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.

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.

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.

Therapeutic Effects of Targeted PPARÉ£ Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo.

Rationale: Atherosclerotic plaque is a chronic inflammatory disorder involving lipid accumulation within arterial walls. In particular, macrophages mediate plaque progression and rupture. While PPARγ agonist is known to have favorable pleiotropic effects on atherogenesis, its clinical application has been very limited due to undesirable systemic effects. We hypothesized that the specific delivery of a PPARγ agonist to inflamed plaques could reduce plaque burden and inflammation without systemic adverse effects. Methods: Herein, we newly developed a macrophage mannose receptor (MMR)-targeted biocompatible nanocarrier loaded with lobeglitazone (MMR-Lobe), which is able to specifically activate PPARγ pathways within inflamed high-risk plaques, and investigated its anti-atherogenic and anti-inflammatory effects both in in vitro and in vivo experiments. Results: MMR-Lobe had a high affinity to macrophage foam cells, and it could efficiently promote cholesterol efflux via LXRα-, ABCA1, and ABCG1 dependent pathways, and inhibit plaque protease expression. Using in vivo serial optical imaging of carotid artery, MMR-Lobe markedly reduced both plaque burden and inflammation in atherogenic mice without undesirable systemic effects. Comprehensive analysis of en face aorta by ex vivo imaging and immunostaining well corroborated the in vivo findings. Conclusion: MMR-Lobe was able to activate PPARγ pathways within high-risk plaques and effectively reduce both plaque burden and inflammation. This novel targetable PPARγ activation in macrophages could be a promising therapeutic strategy for high-risk plaques.

Clinical characteristics and outcomes of patients with coronary artery spasm who initially presented with acute myocardial infarction.

BACKGROUND: The long-term clinical outcomes of coronary artery spasm (CAS) patients presented with acute myocardial infarction (AMI) compared to those who did not present with AMI has rarely been investigated. METHODS: From November 2004 to May 2014, a total of 3360 patients who were confirmed as CAS by the acetylcholine (Ach) provocation test and without significant coronary lesion were retrospectively analyzed. AMI was an initial presentation in 34 patients [CAS-myocardial infarction (MI) group], and not in other 3326 patients (CAS group). The clinical outcomes up to 5 years were compared between the two groups. RESULTS: Baseline characteristics and cardiovascular risk factors did not differ between the two groups, except the higher smoking rate in CAS-MI group (38.2 vs. 23.5%, P=0.046). During a mean follow-up period of 1211±583 days, the cumulative incidence of recurrent angina [hazard ratio (HR): 2.71; 95% confidence interval (CI): 1.20-6.13; P=0.016], MI (HR: 33.89; 95% CI: 8.76-131.1; P<0.001) and major adverse cardiovascular events (MACE; HR: 10.94; 95% CI: 3.83-31.22; P<0.001) were significantly higher in the CAS-MI group. After propensity score matched analysis (1 : 5 matching; n=186, C-statistic=0.834), the incidences of recurrent angina (HR; 4.68; 95% CI: 1.62-13.5; P=0.004) and MACE (HR: 12.2; 95% CI: 2.23-67.3; P=0.003) remained higher in the CAS-MI group. CONCLUSION: The CAS-MI group patients were associated with higher incidence of recurrent angina, MI, and MACE compared to CAS group patients. More intensive antispastic medication might be needed for these patients, and further study will be necessary to determine which treatment can improve the prognosis of CAS-MI patients.

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.

Impact of old age on clinical and angiographic characteristics of coronary artery spasm as assessed by acetylcholine provocation test.

BACKGROUND: Smoking and other risk factors have been well known as important factors of variant angina or coronary artery spasm (CAS). However, clinical features related to age on coronary artery spasm have been rarely evaluated. METHODS: We evaluated 3155 consecutive patients with insignificant coronary artery lesion. Patients underwent Acetylcholine (Ach) provocation test for induction of CAS. CAS was defined as > 70% luminal narrowing of coronary arteries during Ach provocation test. The results of Ach provocation test were compared among age groups; < 45 years (Group 1), 45-54 years (Group 2), 55-64 years (Group 3), and ≥ 65 years (Group 4). RESULTS: Older patients had higher incidence of hypertension, diabetes, but lower incidence rate of current smoking, male sex compared with younger patients. Positive Ach provocation test finding was frequently showed with aging (47.36% vs. 58.3% vs. 62.6% vs. 61.5%; P < 0.001). Multivariate logistic analysis showed that age, male, and myocardial bridge were independent predictors of CAS induced by Ach provocation test. CONCLUSION: Our present study showed that old age was independent predictor for Ach-induced significant coronary artery spasm.

Impact of Cigarette Smoking: a 3-Year Clinical Outcome of Vasospastic Angina Patients.

BACKGROUND AND OBJECTIVES: Cigarette smoking is a risk significant factor in coronary artery disease (CAD) and vasospastic angina (VSA). However, it is largely unknown whether smoking adds to any long-term clinical risk in VSA patients. SUBJECTS AND METHODS: A total of 2797 patients without significant CAD underwent acetylcholine (Ach) provocation test between November 2004 and October 2010. Patients were divided into three groups, based on the presence of coronary artery spasm (CAS) and smoking habits (non-CAS group: n=1188, non-smoking CAS group: n=1214, smoking CAS group: n=395). All CAS patients were prescribed with anti-anginal medications for at least 6 months. The incidence of major clinical outcomes and recurrent angina of these groups were compared up to 3 years. RESULTS: There were considerable differences in the baseline clinical and angiographic characteristics among the three groups, but there was no difference in the endpoints among the three groups (including individual and composite hard endpoints) such as death, myocardial infarction, de novo percutaneous coronary intervention, cerebrovascular accident, and major adverse cardiac events. However, there was a higher incidence of recurrent angina in both the non-smoking CAS group and smoking CAS group, as compared to the non-CAS group. In multivariable adjusted Cox-proportional hazards regression analysis, smoking CAS group exhibited a higher incidence of recurrent angina compared with the non-CAS group (hazard ratio [HR]; 2.46, 95% confidence interval [CI]; 1.46-4.14, p=0.001) and non-smoking CAS group (HR; 1.76, 95% CI; 1.08-2.87, p=0.021). CONCLUSION: Cigarette smoking CAS group exhibited higher incidence of recurrent angina during the 3-year clinical follow-up compared with both the non-CAS group and non-smoking CAS group. Quitting of smoking, paired with intensive medical therapy and close clinical follow-up, can help to prevent recurrent angina.

Comparison of short-term clinical outcomes between ticagrelor versus clopidogrel in patients with acute myocardial infarction undergoing successful revascularization; from Korea Acute Myocardial Infarction Registry-National Institute of Health.

BACKGROUND: Although ticagrelor has been well-known to improve clinical outcomes in patients with acute myocardial infarction (AMI) without increased bleeding risk, its clinical impacts have not been well established in East Asian patients. METHODS: Between November 2011 and June 2015, a total of 8010 patients (1377 patients were prescribed ticagrelor and 6633 patients clopidogrel) undergoing successful revascularization were analyzed from Korea Acute Myocardial Infarction Registry-National Institute of Health. The patients who discontinued or occurred in-hospital switching between two antiplatelet agents were excluded. RESULTS: After propensity score matching (1377 pairs), no difference in the composite of cardiac death, MI, stroke, or target vessel revascularization at 6months was observed between two groups (4.2% vs. 4.9%, p=0.499). However, the incidences of in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding were higher in ticagrelor than clopidogrel (2.6% vs. 1.2%, p=0.008; 3.8% vs. 2.5%, p=0.051). The in-hospital mortality was higher in patients with than those without TIMI major bleeding (11.3% vs. 0.9%, p<0.001). In a subgroup analysis, a higher risk for in-hospital TIMI major bleeding with ticagrelor was observed in patients≥75years or with body weight<60kg (odd ratio [OR]=3.209; 95% confidence interval [CI]=1.356-7.592) and in those received trans-femoral intervention (OR=1.996; 95% CI=1.061-3.754). CONCLUSIONS: Our study shows that ticagrelor did not reduce ischemic events yet, however, was associated with increased risk of bleeding complications compared with clopidogrel. Further large-scale, long-term, randomized trials should be required to assess the outcomes of ticagrelor for East Asian patients with AMI.

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).

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors.

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

Fully integrated high-speed intravascular optical coherence tomography/near-infrared fluorescence structural/molecular imaging in vivo using a clinically available near-infrared fluorescence-emitting indocyanine green to detect inflamed lipid-rich atheromata in coronary-sized vessels.

BACKGROUND: Lipid-rich inflamed coronary plaques are prone to rupture. The purpose of this study was to assess lipid-rich inflamed plaques in vivo using fully integrated high-speed optical coherence tomography (OCT)/near-infrared fluorescence (NIRF) molecular imaging with a Food and Drug Administration-approved indocyanine green (ICG). METHODS AND RESULTS: An integrated high-speed intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were constructed based on a clinical OCT platform. For imaging lipid-rich inflamed plaques, the Food and Drug Administration-approved NIRF-emitting ICG (2.25 mg/kg) or saline was injected intravenously into rabbit models with experimental atheromata induced by balloon injury and 12- to 14-week high-cholesterol diets. Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta and iliac arteries was acquired only under contrast flushing through catheter (pullback speed up to ≤20 mm/s). NIRF signals were strongly detected in the OCT-visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to-background ratio was significantly larger in the ICG-injected rabbits than in the saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background ratios were significantly higher in ICG-injected rabbits than in controls (P<0.01) on fluorescence reflectance imaging, which correlated well with the in vivo target-to-background ratios (P<0.01; r=0.85) without significant bias (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and histopathology also corroborated the in vivo imaging findings. CONCLUSIONS: Integrated OCT/NIRF structural/molecular imaging with a Food and Drug Administration -approved ICG accurately identified lipid-rich inflamed atheromata in coronary-sized vessels. This highly translatable dual-modal imaging approach could enhance our capabilities to detect high-risk coronary plaques.

An adult case of tetralogy of fallot accompanied by multiple anomalies including multidirectional coronary artery fistulas.

Multidirectional coronary artery fistulas (CAFs) are rare in patients with tetralogy of Fallot (TOF). We report an adult patient who underwent open-heart surgery for TOF 24 years before the discussed presentation. Coronary angiogram and cardiac computed tomography revealed multidirectional CAFs originating from the left main coronary artery and draining to the left atrium, pulmonary artery and subphrenic artery. The patient also showed additional congenital anomalies, such as persistent left superior vena cava and right-sided aortic arch.

The impact of high sensitivity C-reactive protein level on coronary artery spasm as assessed by intracoronary acetylcholine provocation test.

PURPOSE: High sensitive C-reactive protein (hs CRP) is well known as a strong risk factor of cardiovascular disease (CVD). The aim of this study is to evaluate the impact of elevated hs CRP on coronary artery spasm (CAS) as assessed by intracoronary acetylcholine (ACh) provocation test. MATERIALS AND METHODS: A total of 1729 consecutive patients without significant CVD who underwent coronary angiography and intracoronary ACh test between November 2004 and August 2010 were analyzed. The patients were divided into five groups according to quintiles of hs CRP levels. RESULTS: At baseline, the prevalence of elderly, hypertension, diabetes mellitus, current smoking, and lipid levels were higher in patients with higher hs CRP. During ACh test, the incidences of significant CAS, ischemic electrocardiography (EKG) change, multivessel, and diffuse CAS were higher in patients with higher hs CRP. Multivariate analysis showed that the old age (OR=1.01, CI; 1.0-1.02, p=0.0226), myocardial bridge (OR=3.34, CI; 2.16-5.17, p<0.001), and highest quintile hs CRP (OR=1.54, CI; 1.12-2.18, p=0.008) were independent predictors of ACh induced CAS. However, there was no difference in clinical outcomes up to 12 months. CONCLUSION: In conclusion, higher hs CRP was associated with higher incidence of CAS, worse angiographic characteristics and ischemic EKG change, but was not associated with clinical outcomes.

'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.

Successful retrieval of a fractured and entrapped 0.035-inch terumo wire in the femoral artery using biopsy forceps.

A 0.035-inch guide wire fracture and entrapment in a peripheral artery is a very rare complication, but when it does occur it may lead to life-threatening complications, such as perforation, thrombus formation, embolization, and subsequent limb ischemia. We describe our experience of successfully retrieving a fractured 0.035-inch Terumo guide wire in the external iliac artery using a biopsy forcep.

Multivessel versus single vessel spasm, as assessed by the intracoronary acetylcholine provocation test, in Korean patients.

1. Coronary artery spasm (CAS) is known to be a major cause of myocardial ischaemia. Multivessel coronary spasm (MVS) in particular is likely to induce more severe and prolonged myocardial ischaemia than single vessel spasm (SVS). 2. In the present study, a total of 1082 consecutive patients without significant coronary artery disease who underwent an acetylcholine (ACh) provocation test between March 2004 and April 2009 were investigated. Patients were divided into three groups: an MVS group (n = 275), an SVS group (n = 376) and a non-CAS group (n = 431). Differences in clinical and angiographic characteristics following the ACh provocation test were evaluated between the MVS, SVS and non-CAS groups. 3. At baseline, patients in the MVS group had the highest prevalence of peripheral artery disease (PAD), hyperlipidaemia, smoking and old age, as well as the highest triglyceride levels. Calcium channel blockers were most frequently prescribed in MVS patients before the ACh test. During the ACh test, the highest prevalence of chest pain, ischaemic electrocardiogram changes, baseline spasms and diffuse and severe spasms were observed in the MVS group. The response rate to lower ACh doses that induce CAS was also higher in the MVS group. Multivariate analysis showed that the presence of PAD (odds ratio (OR) 2.0; P = 0.006) and baseline spasm (OR 1.4; P = 0.045) were independent predictors of ACh-induced MVS. 4. In conclusion, ischaemic symptoms, diffuse and severe spasm and baseline spasm were more frequently associated with MVS patients, suggesting more intensive medical therapies and close clinical follow up would be required for this patient group.

Association between aortic calcification and stable obstructive coronary artery disease.

BACKGROUND: Coronary artery calcification (CAC) is correlated with aortic calcification (AC) and predicts coronary atherosclerosis as well as obstructive coronary artery disease (OCAD). This study aims to investigate whether AC predicts OCAD independent of CAC and its incremental value in predicting OCAD with CAC. METHODS: Among the consecutive patients who underwent 64-slice multidetector CT (MDCT), we enrolled 120 stable OCAD (luminal narrowing ≥ 50%) patients and 120 controls without OCAD, matched for cardiovascular risk factors. CAC, thoracic AC, and OCAD were determined by MDCT. RESULTS: The prevalence of AC and CAC were significantly higher in OCAD patients than in controls (64% vs. 48%, p = 0.019; 57% vs. 32%, p < 0.001, respectively). There is a significant correlation between AC and CAC scores in the overall study population (r = 0.528, p < 0.001). In univariate analysis, the odds ratios (ORs) of AC and CAC in predicting OCAD were 1.91 (95% CI, 1.14-3.21) and 2.82 (95% CI, 1.67-4.78), respectively. When an adjustment was made for each other, AC did not maintain a significant association with OCAD, whereas CAC persisted the association (OR, 2.52; 95% CI, 1.42-4.47). Both AC and CAC present as compared to both absent was found to be a more potent predictor for OCAD (OR, 3.37; 95% CI 1.78-6.36, p < 0.001) than CAC alone. CONCLUSIONS: The presence of AC was associated with stable OCAD independently from cardiovascular risk factors, but the association seemed to be based on the close correlation between AC and CAC. However, AC might have an incremental value with CAC for predicting OCAD.

Impaired transport function of the left atrium and left atrial appendage in cryptogenic stroke patients with atrial septal aneurysm and without patent foramen ovale.

AIMS: Although atrial septal aneurysm (ASA) is frequently combined with patent foramen ovale and associated with cryptogenic stroke (CS), a pathophysiologic correlation between CS and ASA alone has not been fully elucidated. The aims of this study were to assess transport functions of the left atrium (LA) and left atrial appendage (LAA), and to evaluate their relationship in CS subjects with ASA alone. METHODS AND RESULTS: This study consisted of 38 CS subjects with ASA alone and 38 matched controls. Transthoracic echocardiography including tissue Doppler imaging was performed in all subjects and transesophageal echocardiography was conducted in CS subjects to assess LAA emptying velocity (LAAev). We also measured soluble P- and E-selectin, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) as indices of prothrombogenic and proinflammatory activity. Although there were no differences in left ventricular functions and baseline characteristics between the two groups, CS subjects had significantly larger LA volume and lower LA active pump function compared with controls. LAAev was significantly correlated with LA active function. CS subjects had significantly higher E-selectin (P = 0.046), IL-6 (P = 0.040), and hs-CRP (P = 0.001) compared with controls. CONCLUSIONS: Compared with controls, LA active pump function was significantly depressed and closely correlated with LAAev in CS subjects with ASA alone. Moreover, plasma levels of E-selectin, IL-6, and hs-CRP were significantly higher in CS subjects with ASA alone. These findings suggest that impaired LA and LAA functions are a crucial pathophysiologic mechanism for ischaemic stroke in subjects with ASA alone.