Mid-Aortic Syndrome in Williams-Beuren Syndrome with an Atypical Small-Sized Deletion of Chromosome 7q11.23 Misdiagnosed as Takayasu Arteritis.

Mid-aortic syndrome (MAS) is a rare condition characterized by stenosis of the distal thoracic and/or abdominal aorta. Williams-Beuren syndrome (WBS) is a relatively rare cause of MAS. We report a case of incidentally diagnosed MAS caused by WBS without typical manifestations caused by an atypical small-sized deletion in chromosome 7q11.23, which was initially misdiagnosed as Takayasu arteritis.

Influence of early dose reduction of ticagrelor on clinical outcomes following percutaneous coronary intervention for complex lesions.

Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk.

Combined Therapy of Low-Dose Angiotensin Receptor-Neprilysin Inhibitor and Sodium-Glucose Cotransporter-2 Inhibitor Prevents Doxorubicin-Induced Cardiac Dysfunction in Rodent Model with Minimal Adverse Effects.

Although cancer-therapy-related cardiac dysfunction (CTRCD) is a critical issue in clinical practice, there is a glaring lack of evidence regarding cardiotoxicity management. To determine an effective and suitable dosage of treatment using angiotensin receptor-neprilysin inhibitors (ARNI) with sodium-glucose cotransporter 2 inhibitors (SGLT2i), we adopted a clinically relevant rodent model with doxorubicin, which would mimic cardiac dysfunction in CTRCD patients. After the oral administration of drugs (vehicle, SGLT2i, ARNI, Low-ARNI/SGLT2i, ARNI/SGLT2i), several physiologic parameters, including hemodynamic change, cardiac function, and histopathology, were evaluated. Bulk RNA-sequencing was performed to obtain insights into the molecular basis of a mouse heart response to Low-ARNI/SGLT2i treatment. For the first time, we report that the addition of low-dose ARNI with SGLT2i resulted in greater benefits than ARNI, SGLT2i alone or ARNI/SGLT2i combination in survival rate, cardiac function, hemodynamic change, and kidney function against doxorubicin-induced cardiotoxicity through peroxisome proliferator-activated receptor signaling pathway. Low-dose ARNI with SGLT2i combination treatment would be practically beneficial for improving cardiac functions against doxorubicin-induced heart failure with minimal adverse effects. Our findings suggest the Low-ARNI/SGLT2i combination as a feasible novel strategy in managing CTRCD patients.

Mechanism of mitral regurgitation in the acute phase of inferior wall myocardial infarction: reduced closing force as a consequence of left ventricular systolic dysfunction in the presence of tethering as a determinant of mitral regurgitation.

BACKGROUND: To delineate the mechanism of mitral regurgitation (MR) in the acute phase of inferior wall myocardial infarction (MI). METHODS AND RESULTS: In 97 patients (age 59 ± 12 years) with acute inferior wall MI, the severity of MR, left ventricular (LV) geometric changes and function within 1.7 ± 1.3 days after MI by echocardiography was retrospectively evaluated. Infarct size was measured within 3.9 ± 1.7 days by cardiac magnetic resonance. Mild MR was present in 16 (16.5%) and moderate MR in 12 (12.4%) of 97 patients. There were no significant differences in mitral annular area, sphericity and distances between papillary muscle tips and the contralateral mitral annulus. However, patients with moderate MR had significantly larger LV end-systolic volume, tenting area and infarct size. There was a graded relationship between the severity of MR and LV ejection fraction. In a multivariable regression analysis, LV ejection fraction and tenting area were found to be independent predictors of the severity of MR (r(2)=0.180, P=0.001). CONCLUSIONS: MR was associated with LV systolic dysfunction, increase in end-systolic LV volume and tethering of mitral leaflet, suggesting reduced closing force as a consequence of LV systolic dysfunction in the presence of leaflet tethering would play a more pivotal role in the development of MR.

Coronary artery responsiveness to ergonovine provocation in patients without vasospatic angina: a quantitative coronary angiography analysis.

Even patients without vasospastic angina show vasoconstriction after intracoronary ergonovine administration. We evaluated the determinants of coronary artery responsiveness to ergonovine in such patients.In 165 patients with no provoked electrocardiographic changes or ischemic chest pain during an intracoronary ergonovine test, total cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were correlated with the arterial luminal diameters before and after ergonovine infusion and after nitroglycerin injection by quantitative coronary angiography analysis.The mean and maximal basal tone (ie, percent change between baseline luminal diameter and diameter after nitroglycerin) were 7.0 ± 9.9% and 27.9 ± 10.8%, respectively. The mean and maximal responsiveness to ergonovine (ie, percent change between minimal diameter during ergonovine infusion and diameter after nitroglycerin) were 30.3 ± 13.6% and 52.7 ± 16.0%, respectively. The TG level (r = 0.191, P = 0.016) and TG/HDL ratio (r = 0.182, P = 0.021) were positively correlated with the basal tone, whereas LDL level (r = 0.155, P = 0.048) and LDL/HDL ratio (r = 0.172, P = 0.030) were positively correlated with the responsiveness to ergonovine. By multivariate analysis, LDL level, LDL/HDL ratio, and smoking were independent predictors of more than 50% responsiveness to ergonovine.Serum lipid profile and smoking influence the basal tone and responsiveness to ergonovine of coronary artery in patients without vaospastic angina.

H2O2-Responsive Antioxidant Nanoparticle Attenuates Whole Body Ischemia/Reperfusion-Induced Multi-Organ Damages.

Mortality and morbidity after cardiac arrest remain high due to ischemia/reperfusion (I/R) injury causing multi-organ damages, even after successful return of spontaneous circulation. We previously generated H2O2-activatable antioxidant nanoparticles formulated with copolyoxalate containing vanillyl alcohol (PVAX) to prevent I/R injury. In this study, we examined whether PVAX could effectively reduce organ damages in a rat model of whole-body ischemia/reperfusion injury (WBIR). To induce a cardiac arrest, 70µl/100 g body weight of 1 mmol/l potassium chloride was administered via the jugular venous catheter. The animals in both the vehicle and PVAX-treated groups had similar baseline blood pressure. After 5.5 minutes of cardiac arrest, animals were resuscitated via intravenous epinephrine followed by chest compressions. PVAX or vehicle was injected after the spontaneous recovery of blood pressure was noted, followed by the same dose of second injection 10 minutes later. After 24 hours, multiple organs were harvested for pathological, biochemical, molecular analyses. No significant difference on the restoration of spontaneous circulation was observed between vehicle and PVAX groups. Analysis of organs harvested 24 hours post procedure showed that whole body I/R significantly increased reactive oxygen species (ROS) generation, inflammatory markers, and apoptosis in multiple organs (heart, brain, and kidney). PVAX treatment effectively blocked ROS generation, reduced the elevation of pro-inflammatory cytokines, and decreased apoptosis in these organs. Taken together, our results suggest that PVAX has potent protective effect against WBIR induced multi-organ injury, possibly by blocking ROS-mediated cell damage.

Clinical features and predictors of masked uncontrolled hypertension from the Korean Ambulatory Blood Pressure Monitoring Registry.

BACKGROUND/AIMS: The clinical characteristics of patients with masked uncontrolled hypertension (MUCH) have been poorly defined, and few studies have investigated the clinical predictors of MUCH. We investigated the demographic, clinical, and blood pressure (BP) characteristics of patients with MUCH and proposed a prediction model for MUCH in patients with hypertension. METHODS: We analyzed 1,986 subjects who were enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) Registry and taking antihypertensive drugs, and classified them into the controlled hypertension (n = 465) and MUCH (n = 389) groups. MUCH was defined as the presence of a 24-hour ambulatory mean systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg in patients treated with antihypertensive drugs, having normal office BP. RESULTS: Patients in the MUCH group had significantly worse metabolic profiles and higher office BP, and took significantly fewer antihypertensive drugs compared to those in the controlled hypertension group. Multivariate logistic regression analyses identified high office systolic BP and diastolic BP, prior stroke, dyslipidemia, left ventricular hypertrophy (LVH, ≥ 116 g/m2 for men, and ≥ 96 g/m2 for women), high heart rate (≥ 75 beats/min), and single antihypertensive drug use as independent predictors of MUCH. A prediction model using these predictors showed a high diagnostic accuracy (C-index of 0.839) and goodness-of-fit for the presence of MUCH. CONCLUSION: MUCH is associated with a high-normal increase in office BP and underuse of antihypertensive drugs, as well as dyslipidemia, prior stroke, and LVH, which could underscore achieving optimal BP control. The proposed model accurately predicts MUCH in patients with controlled office BP.

Epidemiology of Venous Thromboembolism and Treatment Pattern of Oral Anticoagulation in Korea, 2009-2016: a Nationwide Study Based on the National Health Insurance Service Database.

BACKGROUND: The annual incidence of venous thromboembolism (VTE) is increasing, and the treatment pattern of oral anticoagulants (OACs) has changed with introduction of new oral anticoagulants (NOACs). The aims of this study were to assess the annual incidence of VTE in a Korean population and the change of treatment pattern with availability of NOACs using a population-based database. METHODS: Using the Korean National Health Insurance Services database, we identified patients diagnosed with VTE between 2009 and 2016. The annual prevalence of VTE and clinical characteristics and treatment pattern were investigated. The annual incidence of VTE was calculated using direct and indirect methods using the estimated Korean population in 2009 as the reference. RESULTS: The annual incidence of VTE in Korean has increased yearly from 23.9 per 100,000 in 2009 to 42.2 in 2016. The overall rate of OAC prescription for VTE treatment increased from 55.9% to 68% in the same time period. The rate of initiation of NOAC treatment greatly increased, particularly from 2013 onwards, with a 20-fold increase from 2009 to 2016 (2.1% vs. 54.3%). CONCLUSIONS: The annual incidence of VTE in Korea increased by almost two-fold from 2009 to 2016. The rate of initiation of NOAC treatment has increased substantially since 2013, and these agents have surpassed VKAs as the anticoagulant of choice for VTE. This temporal pattern of OAC prescription is consistent with the current clinical guidelines, which indicate NOACs over the warfarin in patients with VTE.

Factors Related to Major Bleeding After Ticagrelor Therapy: Results from the TICO Trial.

Background There is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation. Methods and Results From the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate <60 mL/min per 1.73 m2 were associated with an increased risk of major bleeding. In contrast, 3-month aspirin therapy with continued ticagrelor (versus 12-month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3-month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39-0.90; Pinteraction=0.74). Conclusions Low body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk. Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02494895.

Ischemic and Bleeding Events of Ticagrelor Monotherapy in Korean Patients With and Without Diabetes Mellitus: Insights From the TICO Trial.

Background: Ticagrelor monotherapy after 3 months dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, the impact of this approach among the patient with diabetes remains unknown. Methods: This was a sub-analysis of the Ticagrelor Monotherapy after 3 months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial. After successful PCI, the patients were randomly assigned to ticagrelor monotherapy after 3-months DPAT or to ticagrelor-based 12-months DAPT. We compared ischemic events and bleeding events between the patients with diabetes and without diabetes for 12 months. Ischemic events were defined as death, myocardial infarction, ischemic stroke, transient ischemic attack, stent thrombosis, and any revascularizations. Bleeding events were defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria and Bleeding Academic Research Consortium (BARC) definition. Results: Between August 2015 and October 2018, 3,056 patients were enrolled in the TICO trial, of which 835 (27.3%) had diabetes mellitus. Diabetes mellitus was associated with all evaluated ischemic and bleeding events. No significant differences in any ischemic events were observed in patients with diabetes between ticagrelor monotherapy after 3-months DAPT and ticagrelor-based 12-months DAPT (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.45-1.52, p = 0.540). In patients with diabetes, the overall incidence of bleeding complications during the 12-months follow-up period did not differ between the two treatment groups (HR 0.83, 95% CI 1.48-1.43, p = 0.505). However, ticagrelor monotherapy was significantly reduced both any TIMI bleeding and BARC three or five bleeding events in diabetes patients in the 3-months landmark analysis, after 3-months DAPT period (HR 0.20, 95% CI 0.07-0.59, p = 0.003). Conclusion: In diabetic patients, ticagrelor monotherapy showed a lower incidence of bleeding complications after 3-months DAPT period, without increasing ischemic complications, compared with ticagrelor-based 12-months DAPT (ClinicalTrials.gov Identifier: NCT02494895).

Prevalence and clinical features of bone morphogenetic protein receptor type 2 mutation in Korean idiopathic pulmonary arterial hypertension patients: The PILGRIM explorative cohort.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive chronic disease with poor outcomes. One reason for poor prognosis is the lack of understanding regarding individual variability in response to treatment. Idiopathic PAH (IPAH) patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations have distinct phenotypes that are crucial for individualized therapy but evidence regarding their prevalence and clinical features in the Korean population is lacking. Therefore, the present study aimed to screen Korean IPAH patients for BMPR2 mutations and analyze their clinical phenotypes. METHODS: We enrolled 73 unrelated IPAH patients for BMPR2 mutation screening between March 2010 to November 2015 from 11 hospitals in Korea. Thirty-three lineal family members from 6 families of BMPR2 mutation carriers were also screened. RESULTS: Among 73 patients, 16 (22%) had BMPR2 mutations. Mutation carriers were younger (27 vs. 47 years; p = 0.02) and had a higher mean pulmonary arterial pressure (mPAP) than non-carriers (64 vs. 51 mmHg; p<0.05). Of the 16 individuals with mutations, 5 deletion, 2 splice-site, 6 nonsense, and 3 missense mutations were found, among which, 9 were newly identified mutation types. Patients less than 30 years old had more BMPR2 mutations (44 vs. 14%; p = 0.04) and a higher mPAP (64 vs. 50 mmHg; p = 0.04) compared with those equaled to or over 30 years old. There were no differences in hemodynamic profiles or the proportion of BMPR2 mutation carriers between groups according to sex. CONCLUSION: The prevalence of BMPR2 mutations in Korean IPAH patients was 22%. Mutation carriers were younger and had a poorer hemodynamic profile compared with the non-carriers. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01054105.

Patterns of late gadolinium enhancement are associated with ventricular stiffness in patients with advanced non-ischaemic dilated cardiomyopathy.

AIMS: Despite the prognostic importance of ventricular filling and ventricular-arterial interaction in patients with advanced systolic heart failure, the structural determinants of these parameters have not been fully studied. We aimed to investigate whether patterns of late gadolinium enhancement (LGE) on cardiac magnetic resonance affect ventricular elastic properties or performance in patients with non-ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Patients (n = 49) with markedly reduced systolic function (left ventricular (LV) ejection fraction <35%) due to longstanding non-ischaemic DCM underwent contrast-enhanced cardiac magnetic resonance after comprehensive echo-Doppler evaluations. The single beat-derived end-diastolic elastance, end-systolic elastance, arterial elastance, and dyssynchrony indices were measured by echo. On the basis of LGE patterns, patients could be divided into three groups: non-LGE (n = 18), non-midwall LGE (n = 13), and midwall LGE (n = 18). The midwall LGE group had lower LV systolic longitudinal velocity (4.6 +/- 1.7 for non-LGE vs. 4.3 +/- 1.2 for non-midwall LGE vs. 3.5 +/- 1.0 cm/s for midwall LGE, P = 0.025), higher end-diastolic elastance index (0.41 +/- 0.21 vs. 0.46 +/- 0.31 vs. 0.85 +/- 0.51 respectively, P = 0.008), and a more impaired ventriculoarterial coupling index (3.14 +/- 1.53 vs. 2.88 +/- 1.94 vs. 5.52 +/- 3.18, P = 0.006) than other subgroups. CONCLUSION: Patients with midwall LGE had a higher ventricular stiffness index and more impaired ventriculoarterial coupling when compared with other non-ischaemic DCM patients.

Response of high-sensitivity C-reactive protein to percutaneous coronary intervention in patients with acute coronary syndrome.

Percutaneous coronary intervention (PCI) provokes an inflammatory reaction, as shown by increased concentrations of plasma C-reactive protein (CRP) after PCI. However, the changes of CRP levels after PCI in patients with acute coronary syndrome (ACS) have not been well evaluated. We evaluated the characteristics of the patients with elevated CRP response after PCI and whether an increase in CRP after PCI predicts long-term prognosis in patients with ACS. We studied consecutive 360 patients with ACS who underwent elective coronary stenting. Inflammatory response to PCI was calculated as the difference between the peak postprocedural hsCRP level and the preprocedural hsCRP level (DeltaCRP). Twelve months follow-up data were obtained and clinical outcomes were compared with DeltaCRP. In receiver operating characteristics analyses, the cutoff point of DeltaCRP for major adverse cardiac events (MACE) was 3.0 mg/l, which yielded sensitivity of 61.7% and specificity of 69.7%. The patients with DeltaCRP > 3 mg/l revealed higher incidence of myocardial infarction (37.7 vs 14.6%, P < 0.001), and ACC/AHA type B2/C lesion (81.5 vs 68.7%, P = 0.006) than in patients with low DeltaCRP. White blood cell count, low-density lipoprotein cholesterol, peak creatinine kinase-MB, and peak troponin T were significantly elevated in patients with DeltaCRP > 3 mg/l than in those with < or =3 mg/l. There was significant correlation between DeltaCRP and the changes in troponin T after PCI (r = 0.210, P < 0.001). An increase in hsCRP > 3 mg/l after PCI had a higher predictive value for the occurrence of MACE than low hsCRP elevation (hazard ratio 2.1, P = 0.005). In multivariate analysis, DeltaCRP and peak troponin T were independent predictors of MACE (P < 0.001 and P = 0.013, respectively). In conclusion, postprocedural hsCRP elevation >3 mg/l was associated with higher incidence of MACE in patients with ACS. DeltaCRP determinations may be of value for risk stratification after PCI.

Temporal Variability of Platelet Reactivity in Patients Treated with Clopidogrel or Ticagrelor.

BACKGROUND AND OBJECTIVES: The degree of antiplatelet response to P2Y12 inhibitors has been associated with clinical outcomes. The aim of this study was to test the variability of platelet reactivity over time among patients treated with clopidogrel or ticagrelor. METHODS: A single-center cohort of acute coronary syndrome patients that underwent percutaneous coronary intervention (PCI) was analyzed. Platelet reactivity was measured at baseline, 48 hours after PCI, 1 month, and 6 months after clopidogrel (n=79) or ticagrelor (n=93) treatment. High on-treatment platelet reactivity (HPR) was defined as ≥47 U, assessed by multiple electrode platelet aggregometry. RESULTS: Platelet reactivity in the clopidogrel group increased over time, 38.2±21.7 U at 48 hours, 41.4±22.3 U at 1 month, and 44.7±25.5 U at 6 months (p=0.018, 48 hours to 6 months). However, platelet reactivity in the ticagrelor group was not significantly changed, 21.4±12.6 U at 48 hours, 20.0±12.2 U at 1 month, and 22.8±13.8 U at 6 months (p=0.392). A platelet reactivity change over time of more than 20U was found in 67.1% of the patients with clopidogrel group and 34.4% of ticagrelor group (p<0.001). Between 48 hours and 6 months, 43% of patients changed their responder status in the clopidogrel group, and 13% in the ticagrelor group (p<0.001). CONCLUSIONS: Although ticagrelor treatment resulted in less temporal variability of platelet reactivity than clopidogrel treatment in terms of HPR, platelet reactivity varied over time in a significant proportion of patients.

Comparison of the Infarct Size between the Loading of Ticagrelor and Clopidogrel in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: Ticagrelor is considered a potent antiplatelet agent compared to clopidogrel. However, there are no studies regarding the effect of ticagrelor loading on infarct size in patients with ST-segment elevation myocardial infarction (STEMI) in a primary percutaneous coronary intervention (PCI) setting. SUBJECTS AND METHODS: In this single-center, randomized, open-label study, 188 patients who underwent primary PCI for STEMI were enrolled (92 patients in the clopidogrel group and 96 in the ticagrelor group) and compared the infarct size by technetium-99m (Tc-99m) tetrofosmin single-photon emission computed tomography (SPECT) and serial cardiac biomarker levels between the groups. SPECT was performed at a median of 2 days after PCI. RESULTS: Baseline clinical and procedural characteristics were similar between the groups. Infarct size on SPECT, was similar between the 2 groups (28.1%±34.5% vs. 32.8%±29.2%; p=0.169). At all time-points after PCI (8, 24, and 48 hours), the peak levels of creatine kinase-myocardial band (CK-MB) and troponin T were lower in the clopidogrel group. The clopidogrel group showed lower cumulative troponin T levels than the ticagrelor group (12.59±10.66 vs. 17.67±19.51 ng/mL; p=0.029). CONCLUSION: Ticagrelor loading before primary PCI was not associated with reduced myocardial infarct size during the first 48 hours, compared to clopidogrel loading.

Correlations between High Platelet Reactivity, Extent of Coronary Artery Disease, and Periprocedural Myonecrosis in Patients with Acute Coronary Syndrome.

The purpose of the present study was to evaluate the correlations between high platelet reactivity (HPR) and the extent of coronary atherosclerosis and periprocedural myonecrosis in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). A total of 485 patients who underwent PCI for ACS was studied. HPR was defined as ≥230 platelet reactivity units (PRU) in point-of-care P2Y12 tested by the VerifyNow assay. The incidence of multi-vessel disease (MVD) was higher in patients with HPR than those with no HPR (56.2% vs 45.8%, p=0.023). PRU values progressively increased with the number of diseased coronary arteries (1-vessel disease 221.8±86.7; 2-vessel disease 239.3±90.1; 3-vessel disease 243.4±84.5; p=0.038 by ANOVA). Multivariate analysis revealed that HPR was independently associated with MVD (Odds ratio 1.48, 95% confidence interval 1.01-2.25, p=0.048). Patients with periprocedural myonecrosis showed significantly higher PRU values compared with those without myonecrosis (258.6±94.5 vs. 228.5±85.6, p=0.013). Multivariate analysis revealed that HPR was an independent predictor for periprocedural myonecrosis as defined as any creatine kinase-myocardial band isoenzyme elevation or troponin T elevation. In conclusion, HPR is associated with MVD and periprocedural myonecrosis in patients with ACS and PCI. Thus, platelet reactivity after treatment with clopidogrel might be associated not only with blood clot formation but also with increased coronary atherosclerotic burden.

Antioxidative Activity after Rosuvastatin Treatment in Patients with Stable Ischemic Heart Disease and Decreased High Density Lipoprotein Cholesterol.

BACKGROUND AND OBJECTIVES: The clinical significance of statin-induced high-density lipoprotein cholesterol (HDL-C) changes is not well known. We investigated whether rosuvastatin-induced HDL-C changes can influence the anti-oxidative action of high-density lipoprotein particle. SUBJECTS AND METHODS: A total of 240 patients with stable ischemic heart disease were studied. Anti-oxidative property was assessed by paraoxonase 1 (PON1) activity. We compared the lipid profile and PON1 activity at baseline and at 8 weeks after rosuvastatin 10 mg treatment. RESULTS: Rosuvastatin treatment increased the mean HDL-C concentration by 1.9±9.2 mg/dL (6.4±21.4%). HDL-C increased in 138 patients (57.5%), but decreased in 102 patients (42.5%) after statin treatment. PON1 activity increased to 19.1% in all patients. In both, the patients with increased HDL-C and with decreased HDL-C, PON1 activity significantly increased after rosuvastatin treatment (+19.3% in increased HDL-C responder; p=0.018, +18.8% in decreased HDL-C responder; p=0.045 by paired t-test). Baseline PON1 activity modestly correlated with HDL-C levels (r=0.248, p=0.009); however, the PON1 activity evaluated during the course of the treatment did not correlate with HDL-C levels (r=0.153, p=0.075). CONCLUSION: Rosuvastatin treatment improved the anti-oxidative properties as assessed by PON1 activity, regardless of on-treatment HDL-C levels, in patients with stable ischemic heart disease.

Diurnal variation of flow-mediated dilatation in healthy humans.

INTRODUCTION: The measurement of flow-mediated dilatation (FMD) via ultrasound has been established as a reliable non-invasive measurement of endothelial function. However, the guidelines mention nothing regarding diurnal variation of FMD. Thus, we investigated the FMD in healthy people and diurnal variation of FMD. METHODS: Twenty-five apparently healthy persons participated in this study. All participants had no history of cardiovascular diseases, hypertension, or diabetes and used any medication. For each volunteer, the measurements were repeated in the morning and afternoon on two different days. We checked capillary blood glucose, total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)-cholesterol. RESULTS: The average of FMD measurements was 8.45% ± 2.39%. The mean values of systolic and diastolic blood pressure, heart rate, lipid profiles, and glucose levels were similar between the morning and afternoon measurements after 9-h fasting. There was no significant difference of FMD measurements between the morning and afternoon (8.32% ± 2.27% and 8.58% ± 2.56%, p = 0.329). Moreover, there was significant correlation between FMD in the morning and afternoon (r = 0.856, p < 0.001). CONCLUSIONS: Our study shows measurement of FMD was 8.45% in healthy Koreans. Also, there was no significant difference of FMD measurements between the morning and afternoon.

Effect of High Dose Rosuvastatin Loading before Primary Percutaneous Coronary Intervention on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND AND OBJECTIVES: High dose rosuvastatin loading before percutaneous coronary interventions (PCI) reduces the myocardial damage and the incidence of adverse cardiac events in patients with stable angina and acute coronary syndrome. However, no studies are present yet about rosuvastatin loading in patients with ST-segment elevation myocardial infarction (STEMI) in a primary PCI setting. SUBJECTS AND METHODS: A total of 475 patients who underwent primary PCI for STEMI were studied. The study population was divided into two groups with 208 patients in the statin group=40 mg rosuvastatin loading before primary PCI and 267 patients in the control group=no statin pretreatment. At median 3 days after PCI a single-photon emission computed tomography (SPECT) was performed with technetium 99m tetrofosmin For this study were compared infarct size, corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and the myocardial blush grade (MBG) between the both groups. RESULTS: Baseline clinical and procedural characteristics were similar between the groups. Infarct size, as assessed by SPECT, was significantly smaller (19.0±15.9% vs. 22.9±16.5%, p=0.009) in the statin group than in the control group. Patients of the statin group showed a lower corrected TIMI frame count (28.2±19.3 vs. 32.6±21.4, p=0.020), and higher MBG (2.49±0.76 vs. 2.23±0.96, p=0.001) than the patients of the control group. The multivariate analysis revealed that rosuvastatin loading {odds ratio (OR) 0.61}, pain to balloon time (OR 2.05), anterior myocardial infarction (OR 3.89) and final the MBG (OR 2.93) were independent predictors of a large infarct size. CONCLUSION: A high dose rosuvastatin loading before the primary PCI reduced the infarct size by microvascular myocardial perfusion improvement.