Multimodality Intravascular Imaging Assessment of Plaque Erosion versus Plaque Rupture in Patients with Acute Coronary Syndrome

BACKGROUND AND OBJECTIVES: We assessed plaque erosion of culprit lesions in patients with acute coronary syndrome in real world practice. SUBJECTS AND METHODS: Culprit lesion plaque rupture or plaque erosion was diagnosed with optical coherence tomography (OCT). Intravascular ultrasound (IVUS) was used to determine arterial remodeling. Positive remodeling was defined as a remodeling index (lesion/reference EEM [external elastic membrane area) >1.05. RESULTS: A total of 90 patients who had plaque rupture showing fibrous-cap discontinuity and ruptured cavity were enrolled. 36 patients showed definite OCT-plaque erosion, while 7 patients had probable OCT-plaque erosion. Overall, 26% (11/43) of definite/probable plaque erosion had non-ST elevation myocardial infarction (NSTEMI) while 35% (15/43) had ST elevation myocardial infarction (STEMI). Conversely, 14.5% (13/90) of plaque rupture had NSTEMI while 71% (64/90) had STEMI (p<0.0001). Among plaque erosion, white thrombus was seen in 55.8% (24/43) of patients and red thrombus in 27.9% (12/43) of patients. Compared to plaque erosion, plaque rupture more often showed positive remodeling (p=0.003) with a larger necrotic core area examined by virtual histology (VH)-IVUS, while negative remodeling was prominent in plaque erosion. Overall, 65% 28/43 of plaque erosions were located in the proximal 30 mm of a culprit vessel-similar to plaque ruptures (72%, 65/90, p=0.29). CONCLUSION: Although most of plaque erosions show nearly normal coronary angiogram, modest plaque burden with negative remodeling and an uncommon fibroatheroma might be the nature of plaque erosion. Multimodality intravascular imaging with OCT and VH-IVUS showed fundamentally different pathoanatomic substrates underlying plaque rupture and erosion.

Cholesterol Lowering Effects of Low-dose Statins in Korean Patients

OBJECTIVE: The aim of this study is to compare cholesterol lowering effects of low dose 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in Korean patients. METHODS: A total of 909 consecutive patients were enrolled prospectively according to the criteria of National Cholesterol Education Program guidelines. Lipid profiles were obtained before and 2 months after statin therapy. RESULTS: Atorvastatin 10 mg (n=260), lovastatin 20 mg (n=145), pitavastatin 2 mg (n=80), pravastatin 20 mg (n=28), rosuvastatin 5 mg (n=145), and simvastatin 20 mg (n=208) reduced low density lipoprotein (LDL) cholesterol by -41.8+/-11.0%, -33.8+/-12.8%, -39.3+/-10.8%, -31.5+/-8.9%, -48.8+/-12.3%, and -42.8+/-13.5%, respectively. LDL cholesterol less than 130 mg/dL was achieved in 90.3%, 76.9%, 88.5%, 85.2%, 97.2%, and 94.2%, respectively. The reduction of LDL cholesterol by 30% or more was obtained in 84.4%, 60.7%, 81.6%, 63.0%, 93.0%, and 83.5%, respectively. LDL cholesterol less than 70 mg/dL or the reduction by 50% or more was observed in a small portion of patients and was variable according to the different types of statins. CONCLUSION: A low dose statin was enough to manage dyslipidemia in most Korean patients with low to moderate risks and was even effective in a subpopulation of high risk patients.

Effect of Short-term Fenofibrate Therapy on Blood Creatinine Levels in Patients with Hypertriglyceridemia / 대한내과학회지

BACKGROUND/AIMS: Previous studies have reported that fenofibrate therapy increases blood creatinine levels. The aim of this study was to evaluate the effect of fenofibrate therapy on the renal function in patients with hypertriglyceridemia and to determine the parameters associated with changes in renal functions. METHODS: This prospective study enrolled 86 hypertriglyceridemic patients (triglycerides > or = 200 mg/dL) who were divided into two groups: the fenofibrate group (n = 43), who received 160 mg of fenofibrate, and the control group (n = 43). Lipid profiles and renal function were measured at the beginning of the study and after 2 months. RESULTS: The estimated glomerular filtration rate (eGFR) decreased in the fenofibrate group (p < 0.001), but did not change in the control group (p = 0.80). Accordingly, the decrease was more pronounced in the fenofibrate group than the control group (-18.6 +/- 8.6 vs. 0.9 +/- 9.6%, respectively; p < 0.001). Changes in serum creatinine (p < 0.001) and blood urea nitrogen (p < 0.005) levels were similar to those of eGFR. In a stepwise linear regression analysis, the percent change in creatinine was independently associated with fenofibrate therapy (r = 0.71; p < 0.001) and old age (r = 0.27; p < 0.05) in all patients. In the fenofibrate group, percent change in creatinine was associated with age (r = -0.51; p < 0.001) and smoking (r = 0.42; p < 0.005), while percent change was associated with body mass index (r = 0.31; p < 0.05) in the control group. Elevation of creatinine by 20% or more was associated with fenofibrate therapy (p < 0.001) and old age (p < 0.005) in all patients, and with old age (p < 0.001) in the fenofibrate group. CONCLUSIONS: Short-term fenofibrate therapy significantly impaired the renal function of hypertriglyceridemic patients, and this effect was more pronounced in elderly patients. This finding suggests that creatinine levels should be followed in patients receiving fenofibrate therapy.

Influence of Previous Statin Therapy on Cholesterol-Lowering Effect of Ezetimibe

BACKGROUND AND OBJECTIVES: The inhibition of cholesterol absorption by ezetimibe increases cholesterol synthesis. The effect of inhibition of cholesterol synthesis on cholesterol absorption is controversial. The influence of these interactions on cholesterol levels is unknown. We investigated on the extent to which cholesterol levels were affected by the reaction of one pathway to the inhibition of the other pathway. SUBJECTS AND METHODS: This case-controlled study enrolled 198 patients who needed cholesterol-lowering drugs. Ezetimibe (10 mg) was administered to the patients with (n=58) and without on-going statin therapy (n=58). Simvastatin (20 mg) was administered to the patients treated with (n=41) and without ezetimibe (n=41). RESULTS: Ezetimibe without statin lowered the total cholesterol by 13.3+/-8.8% (p<0.001) and the low density lipoprotein-cholesterol (LDL-C) by 18.7+/-15.3% (p<0.001). Ezetimibe added to statin decreased the total cholesterol by 21.1+/-7.7% (p<0.001) and the LDL-C by 29.9+/-12.6% (p<0.001). The total cholesterol and LDL-C were reduced more by ezetimibe in patients with statin therapy than in those without statin therapy (p<0.001 and p<0.001, respectively). The differences in the effect of simvastatin on total cholesterol and LDL-C between the patients with and without ezetimibe showed borderline significance (p=0.10 and p=0.055, respectively). CONCLUSION: A prior inhibition of cholesterol synthesis by statin enhanced the effect of ezetimibe on total cholesterol and LDL-C by 7.8% and 11.2%, respectively. This finding suggests that ezetimibe increased cholesterol synthesis, resulting in a significant elevation of cholesterol levels.

Effect of Fenofibrate Therapy on Blood Creatinine Levels in Patients with Hypertension and Hypertriglyceridemia

OBJECTIVE: Previous studies have reported that fenofibrate therapy increased blood creatinine levels. We investigated the effect of fenofibrate therapy on creatinine levels in patients with hypertension and hypertriglyceridemia. METHODS: This retrospective study included 36 hypertensive patients with hypertriglyceridemia taking fenofibrate for 1-3 years (Fenofibrate group) and 36 control patients with similar age, sex, follow-up duration, creatinine levels, and lipid levels to those of fenofibrate therapy (Control group). RESULTS: Baseline parameters except lipid profiles were similar between the fenofibrate and control groups. Creatinine levels increased in the fenofibrate group (from 0.90+/-0.18 mg/dL to 1.05+/-0.22 mg/dL, p<0.001) and did not change in the control group (from 0.91+/-0.12 mg/dL to 0.92+/-0.14 mg/dL, p=0.39). The elevation was more pronounced in the fenofibrate group than in the control group (0.15+/-0.12 vs. 0.02+/-0.11 mg/dL, p<0.001). Changes in creatinine levels were only associated with fenofibrate therapy (r=0.52, p<0.001) in the stepwise linear regression analysis. CONCLUSION: Fenofibrate therapy for 1-3 years significantly increased creatinine levels in hypertensive patients with hypertriglyceridemia. This finding suggests that follow-up measurement of creatinine level is necessary with fenofibrate therapy.

Subarachnoid Hemorrhage Mimicking Leakage of Contrast Media After Coronary Angiography

We report a patient who developed subarachnoid hemorrhage (SAH) just after coronary angiography (CAG) with non-ionic contrast media (CM) and minimal dose of heparin. The 55-year-old man had a history of acute ST elevation myocardial infarction that had been treated with primary percutaneous coronary intervention and was admitted for a follow-up CAG. The CAG was performed by the transradial approach, using 1000 U of unfractionated heparin for the luminal coating and 70 mL of iodixanol. At the end of CAG, he complained of nausea and rapidly became stuporous. Brain CT showed a diffusely increased Hounsfield unit (HU) in the cisternal space, similar to leakage of CM. The maximal HU was 65 in the cisternal space. No vascular malformations were detected on cerebral angiography. The patient partially recovered his mental status and motor weakness after 2 days. Two weeks later, subacute SAH was evident on magnetic resonance imaging. The patient was discharged after 28 days.

Oncologic manifestations of neurofibromatosis type 1 in Korea / 대한외과학회지

PURPOSE: The aim of this study was to investigate the incidence and spectrum of malignant tumors in Korean neurofibromatosis type 1 (NF1) patients. METHODS: We retrospectively reviewed 125 patients who were diagnosed with NF1 at a single institution from 1995 to 2010. The incidence, location, histologic type, and radiologic findings of malignant tumors as well as development of multiple primary tumors were analyzed. RESULTS: Eighteen malignant tumors occurred in 16 patients (12.8%) among 125 Korean NF1 patients; 9 carcinomas, 8 sarcomas and 1 central nervous system (CNS) tumor. Five tumors were of nervous system origin and 13 were non-nervous system tumors. The locations of the tumors were as follow: 1 CNS, 2 lung, 3 breast, 3 stomach, 3 small bowel, 1 colon, 1 liver, 1 uterus, 1 neck, and 2 in extremities. Three malignant peripheral nerve sheath tumors (MPNSTs) occurred at the neck and extremity, and one in the liver. All three gastrointestinal stromal tumors (GISTs) had multiple tumors in the jejunum, and one MPNST and one pheochromocytoma were accompanied in two GISTs. Multiple primary tumors, benign or malignant were reported in 4 patients (25.0%), synchronously or metachronously. CONCLUSION: Korean NF1 patients had a high risk of developing malignant tumors. The common malignant tumors in Koreans such as breast, lung and stomach cancers developed frequently in addition to the NF1-related tumors such as MPNST or GIST.

Acute Viral Myopericarditis Presenting as a Transient Effusive-Constrictive Pericarditis Caused by Coinfection with Coxsackieviruses A4 and B3

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications.

Fenofibrate Reduces C-Reactive Protein Levels in Hypertriglyceridemic Patients With High Risks for Cardiovascular Diseases

BACKGROUND AND OBJECTIVES: The effects of fenofibrate on C-reactive protein (CRP) are under debate. We investigated the effect of fenofibrate on CRP levels and the variables determining changes. SUBJECTS AND METHODS: This case-control study enrolled 280 hypertriglyceridemic patients who were managed either with 200 mg of fenofibrate (Fenofibrate group, n=140) or with standard treatment (comparison group, n=140). CRP levels were measured before and after management for 2 months. RESULTS: CRP levels decreased in both the fenofibrate (p=0.003) and comparison (p=0.048) groups. Changes in CRP levels were not significantly different between the two groups (p=0.27) and were negatively associated with baseline CRP levels (r=-0.47, p or =1 mg/L, CRP levels also decreased in both groups (p=0.000 and p=0.001 respectively), however, more in the fenofibrate group than in the comparison group (p=0.025). The reduction of CRP was associated with higher baseline CRP levels (r=-0.29, p=0.001), lower body mass index (BMI, r=0.23, p=0.007), and fenofibrate therapy (r=0.19, p=0.025). CRP levels decreased more in the fenofibrate group than in the comparison group in patients with a BMI < or =26 kg/m2 with borderline significance (-1.21+/-1.82 mg/L vs. -0.89+/-1.92 mg/L, p=0.097). In patients with a high density lipoprotein-cholesterol level <40 mg/dL, CRP levels were reduced only in the fenofibrate group (p=0.006). CONCLUSION: Fenofibrate reduced CRP levels in hypertriglyceridemic patients with high CRP and/or low high density lipoprotein-cholesterol levels and without severe overweight. This finding suggests that fenofibrate may have an anti-inflammatory effect in selected patients.

Effects of the Transition from Premenopause to Postmenopause on Lipids and Lipoproteins: Quantification and Related Parameters

BACKGROUND/AIMS: The aim of this study was to quantitatively measure changes in lipids and lipoproteins during perimenopause and to identify variables related to these changes. METHODS: Among women who had three regular health evaluations over a span of 2-4 years, 34 women remained in the premenopausal state, 34 premenopausal women transitioned to the postmenopausal state, and 36 postmenopausal women were enrolled. The menopausal state was determined not only by a history of amenorrhea but also by levels of female sex hormones. Yearly changes in lipids were calculated using a linear regression of the three measurements. RESULTS: The transition from premenopause to postmenopause was associated with increased total cholesterol and low-density lipoprotein (LDL) cholesterol levels by 7.4 +/- 8.0 mg/dL (4.2 +/- 4.9%) and 6.9 +/- 6.5 mg/dL (6.8 +/- 7.0%) over one year, resulting in an elevation of 19.6 +/- 22.6 mg/dL (10.9 +/- 13.0%) and 18.9 +/- 19.5 mg/dL (18.6 +/- 20.3%), respectively, during perimenopause. There were no changes observed in premenopausal and postmenopausal women. Body weight, blood pressure, high-density lipoprotein (HDL) cholesterol, and triglycerides did not change in any of the three groups. In all women, changes in both total cholesterol and LDL cholesterol were associated with changes in follicle stimulating hormone (r = 0.40, p < 0.001 and r = 0.38, p < 0.001, respectively). Changes in triglycerides were associated with changes in body weight (r = 0.28, p = 0.005). CONCLUSIONS: During perimenopause, total and LDL cholesterol levels increase and these changes in cholesterol are mainly dependent on changes in female sex hormones.

Effects of Ezetimibe Added to Ongoing Statin Therapy on C-Reactive Protein Levels in Hypercholesterolemic Patients

BACKGROUND AND OBJECTIVES: Ezetimibe alone does not decrease C-reactive protein (CRP) levels in hypercholesterolemic patients. However, several reports have suggested that ezetimibe might potentiate the effect of statin not only on cholesterol but also on CRP when administered together. We investigated the effect of ezetimibe on CRP levels in patients taking statins. SUBJECTS AND METHODS: Patients who had not achieved recommended low density lipoprotein-cholesterol (LDL-C) goals with statin therapy were divided into two groups, the ezetimibe group (n=60) and the control group (n=60). A third group of hypercholesterolemic patients without statin therapy was treated with statin (n=59). Patients with CRP level 10 mg/L were excluded. Lipid and CRP levels were measured before therapy commenced, and after 2 months of therapy. RESULTS: Ezetimibe decreased cholesterol and LDL-C levels by 20.2% (p=0.000) and 28.1% (p=0.000) respectively. However, ezetimibe did not reduce CRP levels (from 0.83+/-0.68 to 1.14+/-1.21 mg/dL, p=0.11). CRP levels remained unchanged in the control group (p=0.42). In contrast, statin lowered CRP levels (from 0.82+/-0.73 to 0.65+/-0.57 mg/dL, p=0.008). In patients taking statins, changes in CRP levels were not associated with changes in LDL-C (r=-0.02, p=0.87), but with baseline CRP levels (r=-0.38, p=0.000). CONCLUSION: Ezetimibe failed to reduce CRP levels in hypercholesterolemic patients taking statins despite significant reduction of LDL-C. This finding suggests that the anti-inflammatory effect of statin may not be secondary to cholesterol reduction, but via other mechanisms.

The Frequency of BRAF Mutation in Very Small Papillary Thyroid Carcinomas

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid and BRAF (V600E) is the most frequent genetic alteration in PTCs. The aim of this study was to investigate the frequency of BRAF mutation, especially in very small PTCs. METHODS: We analyzed the presence of the BRAF mutation in PTCs in subgroups defined by tumor size (0.5 cm intervals). RESULTS: Of 140 patients, 85 (60.7%) showed a BRAF mutation. The frequency of BRAF mutation in the subgroup was: 45/70 (64.3%) in tumors less than 0.5 cm in size, 18/28 (64.3%) in 0.6-1 cm tumors, 10/22 (45.5%) in 1.1-1.5 cm tumors, and 12/20 (60.0%) in 1.6-2 cm tumors. There was no statistically significant association between BRAF mutation and tumor size (p = 0.44). Similarly, BRAF mutation was not statistically related to age, sex, stage, perithyroidal extension or lymph node metastasis. On multivariate logistic regression analysis, tumor sizes larger than 0.5 cm were associated with lymph node metastasis (odds ratio, 3.79; 95% confidence interval, 1.81 to 7.91; p < 0.01). CONCLUSIONS: The BRAF mutation is not related to tumor size even in very small PTCs. The similar frequency of BRAF mutation in very small PTCs suggests that the BRAF mutation is a very early event in the tumorigenesis of PTCs.

The Impact of Mitral Annular Calcification on Left Ventricular Function in Nonagenarians

BACKGROUND AND OBJECTIVES: Mitral annular calcification (MAC) is known to be associated with degenerative processes of the cardiac fibrous skeleton and cardiovascular disease mortality. However, MAC has not been evaluated in an extreme age group (patients > or =90 years of age). In this study, the clinical significance of MAC associated with aging was examined in this age group and compared with MAC associated with aging in a younger (20 to 50 years of age) group of patients. SUBJECTS AND METHODS: We assessed echocardiographic parameters in 43 nonagenarians and 51 young patients. In the nonagenarian group, patient's age was 92+/-2 years and 27% were male; in the young control group, patient's age was 36+/-9 years and 51% were male. Comprehensive M-mode and Doppler echocardiography, including tissue Doppler imaging, were performed. The frequency and severity of MAC was assessed from the leading anterior to the trailing posterior edge at its largest width for least 3 cardiac cycles. RESULTS: Echocardiography showed that the left ventricular (LV) end-diastolic dimension was larger in the young controls (p=0.007); however, the ejection fraction (EF) was lower in the nonagenarian group (p=0.001). The frequency of MAC was greater in nonagenarians {42/43 (97%)} than in controls {9/51 (17%), p<0.0001}. The maximal width of MAC was larger in nonagenarians (0.52+/-0.17 mm and 0.05+/-0.13 mm, p<0.0001). MAC was correlated with LV mass index (g/m2) (r=0.280, p=0.014) and EF (%) (r=-0.340, p=0.001). More importantly, early mitral inflow velocity/early diastolic mitral annulus velocity (E/E') was strongly correlated with MAC in non-agenarians (r= 0.683, p<0.0001). CONCLUSION: MAC may be associated with extreme age and increased LV filling pressure in nonagenarians. Further study is necessary to assess the cardiovascular mortality and structural changes related to mitral annulus calcification associated with aging.