND: Although endothelial vasomotor dysfunction is a predictor of cardiovascular events, it remains unclear whether reversibility of endothelial dysfunction in response to risk factor reduction provides prognostic information. METHODS: This study included 251 patients with newly diagnosed coronary artery disease and an impaired flow-mediated dilation (FMD) of the brachial artery (FMD <5.5%). Measurement of FMD was repeated after 6 months for individualized and optimized therapy to reduce risk factors according to American College of Cardiology/American Heart Association guidelines. Patients were followed up for 36 months or until 1 of the following events occurred: cardiac death, nonfatal myocardial infarction, recurrent and refractory angina pectoris requiring coronary revascularization, or ischemic stroke. RESULTS: FMD was persistently impaired (<5.5%) in 104 (41%) patients after 6 months of optimized therapy, whereas it improved (FMD > or =5.5%) in the remaining 147 (59%) patients. During 36 months of follow-up, events occurred in 27 (26%) patients with persistently impaired FMD and in 15 (10%) patients with improved FMD (p < 0.01 by chi-square test). Multivariate Cox hazards analysis showed that persistent impairment of FMD was an independent predictor of events (hazard ratio: 2.9, 95% confidence interval: 1.5 to 6.2, p < 0.01). Baseline FMD before the optimized therapy to reduce risk factor had no significant prognostic information. CONCLUSIONS: Persistent impairment of endothelial vasomotor function despite optimized therapy to reduce risk factors has an adverse impact on outcome in coronary artery disease patients.

Rapid improvement of carotid plaque echogenicity within 1 month of pioglitazone treatment in patients with acute coronary syndrome.

OBJECTIVE: This study examined whether pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, may stabilize vulnerable plaque with use of ultrasound evaluation of carotid artery plaque echolucency in patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM). METHODS AND RESULTS: Treatment with pioglitazone (15 or 30mg/day, n=31) or placebo (n=30) was randomly assigned and initiated within 5 days after the onset of ACS in 61 patients with type 2 DM and echolucent carotid plaques. Vulnerable carotid plaques were assessed by measuring plaque echolucency using carotid ultrasound with integrated backscatter (IBS) before, at 2 weeks, and 1 month and 6 months after initiation of treatment. An increase in IBS value reflects an increase in carotid plaque echogenicity. Calibrated IBS value (intima-media IBS value minus adventitia IBS value) of echolucent carotid plaques did not change at 2 weeks but was significantly increased at 1 month after treatment in the pioglitazone group but not in the placebo group. The increase in calibrated IBS value was not significantly correlated with the effect of pioglitazone on glycemia. CONCLUSIONS: Pioglitazone rapidly improved carotid plaque echolucency within 1 month of therapy initiation in patients with ACS and type 2 DM.

Measurement of the platelet retention rate in a column of collagen-coated beads is useful for the assessment of efficacy of antiplatelet therapy.

INTRODUCTION: A simple, validated method to measure platelet function is unavailable for bedside use. Measurement of platelet retention rate using a column of collagen-coated beads and whole blood is a new, simple assay that reflects platelet aggregation. This study was aimed to examine the utility of this assay to assess efficacy of antiplatelet drug therapy. METHODS: Citrated whole blood (1.5 ml) in a syringe was passed through a polyvinyl tube packed with collagen-coated beads for 40 seconds using a syringe pump. Platelet retention rate in the column was calculated from platelet counts in blood before and after passage. An increase in the retention rate reflects an increase in platelet activity. This new platelet retention assay and the traditional optical aggregometry assay were performed in 331 patients with stable coronary artery disease (CAD). RESULTS: The retention rate was significantly reduced in patients taking dual antiplatelet therapy (aspirin plus clopidogrel or ticlopidine) compared with aspirin alone. There was a significant linear correlation between the platelet retention rate and platelet aggregability measured by the traditional method (r=0.44, p<0.001). In multivariate Cox proportional hazards analysis, higher platelet retention rate was an independent predictor of future cardiovascular events in patients on dual antiplatelet therapy (hazard ratio 3.9, 95% CI 1.6 to 9.5, p=0.003). CONCLUSIONS: Measurement of the platelet retention rate in a column of collagen-coated beads may be useful for monitoring the efficacy of antiplatelet drug therapy in patients with CAD.

Adiponectin is released from the heart in patients with heart failure.

BACKGROUND: Plasma levels of adiponectin are decreased in patients with ischemic heart disease, but increased in patients with heart failure (HF). The source of increased adiponectin levels in patients with HF remains unknown. This study examined whether adiponectin, an adipocyte-derived protein with cardioprotective actions, is released from the heart in patients with HF. METHODS: Plasma adiponectin levels sampled from the aorta, coronary sinus (CS), and peripheral vein (PV) were measure by ELISA in 138 consecutive patients with left ventricular ejection fraction (LVEF) <40% and in 40 normal controls. RESULTS: PV adiponectin levels were significantly higher in patients with either non-ischemic HF (n=81) or ischemic HF (n=57) than controls; levels were similar between patients with non-ischemic HF and those with ischemic HF. There was a significant step-up in adiponectin levels from the aorta to the CS in patients with either non-ischemic HF or ischemic HF but not in controls. The CS-aorta difference in adiponectin levels, which reflect cardiac release of adiponectin, positively correlated with PV levels in patients with either non-ischemic HF or ischemic HF. The CS-aorta difference in adiponectin levels positively correlated with PV levels of brain natriuretic peptide and inversely with LVEF in patients with either non-ischemic HF or ischemic HF. CONCLUSIONS: Adiponectin is released from the heart into the peripheral circulation in proportion to the extent of LV dysfunction in patients with HF irrespective of etiologies of HF.

High serum levels of remnant lipoproteins predict ischemic stroke in patients with metabolic syndrome and mild carotid atherosclerosis.

BACKGROUND AND OBJECTIVE: Metabolic syndrome is prevalently associated with stroke. Triglyceride-rich lipoproteins contribute to atherothrombotic complications in metabolic syndrome. This study examined whether high levels of remnant lipoprotein, atherogenic triglyceride-rich lipoprotein, may be associated with future ischemic stroke in metabolic syndrome. METHODS AND RESULTS: We followed up 292 consecutive patients with metabolic syndrome meeting ATP III criteria and mild carotid plaques for a period of

Rapid stabilization of vulnerable carotid plaque within 1 month of pitavastatin treatment in patients with acute coronary syndrome.

We determined time course of stabilization of echolucent carotid plaques by statin therapy in patients with acute coronary syndrome (ACS). Treatment with 4 mg/d pitavastatin (n = 33) or placebo (n = 32) was initiated within 3 days after onset of ACS in 65 patients with echolucent carotid plaque. Vulnerable carotid plaques were assessed by measuring plaque echolucency using carotid ultrasound with integrated backscatter (IBS) analysis before and 1 month after treatment in all patients. The calibrated IBS value (intima-media IBS value minus adventia IBS) of vulnerable carotid plaques favorably changed at 1 month after treatment in both groups, but the echolucency at 1 month improved more in the pitavastatin than in the placebo group (pitavastatin group: -18.7 +/- 3.3 dB at pretreatment versus -12.7 +/- 2.3 dB at 1 month *P < 0.001; placebo: -19.0 +/- 3.5 dB versus -16.9 +/- 3.2 dB, P < 0.05, *P < 0.01 versus the value at 1 month in placebo group). Levels of CRP, VEGF, and TNFalpha at 1 month were significantly lower in pitavastatin than placebo group. In conclusion, pitavastatin improved carotid plaque echolucency within 1 month of therapy in patients with ACS, in association with decrease in the inflammatory biomarkers related to vulnerable plaques.

Correlation of plasma concentrations of B-type natriuretic peptide with infarct size quantified by tomographic thallium-201 myocardial scintigraphy in asymptomatic patients with previous myocardial infarction.

BACKGROUND: Secretion of A-type (atrial) and B-type (brain) natriuretic peptides (ANP and BNP) increases in relation to left ventricular (LV) dysfunction in patients with myocardial infarction (MI). However, it is unknown what determines the concentrations of ANP and BNP in asymptomatic MI patients with preserved LV function, so the aim of the present study was to examine if they are associated with MI size. METHODS AND RESULTS: Plasma concentrations of ANP and BNP in the peripheral blood were measured in 88 asymptomatic (New York Heart Association class I) patients with previous MI. The infarct size was quantitatively calculated from rest thallium-201 myocardial single photon emission computed tomography. In multivariate linear regression analysis that included MI size, hemodynamic parameters, and age as covariables, only BNP concentrations had a significant association with MI size (p=0.0001). In contrast, ANP concentrations were not significantly correlated with MI size in either the univariate or multivariate analysis. CONCLUSIONS: BNP but not ANP concentrations increased in proportion to the scintigraphic MI size despite the lack of heart failure in asymptomatic patients with previous MI. Thus, the increase in plasma BNP concentrations reflects the MI size, an important determinant of prognosis, in asymptomatic patients with MI.