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.

Prevalence of the CTNNB1 mutation genotype in surgically resected fibromatosis of the breast.

AIMS: To investigate CTNNB1 mutation and ß-catenin expression in resected breast fibromatosis and to identify potential molecular markers of fibromatosis of the breast. METHODS AND RESULTS: We selected 12 patients with fibromatosis of the breast who underwent surgical resection and were confirmed by histological examination. Ultrasonography findings for 10 patients were reviewed and only two cases were suspicious for fibromatosis on imaging. On core needle biopsy for pre-operative diagnoses, only three cases were histologically suspicious for fibromatosis. Mutations in exon 3 of CTNNB1 were detected by direct DNA sequencing in nine (75.0%) cases: all were c.121G>A (p.T41A), which was much more frequent in breast fibromatoses than in other soft tissue lesions. Nuclear ß-catenin expression was observed in all cases and the level of expression was higher in cases with mutation. In eight of nine cases, the matched biopsy specimen showed the same CTNNB1 mutation status as the pre-operative specimen. CONCLUSIONS: In the majority of cases, clinical presentation and breast imaging are highly suspicious for carcinoma. Definitive pre-operative pathological diagnosis by core needle biopsy is difficult. CTNNB1 mutation and nuclear ß-catenin expression are frequently detected in sporadic breast fibromatoses, suggesting their potential as a useful tool to distinguish breast fibromatoses from other neoplasms.

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.

Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation in active adult-onset Still's disease.

INTRODUCTION: C-X-C motif chemokine 10 (CXCL10) is produced in response to interferon-γ, and tumor necrosis factor-α (TNF-α) triggers the accumulation of activated lymphocytes. CXCL13 is constitutively expressed in secondary lymphoid tissues, and the expression is upregulated by TNF-α, via T cell stimulation. It appears that CXCL10 and CXCL13 could play a potential role in the pathogenesis of adult-onset Still's disease (AOSD), therefore, we investigated the associations between CXCL10 and CXCL13 levels and clinical manifestations in patients with active AOSD. METHODS: Blood samples were collected from 39 active AOSD patients, 32 rheumatoid arthritis (RA) patients and 40 healthy controls (HC). Of the AOSD patients, follow-up samples were collected from 15 9.6 ± 9.2 months later. Serum levels of CXCL10 and CXCL13 were determined using enzyme-linked immunosorbent assay. CXCL10, CXCL13, and C-X-C chemokine receptor type 3 (CXCR3) expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes were investigated via immunohistochemistry. RESULTS: The CXCL10 levels in AOSD patients (1,031.3 ± 2,019.6 pg/mL) were higher than in RA (146.3 ± 91.4 pg/mL, p = 0.008) and HC (104.4 ± 47.9 pg/mL, p = 0.006). Also, the CXCL13 levels of AOSD patients (158.8 ± 151.2 pg/mL) were higher than those of RA (54.4 ± 61.1 pg/mL, p < 0.001) and HC (23.5 ± 18.1 pg/mL, p < 0.001). Serum CXCL10 levels correlated with ferritin and systemic scores. Serum CXCL13 levels correlated with those of hemoglobin, C-reactive protein, ferritin, and albumin, and systemic scores. In follow-up AOSD patients, the levels of CXCL10 and CXCL13 fell significantly (153.7 ± 130.1 pg/mL, p = 0.002, and 89.1 ± 117.4 pg/mL, p = 0.001, respectively). On immunohistochemistry, the percentages of inflammatory cells expressing CXCL10 ranged from 1 to 85%, CXCL13 from 1 to 72%, and CXCR3 from 2 to 65%. The percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples exhibiting mucin deposition than in those that did not (p = 0.01). CXCL13 levels were correlated with those of CD4 and CD68. CONCLUSIONS: Serum CXCL10 and CXCL13 levels may serve as clinical markers for assessment of disease activity in AOSD. CXCL10/CXCR3 and CXCL13 may contribute to the inflammatory response, especially skin manifestations thereof, in AOSD.

The pathologic findings of skin, lymph node, liver, and bone marrow in patients with adult-onset still disease: a comprehensive analysis of 40 cases.

Adult-onset Still disease (AOSD) is characterized by fever, skin rash, and lymphadenopathy with leukocytosis and anemia as common laboratory findings. We investigated the characteristic pathologic findings of skin, lymph node, liver, and bone marrow to assist in proper diagnosis of AOSD.Forty AOSD patients were included in the study. The skin (26 patients), lymph node (8 patients), liver (8 patients), or bone marrow biopsies (22 patients) between 1998 and 2013 were retrospectively analyzed. AOSD patients were diagnosed according to the Yamaguchi criteria after excluding common infections, hematological and autoimmune diseases. Immunohistochemistry, immunofluorescence, and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization were performed.Most skin biopsies revealed mild lymphocytic or histiocytic infiltration in the upper dermis. Nuclear debris was frequently found in the dermis in 14 cases (53.8%). More than half of the cases (n = 14, 53.8%) showed interstitial mucin deposition. Some cases showed interface dermatitis with keratinocyte necrosis or basal vacuolization (n = 10; 38.5%). The lymph node biopsies showed a paracortical or diffuse hyperplasia pattern with immunoblastic and vascular proliferation. The liver biopsies showed sparse portal and sinusoidal inflammatory cell infiltration. All cases showed various degrees of Kupffer cell hyperplasia. The cellularity of bone marrow varied from 20% to 80%. Myeloid cell hyperplasia was found in 14 out of the 22 cases (63.6%). On immunohistochemistry, the number of CD8-positive lymphocytes was greater than that of CD4-positive lymphocytes in the skin, liver, and bone marrow, but the number of CD4-positive lymphocytes was greater than that of CD8-positive lymphocytes in the lymph nodes.The relatively specific findings with respect to the cutaneous manifestation of AOSD were mild inflammatory cell infiltration in the upper dermis, basal vacuolization, keratinocyte necrosis, presence of karyorrhexis, and mucin in the dermis. In all cases, pathologic findings in the lymph nodes included paracortical hyperplasia with vascular and immunoblastic proliferation. Skin and lymph node pathology in addition to clinical findings can aid in the diagnosis of AOSD.

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.

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.

Oncologic manifestations of neurofibromatosis type 1 in Korea.

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.

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.

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.

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.

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.

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).

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.