Impact of red blood cell distribution width and mean platelet volume in patients with ST-segment elevation myocardial infarction.

The complete blood cell count is one of the most frequently ordered laboratory tests, and many parameters, including red blood cell distribution width (RDW) and mean platelet volume (MPV), are available. The purpose of this study was to investigate the usefulness of the combination of RDW and MPV in patients with ST-segment elevation myocardial infarction (STEMI). Patients with STEMI who underwent primary percutaneous coronary intervention were retrospectively enrolled (n = 229). The association between RDW as well as MPV and cardiovascular events was investigated. The median age was 67 years, and males made up 85% of the sample. Median RDW was 13.6%, and median MPV was 8.2 fL. During a median follow-up period of 528 days (IQR 331.5-920.5), 41 patients died or experienced major adverse cardiac and cerebrovascular events (MACCEs). Patients with RDW ≧ 13.7% had more deaths or MACCEs with marginal significance (p = 0.0799). Patients with MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0283). Patients with RDW ≧ 13.7% and MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0185). MPV was significantly associated with death or adverse events in patients with STEMI who were treated with primary PCI. RDW had only a weak association with death or adverse events. The results of the combination of MPV and RDW were similar to those of MPV.

Global Strain Measured by Three-Dimensional Speckle Tracking Echocardiography Is a Useful Predictor for 10-Year Prognosis After a First ST-Elevation Acute Myocardial Infarction.

BACKGROUND: Three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) is associated with left ventricular (LV) remodeling and 1-year prognosis. This study investigated the clinical significance of 3D-STE in predicting the long-term prognosis of patients with STEMI.Methods and Results:A total of 270 patients (mean age 64.6 years) with first-time STEMI treated with reperfusion therapy were enrolled. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Patients were followed up for a median of 119 months (interquartile range: 96-129 months). The primary endpoint was occurrence of a major adverse cardiac event (MACE: cardiac death, heart failure with hospitalization), and 64 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 3D-STE indices were stronger predictors of MACE compared with those of 2D-STE. Additionally, 3D-global longitudinal strain (GLS) was the strongest predictor for MACE followed by 3D-global circumferential strain (GCS). The Kaplan-Meier curve demonstrated that 3D-GLS >-11.0 was an independent predictor for MACE (log-rank χ2=132.2, P<0.0001). When combined with 3D-GCS >-18.3, patients with higher values of 3D-GLS and 3D-GCS were found to be at extremely high risk for MACE. CONCLUSIONS: Global strain measured by 3D-STE immediately after the onset of STEMI is a clinically significant predictor of 10-year prognosis.

Skeletal muscle mass is associated with glycemic variability in patients with ST-segment elevation myocardial infarction.

Skeletal muscle function has been studied to determine its effect on glucose metabolism; however, its effect on glycemic variability (GV), which is a significant glycemic marker in patients with coronary artery disease, is unknown. The aim of the present study was to elucidate the association between skeletal muscle mass and GV. Two hundred and eight consecutive ST-segment elevation myocardial infarction (STEMI) patients who underwent continuous glucose monitoring to evaluate mean amplitude of glycemic excursion (MAGE) as GV and a dual-energy X-ray absorptiometry (DEXA) to evaluate skeletal muscle mass were enrolled. Skeletal muscle index (SMI) level was calculated as skeletal muscle mass divided by height squared (kg/m2). SMI level in men had a weak inverse correlation with Log MAGE level by the linear regression model in diabetes mellitus (DM) patients (R2 = 0.139, P = 0.004) and even in non-DM patients (R2 = 0.068, P = 0.004). Multivariate linear regression analysis with a stepwise algorithm (age, male sex, body mass index [BMI], hemoglobin A1c [HbA1c], fasting glucose, HOMA-IR, and SMI; R2 = 0.203, P < 0.001) demonstrated that HbA1c level (B = 0.077, P < 0.001) and SMI level (B = - 0.062, P < 0.001) were both independently associated with Log MAGE level. This association was also confirmed in limited non-DM patients with a subgroup analysis. SMI level was associated with Log MAGE level (B = - 0.055, P = 0.001) independent of BMI or HbA1c level. SMI level was inversely associated with MAGE level independent of glucose metabolism in STEMI patients, suggesting the significance of skeletal muscle mass as blood glucose storage for glucose homeostasis to reduce GV.

Clinical impact of admission urinary 8-hydroxydeoxyguanosine level for predicting cardiovascular mortality in patients with acute coronary syndrome.

The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.92 ng/mg creatinine; and a low admission urinary 8-OHdG group, 382 patients with admission urinary 8-OHdG < 17.92 ng/mg creatinine. The patients were followed up for a median period of 34 months. The primary and secondary end points were the incidence of cardiovascular death and major cardiovascular events (MACE) composed of cardiovascular death, non-fatal myocardial infarction, or urgent hospitalization for heart failure. Of the 551 patients, cardiovascular deaths and MACE occurred in 14 (2.5%) and 35 (6.4%), respectively. The Kaplan-Meier estimate of the event-free rate revealed cardiovascular deaths and MACE were more likely in the high admission 8-OHdG group than in the low admission 8-OHdG group (log rank, both P < 0.001). Multiple adjusted Cox proportional hazards analysis indicated that high admission urinary 8-OHdG was an independent predictor of cardiovascular death (hazard ratio [HR] 7.642, P = 0.011) and MACE (HR 2.153, P = 0.049). High admission urinary 8-OHdG levels predict cardiovascular mortality after adjustment in patients with ACS.

Characteristics and Prognosis of Patients with Vasospastic Angina Diagnosed by a Provocation Test with Secondary Prevention Implantable Cardioverter Defibrillator.

This study aimed to evaluate the characteristics and prognosis of patients with vasospastic angina (VSA) diagnosed by a provocation test with a secondary prevention implantable cardioverter defibrillator (ICD), compared with patients with organic coronary stenosis. We retrospectively evaluated 309 consecutive patients who received an ICD implantation between January 2010 and March 2018 in our institutions. Of these patients, 206 were implanted with an ICD for secondary prevention. In these 206 patients, 40 with VSA and 72 with organic coronary stenosis were evaluated. Patients with VSA were characterized by younger age (56.1 ± 13.1 versus 69.2 ± 9.5 years, respectively), and a lower prevalence of diabetes (15.0% versus 40.3%, respectively) and heart failure (2.5% versus 26.4%, respectively) than patients with organic coronary stenosis (P < 0.001). Using the Kaplan-Meier analysis, with the VSA group as the reference, the incidence of appropriate ICD shock was similar between the two groups (hazard ratio, 0.85; 95% confidence interval, 0.341-2.109; P = 0.722). The incidence of ventricular fibrillation was significantly higher in the VSA group (hazard ratio, 0.22; 95% confidence interval, 0.057-0.814; P = 0.024), whereas the incidence of major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, and heart failure, was significantly higher in the organic coronary stenosis group (hazard ratio, 13.1; 95% confidence interval, 1.756-98.17; P = 0.012). In conclusion, patients with VSA with an ICD implanted for secondary prevention have a higher risk of ventricular fibrillation and lower risk of major adverse cardiac events than patients with organic coronary stenosis.

Direct Oral Anticoagulant Therapy for Cancer-Associated Venous Thromboembolism in Routine Clinical Practice.

BACKGROUND: The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for cancer-associated venous thromboembolism (VTE) in routine clinical practice remain unclear. Moreover, data on long-term outcomes in patients with cancer-associated VTE who received DOAC therapy are limited.Methods and Results:This retrospective study enrolled 1,096 consecutive patients with acute VTE who received warfarin or DOAC therapy between April 2014 and May 2017. The mean follow-up period was 665±490 days. The number of cancer-associated VTE patients who received DOAC therapy was 334. Patients who could not be followed up and those prescribed off-label under-dose DOAC were excluded. Finally, 303 patients with cancer-associated VTE were evaluated. The number of cases of major bleeding and VTE recurrence was 54 (17.8%) and 26 (8.6%), respectively. In the multivariate analysis, the factors correlated with major bleeding were high cancer stage, high performance status, liver dysfunction, diabetes mellitus, and stomach cancer; those correlated with recurrent VTE were initial diagnosis of pulmonary embolism, uterine cancer, and previous cerebral infarction. Major bleeding was an independent risk factor of all-cause death. In the Kaplan-Meier analysis, those who received prolonged DOAC therapy had lower composite major bleeding and recurrent VTE risks than those who did not. CONCLUSIONS: In DOAC therapy for cancer-associated VTE, major bleeding prevention is important because it is an independent risk factor of death.

Long-Term Clinical Outcomes After Filter Protection During Percutaneous Coronary Intervention in Patients With Attenuated Plaque　- 1-Year Follow up of the VAMPIRE 3 (Vacuum Aspiration Thrombus Reemoval 3) Trial.

BACKGROUND: Selective use of distal filter protection during percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) decreased the incidence of no-reflow phenomena and in-hospital serious adverse cardiac events compared with conventional PCI in patients with attenuated plaque ≥5 mm; however, its long-term clinical outcome remains unknown.Methods and Results:Patients who had ACS with attenuated plaque ≥5 mm were assigned to receive distal protection (DP) (n=98) or conventional treatment (CT) (n=96). The rate of major adverse cardiovascular events (MACE), a composite of death from any cause, non-fatal myocardial infarction, or target vessel revascularization (TVR) at 1 year, was the pre-specified secondary endpoint of the trial. MACE at 1 year occurred in 12 patients (12.2%) in the DP group and 3 patients (3.1%) in the CT group (P=0.029), which was driven by a higher risk of TVR (11 [11.2%] vs. 2 [2.1%], P=0.018). In patients treated with bare-metal stents (n=42), MACE occurred in 25.0% of the patients in the DP group and in none of the patients in the CT group (P=0.029), whereas in patients treated with drug-eluting stents (n=151), rates of MACE were similar in the groups (8.1% vs. 3.9%, P=0.32). CONCLUSIONS: In ACS patients with attenuated plaque ≥5 mm, the 1-year rates of MACE were higher in the DP group than in the CT group. This effect might be mitigated by the use of drug-eluting stents.

Platelet-Derived Thrombogenicity Measured by Total Thrombus-Formation Analysis System in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Prompt and potent antiplatelet effects are important aspects of management of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We evaluated the association between platelet-derived thrombogenicity during PPCI and enzymatic infarct size in STEMI patients.Methods and Results:Platelet-derived thrombogenicity was assessed in 127 STEMI patients undergoing PPCI by: (1) the area under the flow-pressure curve for the PL-chip (PL18-AUC10) using the total thrombus-formation analysis system (T-TAS); and (2) P2Y12reaction units (PRU) using the VerifyNow system. Patients were divided into 2 groups (High and Low) based on median PL18-AUC10during PPCI. PRU levels during PPCI were suboptimal in both the High and Low PL18-AUC10groups (median [interquartile range] 266 [231-311] vs. 272 [217-317], respectively; P=0.95). The percentage of final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was lower in the High PL18-AUC10group (75% vs. 90%; P=0.021), whereas corrected TIMI frame count (31.3±2.5 vs. 21.0±2.6; P=0.005) and the incidence of slow-flow/no-reflow phenomenon (31% vs. 11%, P=0.0055) were higher. The area under the curve for creatine kinase (AUCCK) was greater in the High PL18-AUC10group (95,231±7,275 IU/L h vs. 62,239±7,333 IU/L h; P=0.0018). Multivariate regression analysis identified high PL18-AUC10during PPCI (ß=0.29, P=0.0006) and poor initial TIMI flow (ß=0.37, P<0.0001) as independent determinants of AUCCK. CONCLUSIONS: T-TAS-based high platelet-derived thrombogenicity during PPCI was associated with enzymatic infarct size in patients with STEMI.

Prognostic Significance of a Combination of QRS Score and E/e' Obtained 2 Weeks After the Onset of ST-Elevation Myocardial Infarction.

BACKGROUND: The early mitral inflow velocity to mitral early diastolic velocity ratio (E/e') and electrocardiogram (ECG) determination of QRS score are useful for risk stratification in patients with ST-elevation myocardial infarction (STEMI).Methods and Results:In this study, 420 consecutive patients (357 male; mean [±SD] age 63.6±12.2 years) with first-time STEMI who successfully underwent primary percutaneous coronary intervention within 12 h of symptom onset were followed-up for 5 years (median follow-up 67 months). Echocardiography, ECG, and blood samples were obtained 2 weeks after onset. Infarct size was estimated by the QRS score after 2 weeks (QRS-2wks) and creatine phosphokinase-MB concentrations (peak and area under the curve). The primary endpoint was death from cardiac causes or rehospitalization for heart failure (HF). During follow-up, 21 patients died of cardiac causes and 62 had HF. Multivariate Cox proportional hazard analysis showed that mean E/e' (hazard ratio [HR] 1.152; 95% confidence interval [CI] 1.088-1.215; P<0.0001), QRS-2wks (HR 1.153; 95% CI 1.057-1.254; P<0.0001), and hypertension (HR 1.702; 95% CI 1.040-2.888; P=0.03) were independent predictors of the primary endpoint. Kaplan-Meier curve analysis showed that patients with QRS-2wks >4 and mean E/e' >14 were at an extremely high risk of cardiac death or HF (log rank, χ2=116.3, P<0.0001). CONCLUSIONS: In patients with STEMI, a combination of QRS-2wks and mean E/e' was a simple but useful predictor of cardiac death and HF.

Impact of Total Antithrombotic Effect on Bleeding Complications in Patients Receiving Multiple Antithrombotic Agents.

BACKGROUND: Few reports have evaluated the total antithrombotic effect of multiple antithrombotic agents. Methods and Results: Thrombus formation was evaluated with the Total Thrombus-formation Analysis System (T-TAS®) using 2 types of microchips in 145 patients with stable coronary artery disease receiving oral anticoagulants plus single- or dual-antiplatelet therapy. The PL-chip coated with collagen is designed for analysis of the platelet thrombus formation process under shear stress condition (18 µL/min). The AR-chip coated with collagen and tissue thromboplastin is designed for analysis of the fibrin-rich platelet thrombus formation process under shear stress condition (4 µL/min). The results were expressed as an area under the flow pressure curve (PL18-AUC10and AR4-AUC30, respectively). Bleeding events occurred in 43 patients during a 22-month follow-up. AR4-AUC30was significantly lower in patients with bleeding events than in those without (584 [96-993] vs. 1,028 [756-1,252], P=0.0003). Multivariate logistic regression analysis identified AR4-AUC30(odds ratio 3.18) as a significant predictor of bleeding events, in addition to baseline anemia and usage of the standard dose of direct oral anticoagulants. However, PL18-AUC10was not significantly related to bleeding events. CONCLUSIONS: A lower AR4-AUC30level was associated with increasing risk of subsequent bleeding complications in patients with stable coronary artery disease who received multiple antithrombotic agents.

Comparison between instantaneous wave-free ratio versus morphometric assessments by intracoronary imaging.

Anatomical measurements obtained by intracoronary imaging devices are reported to correlate significantly with fractional flow reserve (FFR). Instantaneous wave-free ratio (iFR) is a nonhyperemic index of stenosis severity with discordant reports regarding its accuracy in relation to FFR. There is no information on the correlation of iFR with measurements derived from intracoronary imaging devices. The purpose of this study was to assess the relationship among iFR, intravascular ultrasound (IVUS), and optical frequency domain imaging (OFDI) parameters. Eighty lesions in 72 patients who underwent elective angiography and had intermediate lesions were enrolled. All lesions were assessed by iFR, FFR, IVUS, and OFDI. iFR was ≤ 0.89 in 21 (26%) lesions and FFR was ≤ 0.80 in 41 (51%) lesions. iFR correlated significantly with both IVUS-derived minimum lumen area (MLA) (r = 0.375, p = 0.003) and OFDI-derived MLA (r = 0.357, p = 0.005). FFR also correlated significantly with both IVUS-derived MLA (r = 0.472, p < 0.001) and OFDI-derived MLA (r = 0.445, p < 0.001). Among the lesions with FFR ≤ 0.80, iFR > 0.89 (mismatch) was observed in 20 lesions. There was no lesion with iFR ≤ 0.89 (reverse mismatch) among the lesions with FFR > 0.80. The lesion location among three major coronary vessels was related with the discrepancy between iFR and FFR (p = 0.007). In conclusion, iFR and FFR showed a significant correlation with IVUS and OFDI measurements. The discrepancy of iFR and FFR was associated with the lesion locations.

Acute anterior myocardial infarction with pectus carinatum.

We presented a case of acute anterior myocardial infarction caused by left anterior descending artery occlusion in a patient with pectus carinatum. The electrocardiogram (ECG) on admission showed counterclockwise rotation and T wave inversion only in leads V1-V2. Computed tomography revealed that this patient with pectus carinatum had greater septal angle. Electrocardiographic counterclockwise rotation due to greater septal angle in pectus carinatum led to atypical ECG findings of acute myocardial infraction.

Glycemic variability determined with a continuous glucose monitoring system can predict prognosis after acute coronary syndrome.

BACKGROUND: Impaired glucose metabolism is an established risk factor for coronary artery disease. Previous studies revealed that glycemic variability (GV) is also important for glucose metabolism in patients with acute coronary syndrome (ACS). We explored the association between GV and prognosis in patients with ACS. METHODS: A total of 417 patients with ACS who received reperfusion wore a continuous glucose monitoring system (CGMS) in a stable phase after admission and were monitored for at least 24 consecutive h. The mean amplitude of glycemic excursion (MAGE) was calculated as a marker of GV. We divided into two groups based on the highest tertile levels of MAGE (MAGE = 52 mg/dl). The groups were followed up for a median of 39 months [IQR 24-50 months]. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE). RESULT: During follow-up, 66 patients experienced MACCE (5 patients had cardiovascular death, 14 had recurrence of ACS, 27 had angina requiring revascularization, 8 had acute decompensated heart failure, and 16 had a stroke). MACCE was more frequently observed in the high MAGE group (23.5% vs. 11.6%, p = 0.002). In multivariate analysis, high MAGE was an independent predictive factor of poor prognosis for MACCE (odds ratio, 1.84; 95% confidence interval, 1.01-3.36; p = 0.045). CONCLUSION: Glycemic variability determined with a CGMS is a predictor of prognosis in patients with ACS without severe DM. Trial registration UMIN 000010620. Registered April 1st 2012.

Glycemic Variability on Continuous Glucose Monitoring System Correlates With Non-Culprit Vessel Coronary Plaque Vulnerability in Patients With First-Episode Acute Coronary Syndrome - Optical Coherence Tomography Study.

BACKGROUND: Glycemic variability (GV) is associated with coronary plaque rupture at the culprit lesion in acute myocardial infarction (AMI). The present study determined the relationship between GV and coronary plaque vulnerability in the non-culprit vessel. METHODS AND RESULTS: The present prospective study involved 46 patients with first-episode acute coronary syndrome (ACS) who underwent optical coherence tomography in the non-culprit vessel. The relationship between GV, assessed with continuous glucose monitoring system, and the presence of thin-cap fibroatheroma (TCFA) at the non-culprit plaque with mild-to-moderate stenosis in the non-culprit vessel, was assessed. GV was quantified using mean amplitude of glycemic excursion (MAGE). Patients were divided into tertiles according to MAGE. TCFA was observed in 13 (28%) of the 46 patients. Fibrous cap thickness was thinner (MAGE tertiles: high, 80±40 µm; intermediate, 152±122 µm; low, 155±102 µm; P=0.01), and TCFA was more common (MAGE tertiles: high, 50%; intermediate, 27%; low, 7%; P=0.03) in patients with high MAGE. On multivariate logistic analysis high MAGE was the only significant determinant of TCFA, independent of coronary risk factors (OR, 5.000; P=0.021), homeostasis model assessment of insulin resistance, and hemoglobin A1c(OR, 5.674; P=0.018). CONCLUSIONS: High MAGE measured early after the onset of first-episode ACS correlated with thinner fibrous cap thickness and higher prevalence of TCFA at the non-culprit plaque in the non-culprit vessel.

Relationship Between Thickness of Calcium on Optical Coherence Tomography and Crack Formation After Balloon Dilatation in Calcified Plaque Requiring Rotational Atherectomy.

BACKGROUND: Target lesion calcification is known to influence percutaneous coronary intervention. We evaluated the effects of rotational atherectomy (RA) and subsequent balloon angioplasty on calcified coronary lesions using optical coherence tomography (OCT). METHODS AND RESULTS: Thirty-seven calcified lesions in 36 patients were treated with RA followed by balloon angioplasty and stent implantation. In all patients, serial OCT images obtained after RA, after balloon angioplasty, and after stent implantation were analyzed at 1-mm intervals. The arc and thickness of the calcium component were measured after RA. The formation of calcium cracks was assessed after balloon angioplasty. A total of 625 segments were analyzed. The formation of calcium crack after balloon angioplasty was associated with greater stent cross-sectional area (7.38±1.92 vs. 7.13±1.68 mm(2), P=0.035) as well as greater lumen gain (3.89±1.53 vs. 3.40±1.46 mm(2), P<0.001). Segments with calcium cracks after angioplasty had a larger median calcium arc (360°, IQR, 246-360° vs. 147°, IQR, 118-199°, P<0.001) and a thinner calcium thickness (0.53±0.28 vs. 1.02±0.42 mm, P<0.001) than those without. The optimal thresholds of calcium arc and calcium thickness for the prediction of cracks were 227° and 0.67 mm, respectively. CONCLUSIONS: Larger calcium arc and thinner calcium thickness were associated with formation of calcium crack. Presence of calcium crack was the important determinant of optimal stent expansion. (Circ J 2016; 80: 1413-1419).

Plasma Glucagon-Like Peptide-1 and Tissue Characteristics of Coronary Plaque in Non-Diabetic Acute Coronary Syndrome Patients.

BACKGROUND: The relationship between plasma glucagon-like peptide-1 (GLP-1) and coronary plaque characteristics in humans remains unclear. METHODS AND RESULTS: A total of 85 culprit coronary vessels excluding the 10-mm culprit segments in non-diabetic patients with acute coronary syndrome (ACS) were examined using integrated backscatter intravascular ultrasound, performed using a 40-MHz intravascular catheter before PCI. All patients underwent 75-g oral glucose tolerance test (OGTT), and the plasma GLP-1 response was evaluated on the basis of the area under the GLP-1 concentration-time curve (GLP-1 AUC) from 0 to 120 min. Patients in the low GLP-1 AUC tertile had a significantly greater percentage lipid area than did patients in the intermediate and high tertiles (low tertile vs. intermediate tertile vs. high tertile: 57.3 ± 12.1% vs. 47.2 ± 15.4% vs. 46.3 ± 12.7%, P<0.01, ANOVA) and a smaller percentage fibrosis area (38.1 ± 9.4% vs. 44.6 ± 11.5% vs. 45.7 ± 9.0%; P=0.01, ANOVA). On multiple regression analysis, low GLP-1 AUC tertile was independently associated with percentage lipid area. CONCLUSIONS: Low plasma GLP-1 during 75-g OGTT is associated with increased lipid content in non-diabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients.

Effects of 4 Statins on Regression of Coronary Plaque in Acute Coronary Syndrome.

BACKGROUND: There is no information on differences in the effects of moderate- and low-intensity statins on coronary plaque in patients with acute coronary syndrome (ACS). The aim of this study was to compare the effects of 4 different statins in patients with ACS, using intravascular ultrasound (IVUS). METHODS AND RESULTS: A total of 118 patients with ACS who underwent IVUS before percutaneous coronary intervention and who were found to have mild to moderate non-culprit coronary plaques were randomly assigned to receive either 20 mg/day atorvastatin or 4 mg/day pitavastatin (moderate-intensity statin therapy), or 10 mg/day pravastatin or 30 mg/day fluvastatin (low-intensity statin therapy). IVUS at baseline and at end of 10-month treatment was available in 102 patients. Mean percentage change in plaque volume (PV) was -11.1±12.8%, -8.1±16.9%, 0.4±16.0%, and 3.1±20.0% in the atorvastatin, pitavastatin, pravastatin, and fluvastatin groups, respectively (P=0.007, ANOVA). Moderate-intensity statin therapy induced regression of PV, whereas low-intensity statin therapy produced insignificant progression (-9.6% vs. 1.8%, P<0.001). On multivariate linear regression analysis, moderate-intensity statin therapy (P=0.02) and uric acid at baseline (P=0.02) were significant determinants of large percent PV reduction. LDL-C at follow-up did not correlate with percent PV change. CONCLUSIONS: Moderate-intensity statin therapy induced regression of coronary PV, whereas low-intensity statin therapy resulted in slight progression of coronary PV in patients with ACS. (Circ J 2016; 80: 1634-1643).

Clinical Impact of the Cardio-Ankle Vascular Index for Predicting Cardiovascular Events After Acute Coronary Syndrome.

BACKGROUND: We hypothesized the cardio-ankle vascular stiffness index (CAVI) could predict future cardiovascular events. METHODS AND RESULTS: We enrolled 288 consecutive patients with acute coronary syndrome (ACS) who underwent CAVI measurement soon after the onset of ACS. Exclusion criteria were as follows: unable to detect significant stenosis by coronary angiography, severe aortic insufficiency, peripheral artery disease, atrial fibrillation (AF), informed consent was not given. We divided the patients into 2 groups according to the cutoff value of CAVI determined by receiver-operating characteristics curve for the prediction of cardiovascular events: low CAVI group, 135 patients with CAVI ≤8.325; high CAVI group, 153 patients with CAVI >8.325. Patients were followed up for a median period of 15 months. The primary and secondary endpoints were the incidence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke), and nonfatal ischemic stroke. Of the 288 patients, cardiovascular events occurred in 19 patients (6.6%). The Kaplan-Meier estimate of the event-free rate revealed cardiovascular events occurred more frequently in the high CAVI group than in the low CAVI group (log-rank, P<0.001). Multiple adjusted Cox proportional hazards analysis, including age, indicated the high CAVI group was an independent predictor of cardiovascular events (hazard ratio [HR] 18.00, P=0.005), and nonfatal ischemic stroke (HR 9.371, P=0.034). CONCLUSIONS: High CAVI is an independent predictor of cardiovascular events and nonfatal ischemic stroke in patients with ACS. (Circ J 2016; 80: 1420-1426).

Pharmacodynamic Assessment of Platelet Reactivity After a Loading Dose of Prasugrel or Clopidogrel in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Few studies have compared the platelet reactivity of prasugrel and clopidogrel in the acute phase of ST-segment elevation myocardial infarction (STEMI).Methods and Results:Primary percutaneous coronary intervention (PCI) was performed in 78 patients with STEMI within 12 h of onset. Patients were randomly assigned to receive a Japanese standard loading dose of prasugrel 20 mg or clopidogrel 300 mg. Platelet reactivity was serially assessed using the VerifyNow-P2Y12 assay, the results of which were expressed as P2Y12-reaction-units (PRU). PRU values were significantly lower in the prasugrel group (n=38) than in the clopidogrel group (n=40) at 3 h, 24 h, and 14 days after loading (191±101 vs. 271±50, 147±80 vs. 261±57, and 171±67 vs. 221±70, respectively, P<0.05), although the PRU levels at baseline (231±57 vs. 237±58, P=0.65) and 1 h after loading (282±65 vs. 291±62, P=0.54) were similar. As compared with the baseline values, the PRU levels at 1, 3 and 24 h after clopidogrel loading were significantly higher (respectively, P<0.05), whereas only the PRU at 1 h after prasugrel was elevated (P<0.001). CONCLUSIONS: In Japanese patients with STEMI who undergo primary PCI, prasugrel provides stronger platelet inhibition than clopidogrel from 3 h after loading, whereas platelet reactivity remained elevated within 24 h after clopidogrel loading. (Circ J 2016; 80: 2520-2527).

Association between blood glucose variability and coronary plaque instability in patients with acute coronary syndromes.

BACKGROUND: Blood glucose variability is receiving considerable attention as a new risk factor for coronary artery disease. This study aimed to investigate the association between blood glucose variability and coronary plaque tissue characteristics. METHODS: In 57 patients with acute coronary syndrome, integrated backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed before balloon dilatation or stent implantation in the culprit vessels. Standard IVUS indices were evaluated for volume index (volume/length), and plaque components were measured by IB-IVUS for percent tissue volume. In addition to conventional glucose indicators, blood glucose variability in a stable state was determined by calculating the mean amplitude of glycemic excursions (MAGE) using a continuous glucose monitoring system. RESULTS: Higher MAGE values were significantly correlated with larger percent plaque volumes (r = 0.32, p = 0.015), and increased lipid (r = 0.44, p = 0.0006) and decreased fibrous (r = -0.45, p = 0.0005) plaque components. In contrast, HbA1c or fasting plasma glucose values were not significantly correlated with plaque volumes and percent plaque components. Homeostasis model assessment of insulin resistance values were positively correlated with vessel (r = 0.35, p = 0.007) and plaque (r = 0.27, p = 0.046) volumes, but not with percent plaque components. In multiple regression analysis, higher MAGE values were independently associated with increased lipid (ß = 0.80, p = 0.0035) and decreased fibrous (ß = -0.79, p = 0.0034) contents in coronary plaques. CONCLUSIONS: Among all glucose indicators studied, only higher blood glucose variability was an independent determinant of increased lipid and decreased fibrous contents with larger plaque burden, suggesting blood glucose variability as one of the important factors related to coronary plaque vulnerability.