Kyoo-Rok Han

Percutaneous coronary intervention results in acute increases in oxidized phospholipids and lipoprotein(a): short-term and long-term immunologic responses to oxidized low-density lipoprotein.

Background— This study was performed to assess whether oxidized low-density lipoprotein (OxLDL) levels are elevated after percutaneous coronary intervention (PCI). Methods and Results— Patients (n= 141) with stable angina pectoris undergoing PCI had serial venous blood samples drawn before PCI, after PCI, and at 6 and 24 hours, 3 days, 1 week, and 1, 3, and 6 months. Plasma levels of OxLDL-E06, a measure of oxidized phospholipid (OxPL) content on apolipoprotein B-100 detected by antibody E06, lipoprotein(a) [Lp(a)], autoantibodies to malondialdehyde (MDA)-LDL and copper-oxidized LDL (Cu-OxLDL), and apolipoprotein B-100–immune complexes (apoB-IC) were measured. OxLDL-E06 and Lp(a) levels significantly increased immediately after PCI by 36% (P < 0.0001) and 64% (P < 0.0001), respectively, and returned to baseline by 6 hours. In vitro immunoprecipitation of Lp(a) from selected plasma samples showed that almost all of the OxPL detected by E06 was bound to Lp(a) at all time points, except in the post-PCI sample, suggesting independent release and subsequent reassociation of OxPL with Lp(a) by 6 hours. Strong correlations were noted between OxLDL-E06 and Lp(a) (r = 0.68, P < 0.0001). MDA-LDL and Cu-OxLDL autoantibodies decreased, whereas apoB-IC levels increased after PCI, but both returned to baseline by 6 hours. Subsequently, IgM autoantibodies increased and peaked at 1 month and then returned to baseline, whereas IgG autoantibodies increased steadily over 6 months. Conclusions— PCI results in acute plasma increases of Lp(a) and OxPL and results in short-term and long-term immunologic responses to OxLDL. OxPL that are released or generated during PCI are transferred to Lp(a), suggesting that Lp(a) may contribute acutely to a protective innate immune response. In settings of enhanced oxidative stress and chronically elevated Lp(a) levels, the atherogenicity of Lp(a) may stem from its capacity as a carrier of proinflammatory oxidation byproducts.

Reduced In Vivo Aortic Uptake of Radiolabeled Oxidation-Specific Antibodies Reflects Changes in Plaque Composition Consistent With Plaque Stabilization

Objective—Labeled oxidation-specific antibodies (Ox-AB) detect, quantify, and noninvasively image lipid-rich atherosclerotic lesions. However, it is unknown whether Ox-AB detect plaque stabilization. Methods and Results—The aortic uptake of intravenously injected 125I-MDA2 (Ox-AB to malondialdehyde [MDA]–low-density lipoprotein [LDL]) was quantitated in: (1) LDL receptor−/− mice with established atherosclerosis continued on Western diet (Progression) or switched to chow (Regression) or chow+vitamins E and C (Regression-VIT) for 6 months; and (2) Watanabe rabbits (3- to 57-months old) with naturally evolved atherosclerotic lesions. In mice, the Progression group had more extensive atherosclerosis, higher 125I-MDA2 uptake, high concordance of Sudan (lipid)-staining and 125I-MDA2 uptake, and stronger oxidized LDL (OxLDL) and macrophage immunostaining than both Regression groups. In contrast, the Regression groups showed Sudan-positive lesions with focally diminished 125I-MDA2 uptake, which coincided with reduced OxLDL and macrophages but more smooth muscle cells (SMCs) and collagen. In rabbits, areas of increased 125I-MDA2 uptake were associated with high Sudan concordance and strong immunostaining for OxLDL and macrophages. Interestingly, advanced lesions with focally diminished 125I-MDA2 uptake showed stronger immunostaining for SMCs and collagen, particularly at the fibrous cap. Conclusion—Ox-AB uptake is focally diminished in plaques displaying accepted features of plaque stability. Imaging techniques to detect the presence and depletion of OxLDL may be useful in assessing plaque stabilization.

Safety and Efficacy of Second-Generation Everolimus-Eluting Xience V Stents Versus Zotarolimus-Eluting Resolute Stents in Real-World Practice Patient-Related and Stent-Related Outcomes From the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries

OBJECTIVESnThis study sought to compare the safety and efficacy of the Xience V/Promus everolimus-eluting stent (EES) (Abbott Vascular, Temecula, California) with the Endeavor Resolute zotarolimus-eluting stent (ZES-R) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer cohorts.nnnBACKGROUNDnOnly 2 randomized controlled trials have compared these stents.nnnMETHODSnThe EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with the EES and 1,998 patients treated with the ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure [TLF]) and patient-related composite outcomes were compared in crude and propensity score-matched analyses.nnnRESULTSnOf 5,054 patients, 3,830 (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (82 [2.7%] vs. 58 [2.9%], p = 0.662) and the patient-related outcome (225 [7.4%] vs. 153 [7.7%], p = 0.702) did not differ between EES and ZES-R, respectively, at 1 year, which was corroborated by similar results from the propensity score-matched cohort. The rate of definite or probable stent thrombosis (18 [0.6%] vs. 7 [0.4%], p = 0.306) also was similar. In multivariate analysis, off-label indication was the strongest predictor of TLF (adjusted hazard ratio: 2.882; 95% confidence interval: 1.226 to 6.779; p = 0.015).nnnCONCLUSIONSnIn this robust real-world registry with unrestricted use of EES and ZES-R, both stents showed comparable safety and efficacy at 1-year follow-up. Overall incidences of TLF and definite stent thrombosis were low, even in the patients with off-label indication, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents.

Sex Differences in Management and Mortality of Patients With ST-Elevation Myocardial Infarction (from the Korean Acute Myocardial Infarction National Registry)

There has been controversy over the disparity between men and women with regard to the management and prognosis of acute myocardial infarction. Analyzing nationwide multicenter prospective registries in Korea, the aim of this study was to determine whether female gender independently imposes a risk for mortality. Data from 14,253 patients who were hospitalized for ST-segment elevation myocardial infarction from November 2005 to September 2010 were extracted from registries. Compared to men, women were older (mean age 56 ± 12 vs 67 ± 10 years, p < 0.001), and female gender was associated with a higher frequency of co-morbidities, including hypertension, diabetes, and dyslipidemia. Women had longer pain-to-door time and more severe hemodynamic status than men. All-cause mortality rates were 13.6% in women and 7.0% in men at 1 year after the index admission (hazard ratio for women 2.01, 95% confidence interval 1.80 to 2.25, p < 0.001). The risk for death after ST-segment elevation myocardial infarction corresponded highly with age. Although the risk remained high after adjusting for age, further analyses adjusting for medical history, clinical performance, and hemodynamic status diminished the gender effect (hazard ratio 1.00, 95% confidence interval 0.86 to 1.17, p = 0.821). Propensity score matching, as a sensitivity analysis, corroborated the results. In conclusion, this study shows that women have a comparable risk for death after ST-segment elevation myocardial infarction as men. The gender effect was accounted for mostly by the womens older age, complex co-morbidities, and severe hemodynamic conditions at presentation.

Impact of Body Mass Index and Waist-to-Hip Ratio on Clinical Outcomes in Patients With ST-Segment Elevation Acute Myocardial Infarction (from the Korean Acute Myocardial Infarction Registry)

The relation between body mass index (BMI) and waist-to-hip ratio (WHR) to clinical outcomes in patients with ST-segment elevation acute myocardial infarction (MI) has not been well described. As part of the Korean Acute MI Registry, we enrolled 3,734 eligible patients who were diagnosed with ST-segment elevation acute MI. The study population was categorized by BMI (into 4 groups according to the World Health Organization classification for the Asian population) and WHR (into 2 sets of 4 groups, 1 set for men and another for women, based on the INTERHEART study). Baseline characteristics and clinical outcomes were analyzed and compared among the BMI and WHR categories. Mean follow-up duration was 199 +/- 37 days. In the BMI category, underweight versus obese patients were older, were more likely to present with heart failure, and underwent guideline-based treatments less frequently. In the WHR category, the reverse trends were apparent for the latter factors except treatment-use frequencies. The highest mortality rate was observed in patients with the lowest BMI and the highest WHR. In an adjusted model, the highest WHR (hazard ratio 5.57, 95% confidence interval 1.53 to 12.29, p = 0.009) and the underweight (hazard ratio 2.88, 95% confidence interval 1.17 to 6.08, p = 0.021) categories within the 2 anthropometric indexes remained as mortality risk factors. In conclusion, the relation between obesity and prognosis after ST-segment elevation acute MI appears complex and should be further assessed in larger population-based cohort studies to determine the associations apparent in this study.

Reasonable Duration of Clopidogrel Use After Drug-Eluting Stent Implantation in Korean Patients

Current guidelines recommend that clopidogrel be given to patients for 12 months after drug-eluting stent (DES) implantation. However, the evidence is insufficient to support the benefit of long-term clopidogrel therapy, especially in Asian patients. The aim of this study was to evaluate whether different durations of clopidogrel use might influence long-term outcomes after DES implantation. A total of 844 patients from 4 medical centers in Korea who had undergone successful DES implantation from November 2004 to April 2006 were enrolled. Patients who were event free at 6-month follow-up were divided into 2 groups by clopidogrel use (575 users, 163 nonusers) and followed. The end point was a composite of death, myocardial infarction, and stent thrombosis. During 1,056.4 patient-years of follow-up (median 2.02), there were 7 deaths, 3 myocardial infarctions, and 2 episodes of stent thrombosis. No significant differences in the primary end point were observed between clopidogrel users and nonusers (cumulative incidence 2.9% vs 2.8%, p = 0.578; adjusted hazard ratio 0.67, 95% confidence interval 0.16 to 2.77). In analysis with time-dependent covariates, the incidence rates of the primary end point during observation periods with and without clopidogrel were similar, although the effect estimates were broad (9.9 with and 10.6 without clopidogrel per 1,000 patient-years; adjusted hazard ratio 0.52, 95% confidence interval 0.09 to 3.17). Interestingly, the effect estimates from propensity score analyses, although they also had wide confidence intervals, were closer to the null than those from conventional Cox analyses. In conclusion, this cohort of Korean patients failed to show an absolute benefit of long-term clopidogrel therapy after DES implantation. The benefit of clopidogrel use beyond 6 months after DES implantation remains uncertain, and hence the decision to use long-term dual-antiplatelet therapy should be based on the risk factors of each patient.

Efficacy and Safety of Morning Versus Evening Dose of Controlled-Release Simvastatin Tablets in Patients With Hyperlipidemia: A Randomized, Double-Blind, Multicenter Phase III Trial

BACKGROUNDnFlexibility in the recommended dosing time for a statin may improve patient compliance.nnnOBJECTIVEnThis study was designed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia. It was carried out as a requirement to obtain authorization from the Korean regulatory agency to market the product.nnnMETHODSnIn this prospective, randomized, double-blind, multicenter, placebo-controlled Phase III study, we randomly assigned 132 patients with hypercholesterolemia to a morning-dose group or an evening-dose group. Patients in the morning-dose group received 20 mg controlled-release simvastatin in the morning and a placebo in the evening, and those in the evening-dose group received a placebo in the morning and 20 mg controlled-release simvastatin in the evening.nnnRESULTSnAfter 8 weeks of the treatment, the difference in the mean change of LDL-C between the morning-dose and evening-dose groups was -2.78% (95% confidence interval, -7.65 to 2.10). The changes in total cholesterol, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) after treatment did not differ between groups. Also, the achievement rates of the target LDL-C goal suggested by the dyslipidemia treatment guideline of the Korean Society of Lipidology and Atherosclerosis were not different. No serious adverse event was observed in either group. Mild and moderate adverse events were observed similarly in both groups.nnnCONCLUSIONSnAlthough controlled-release simvastatin significantly reduces LDL-C levels with good tolerability in Korean adults with dyslipidemia, the time of administration does not affect its efficacy.

Six-Month Versus 12-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents

Background— The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents.nnMethods and Results— We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P =0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96; P =0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47; P =0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03; P =0.005) among diabetic patients.nnConclusions— Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials.nnClinical Trial Registration— URL: . Unique identifier: [NCT00698607][1].nn# Clinical Perspective {#article-title-31}nn [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00698607&atom=%2Fcirculationaha%2F125%2F3%2F505.atomBackground— The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results— We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03; P=0.005) among diabetic patients. Conclusions— Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.

Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension

Background and Objectives Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. Subjects and Methods In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). Results Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 {from 81.5±5.3 to 71.8±9.9 beats/minute (difference, -9.9±9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6±8.2 to 132.9±13.5 mmHg, p<0.0001; SiDBP: from 96.9±5.4 to 88.3±8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4±13.5 to 133.8±11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7±8.7 to 87.5±9.5 mmHg, p<0.0001). Conclusion Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension.

Changes in smoking behavior and adherence to preventive guidelines among smokers after a heart attack

Objective Risk factor modification is key to preventing subsequent cardiac events after a heart attack. This study was designed to investigate the disparity between preventive guidelines and clinical practice among smoking patients. Methods The study was carried out in smokers admitted with myocardial infarction (MI). A total of 275 patients who had been regularly followed for over one year after MI were randomly selected and enrolled in this study. We investigated changes in smoking behavior and the adherence rate to ACC/AHA Guidelines for secondary prevention in patients with coronary artery disease at the time of, and one year after, the index event. Results The study population consisted of 275 patients (97.1% males) with a mean age of 57.0 ± 11.2 years. Achievement of target goals at one year was as follows: smoking cessation, 52.3%; blood pressure, 83.9%; HbA1c, 32.7%; lipid profile, 65.5%; and body mass index (BMI), 50.6%. Over one year, 80% of the patients attempted to quit smoking; 27% of them re-started smoking within one month after discharge while 65% succeeded in cessation of smoking. At one year, only 52% of the patients overall had stopped smoking. From the multivariate logistic analysis including smoking patterns and clinical characteristics, the severity of coronary artery disease was the only independent predictor for smoking cessation (Relative risk (RR): 1.230; P = 0.022). Conclusions Only a small percentage of MI patients adhere to guidelines for secondary prevention and a sizable proportion fail to stop smoking. These findings underscore the need for an effective patient education system.