Sunki Lee

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.

Relationship between uric acid and blood pressure in different age groups

IntroductionSerum uric acid (UA) has been known to have a positive association with blood pressure (BP). However, the relationship between serum UA and BP in different age groups is unclear.MethodsA total of 45,098 Koreans who underwent health examinations at Korea Association of Health Promotion with no history of taking drugs related with UA and/or BP were analyzed for determining the relationship between serum UA and BP.ResultsIn men <40, serum UA was significantly associated with systolic (β = 0.25, p = 0.002) and diastolic BP (β = 0.41, p < 0.001) after adjustment for age, diabetes, dyslipidemia, body mass index, and estimated glomerular filtration rate. Men between ages 40 and 59 showed similar results regarding diastolic BP. The association between serum UA and BP was stronger in women <40 (β = 0.54, p < 0.001 for systolic BP; β = 0.65, p < 0.001 for diastolic BP) and in between 40 and 59 (β = 0.51, p < 0.001 for diastolic BP). The association was not significant in men and women ≥60. The odds ratios (ORs) of hyperuricemia for hypertension were 1.25 (95% confidence interval [CI], 1.08 to 1.45; p = 0.003) and 1.33 (95% CI, 1.11 to 1.60; p = 0.002) in men <40 and in between 40 and 59, respectively, in the multivariate analysis. The OR was 2.60 (95% CI, 1.37 to 4.94; p = 0.0034) in women <40. The relationship between hyperuricemia and hypertension was not significant in other age/gender groups.DiscussionIn contrast to the elderly of 60 and over, the non-elderly showed significant associations between serum UA and BP.

Five-year clinical outcomes in patients with significant coronary artery spasm: A propensity score-matched analysis

BACKGROUND Coronary artery spasm (CAS) is known to be a risk factor of acute coronary syndrome and angina pectoris. However, there is no currently available data with larger study population regarding long-term clinical outcomes of CAS in real world clinical practice. OBJECTIVES We evaluated the prevalence of CAS and the impact of CAS on 5-year clinical outcomes in a series of Asian CAS patients documented by intracoronary acetylcholine (Ach) provocation test. METHODS A total of 1413 consecutive patients without significant coronary artery disease (CAD) who underwent Ach provocation test between Nov. 2004 and Oct. 2008 were enrolled. Significant CAS was defined as >70% of narrowing by incremental intracoronary injection of 20, 50 and 100 μg. Patients were divided into two groups based on the presence of significant CAS (the non-CAS group: n=640, the CAS group; n=773). To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression model. RESULTS A total of 54.7% (773/1413) patients were diagnosed as CAS documented by Ach provocation test. After PSM analysis, 2 propensity-matched groups (451 pairs, n=902, C-statistic=0.677) were generated. Despite of similar incidence of individual hard endpoints including mortality, myocardial infarction and revascularization, the CAS group showed the higher trend of recurrent angina requiring follow up angiography than the non-CAS group up to 5 years (HR; 1.56, 95% C.I.; 0.99-2.46, p=0.054). CONCLUSIONS The prevalence of CAS was 54.7%. Although the cumulative incidence of recurrent angina requiring follow up coronary angiography seems to be increased up to 5 years in CAS patients, CAS patients was not associated with major individual and composite clinical outcomes such as mortality, MI, PCI, CVA with optimal medical therapy as compared with patients without CAS.

Impact of Statin Use on Development of New-Onset Diabetes Mellitus in Asian Population.

There have been several reports showing that the statin use is associated with new-onset diabetes mellitus (DM). The aim of the present study was to evaluate the impact of chronic statin use on development of new-onset DM in a series of Asian population. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2010. A total of 10,994 patients without a history of diabetes were analyzed. Baseline lipid profiles, fasting glucose, Hemoglobin (Hb) A1c, and glucose tolerance tests were measured in all patients before statin treatment. Included patients had HbA1c ≤ 5.7% and fasting glucose level ≤ 100 (mg/dl). The patients were divided into 2 groups according to the use of statins (the statin group, n = 2,324 patients and the nonstatin group, n = 8,670 patients). To adjust baseline potential confounders, a propensity score-matched analysis was performed using logistic regression model. After propensity score matching, 2 propensity-matched groups (1,699 pairs, n = 3,398, C statistic = 0.859) were generated and analyzed. After propensity score matching, baseline characteristics of both groups were balanced except that the statin group was older and had higher rate of coronary artery disease compared with the nonstatin group. During a 3-year follow-up, the statin group had higher incidence of new-onset DM compared with the nonstatin group (hazard ratio 1.99, 95% CI 1.36 to 2.92, p <0.001), but the statin group showed lower incidence of major adverse cerebral-cardiovascular events compared with the nonstatin group (hazard ratio 0.40, 95% CI 0.19 to 0.85, p <0.001). In the present study, although the use of statins was associated with higher rate of new-onset DM, it markedly improved 3-year cardiovascular outcomes in Asian population.

Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: Three-year clinical outcomes

BACKGROUND High dose atorvastatin is known to be associated with new onset diabetes mellitus (NODM) in patients with high risk for developing diabetes mellitus (DM). However, low dose atorvastatin is more commonly used as compared with high dose atorvastatin. The aim of this study is to investigate the impact of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to three years in Asian patients. METHODS From January 2004 to September 2009, we investigated a total of 3566 patients who did not have DM. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM (C-statistics: 0.851), a total of 818 patients (LDA group, n=409 patients and control group, n=409 patients) were enrolled for analysis. RESULTS Before PSM, the cumulative incidence of NODM (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007), and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at three-years were higher in the LAD group. However, after PSM, there was a trend toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two groups. In multivariable analysis, the LDA administration was tended to be an independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050). CONCLUSIONS In this study, the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group. However, large-scale randomized controlled trials will be needed to get the final conclusion.

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.

Enhancement of biodegradability of EDTA by gamma-ray treatment

Radiation treatment with gamma-rays was used to improve the biodegradability of EDTA that is known to be a non-biodegradable substance. The effect of metal ions and catalysts on the treatment of EDTA was studied first. The removal of EDTA was definitely decreased in the presence of metal ions such as Cr(III), Cd(II), Pb(II) and Cu(II) at doses greater than 3 kGy. The addition of a TiO2

Prevalence of Gastrointestinal Diseases and Treatment Status in Noncardiac Chest Pain Patients

Background and Objectives We evaluated the prevalence of gastroesophageal reflux diseases (GERD) in noncardiac chest pain (NCCP) patients, risk factors for GERD, and status of prescriptions for GERD in Korean population. Subjects and Methods This was a retrospective non-interventional observational nation-wide 45-center study. Patients with a normal coronary angiogram (CAG) and upper gastroendoscopy within 2 years after CAG were enrolled. The prevalence of GERD was examined. Other gastrointestinal diseases including peptic ulcer diseases or gastritis were also examined. Risk factors for GERD were compared between the GERD group and non-GERD group. The ratio of patients medicated for gastrointestinal diseases (antacids or proton-pump inhibitor) was also examined. Results Nine hundred four patients were enrolled. Among the NCCP patients, GERD was present in 436 (48.2%), peptic ulcer disease in 154 patients (17.0%), and gastritis in 659 (72.9%). There was no difference in risk factors for GERD between the GERD and non-GERD patients. Medications for GERD and other gastrointestinal diseases were prescribed in 742 (82.1%) patients. Conclusion GERD was common (42.8%) in Korean NCCP patients and most (82.1%) received the prescription of gastrointestinal medications. No differences were evident in risk factors between GERD and non-GERD patients.

Impact of Angiotensin Converting Enzyme Inhibitor versus Angiotensin Receptor Blocker on Incidence of New-Onset Diabetes Mellitus in Asians

Purpose Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) are associated with a decreased incidence of new-onset diabetes mellitus (NODM). The aim of this study was to compare the protective effect of ACEI versus ARBs on NODM in an Asian population. Materials and Methods We investigated a total of 2817 patients who did not have diabetes mellitus from January 2004 to September 2009. To adjust for potential confounders, a propensity score matched (PSM) analysis was performed using a logistic regression model. The primary end-point was the cumulative incidence of NODM, which was defined as having a fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5%. Multivariable cox-regression analysis was performed to determine the impact of ACEI versus ARB on the incidence of NODM. Results Mean follow-up duration was 1839±1019 days in all groups before baseline adjustment and 1864±1034 days in the PSM group. After PSM (C-statistics=0.731), a total 1024 patients (ACEI group, n=512 and ARB group, n=512) were enrolled for analysis and baseline characteristics were well balanced. After PSM, the cumulative incidence of NODM at 3 years was lower in the ACEI group than the ARB group (2.1% vs. 5.0%, p=0.012). In multivariate analysis, ACEI vs. ARB was an independent predictor of the lower incidence for NODM (odd ratio 0.37, confidence interval 0.17-0.79, p=0.010). Conclusion In the present study, compared with ARB, chronic ACEI administration appeared to be associated with a lower incidence of NODM in a series of Asian cardiovascular patients.

Impact of Renin-Angiotensin System Inhibitors on Long-Term Clinical Outcomes of Patients With Coronary Artery Spasm.

Background Coronary artery spasm (CAS) is a well‐known endothelial dysfunction, and a major cause of vasospastic angina (VSA). The renin–angiotensin system (RAS) is known to be closely associated with endothelial function. However, there are only a few studies that investigated the impact of RAS inhibitor on long‐term clinical outcomes in VSA patients. Methods and Results A total of 3349 patients with no significant coronary artery disease, diagnosed with CAS by acetylcholine provocation test were enrolled for this study. Significant CAS was defined as having ≥70% narrowing of the artery after incremental injections of 20, 50, and 100 μg of acetylcholine into the left coronary artery. Patients were divided into 2 groups according to whether the prescription included RAS inhibitor or not (RAS inhibitor group: n=666, non‐RAS inhibitor group; n=2683). To adjust for any potential confounders that could cause bias, propensity score matching (PSM) analysis was performed using a logistic regression model. After PSM analysis, 2 matched groups (524 pairs, n=1048 patients, C‐statistic=0.845) were generated and their baseline characteristics were balanced. During the 5‐year clinical follow‐up, the RAS inhibitor group showed a lower incidence of recurrent angina (8.7% versus 14.1%, P=0.027), total death (0.0% versus 1.3%, P=0.045), and total major adverse cardiovascular events (1.0% versus 4.1%, P=0.026) than the non‐RAS inhibitor group. Conclusions Chronic RAS inhibitor therapy was associated with lower incidence of cardiovascular events in VSA patients in the 5‐year clinical follow‐up.