Impact of left atrial appendage closure on cardiac functional and structural remodeling: A difference-in-difference analysis of propensity score matched samples.

BACKGROUND: Although the safety and efficacy of left atrial (LA) appendage (LAA) closure (LAAC) in nonvalvular atrial fibrillation (NVAF) patients have been well documented in randomized controlled trials and real-world experience, there are limited data in the literature about the impact of LAAC on cardiac remodeling. The aim of the study was to examine the impact of LAAC on cardiac functional and structural remodeling in NVAF patients. METHODS: Between March 2014 and November 2016, 47 NVAF patients who underwent LAAC were included in this study (LAAC group). A control group (non-LAAC group) was formed from 141 NVAF patients without LAAC using propensity score matching. The difference-in-difference analysis was used to evaluate the difference in cardiac remodeling between the two groups at baseline and follow-up evaluations. RESULTS: The LAAC group had a larger increase in LA dimension, volume and volume index than the non-LAAC group (+3.9 mm, p = 0.001; +9.7 mL, p = 0.006 and +5.9 mL/m2, p = 0.011, respectively). Besides, a significant increase in E and E/e' ratio was also observed in the LAAC group (+14.6 cm/s, p = 0.002 and +2.3, p = 0.028, respectively). Compared with the non-LAAC group, left ventricular (LV) ejection fraction and fractional shortening decreased in LAAC patients, but were statistically insignificant (-3.5%, p = 0.109 and -2.0%, p = 0.167, respectively). CONCLUSIONS: There were significant increases in LA size and LV filling pressure among NVAF patients after LAAC. These impacts of LAAC on cardiac functional and structural remodeling may have some clinical implications that need to be addressed in future studies.

Morphological characteristics of optical coherence tomography defined plaque fissure in patients with acute coronary syndrome.

We assessed the plaque disruption in 245 consecutive patients with acute coronary syndrome undergoing percutaneous coronary intervention. The plaque fissure was diagnosed with optical coherence tomography, and intravascular ultrasound was used to determine arterial remodeling. Of them, 26 fissures were found in this study. The definite fissure was seen in 17 (65.4%) and probable fissure was seen in 9 (34.6%) patients. In 18 (69.2%), plaque fissure component was lipidic or thin-capped fibroatheroma. Eighteen (69.2%) of fissured plaque were seen within 30 mm of coronary ostium. Combined plaque fissure with plaque rupture/erosion was seen in 21 (80.8%) cases. The isolated fissure was seen in 5 (19.2%). Compared to the maximal necrotic core site of the ruptured plaque, the fissure site showed a smaller %necrotic core (p = 0.012), however, greater in fissure site than minimal lumen area site (24.93 ± 11.50% vs 15.34 ± 10.40%, p < 0.0001). The remodeling index was higher at fissure site as compared to minimal lumen area site (1.02 ± 0.22 vs 0.94 ± 0.27; p = 0.047), but similar to the rupture plaque (p = 0.31). The frequency of positive remodeling was 34.6% (9/26) at the plaque fissure. Although the plaque fissure can be interchangeable with the rupture in acute coronary syndrome, the limited extension to the small lipid core might and less positive remodeling provoke a fissuring of the plaque. Further study is necessary to assess the plaque fissure.

Plaque Vulnerability as Assessed by Radiofrequency Intravascular Ultrasound in Patients with Valvular Calcification.

BACKGROUND: Cardiac valvular calcification is associated with the overall coronary plaque burden and considered an independent cardiovascular risk and prognostic factor. The purpose of this study was to evaluate the relationship between the presence of valvular calcification and plaque morphology and/or vulnerability. METHODS: Transthoracic echocardiography was used to assess valvular calcification in 280 patients with coronary artery disease who underwent radiofrequency intravascular ultrasound (Virtual Histology IVUS, VH-IVUS). A propensity score-matched cohort of 192 patients (n = 96 in each group) was analyzed. Thin-capped fibroatheroma (TCFA) was defined as a necrotic core (NC) >10% of the plaque area with a plaque burden >40% and NC in contact with the lumen for ≥3 image slices. A remodeling index (lesion/reference vessel area) >1.05 was considered to be positive. RESULTS: Patients were divided into two groups: any calcification in at least one valve (152 patients) vs. no detectable valvular calcification (128 patients). Groups were similar in terms of age, risk factors, clinical diagnosis, and angiographic analysis after propensity score-matched analysis. Gray-scale IVUS analysis showed that the vessel size, plaque burden, minimal lumen area, and remodeling index were similar. By VH-IVUS, % NC and % dense calcium (DC) were greater in patients with valvular calcification (p = 0.024, and p = 0.016, respectively). However, only % DC was higher at the maximal NC site by propensity score-matched analysis (p = 0.029). The frequency of VH-TCFA occurrence was higher depending on the complexity (p = 0.0064) and severity (p = 0.013) of valvular calcification. CONCLUSIONS: There is a significant relationship between valvular calcifications and VH-IVUS assessment of TCFAs. Valvular calcification indicates a greater atherosclerosis disease complexity (increased calcification of the coronary plaque) and vulnerable coronary plaques (higher incidence of VH-TCFA).

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.

Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart.

AIMS: Left atrial (LA) fibrosis caused by various pathological stimuli is a common finding. However, the difference of atrial remodelling via haemodynamic change in diverse cardiomyopathy has not been elucidated. METHODS AND RESULTS: Male Sprague-Dawley rats (6-8 weeks, n = 180) were randomly assigned to three groups and corresponding sham control groups: (i) ischaemic cardiomyopathy, (ii) left ventricular hypertrophy (LVH), and (iii) dilated cardiomyopathy. At 12 weeks after operation, atrial fibrillation (AF) inducibility and duration were assessed by in vivo burst transoesophageal pacing. Using the Langendorff apparatus, left ventricular (LV) function and pressure were measured. The expression of connexin-43 (Cx43) and alpha-smooth muscle actin (α-SMA) in atrial tissues was assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining. Fibrosis was analysed by Masson's trichrome staining. Compared with controls, the LA weight/heart weight ratio was increased in the LVH group alone, and was significantly correlated with AF duration (P < 0.001, R = 0.388). Atrial fibrillation inducibility and duration were higher and longer only in the LVH group (P = 0.002, 0.079, respectively), and isolated LV diastolic dysfunction and elevated LV pressure were observed. Although α-SMA expression and fibrosis were increased in all three cardiomyopathy models, down-regulation of Cx43 expression in the LA was observed in the LVH group alone. CONCLUSION: Chronic pressure overload in the absence of LV systolic dysfunction resulted in LA hypertrophy and increased susceptibility to AF, which might be related to conduction abnormality via decreased expression and lateral distribution of Cx43 as well as interstitial fibrosis.

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.

Frequency and evolution of thin-capped fibroatheromas in left main coronary artery as assessed by serial virtual histology intravascular ultrasound analysis.

BACKGROUND: The objective of the current study was to assess thin-capped fibroatheroma (TCFA) of the left main coronary artery (LMCA) and its changes after statin therapy. METHODS: We assessed the frequency and distribution of virtual histology intravascular ultrasound (VH-IVUS) thin-capped fibroatheroma (VH-TCFA) in the LMCA in 500 patients. Serial VH-IVUS examinations were available in 50 patients at 12-month follow-up. RESULTS: The incidence of LM-TCFA was 8.8% (44/500). IVUS LMCA length was longer in patients with VH-TCFA vs without VH-TCFA. Reference external elastic membrane (EEM) area was similar, but reference lumen area and minimal lumen area were smaller in LMCA with VH-TCFA vs without VH-TCFA (P<.001). LMCA with VH-TCFA had a higher plaque burden (P<.001), a larger necrotic core area (P<.001), and more dense calcium (P<.001) at the maximum necrotic core (NC) site vs LMCA without VH-TCFA. In patients with an LMCA length greater than the median, 62% were located in the distal half of the LMCA. After 12 months of statin therapy, only 44.4% (4/9) of VH-TCFA had evolved to a non- VH-TCFA phenotype and 3 new VH-TCFA had appeared. CONCLUSION: VH-TCFAs are clustered in the distal half of the LMCA with infrequent positive remodeling. It might persist despite the usual dose of statin therapy. Further study should confirm the changes in large vessels like the LMCA.

DICOM-based intravascular ultrasound signal intensity analysis: an Echoplaque Medical Imaging Bench study.

BACKGROUND: Most intravascular ultrasound (IVUS) data are stored digitally using the Digital Imaging and Communications in Medicine (DICOM) standard. This allows random access to studies and improves on the major limitation of conventional grayscale IVUS. METHODS: We harvested 129 coronary arteries from 43 autopsied cases. Grayscale IVUS and virtual histology-IVUS imaging were performed beginning 30 mm distal to the ostium of each coronary artery. Grayscale IVUS was processed; and the signal intensity was determined from DICOM-stored images using a new Medical Imaging Bench system (Echoplaque-MIB). We compared 436 regions of interest. The accuracy rate was expressed using the interpolation method and 95% confidence interval (CI). RESULTS: Patients' mean age was 49±9 years and 82% were men. Four patients succumbed to sudden cardiac death and 39 to noncardiac death. Grayscale IVUS signal intensity of dense calcium was 215±21.1 (95% CI: 207-223), that of fibrotic plaque was 75±17.8 (95% CI: 72-79), and that of fibrofatty plaque was 55±11.3 (95% CI: 52-59); however, the signal intensity of the necrotic core was between fibrotic plaque and dense calcium of 161±27.4 (95% CI: 153-168). Using the interpolation method, the cutoff values were as follows: fibrofatty plaque 0-65, fibrotic plaque 66-105, necrotic core 106-187, and dense calcium of at least 188. Overall, MIB grayscale had a 78.1% sensitivity and a 91.9% specificity versus histopathology. CONCLUSION: Plaque characterization using DICOM-based grayscale IVUS signal intensity analysis may improve on the major limitation of conventional grayscale IVUS: its inability to assess plaque composition.

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<0.001). In patients with a baseline CRP level ≥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 ≤26 kg/m(2) 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.

Relation Between RR Intervals and Early Diastolic Mitral Annular Velocities in Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Irregular RR intervals in atrial fibrillation (AF) make beat-to-beat changes in left ventricular (LV) systolic performance. Early diastolic mitral annular velocity (E') is one of the well-established parameters for evaluating LV diastolic function. The relation between RR intervals and E's is unknown. The aim of this study was to observe the influence of continuous changes in RR interval on the parameter for diastolic function in AF. SUBJECTS AND METHODS: Echocardiography was performed in 117 patients with AF. E' was adjusted for the effect of pre-preceding RR interval (RR-2) using the logarithmic equation between RR-2 and E'. The logarithmic equation between adjusted E' and preceding RR interval (RR-1) was calculated. RESULTS: The slope in the relation between RR-1 and E' varied from -2.5 to 2.6. The slope was lower (more likely negative) in patients with higher ratio of early diastolic mitral flow velocity (E) to E' (r=-0.21, p=0.023), ischemic heart disease (IHD, r=0.21, p=0.026), and higher systolic blood pressure (r=-0.19, p=0.046). When patients were divided into these 3 groups on the basis of slope, the lowest slope group (<-0.55, n=39) was associated with higher E'/E (p=0.004) and IHD (p=0.018) compared with the highest slope group (>0.57, n=39). The slope with regards to the relationship between RR-2 and E' also varied from -3.4 to 3.1. CONCLUSION: Changes in RR intervals had variable effects on E's according to clinical variables in AF.

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.

Relationship between coronary artery plaque composition by virtual histology intravascular ultrasound analysis and brachial-ankle pulse wave velocity in patients with coronary artery disease.

OBJECTIVE: Brachial-ankle pulse wave velocity (baPWV) is an indicator of atherosclerotic cardiovascular risks. To identify patients with coronary atherosclerosis before the onset of angina pectoris or myocardial infarction will be desirable. METHODS: We measured the ankle-brachial index and baPWV in 150 consecutive patients with coronary artery disease (CAD). Virtual histology intravascular ultrasound (VH-IVUS) imaging was available in target lesions of 130 patients with symptomatic CAD before percutaneous intervention. Patients were divided into two groups: baPWV of greater than or equal to 1600 cm/s (74 patients) and baPWV of less than 1600 cm/s (56 patients). RESULTS: Patient age was 66±8.33 years in baPWV of greater than or equal to 1600 cm/s group versus 56±10.27 years in baPWV of less than 1600 cm/s group (P<0.0001). Although plaque burden and remodeling index were similar, minimal lumen area was smaller in baPWV of greater than or equal to 1600 cm/s group (P=0.039); and lesion length was longer in the baPWV of greater than or equal to 1600 cm/s group (P=0.033). VH-IVUS analysis of coronary artery plaque composition showed that percent mean and percent maximum dense calcium were higher in the baPWV of greater than or equal to 1600 cm/s group (P=0.0037), and percent maximal calcium correlated with baPWV (r=0.278, P=0.001). CONCLUSION: We concluded that there is a significant relationship between baPWV and the VH-IVUS assessment of CAD. A high baPWV indicates more severe CAD (smaller minimal lumen area and longer lesion length) and greater atherosclerosis disease complexity (more calcified coronary plaque).

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.

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.

Disappearance of angina pectoris by lipid-lowering in type III hyperlipoproteinemia.

Type III hyperlipoproteinemia is a rare familial disease characterized by marked elevations of serum cholesterol and triglyceride levels caused by an accumulation of remnant lipoproteins in apolipoprotein E2/E2 homozygotes. It is associated with an increased risk for premature atherosclerotic vascular disease. A 55-year-old woman was diagnosed as having type III hyperlipoproteinemia on the basis of skin lesions, serum lipid levels, lipid electrophoresis, and apolipoprotein E genotyping and stable angina pectoris on the basis of typical symptoms and treadmill exercise electrocardiographic results. After 1 year of combination therapy with atorvastatin and fenofibrate, skin xanthomata disappeared, leaving minimal remnants. In addition, there was no exertional chest pain, and treadmill exercise electrocardiographic results were negative. This finding was confirmed by coronary computed tomographic angiography. This case suggests that proper medical therapy can induce the regression of uncomplicated coronary lesions in type III hyperlipoproteinemia.

The effect of aspirin on C-reactive protein in hypertensive patients.

High level of C-reactive protein (CRP), most popular inflammatory marker, increases the risk of thrombotic cardiovascular events. Aspirin, which has both anti-inflammatory and anti-thrombotic effects, has the potential to influence CRP release. Several studies have been reported investigating clinical effects of aspirin on CRP levels. Some studies have reported aspirin reduced CRP levels, but other studies did not. This study was designed to assess the effect of low-dose aspirin on CRP levels in controlled hypertensive patients who had low inflammatory burden. Two hundred twenty-five patients with controlled hypertension were randomly divided into two groups; aspirin group (n = 122, 100 mg of aspirin) and the control group (n = 134). Patients with a CRP level >1 mg/dL (10 mg/L) were excluded because these high levels suggest infection. C-reactive protein level and lipid profiles were measured before therapy and 3 months after therapy. There were no differences in baseline clinical characteristics between the two groups. Low-dose aspirin showed no significant influence on CRP levels over 3 months (from 0.10 ± 0.0099 to 0.12 ± 0.0097 mg/dL, p = 0.12). Statin therapy did not influence CRP levels. Aspirin-resistance also had no influence on CRP levels. We conclude that low-dose aspirin has no significant effect on decreasing CRP levels in the patients with controlled hypertension which had low inflammatory burden. The anti-inflammatory mechanism may not play an important role in the cardioprotective effect of aspirin in the population with low inflammatory burden such as controlled hypertensive patients.

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 >/=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/m(2)) (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.

Association of the parameters derived from the relation between RR intervals and left ventricle performance with a history of heart failure in patients with atrial fibrillation.

Parameters derived from the relation between RR intervals and left ventricular (LV) performance in atrial fibrillation (AF) have been useful to evaluate systolic LV function. This study investigated the association of these parameters with a history of heart failure. Echocardiography was performed in 107 patients with AF. LV outflow peak ejection velocity (Vpe) was adjusted for the effect of pre-preceding RR interval (RR-2) using the logarithmic equation between RR-2 and Vpe. The logarithmic equation between adjusted Vpe and preceding RR interval (RR-1) was calculated in the co-ordinates with RR-1 from 0.6 to 1 second. From this equation, the ratio of slope to Vpe at RR-1 = 1 second (slope/Vpe-1) was obtained. When patients were divided into 2 groups according to a history of heart failure, old age, high slope/Vpe-1, mitral regurgitation, and left atrial enlargement independently predicted the occurrence of heart failure. Fractional shortening was not different between the 2 groups. In patients with normal LV size and without significant regurgitation (n = 69), old age and high slope/Vpe-1 independently predicted the occurrence of heart failure. Areas under the receiver operating characteristics curve of slope/Vpe-1 for identifying heart failure were 0.72 (p <0.000) and 0.74 (p <0.001) in all patients and in patients with normal LV size, respectively. In conclusion, the new parameter, slope/Vpe-1, was one of the most useful predictors for the occurrence of heart failure in AF and was superior to the classic hemodynamic parameters. This parameter might be determined not only by systolic function but also by diastolic function of the left ventricle.

Atherosclerotic progression attenuates the expression of Nogo-B in autopsied coronary artery: pathology and virtual histology intravascular ultrasound analysis.

The relation of Nogo-B to atherosclerotic plaque progression is not well understood. Thus, the purpose of this study was to assess the expression of Nogo-B in fibroatheromas (FA) of different stages, classified using virtual histology intravascular ultrasound (VH-IVUS) analysis in 19 autopsied cases of non-sudden cardiac death. VH-IVUS imaging analysis was performed 30 mm from the ostium of each coronary artery. VH-IVUS revealed 11 early FAs (34.5+/-8.3 yr), 12 late FAs (42.6+/-16.6 yr), 8 thick-cap FAs (TkCFAs) (46.4+/-11.1 yr), and 6 thin-cap FAs (TCFAs) (51.8+/-6.8 yr). TkCFAs and TCFAs were defined as advanced FA. FA progression advanced with age (P=0.04). VH-IVUS analysis of small, early FAs showed smaller necrotic cores and relatively less calcium compared to more advanced FAs with large necrotic cores (P<0.001). Histopathology and immunohistochemical stains demonstrated that early or late FAs had smaller necrotic cores, less empty space of decalcification, and greater Nogo-B expression compared to advanced FAs (vs. early FA, P=0.013; vs. late FA, P=0.008, respectively). These findings suggest that FA progression is inversely associated with Nogo-B expression. Local reduction of Nogo-B may contribute to plaque formation and/or instability.

Comparison of the efficacy and tolerability of pitavastatin and atorvastatin: an 8-week, multicenter, randomized, open-label, dose-titration study in Korean patients with hypercholesterolemia.

BACKGROUND: Although previous studies have examined the efficacy of pitavastatin, its tolerability and effects on lipid concentrations have not been compared with those of atorvastatin in a multicenter, randomized study. OBJECTIVE: This trial compared the efficacy and tolerability of pitavastatin and atorvastatin in hypercholesterolemic Korean adults. METHODS: This 8-week, multicenter, randomized, open-label, dose-titration study was conducted at 18 clinical centers in Korea between May 2005 and February 2006. After a 4-week dietary lead-in period, patients with hypercholesterolemia were randomized to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d. Patients who had not reached the low-density lipoprotein cholesterol (LDL-C) goal by week 4 received a double dose of the assigned medication for an additional 4 weeks. Efficacy was evaluated in terms of achievement of the National Cholesterol Education Program Adult Treatment Panel III LDL-C goals and changes from baseline in other lipids and high-sensitivity C-reactive protein (hs-CRP). The tolerability profile was assessed by physical and electro-cardiographic examinations, laboratory tests, and recording adverse reactions at all visits. RESULTS: A total of 268 patients were randomized to treatment, and 222 (82.8%) completed the study (149 women, 73 men; mean age, 59 years; mean weight, 63.5 kg). At the end of the study, there was no significant difference between the pitavastatin and atorvastatin groups in the proportion of patients achieving the LDL-C goal (92.7% [102/110] vs 92.0% [103/112], respectively). In addition, there were no significant differences between groups in terms of the percent changes from baseline in LDL-C, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), or hs-CRP. Twenty-six of 136 patients (19.1%) taking pitavastatin reported 35 treatment-emergent adverse reactions; 33 of 132 patients (25.0%) taking atorvastatin reported 39 treatment-emergent adverse reactions. Elevations in creatine kinase were observed in 6 patients (4.4%) in the pitavastatin group and 7 patients (5.3%) in the atorvastatin group. There were no serious adverse drug reactions in either group. CONCLUSIONS: In these adult Korean patients with hypercholesterolemia, pitavastatin and atorvastatin did not differ significantly in terms of the proportions of patients achieving the LDL-C goal; reductions in LDL-C, total cholesterol, and triglycerides; or increases in HDL-C. Both drugs were well tolerated.