An Oligoimide Particle as a Pickering Emulsion Stabilizer.

A pyromellitic dianhydride (PMDA) and 4,4'-oxydianiline (ODA)-based oligoimide (PMDA-ODA) was synthesized by a one-step procedure using water as a solvent. The PMDA-ODA particles showed excellent partial wetting properties and were stably dispersed in both water and oil phases. A stable dispersion was not obtained with comparison PMDA-ODA particles that were synthesized by a conventional two-step method using an organic solvent. Both oil-in-water and water-in-oil Pickering emulsions were prepared using the oligoimide particles synthesized in water, and the size of the emulsion droplet was controlled based on the oligoimide particle concentration. The oligoimide particles were tested to prepare Pickering emulsions using various kinds of oils. The oil-in-water Pickering emulsions were successfully applied to prepare microcapsules of the emulsion droplets. Our new Pickering emulsion stabilizer has the advantages of easy synthesis, no need for surface modification, and the capability of stabilizing both oil-in-water and water-in-oil emulsions.

Current Awareness and Use of the Strain Echocardiography in Routine Clinical Practices: Result of a Nationwide Survey in Korea.

BACKGROUND: Because conventional echocardiographic parameters have several limitations, strain echocardiography has often been introduced in clinical practice. However, there are also obstacles in using it in clinical practice. Therefore, we wanted to find the current status of awareness on using strain echocardiography in Korea. METHODS: We conducted a nationwide survey to evaluate current use and awareness of strain echocardiography from the members of the Korean Society of Echocardiography. RESULTS: We gathered total 321 questionnaires from 25 cardiology centers in Korea. All participants were able to perform or interpret echocardiographic examinations. All participating institutions performed strain echocardiography. Most of our study participants (97%) were aware of speckle tracking echocardiography and 185 (58%) performed it for clinical and research purposes. Two-dimensional strain echocardiography was the most commonly used modality and left ventricle (LV) was the most commonly used cardiac chamber (99%) for clinical purposes. Most of the participants (89%) did not think LV strain can replace LV ejection fraction (LVEF) in their clinical practice. The common reasons for not performing routine use of strain echocardiography was diversity of strain measurements and lack of normal reference value. Many participants had a favorable view of the future of strain echocardiography. CONCLUSION: Most of our study participants were aware of strain echocardiography, and all institutions performed strain echocardiography for clinical and research purposes. However, they did not think the LV strain values could replace LVEF. The diversity of strain measurements and lack of normal reference values were common reasons for not using strain echocardiography in clinical practice.

The changes of individual carotid artery wall layer by aging and carotid intima-media thickness value for high risk.

AIM: It is still unclear which layer (intima or media) is mainly involved in increased carotid intima-media thickness (CIMT) by aging and also unclear regarding CIMT value suggesting high cardiovascular risk, although 75th percentile value of CIMT is known as a high risk in asymptomatic adults. We sought to find the changes of carotid intima thickness (CIT) and carotid media thickness (CMT) by aging and the 75th percentile value of CIMT in asymptomatic Korean adults. METHOD: This is an observational cohort study. Carotid ultrasound findings (n=2204 from 12 hospitals) were prospectively collected. The carotid images were sent to Korea Research Institute of Standards and Science for analysis using specialized software which can measure intima and media wall also. RESULTS: Mean age was 58.1±13.5 years old (52% of men). Pearson's correlation coefficient between age and right CIMT (r=.489, P<.001) and right CMT (r=.482, P<.001) was higher than that between age and right CIT (r=.284, P<.001). Mean right CIMT in male and female was 0.696±0.163 and 0.686±0.167 mm (P=.180), and the 75 percentile value was 0.778 and 0.771 mm, respectively. Mean right CIT was 0.311±0.069 and 0.303±0.064 mm (P=.009), and mean right CMT was 0.391±0.124 and 0.388±0.131 mm (P=.694) in male and female, respectively. Left carotid ultrasound findings showed similar to the right one. CONCLUSION: An increased CIMT by aging was mainly due to increased CMT rather than CIT in asymptomatic adults. The 75th percentile values of right CIMT were 0.778 and 0.771 mm in asymptomatic Korean male and female adults, respectively.

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.

Gender Difference in Arterial Stiffness in a Multicenter Cross-Sectional Study: The Korean Arterial Aging Study (KAAS).

Elevated arterial stiffness has emerged as an important risk factor for future cardiovascular (CV) events in men and women. However, gender-related differences in arterial stiffness have not been clearly demonstrated. We thus determine whether gender affects arterial stiffness in subjects with and without CV risk factors. We consecutively enrolled 1,588 subjects aged 17-87 years (mean age: 46.5; 51% women) from the Korean Arterial Aging Study (KAAS), which is a multicenter registry from 13 university hospitals in Korea for the evaluation of arterial stiffness. We compared markers of arterial stiffness - central augmentation index (AIx), aortic pulse wave velocity (PWV), and pulse pressure (PP) amplification - in apparently healthy men and women without risk factors with those in high-risk subjects with a smoking habit, hypertension, diabetes, and dyslipidemia but without drug treatment. Aortic PWV and PP amplification were significantly higher in men than in women (7.78 ± 1.16 vs. 7.64 ± 1.15 m/s, p = 0.015, and 1.39 ± 0.22 vs. 1.30 ± 0.18, p < 0.001, respectively). However, women had a significantly higher central AIx than men (23.5 ± 11.9 vs. 16.1 ± 12.6%, p < 0.001). The central AIx and aortic PWV values were significantly higher in the high-risk group than in the healthy group for both men and women. In men, central AIx and aortic PWV were associated positively with age and blood pressure, and negatively with body mass index. In women, central AIx was positively related to age, diastolic blood pressure, and serum cholesterol levels. Aortic PWV was positively related to age, systolic blood pressure, fasting glucose, and heart rate. PP amplification was associated negatively with age and blood pressure and positively with heart rate in both men and women. In conclusion, arterial stiffness is mainly determined by sex, age, and blood pressure. Markers of arterial stiffness differ between men and women. Dyslipidemia and glucose contribute to a modest increase in arterial stiffness only in women. Therefore, the arteries of women may be more vulnerable to CV risk factors than those of men.

Long-Term Predictors of Clinical Events after Off-Label Use of Drug-Eluting Stent beyond 1 Year.

BACKGROUND AND OBJECTIVES: We evaluated the long-term outcomes and predictors of clinical events after off-label use of drug-eluting stents (DES) beyond 1 year after procedure. SUBJECTS AND METHODS: A total of 518 patients who underwent DES implantation for off-label indications and did not have any major adverse cardiac events (MACE) during the first year were analyzed. The occurrence of MACE, including cardiac death, myocardial infarction (MI), stent thrombosis and target vessel revascularization, were evaluated for a median 1179 days (interquartile range 769-1541) after the first year. RESULTS: Major adverse cardiac events occurred in 43 patients (8.3%) including 8 cases (1.5%) of cardiac death, 9 cases (1.7%) of MI, 24 cases (4.6%) of target vessel revascularization, and 11 cases (2.1%) of stent thrombosis. Patients with MACE had a higher serum creatinine level, higher incidence of in-stent restenosis lesion, more overlapping stents, a greater number of stents, and longer stents than did patients without MACE. Multivariate analysis revealed that serum creatinine level >1.5 mg/dL {hazard ratio (HR) 2.3, p=0.019}, stent length >33 mm (HR 2.4, p=0.035), and in-stent restenosis lesions (HR 2.4, p=0.040) were independent risk factors for MACE. Patients with DES length >33 mm had a higher incidence of MACE than those with DES length ≤33 mm (HR 2.7, log rank p=0.002). CONCLUSION: The risk of stent thrombosis and target vessel revascularization persisted in patients undergoing off-label DES implantation beyond 1-year follow-up. A total DES length >33 mm was a significant procedural predictor associated with the incidence of MACE.

Rosuvastatin-induced high-density lipoprotein changes in patients who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Clinical significance of statin-induced high-density lipoprotein cholesterol (HDL-C) changes is not well known. We investigated the factors affecting rosuvastatin-induced HDL-C changes and their correlation with 12-month major adverse cardiovascular events (MACE) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We analyzed 556 consecutive NSTE-ACS patients who underwent PCI and received rosuvastatin 10mg before discharge. We measured serum lipids, including total cholesterol, triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and HDL-C at baseline and at 4 weeks. The relationship between on-treatment lipid levels, baseline lipid levels, and 12-month MACE was assessed. RESULTS: Rosuvastatin treatment increased the mean HDL-C concentration by 1.1 ± 9.8 mg/dl (4.3 ± 23.0%). HDL-C was increased in 312 patients (56.1%), but decreased in 244 patients (43.9%) after statin treatment. Changes in HDL-C during first month were inversely correlated with baseline HDL-C levels (r=-0.379, p<0.001). The patients with increased HDL-C showed higher baseline TG levels but lower on-treatment TG levels. Changes in TG were correlated with changes in HDL-C (r=-0.212, p<0.001). The incidence of 12-month MACE according to changes in HDL-C was similar between the two groups (11.9% vs. 12.3%, p=0.875). Multivariate analysis revealed that baseline HDL-C level was the only significant predictor of rosuvastatin-induced HDL-C changes. CONCLUSION: Baseline HDL-C concentration was an independent predictor of rosuvastatin-induced HDL-C changes. Statin-induced HDL-C changes did not predict 12-month MACE in patients with NSTE-ACS.

The Number of Endothelial Progenitor Cells is Decreased in Patients With Non-Dipper Hypertension.

BACKGROUND AND OBJECTIVES: Circulating endothelial progenitor cells (EPCs) play a key role in the maintenance of endothelial homeostasis and promote vascular repair. A reduced number of EPCs and the functional activity have been associated with several cardiovascular risk factors. However, the relationship between the number of EPCs and circadian rhythm of the blood pressure (BP) remains unclear. The purpose of the present study was to evaluate the relationship between the circadian rhythm of the BP and EPCs in patients with essential hypertension. SUBJECTS AND METHODS: A total of 45 patients with essential hypertension who were newly identified by outpatient BP measurements, underwent 24-hour ambulatory BP monitoring. Among the 45 patients with essential hypertension, 20 were classified as dippers (12 men and 8 women; mean age 48±14 years) and 25 as non-dippers (14 men and 11 women; mean age 52±18 years). The EPC count was isolated from the peripheral bloodstream and quantified by flow cytometry. RESULTS: The baseline clinical characteristics were similar between the dipper and non-dipper hypertensive patients. The circulating EPCs were statistically reduced in the non-dipper patients as compared to the dippers (104±60 vs. 66±47 EPCs per 106 mononuclear cells, p=0.027). The circulating EPC level correlated positively with the circadian changes in the systolic and diastolic BP (r=0.435, p=0.003, and r=0.310, p=0.038, respectively). CONCLUSION: The present study demonstrated that the EPC count was reduced in the peripheral bloodstream in non-dipper hypertensive patients.

Evaluation of the dose-response relationship of amlodipine and losartan combination in patients with essential hypertension: an 8-week, randomized, double-blind, factorial, phase II, multicenter study.

BACKGROUND: Despite recommendations for more intensive treatment and the availability of several effective treatments, hypertension remains uncontrolled in many patients. OBJECTIVE: The aim of this study was to determine the dose-response relationship and assess the efficacy and safety of amlodipine or losartan monotherapy and amlodipine camsylate/losartan combination therapy in patients with essential hypertension. METHODS: This was an 8-week, randomized, double-blind, factorial design, phase II, multicenter study conducted in outpatient hospital clinics among adult patients aged 18-75 years with essential hypertension. At screening, patients received placebo for 2-4 weeks. Eligible patients (n=320) were randomized to one of eight treatment groups: amlodipine 5 mg or 10 mg, losartan 50 mg or 100 mg, amlodipine camsylate/losartan 5 mg/50 mg, 5 mg/100 mg, 10 mg/50 mg, or 10 mg/100 mg. MAIN OUTCOME MEASURES: The assumption of strict superiority was estimated using the mean change in sitting diastolic blood pressure (DBP) at 8 weeks. Safety was monitored through physical examinations, vital signs, laboratory test results, ECG, and adverse events. RESULTS: The reduction in DBP at 8 weeks was significantly greater in patients treated with the combination therapies compared with the respective monotherapies for all specified comparisons except amlodipine camsylate/losartan 10 mg/100 mg versus amlodipine 10 mg. The incidence of adverse events in the group of patients treated with the amlodipine camsylate/losartan 10 mg/50 mg combination tended to be higher than for any other group (27.9%, 12/43); however, the effect was not statistically significant. CONCLUSION: Combination amlodipine camsylate/losartan (5 mg/50 mg, 5 mg/100 mg and 10 mg/50 mg) resulted in significantly greater BP lowering compared with amlodipine or losartan monotherapy, and was determined to be generally safe and tolerable in patients with essential hypertension. CLINICAL TRIAL REGISTRATION: Registered at clinicaltrials.gov: NCT00942344.

Comparative efficacy and safety profile of amlodipine 5 mg/losartan 50 mg fixed-dose combination and amlodipine 10 mg monotherapy in hypertensive patients who respond poorly to amlodipine 5 mg monotherapy: an 8-week, multicenter, randomized, double-blind phase III noninferiority study.

BACKGROUND: The number of hypertensive patients achieving treatment targets is not ideal with therapies that engage a single mechanism of action, and combination therapies using different mechanisms of action can increase drug efficacy in a synergistic way. OBJECTIVE: This noninferiority study compared the clinical efficacy and safety profile of fixed-dose combination of amlodipine/losartan 5/50 mg and amlodipine 10 mg monotherapy in essential hypertensive patients who respond poorly to amlodipine 5 mg monotherapy. METHODS: This was a double-blind, multicenter, randomized trial of hypertensive patients (N = 185) aged ≥18 years taking amlodipine 5 mg during the run-in treatment period but failed to achieve sitting diastolic blood pressure (DBP) <90 mm Hg. After randomization into the amlodipine/losartan 5/50 mg fixed-dose combination group (n = 92) and the amlodipine 10 mg monotherapy group (n = 93), treatment was maintained without dose escalation for 8 weeks. The noninferiority margin was prespecified as 4 mm Hg after 8 weeks of treatment for the difference of the average change in DBP between treatments. The primary efficacy evaluation of noninferiority was tested using a confidence interval approach with a 97.5% 1-sided lower confidence limit using the average difference in DBP measured at baseline and 8 weeks. RESULTS: After 8 weeks, the DBP of both groups decreased from baseline by 8.9 (6.1) and 9.4 (7.5) mm Hg, respectively (difference = -0.5 [6.9] mm Hg, 95% CI: -2.5 to 1.5). Secondary end points of reductions in DBP after 4 weeks (-8.1 [6.7] vs -9.9 [7.3] mm Hg, difference = -1.8 mm Hg, 95% CI: -3.9 to 0.2) and sitting systolic blood pressure after 4 (-10.2 [11.8] vs -12.8 [10.2] mm Hg, difference = -2.6 mm Hg, 95% CI: -5.9 to 0.6) and 8 weeks (-12.2 [11.0] vs -13.4 [11.3] mm Hg, difference = -1.2 mmHg, 95% CI: -4.4 to 2.1) were comparable between the 2 treatment groups. There were 38 adverse events in 20 patients (21.7%) in the amlodipine/losartan 5/50 mg fixed-dose combination group and 31 in 24 patients (26.1%) in the amlodipine 10 mg monotherapy group; most were mild. There were 7 adverse events in 6 patients (6.5%) related to treatment in the fixed-dose combination group and 13 in 10 patients (10.9%) in the monotherapy group (P = 0.30). CONCLUSIONS: Fixed-dose combination amlodipine/losartan 5/50 mg was not inferior in terms of reductions in DBP after 8 weeks of treatment and had comparable safety profile to amlodipine 10 mg in patients who did not respond to amlodipine 5 mg monotherapy. ClinicalTrials.gov identifier: NCT00940667.

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.

Left ventricular thrombus associated with takotsubo cardiomyopathy: a cardioembolic cause of cerebral infarction.

Takotsubo cardiomyopathy, also called stress-induced cardiomyopathy, usually occurs in patients with severe emotional or physiologic stress. The prognosis is favorable, and the wall motion abnormlities normalize within weeks. However, stress-induced cardiomyopathy is rarely assosicated with left ventricular thrombus and thromboembolic complications. Here, we report a case of stress-induced cardiomyopathy with left ventricular thrombus that embolized to cause cerebral infarction.

Effect of previous statin therapy in patients with acute coronary syndrome and percutaneous coronary intervention.

BACKGROUND AND OBJECTIVES: Statin therapy after percutaneous coronary intervention (PCI) has been associated with reduced major adverse cardiovascular events (MACE). However, it has been less clear as to whether statin therapy before acute coronary syndrome (ACS) is beneficial. We studied the effect of previous statin therapy, initiated ≥1 month before PCI, on the outcome of patients with ACS who had undergone early invasive strategies. SUBJECTS AND METHODS: We stratified 479 consecutive patients with ACS who had undergone PCI, according to preprocedural statin administration as follows: previous statin-treated patients (statin group, n=237) and statin-naive patients (control group, n=242). The incidence of periprocedural myocardial infarction (MI) and in-hospital MACE was assessed. RESULTS: The incidence of Braunwald class III angina and MI presentation were significantly lower in the statin group than in the control group. Angiographic and procedural characteristics were similar between the two groups; however, slow/no reflow phenomenon occurred more frequently in the control group. After PCI, the incidence of periprocedural MI was higher in the control group than in the statin group (6.6% vs. 2.1%, p=0.016). Multivariate analysis revealed that no prior use of statin {odds ratio (OR)=2.8; 95% confidence interval (CI)=1.1-7.2; p=0.038), procedural complication (OR=4.0; 95% CI=1.5-10.5; p=0.004), stent overlap (OR=4.7; 95% CI=1.3-16.4; p=0.015), and old age (OR=3.2; 95% CI=1.2-8.0; p=0.016) were independent predictors for in-hospital MACE. CONCLUSION: Previous statin therapy before ACS was associated with milder clinical presentation and lower incidence of in-hospital MACE after early invasive strategies. The beneficial outcome is attributable to a significant reduction in periprocedural MI after PCI.

12-month follow-up results of high dose rosuvastatin loading before percutaneous coronary intervention in patients with acute coronary syndrome.

BACKGROUND: Statin pretreatment before percutaneous coronary intervention (PCI) is associated with a reduced incidence of short-term adverse events and periprocedural myocardial infarction (MI). However, the long-term effects of statin pretreatment have not been evaluated. METHODS: Consecutive 445 patients with acute coronary syndrome (ACS) who underwent PCI were randomly assigned to receive no statin treatment before PCI (control group, n=220) or to receive 40 mg rosuvastatin loading before PCI (rosuvastatin group, n=225). The incidence of major adverse cardiac events (MACE), including cardiac death, non-fatal MI, non-fatal stroke, and any ischemia-driven revascularization, was assessed after 12 months. RESULTS: During 11±3 months of follow-up, MACE occurred in 20.5% of patients in the control group and 9.8% of patients in the rosuvastatin group (p=0.002). The Kaplan-Meier curves showed that the incidence of death and non-fatal MI was significantly greater in the control group than in the rosuvastatin group (hazard ratio, 3.71; p=0.021). High-sensitivity C-reactive protein levels were less elevated in the rosuvastatin group than in the control group at 24 h after PCI. Multivariate analysis revealed that rosuvastatin loading was an independent predictor of a reduction in the risk of MACE at 12 months (odds ratio, 0.5; p=0.006). CONCLUSIONS: High dose rosuvastatin loading before PCI significantly improved 12-month clinical outcomes in patients with ACS who underwent an early invasive strategy.

Effects of omeprazole on the antiplatelet activity of clopidogrel.

Clopidogrel is used with aspirin as a standard combined treatment in patients with acute coronary syndrome. A proton pump inhibitor (PPI) is often administered to patients receiving antiplatelet therapy. However, PPI use with clopidogrel was recently shown to result in increased risk of major cardiovascular events when compared to clopidogrel use alone. Therefore, the aim of the present study was to evaluate the effects of omeprazole, a PPI, on the antiplatelet effect of clopidogrel.We divided 20 healthy volunteers into 2 groups (n = 10 each). Twenty-four hours after a 300 mg loading dose of clopidogrel, one group received a dosage of 75 mg/day of clopidogrel and a placebo for 14 days, followed 3 weeks later by the same protocol but with coadministration of 75 mg/day clopidogrel and 20 mg/day omeprazole instead. The other group received the same treatment but in reverse order. Antiplatelet activity was assessed in terms of the P2Y12 reaction unit (PRU) and percentage inhibition using a VerifyNow P2Y12 assay system.The PRU of the omeprazole-treated subjects was significantly higher than that of the omeprazole-untreated subjects on day 14 (281.3 +/- 54.0 versus 240.0 +/- 72.2, P = 0.048). The percentage inhibition showed a decrease after the 14-day omeprazole treatment (22.7 +/- 29.9% versus 35.1 +/- 18.7%, P = 0.014). Consequently, omeprazole reduces the antiplatelet effect of clopidogrel, suggesting that careful treatment planning is required when administering omeprazole to patients on clopidogrel therapy.

Cardioprotective effects of alpha-lipoic Acid on myocardial reperfusion injury: suppression of reactive oxygen species generation and activation of mitogen-activated protein kinase.

BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) and mitogen-activated protein (MAP) kinase play an important role in the development of myocardial reperfusion injury. In this study, we examined whether treatment with alpha-lipoic acid (ALA) before reperfusion could prevent myocardial reperfusion injury in vivo. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to a 45-minute left anterior descending coronary artery ligation followed by 45- or 10-minute reperfusion. ALA was administered 10 minutes prior to reperfusion. The infarct size ratio of the infarct area to the ischemic area at risk, was measured based on 10, 25, 50, and 100 mg/kg of ALA, with propidium iodide (PI) fluorescence. Apoptosis was evaluated by TdT-mediated dUDP nick end labeling (TUNEL) staining. The generation of intracellular ROS was evaluated using the fluorogenic probe, dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA). Western blot analysis was performed for MAP kinase (pERK 1/2 and pJNK 1/2) activity. RESULTS: The infarct size, according to ALA dose, was significantly suppressed 29.1% with ALA 25 mg/kg (p<0.0001), 41.5% with 50 mg/kg (p<0.05), and 41.4% with 100 mg/kg (p<0.05) compared to the controls (54.3%). However, the results were not significantly different with 47.2% of the ALA 10 mg/kg (p=0.192). A few apoptotic nucleoli were detected in the ALA 25 mg/kg group, but were frequently detected in the control group. The ROS generation was significantly suppressed (p<0.0001), the activity of pERK 1/2 was significantly increased (p<0.05) and the activity of pJNK 1/2 was significantly decreased (p<0.05) in the ALA 25 mg/kg group compared to the controls. CONCLUSION: The results of this study suggested that adequate doses of ALA before reperfusion was effective for the prevention of myocardial reperfusion injury in vivo. This cardioprotective activity of ALA might be associated with an anti-apoptotic effect of ALA via suppression of ROS generation, increase of pERK 1/2 and decrease of pJNK 1/2 activity.

Alteration of ventricular repolarization by intracoronary infusion of normal saline in patients with variant angina.

BACKGROUND AND OBJECTIVES: During coronary angiography and interventional procedures, catheters that are engaged in a coronary ostium are routinely flushed, typically with normal saline, to expel blood from the catheter or to inject a pharmacologic agent. Saline contains sodium and chloride ions. Such injections may affect the electrophysiologic properties of the myocardium; however, the effect of normal saline on ventricular repolarization has not been established in patients with variant angina. SUBJECTS AND METHODS: We studied 51 consecutive patients with variant angina. Five mL of normal saline (NS) or 5% dextrose solution (DW) were infused into the left coronary artery in random order. We measured the heart rate, QT interval, and T-wave amplitude using Mac-Lac 5.2. RESULTS: The baseline clinical characteristics were not different between the NS {n=30 (14 males); mean age, 56+/-10 years} and the 5% DW groups {n=21 (7 males); mean age, 59+/-10 years}. The changes in the mean corrected QT (QTc) interval were significantly increased at the time of infusion of NS compared to 5% DW (45.1+/-30.3 vs. 20.9+/-23.3 ms, p=0.004). There was a T-wave amplitude change >0.2 mV in at least one-lead in 27 patients (90.0%) during NS infusion compared to 7 patients (33.3%) during 5% DW infusions (p=0.001). No significant changes in heart rate and blood pressure were noted during of the infusions. CONCLUSION: NS was associated with prolongation of ventricular repolarization in patients with variant angina.

Clinical significance of on-treatment triglyceride level in patients treated by percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome.

BACKGROUND/AIMS: The use of statins in patients with acute coronary syndrome (ACS) has increased, and reduced levels of low-density lipoprotein cholesterol (LDL-C) lead to lower coronary event rates. We studied the effect of lipid levels during statin treatment on prognosis in patients with ACS and percutaneous coronary intervention (PCI). METHODS: Between January 2005 and May 2007, 325 ACS patients who underwent PCI and received statins were evaluated. We measured serum lipid levels at baseline and 4 weeks. The relationships between on-treatment levels of triglyceride (TG) and LDL-C and one-year major adverse cardiac events (MACE) were assessed. RESULTS: At 4 weeks, the mean LDL-C level was 72.5+/-23.8 mg/dL and the mean TG was 123.2+/-62.8 mg/dL. MACE occurred in 41 cases (12.6%). Baseline serum lipid levels were similar between the patients with and those without MACE. However, the patients with MACE showed significantly higher TG level at 4 weeks (149.6+/-81.4 vs. 119.3+/-58.9 mg/dL, p=0.026) than those without. High on-treatment TG level (>or=150 mg/dL) were associated with increased adverse events compared to lower TG level in a univariate analysis (hazard ratio [HR], 3.3; p<0.001). In a multivariate analysis, high 4-week TG level after statin treatment was an independent predictor for MACE (HR, 4.01; 95% confidence interval, 1.85 to 9.06; p=0.001), however, baseline TG and LDL-C levels were not. CONCLUSIONS: High on-treatment TG level (>or=150 mg/dL) was associated with a higher risk of MACE. This finding supports the concept that achieving low TG levels may be an important therapeutic parameter in statin-treated patients following ACS and PCI.