Impact of chronic outward force on arterial responses of proximal and distal of long superficial femoral artery stent.

BACKGROUND: Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA. METHODS: In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis. RESULTS: We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. The baseline diameter was 6.8 ± 0.71 mm and length were 97.0 ± 33.8 mm for the SENS. The ratio of the diameter of the stent to the reference vessel was 1.3 ± 0.24 at the proximal portion and 1.53 ± 0.27 at the distal portion (P < 0.001). In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). All 11 pigs survived for 4 weeks after SENS implantation. The vessel diameter was 4.04 ± 0.40 mm (control group) vs 4.45 ± 0.63 mm (oversized group), and the implanted stent diameter was 5.27 ± 0.46 mm vs. 7.18 ± 0.4 mm (P = 0.001). The stent-to-vessel diameter ratio was 1.31 ± 0.12 versus 1.63 ± 0.20 (P < 0.001). After 4 weeks, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm2 vs. 8.53 ± 5.18 mm2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001). CONCLUSIONS: COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.

A relationship between unrecognized anaemia and the development of type 2 diabetes mellitus in patient with cardiovascular risks.

Studies on anaemia in diabetic patients are well known. However, the data regarding association of anaemia on the development of diabetes mellitus (DM) are very limited. We aimed to evaluate the association of anaemia on the development of DM and major clinical outcomes in a series of the Korean population during 5-year clinical follow-up. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2013. A total of 17 515 subjects without a history of DM were analysed. The World Health Organization definition of anaemia was used. Patients were divided into the anaemia group (n = 2907 patients) and the non-anaemia group (n = 14 608 patients). The primary endpoint was the development of DM. To adjust baseline potential confounders, a propensity score matching (PSM) analysis was performed. After PSM analysis, two matched groups (2731 pairs) were generated and their baselines characteristics were balanced. During 5-year follow-up, the anaemia group had a higher incidence of type 2 DM (10.7% vs 7.7%; hazard ratio [HR], 1.356; 95% confidence interval [CI], 1.021-1.802; P = .035), and total death (2.6% vs 1.2%; HR, 2.449; 95% CI, 1.337-4.486; P = .004) compared to the non-anaemia group. In the present study, anaemia was associated with higher rate of the development of DM and mortality during 5-year clinical follow-up. A randomized trial is needed to determine whether this results can be reproducible or not for the final conclusion.

Cilostazol-based triple versus potent P2Y12 inhibitor-based dual antiplatelet therapy in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

Although potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) has replaced clopidogrel-based therapy as the standard treatment in patients with acute myocardial infarction (AMI), there is a concern about the risk of bleeding in East Asian patients. We compared the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAT) with potent P2Y12 inhibitor-based DAPT in Korean patients. A total of 4152 AMI patients who underwent percutaneous coronary intervention (PCI) in the Korea Acute Myocardial Infarction Registry were analyzed retrospectively. Patients were divided into two groups: the TAT group (aspirin + clopidogrel + cilostazol, n = 3161) and the potent DAPT group (aspirin + potent P2Y12 inhibitors [ticagrelor or prasugrel], n = 991). Major clinical outcomes at 30 days and 2 years were compared between the two groups using propensity score matching (PSM) analysis. After PSM (869 pairs), there were no significant differences between the two groups in the incidence of total death, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and stroke at 30 days and 2 years. However, the Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were significantly lower in the TAT group compared with the potent DAPT group at 2 years (6.4% vs. 3.6%, p = 0.006). In Korean AMI patients undergoing PCI, TAT with cilostazol was associated with lower bleeding than the potent P2Y12 inhibitor-based DAPT without increased ischemic risk. These results could provide a rationale for the use of TAT in East Asian AMI patients.

Selective ß1-Blockers Are Not Associated With New-onset Diabetes Mellitus in Hypertensive Patients.

BACKGROUND: Although ß-blockers are known to increase new-onset diabetes mellitus (DM), previous evidence have been controversial. It has been suggested that newer vasodilatory ß-blockers yield better glycemic control than older nonselective agents. The aim of this study was to evaluate the diabetogenicity of currently used newer ß-blockers based on ß1 receptor selectivity in a series of Asian population. METHODS: We investigated a total of 65,686 hypertensive patients without DM from 2004 to 2014. Patients with hemoglobin (Hb) A1c ≤6.0%, fasting blood glucose ≤110 mg/dL, and no history of diabetes or diabetic treatment were enrolled for analysis. Patients were divided into the ß-blockers group and non-ß-blockers group. Propensity score matching (PSM) analysis using a logistic regression model was performed to adjust for potential confounders. The primary end point was the cumulative incidence of new-onset DM, defined as a fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5%, and major adverse cardiac and cerebral events (MACCE), defined as a composite of total death, nonfatal myocardial infarction, and cerebrovascular accidents. We investigated predictors of new-onset DM and MACCE based on 2 models, including clinical risk factors and co-medications, respectively. RESULTS: Mean follow-up duration was 30.91 ± 23.14 months in the entire group before adjustment. The ß-blockers group had a significantly higher incidence of new-onset DM and MACCE than the non-ß-blockers group. After PSM, analysis of a total of 2284 patients (1142 pairs, C-statistic = 0.752) showed no difference between the 2 groups in new-onset DM or MACCE. In multivariate analysis after PSM, baseline HbA1c, stroke, heart failure, nonselective ß-blockers, and age were independent predictors of new-onset DM. Selective ß1-blockers did not increase new-onset DM after adjustment for other antihypertensive medication and statins. CONCLUSIONS: In the era of newer ß-blockers, selective ß1-blockers were not associated with new-onset DM. More evidence is needed to verify this relationship and the underlying mechanisms.

Hyperuricaemia and development of type 2 diabetes mellitus in Asian population.

Recently, meta-analysis studies reported that hyperuricaemia is associated with higher incidence of type 2 diabetes mellitus (T2DM), however, there are limited data on the Asian population. The aim of this observational study is to estimate the long-term impact of hyperuricaemia on the new-onset T2DM and cardiovascular events. This study is based on a single-centre, all-comers, and large retrospective cohort. Subjects that visited from January 2004 to February 2014 were enrolled using the electronic database of Korea University Guro Hospital. A total of 10 505 patients without a history of T2DM were analyzed for uric acid, fasting glucose and haemoglobin (Hb) A1c level. Inclusion criteria included both Hb A1c <5.7% and fasting glucose level <100 mg/dL without T2DM. Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dL in men, and ≥6.5 mg/dL in women. To adjust baseline confounders, a propensity score matching (PSM) analysis was performed. The impact of hyperuricaemia on the new-onset T2DM and cardiovascular events were compared with the non-hyperuricaemia during the 5-year clinical follow-up. After PSM, baseline characteristics of both groups were balanced. In a 5-year follow-up, the hyperuricaemia itself was a strong independent predictor of the incidence of new-onset T2DM (HR, 1.78; 95% CI, 1.12 to 2.8). Hyperuricaemia was a strong independent predictor of new-onset T2DM, which suggests a substantial implication for a correlation between uric acid concentration and insulin resistance (or insulin sensitivity). Also, hyperuricaemia is substantially implicated in cardiovascular risks and the further long-term cardiovascular events in the crude population, but it is not an independent predictor of long-term cardiovascular mortality in the matched population.

Changes in Left Atrial Transport Function in Patients Who Maintained Sinus Rhythm After Successful Radiofrequency Catheter Ablation for Atrial Fibrillation: A 1-Year Follow-Up Multislice Computed Tomography Study.

BACKGROUND: Functional remodeling of left atrium (LA) after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) has not been fully elucidated. This study aimed to determine the impact of RFCA on LA transport function in patients who maintained sinus rhythm (SR) after AF ablation. METHODS AND RESULTS: A total of 96 patients (paroxysmal AF [PAF] = 52) who maintained SR during 1 year after AF ablation were enrolled. Multislice computed tomography was performed to determine LA volume (LAV) and LA emptying fraction (LAEF) at pre-RFCA and 1-year post-RFCA. Creatine kinase-MB (CK-MB) and troponin-T levels were analyzed 1-day post-RFCA. At 1-year post-RFCA, mean LAV and LAEF decreased in overall patients. Based on LAEF change (ΔLAEF) cutoff of 5.0%, LAEF reduced in 41 patients (worsened group) and improved or showed no change in 55 patients (preserved group). Compared with preserved group, worsened group had a higher proportion of PAF, higher levels of CK-MB and troponin-T, and additional LA ablation. ΔLAEF was inversely correlated with CK-MB and troponin-T levels. Subgroup analysis showed that LAEF significantly decreased in PAF patients who underwent additional LA ablation. Multivariate analysis revealed that high baseline LAEF and additional LA ablation were independent predictors for worsened LAEF. CONCLUSIONS: Although SR was maintained for 1 year after AF ablation, LAEF as well as LAV decreased. The extent of LAEF deterioration was significantly associated with the amount of iatrogenic myocardial damage. Our data indicate that extensive atrial ablation may lead to LA functional deterioration, especially in patients with PAF.

Air pollution and short-term clinical outcomes of patients with acute myocardial infarction.

Ambient air pollution is well-known to be a serious risk factor for cardiovascular diseases, stroke, and death. However, the association between air pollutants (AP) exposure and short-term clinical outcomes in acute myocardial infarction (AMI) patients (pts) has not been elucidated well. In the present study, 37 880 AMI pts were enrolled from October 2005 to December 2013 in a nationwide large-scale, prospective, multicentre Korea AMI registry (KAMIR registry; http://www.kamir.or.kr). We obtained data on AP (e.g., NO2 , SO2 , CO, O3 and PM10 ) from the Korean National Institute of Environmental Research (NIER; http://www.nier.go.kr). Clinical endpoints included death, recurrent myocardial infarction (Re-MI), any revascularization and composite of all-cause death and Re-MI. Exposure to AP is defined as the average exposure to AP within 24 hours before AMI admission. We observed that a 0.01 part per million (ppm) increase in NO2 concentration, 0.001 ppm increase in SO2 concentration, and 0.1 ppm increase in CO concentration each increased the risk of total death by 9.7% (95% CI, 6.2%-13.4%), 1.9% (95% CI, 0.3%-3.6%), and 2.1% (95% CI, 0.5%-3.9%), respectively. Exceptionally, O3 decreased the risk of total death by 0.6% (95% CI -0.2% to -1.0%) per 0.01 ppm increase. PM10 was not related to any cardiovascular events. AP were each stratified into five quintiles according to ranges of AP levels. After adjusting analysis for risk variables, only high quintiles (Q4, Q5) of NO2 were positively associated with total death, cardiac death and MI, while SO2 , CO, O3 and PM10 were shown to be not related to any cardiovascular events at all levels. In AMI patients, each AP and its concentration has shown a different effect to short-term mortality and cardiovascular events.

Intracoronary dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular imaging with a clinical dose of indocyanine green for the assessment of high-risk plaques and stent-associated inflammation in a beating coronary artery.

AIMS: Inflammation plays essential role in development of plaque disruption and coronary stent-associated complications. This study aimed to examine whether intracoronary dual-modal optical coherence tomography (OCT)-near-infrared fluorescence (NIRF) structural-molecular imaging with indocyanine green (ICG) can estimate inflammation in swine coronary artery. METHODS AND RESULTS: After administration of clinically approved NIRF-enhancing ICG (2.0 mg/kg) or saline, rapid coronary imaging (20 mm/s pullback speed) using a fully integrated OCT-NIRF catheter was safely performed in 12 atheromatous Yucatan minipigs and in 7 drug-eluting stent (DES)-implanted Yorkshire pigs. Stronger NIRF activity was identified in OCT-proven high-risk plaque compared to normal or saline-injected controls (P = 0.0016), which was validated on ex vivo fluorescence reflectance imaging. In vivo plaque target-to-background ratio (pTBR) was much higher in inflamed lipid-rich plaque compared to fibrous plaque (P < 0.0001). In vivo and ex vivo peak pTBRs correlated significantly (P < 0.0022). In vitro cellular ICG uptake and histological validations corroborated the OCT-NIRF findings in vivo. Indocyanine green colocalization with macrophages and lipids of human plaques was confirmed with autopsy atheroma specimens. Two weeks after DES deployment, OCT-NIRF imaging detected strong NIRF signals along stent struts, which was significantly higher than baseline (P = 0.0156). Histologically, NIRF signals in peri-strut tissue co-localized well with macrophages. CONCLUSION: The OCT-NIRF imaging with a clinical dose of ICG was feasible to accurately assess plaque inflammation and DES-related inflammation in a beating coronary artery. This highly translatable dual-modal molecular-structural imaging strategy could be relevant for clinical intracoronary estimation of high-risk plaques and DES biology.

Three-Year Major Clinical Outcomes of Angiography-Guided Single Stenting Technique in Non-Complex Left Main Coronary Artery Diseases.

There is limited long-term comparative clinical outcome data concerning angiography- versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in non-complex left main coronary artery (LMCA) disease treated with the single stenting technique in the drug-eluting stent (DES) era.The aim of this study was to investigate whether angiography-guided stenting is comparable to IVUS-guided stenting during 3-year clinical follow-up periods in patients with non-complex LM disease treated with the single stenting technique.A total of 196 patients treated with either angiography-guided (n = 74) or IVUS-guided (n = 122) PCI were included. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as total death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-target vessel revascularization (Non-TVR). To adjust for any potential confounders, propensity score (PS) adjusted analysis was performed.During 3-year follow-up, the PS adjusted Cox-proportional hazard ratio (HR) was not significantly different between the two groups for total death, cardiac death, and MI. Also, TLR and the combined rates of TVR and non-TVR were not significantly different. Finally, MACE was not significantly different between the two groups (HR: 0.63, 95% Confidence interval (CI): 0.33-1.17; P = 0.149).Angiography-guided PCI for non-complex LMCA diseases treated with the single stenting technique showed comparable results compared with IVUS-guided PCI in reducing clinical events during 3-year clinical follow-up in the DES era. Although IVUS guided PCI is the ideal strategy, angiography-guided PCI can be an option for LMCA PCI in some selected cases.

Multicenter Cohort Study of Acute Myocardial Infarction in Korea　- Interim Analysis of the Korea Acute Myocardial Infarction Registry-National Institutes of Health Registry.

BACKGROUND: The Korea Acute Myocardial Infarction Registry (KAMIR)-National Institutes of Health (NIH) registry has the aim of evaluating the clinical characteristics, management, and long-term outcomes of patients with acute myocardial infarction (AMI) in Korea. METHODS AND RESULTS: Patients hospitalized for AMI in 20 tertiary university hospitals in Korea have been enrolled since November 2011. The study is expected to complete the scheduled enrollment of approximately 13,000 patients in October 2015, and follow-up duration is up to 5 years for each patient. As of October 2015, an interim analysis of 13,623 subjects was performed to understand the baseline clinical profiles of the study population. The mean age was 64.1 years; 73.5% were male; and 48.2% were diagnosed with ST-segment elevation AMI. Hypertension is a leading cause of AMI in Korea (51.2%), followed by smoking (38.5%) and diabetes mellitus (28.6%). Percutaneous coronary intervention was performed in 87.4% and its success rate was very high (99.4%). In-hospital, 1-year, and 2-year mortality rates were 3.9%, 4.3%, and 8.6%, respectively. The rates of major adverse cardiac events at 1 and 2 years were 9.6% and 18.8%, respectively. CONCLUSIONS: This analysis demonstrated the clinical characteristics of Korean AMI patients in comparison with those of other countries. It is necessary to develop guidelines for Asian populations to further improve their prognosis. (Circ J 2016; 80: 1427-1436).

Comparisons of everolimus and Paclitaxel-eluting stents in patients with acute myocardial infarction.

BACKGROUND: It has been established that the newer-generation drug-eluting stent (DES) everolimus-eluting stent (EES) is superior to the first-generation DES paclitaxel-eluting stent (PES). However, the advantages of EES over PES in the setting of acute myocardial infarction (AMI) need to be fully elucidated. METHODS: The present analysis enrolled 2,911 AMI patients receiving PES (n = 1,210) or EES (n = 1,701) in a large-scale, prospective, multicenter Korea Acute Myocardial Infarction Registry (KAMIR). Propensity score matching was used to adjust for baseline biases in clinical and angiographic characteristics, yielding a total of 2,398 patients (1,199 receiving PES and 1,199 receiving EES). Various clinical outcomes at 1 year were compared between the two propensity score matched groups. Target lesion failure (TLF) was defined as the composite of cardiac death, recurrent nonfatal myocardial infarction (Re-MI), or target lesion revascularization (TLR). RESULTS: Baseline clinical and angiographic characteristics were comparable between the two groups after propensity score matching. Clinical outcomes of the propensity score matched patients showed that the rates of in-hospital and 1-year cardiac and all-cause death were similar between the two groups. But patients in the EES group had significantly lower incidences of Re-MI (1.4% vs 2.8%, P = 0.002), TLR (1.2% vs 3.1%, P = 0.001), TLF (6.4% vs 10.2%, P = 0.001), and probable or definite stent thrombosis (0.3% vs 1.8%, P < 0.001) than did those in the PES group. CONCLUSIONS: The present propensity matched analysis suggests that the use of EES in the setting of AMI appears to be superior to PES in reducing TLF, and stent thrombosis.

Impact of high lipoprotein(a) levels on in-stent restenosis and long-term clinical outcomes of angina pectoris patients undergoing percutaneous coronary intervention with drug-eluting stents in Asian population.

Lipoprotein(a) (Lp(a)) is known to be associated with cardiovascular complications and atherothrombotic properties in general populations. However, it has not been examined whether Lp(a) levels are able to predict adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). A total of 595 consecutive patients with angina pectoris who underwent elective PCI with DES were enrolled from 2004 to 2010. The patients were divided into two groups according to the levels of Lp(a): Lp(a) < 50 mg/dL (n = 485 patients), and Lp(a) ≥ 50 mg/dL (n = 111 patients). The 6-9-month angiographic outcomes and 3-year cumulative major clinical outcomes were compared between the two groups. Binary restenosis occurred in 26 of 133 lesions (19.8%) in the high Lp(a) group and 43 of 550 lesions (7.9%) in the low Lp(a) group (P = 0.001). In multivariate analysis, the reference vessel diameter, low density lipoprotein cholesterol, total lesion length, and Lp(a) ≥ 50 mg/dL were predictors of binary restenosis. In the Cox proportional hazards regression analysis, Lp(a) > 50 mg/dL was significantly associated with the 3-year adverse clinical outcomes including any myocardial infarction, revascularization (target lesion revascularization (TLR) and target vessel revascularization (TVR)), TLR-major adverse cardiac events (MACEs), TVR-MACE, and All-MACEs. In our study, high Lp(a) level ≥ 50 mg/dL in angina pectoris patients undergoing elective PCI with DES was significantly associated with binary restenosis and 3-year adverse clinical outcomes in an Asian population.

Concurrent Carotid Inflammation in Acute Coronary Syndrome as Assessed by (18)F-FDG PET/CT: A Possible Mechanistic Link for Ischemic Stroke.

BACKGROUND: Patients with acute coronary syndrome (ACS) are prone to ischemic stroke (IS) especially during the early phase. ACS patients are more likely to have concurrent complex carotid plaques which, when destabilized, may serve as a source of distal embolism. This study investigated whether inflammatory activity in carotid artery was increased in ACS survivors compared to chronic stable angina (CSA) patients. METHODS: We prospectively enrolled 74 patients with ACS or CSA (39 ACS patients versus 35 CSA patients), and fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed within 1 week after diagnosis. Carotid PET signal was quantified as standardized uptake value (SUV) and target-to-background ratio (TBR, carotid SUV/jugular venous SUV). RESULTS: Baseline characteristics were similar between groups. TBRs and SUVs were significantly higher in the carotid arteries of ACS patients than those of CSA patients (P < .001). Systemic inflammatory biomarker correlated significantly with carotid FDG uptake (high-sensitivity C-reactive protein versus average SUV: r = .361, P = .002), and the presence of cardiovascular risk factors was also related to inflammation activity. During follow-up, 3 cerebrovascular events occurred in ACS patients (including 1 early IS in a patient with severe baseline carotid inflammation), whereas none in CSA patients (P = .057). CONCLUSIONS: This study provided in vivo evidence that ACS survivors might experience concurrent carotid arterial inflammation. Our findings supported the role of systemic immune activation contributing to multiarterial instability in symptomatic atherosclerosis as a possible mechanistic link between ACS and IS.

Impact of hyperuricemia on 5-year clinical outcomes following percutaneous transluminal angioplasty.

BACKGROUND: Although the correlation between hyperuricemia and cardiovascular disease (CVD) is well known, there have been limited data regarding the impact of hyperuricemia on long-term clinical outcomes in patients with peripheral arterial disease (PAD) after percutaneous transluminal angioplasty (PTA). METHODS: A total of 718 patients who underwent PTA for PAD were enrolled. The patients were divided into the hyperuricemia group (N = 168) and the normal group (N = 550). Hyperuricemia was defined as a uric acid level ≥ 7.0 mg/dL in men, and ≥ 6.5 mg/dL in women. The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction (MI), any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was major adverse limb event (MALE), including any repeated PTA, and target extremity surgery (TES). Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust potential confounders. RESULTS: After IPTW matching analysis, compared to the normal group, the hyperuricemia group was not associated with increased MACCE but was associated with an increased incidence of MI (2.6 % vs. 0.5 %, p = 0.001), and coronary revascularization (6.7 % vs. 3.9 %, p = 0.018). Also, the hyperuricemia group was associated with a higher incidence of MALE (45.3 % vs. 28.9 %, p < 0.001), including target extremity revascularization (TER; 25.1 % vs. 15.9 %, p < 0.001), non-TER (11.5 % vs. 5.6 %, p < 0.001), and TES (22.8 % vs. 16.2 %, p = 0.002). CONCLUSIONS: In the present study, hyperuricemia was associated with worse clinical outcomes in PAD patients following PTA during 5-year clinical follow-up. Further investigations should be made regarding the clinical benefit of controlling hyperuricemia on clinical outcomes.

Impact of hyperuricemia on 5-year clinical outcomes in patients with critical limb ischemia following percutaneous transluminal angioplasty.

BACKGROUND: A growing evidence on the correlation between hyperuricemia and cardiovascular disease (CVD) has been previously reported. However, there have been limited data on the impact of hyperuricemia on long-term clinical outcomes in patients with critical limb ischemia (CLI) who underwent percutaneous transluminal angioplasty (PTA). METHODS: A total of 425 peripheral artery disease patients who underwent PTA for CLI were enrolled. The patients were divided into the hyperuricemia group (n = 101) and the normal group (n = 324). The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction, any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was a major adverse limb event (MALE), including any repeated PTA, and target extremity surgery. Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust for potential confounders. RESULTS: After IPTW matching analysis, compared to the normal group, the hyperuricemia group was associated with a higher incidence of MACCE (20.7% vs. 13.6%, hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.15-2.38, P  = 0.006) including non-cardiac death (11.7% vs. 6.3%, HR: 1.95, 95% CI: 1.19-3.19, P  = 0.006) and MALE (47.7% vs. 36.0%, HR: 1.62, 95% CI: 1.23-2.13, P  = 0.001) including non-target extremity revascularization (15.0% vs. 6.8%, HR: 2.42, 95% CI: 1.52-3.84, P  < 0.001). CONCLUSION: In the present study, hyperuricemia was associated with worse clinical outcomes in patients with CLI following PTA during 5-year clinical follow-up. Efficacy of controlling hyperuricemia in improving clinical outcomes should be evaluated in further studies.

Angiographic and clinical characteristics according to intracoronary acetylcholine dose in patients with myocardial bridge.

OBJECTIVES: It is well known that myocardial bridge (MB) is a risk factor of vasospastic angina. However, clinical and angiographic characteristics according to different acetylcholine (ACh) dose in patients with MB are not clarified yet. METHODS: A total 483 consecutive patients who had angiographically proven MB underwent the intracoronary ACh provocation test. ACh was injected by incremental doses of 20, 50 and 100 µg into the left coronary artery. We evaluated the clinical and angiographic characteristics of patients with MB according to 3 different ACh doses. RESULTS: The baseline clinical and procedural characteristics are well balanced among the three groups. The MB patients who responded to the lower ACh dose (20 µg) had higher incidence of baseline spasm, severe vasospasm and diffuse long spasms (>30 mm) than those who responded to the higher doses (50 and 100 µg). The incidence of 12-month mortality and recurrent chest pain was higher in the lower ACh dose group (20 µg). CONCLUSION: The patients with MB significantly reacting at the low ACh dose had more pronounced baseline spasm, severe and diffuse long coronary artery spasm, higher 12-month mortality and recurrent chest pain than those reacting with the higher ACh doses, suggesting that more intensive medical therapy will be required.

Results of a 14-Week, Multicenter, Prospective, Randomized, Open-Label, Noninferiority Clinical Trial Comparing the Antihypertensive Effect and Edema Incidence of Lacidipine and Amlodipine in Older Korean Patients with Mild-to-Moderate Hypertension.

BACKGROUND: It has been shown that administration of lacidipine markedly reduces systolic blood pressure in elderly patients with hypertension without increasing the incidence of cardiovascular events and total mortality. But in Korea, there were no available data about the effectiveness and safety of lacidipine. OBJECTIVES: The goal of our study was to compare the effect of lacidipine and amlodipine besylate on sitting systolic blood pressure (SBP) and edema regression time as primary parameters, and sitting diastolic blood pressure (DBP) and tolerability as a secondary parameter in patients with hypertension. METHOD: This was a prospective, randomized, open-label, noninferiority study in which patients received 14 weeks of treatment with either lacidipine or amlodipine besylate. Patients aged 55 to 80 years having uncomplicated, mild-to-moderate essential hypertension (SBP 140 to <180 mm Hg or DBP ≥90 mm Hg) and receiving no antihypertensive medications during the 2 weeks before randomization were randomly assigned to receive lacidipine or amlodipine. The incidence of adverse events was also assessed. RESULTS: In total, 315 patients (154 men, mean age 67.6 years) were included in the intent-to-treat analysis and randomly assigned to receive lacidipine (n = 162) or amlodipine besylate (n = 153); 286 patients were included in the per-protocol analysis (n = 150 for lacidipine, n = 136 for amlodipine) (12 in the lacidipine group and 17 in the amlodipine group were excluded from the per-protocol analysis due to consent withdrawal or protocol violation). There were no differences in demographic profiles between the 2 groups. Mean (SD) SBP changes at 14 weeks were -18.9 (12.7) mm Hg in the lacidipine group and -20.6 (12.4) mm Hg in the amlodipine group (P >0.05). Because the 1-sided 95% CI for the difference in mean SBP changes between groups (-4.18 to 0.72) was within the pre-specified lower limit (-5 mm Hg), lacidipine was considered noninferior to amlodipine. There were no differences in mean edema regression time and in mean DBP changes. These results were consistent in the isolated systolic hypertension subgroup analysis. The overall incidence of clinical adverse events was comparable between the 2 groups (ie, 7.4% in the lacidipine group and 11.1% in the amlodipine group [P >0.05]). The most common adverse events were headache and facial flushing (5 out of 162 patients [3.1%] in the lacidipine group and 11 out of 153 patients [7.2%] in the amlodipine group]. CONCLUSIONS: Fourteen weeks of lacidipine treatment significantly reduced blood pressure in older Korean patients with mild-to-moderate hypertension. The efficacy of lacidipine was not inferior to that of amlodipine besylate and tolerability was comparable between the 2 treatment groups. ClinicalTrials.gov identifier: NCT00460915.

'Smoker's paradox' in young patients with acute myocardial infarction.

1. Of the patients suffering from acute myocardial infarction (AMI), smokers are younger than non-smokers, which may be a major confounding factor causing 'smoker's paradox'. Therefore, in the present study we evaluated the 'smoker's paradox' in young patients with AMI.2. In all, 1218 young AMI patients (≤ 45 years of age), comprising 990 smokers and 228 non-smokers, were enrolled in the present study. In-hospital and 8 months clinical outcomes were compared between the smokers and non-smokers. 3. Baseline clinical characteristics showed that smokers were more likely to be male (97.9% vs 72.4%; P < 0.001) and had a higher rate of ST-segment elevation myocardial infarction (71.3% vs 59.5%; P = 0.001) than non-smokers. Clinical outcomes showed that smokers had lower rates of in-hospital cardiac death (0.8% vs 3.5%; P = 0.004), total death (0.8% vs 3.5%; P = 0.004) and 8 months cardiac death (1.1% vs 3.9%; P = 0.006) and total death (1.3% vs 4.4%; P = 0.005) than non-smokers. Multivariable logistic analysis showed that current smoking was an independent protective predictor of 8 months cardiac death (odds ratio (OR) 0.25; 95% confidence interval (CI) 0.07-0.92; P = 0.037) and total death (OR 0.26; 95% CI 0.09-0.82; P = 0.021). Subgroup analysis in patients who underwent percutaneous coronary intervention after AMI showed that current smoking was an independent protective predictor of 8 months total major adverse cardiac events (OR 0.47; 95% CI 0.23-0.97; P = 0.041). 4. Current smoking seems to be associated with better clinical outcomes in young patients with AMI, suggesting the existence of the 'smoker's paradox' in this particular subset of patients.

Standard versus high loading doses of clopidogrel in Asian ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: insights from the Korea Acute Myocardial Infarction Registry.

BACKGROUND: The optimal loading dose of clopidogrel in Asian patients with ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. We compared bleeding, vascular complications, and midterm outcomes of a 300-mg versus a 600-mg loading dose of clopidogrel in a large series of Korean patients with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 2,664 STEMI patients (age 61.96 ± 11.91 years, men 70.4%) who underwent primary PCI were enrolled in this study. The patients were divided into a standard loading dose group (300 mg; n = 1,447 patients) and a high loading dose group (600 mg; n = 1,217 patients). Bleeding and vascular complications, and in-hospital and clinical outcomes up to 12 months were compared between the 2 groups. RESULTS: In-hospital bleeding and vascular complications were similar between the 2 groups. There were no differences in bleeding and vascular complications and in 1- and 12-month clinical outcomes, including mortality, myocardial infarction, repeated PCI, and major adverse cardiac events, between the 2 groups. These findings were consistent even after the propensity score-matched analysis. CONCLUSIONS: The standard loading dose of clopidogrel may be as safe and similarly effective as the high loading dose in Asian STEMI patients undergoing primary PCI.

Improved endothelial function in patients with atrial fibrillation through maintenance of sinus rhythm by successful catheter ablation.

BACKGROUND: Although atrial fibrillation (AF) is a risk factor for endothelial dysfunction (ED), the effect of catheter ablation (CA) on AF-associated ED has not been evaluated. The aims of this study are to determine if the degree of ED predicts the outcome of AF ablation and to evaluate whether ED can be improved through restoring sinus rhythm (SR) by successful CA. METHODS: This study prospectively enrolled 80 subjects who underwent CA for AF (paroxysmal AF = 61, persistent AF = 19). Eighty subjects with no history of AF were enrolled as controls, all of whom were matched by age, gender, body mass index, and atherosclerotic risk factor distribution. Brachial artery flow-mediated dilatation (FMD) was measured at baseline, and at 1 month and 6 months post CA in AF subjects who remained in SR. Among controls, FMD was measured at baseline and at 6 months. We used high sensitivity C-reactive protein (hs-CRP), interleukin-6, soluble E- or P-selectin, and endothelin-1 as biomarker indices for inflammation and/or ED. RESULTS: Compared with controls, AF subjects had lower FMD at baseline (FMD(baseline), P < 0.001). After successful CA, FMD was significantly improved at 1 month and 6 months, nearly approaching control levels. A multivariate analysis revealed that FMD(baseline), hs-CRP, and left atrial volume (LAV) were independent predictors for arrhythmia recurrence after CA. Other biomarkers were not related to rhythm outcome. CONCLUSION: AF subjects have significantly impaired FMD, which can be reversed through maintenance of SR by successful CA. FMD(baseline), hs-CRP, and LAV are important predictors for AF recurrence after CA.