Relationship of warfarin versus DOACs with thrombogenic milieu in the left atrium among patients with nonvalvular atrial fibrillation.

BACKGROUND: Thrombogenic milieu (TM) within the left atrium plays a pivotal role in the pathogenesis of thromboembolic events, for which anticoagulation treatment is indicated typically on the mandatory basis. Little is known, however, about which regimen of anticoagulation, warfarin or direct oral anticoagulants (DOACs), is more likely associated with TM. We evaluated relative relationship of the two treatment options with concurrently-observed TM in patients with nonvalvular atrial fibrillation (AF) who underwent transesophageal echocardiography. METHODS: TM was defined as the presence of either left atrial spontaneous echo contrast (SEC) or thrombus, or both. To determine which regimen was more likely related to TM, we firstly compared the prevalence of TM in 208 patients taking warfarin (Warfarin group) versus 486 patients taking DOACs (DOAC group); and secondly, did the same analysis after propensity score matching. RESULTS: Warfarin group was more likely associated with TM compared with DOAC group (46% vs 29%, p < 0.001). Similar findings were observed for dense SEC (18% vs 7%, p < 0.001) and thrombus (4% vs 1%, p = 0.057). The propensity score matching (198 patients for each group), where several baseline parameters were matched including age, gender, chronicity of AF, estimated glomerular filtration rate and B-type natriuretic peptide as well as the left ventricular ejection fraction, resulted in similar findings to the original groups (TM, 47% vs 32%, p = 0.002; dense SEC, 18% vs 7%, p = 0.001; thrombus, 4% vs 1%, p = 0.047). CONCLUSIONS: This study may strengthen the data on randomized trials that DOACs are superior to warfarin in preventing thromboembolic events in nonvalvular AF patients. Further studies are required to elucidate the details behind this difference.

Left atrial spontaneous echo contrast occurring in patients with low CHADS2 or CHA2DS2-VASc scores.

BACKGROUND: Left atrial spontaneous echo contrast (LASEC) is common in patients with atrial fibrillation (AF), although scarce information exists on LASEC occurring in nonvalvular AF patients who have low thromboembolic risk scores. We therefore examined prevalence and determinants of LASEC under low CHADS2 or CHA2DS2-VASc scores in these patients. METHODS: Among 713 patients who underwent transesophageal echocardiography, 349 with a CHADS2 score < 2 (CHADS2 group) (93 women, mean age 65 years) and 221 with a CHA2DS2-VASc score < 2 (CHA2DS2-VASc group) (39 women, mean age 62 years) were separately examined for clinical and echocardiographic findings. RESULTS: LASEC was found in 77 patients of CHADS2 group (22%) and in 41 of CHA2DS2-VASc group (19%). Multivariate logistic regression analysis, adjusted for several parameters including non-paroxysmal AF, LA enlargement (LA diameter ≥ 50 mm), left ventricular (LV) hypertrophy, and an elevated B-type natriuretic peptide (BNP) (BNP ≥200 pg/mL) revealed that for CHADS2 group, non-paroxysmal AF (Odds ratio 5.65, 95%CI 3.08-10.5, P < 0.001), BNP elevation (Odds ratio 3.42, 95%CI 1.29-9.06, P = 0.013), and LV hypertrophy (Odds ratio 2.26, 95%CI 1.19-4.28, P = 0.013) were significant independent determinants of LASEC, and that for CHA2DS2-VASc group, non-paroxysmal AF (Odds ratio 3.38, 95%CI 1.51-7.54, P = 0.003) and LV hypertrophy (Odds ratio 2.53, 95%CI 1.13-5.70, P = 0.025) were significant independent determinants of LASEC. CONCLUSIONS: LASEC was present in a considerable proportion of patients with nonvalvular AF under low thromboembolic risk scores. Information on AF chronicity, BNP, and LV hypertrophy might help identify patients at risk for thromboembolism, although large-scale studies are necessary to confirm our observations.

Usefulness of tissue Doppler-derived atrial electromechanical delay for identifying patients with paroxysmal atrial fibrillation.

BACKGROUND: Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD) has been reported to be useful for detecting paroxysmal atrial fibrillation (PAF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with PAF. METHODS: We retrospectively analyzed TDI recordings to obtain AEMD in 63 PAF patients. Thirty-three patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 50 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A' for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus. RESULTS: There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 9 mL/m2 vs. 27 ± 5 mL/m2). PAF patients had longer AEMD, particularly for the lateral EMD (75 ± 23 ms), compared with disease (62 ± 22 ms, P = 0.009) and healthy (54 ± 24 ms, P < 0.001) controls. Multivariate logistic regression analysis revealed that the lateral EMD (OR 1.25, 95%CI 1.03-1.52, P = 0.023), along with the left atrial volume index (OR 2.25, 95%CI 1.44-3.51, P < 0.001), was one of the significant independent associates of identifying PAF patients. CONCLUSIONS: This cross-sectional study indicates that even analyzed together with MRFs patients, AEMD remains useful for identifying patients at risk for AF. Our results need to be confirmed by a large-scale prospective study.

Atrial Arrhythmias and Atrial Involvement in Cardiac Sarcoidosis.

Severe ventricular arrhythmias such as high-grade atrioventricular block and ventricular tachycardia may cause lethal conditions or sudden death in patients with cardiac sarcoidosis (CS). Physicians should examine patients carefully for these conditions and treat them appropriately. As arrhythmias are being better diagnosed and treated, physicians are increasingly aware of atrial arrhythmias, which have not been focused upon as CS-related conditions, in patients with CS. This article reports a case of atrial flutter in sarcoidosis, and discusses literature findings on atrial arrhythmias and atrial involvement of CS. It is highly likely that atrial arrhythmia and supraventricular conduction disorder associated with or caused by CS are more common than previously thought. Physicians should pay careful attention for these conditions in the diagnosis and treatment of CS.

A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis.

Immunoglobulin G4 (IgG4)-related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum IgG4 levels and histological findings of IgG4-positive plasmacytic infiltration. IgG4-related disease may appear synchronously or metachronously in a wide variety of organs. The current patient was found to have pericardial effusion and retroperitoneal fibrosis. He was subsequently diagnosed with coronary artery stenosis. (18)F-FDG positron emission tomography showed enhanced FDG uptake in lymph nodes as well as pericardial and peri-aortic tissue. Histopathology of the mediastinal lymph node showed the infiltration of numerous IgG4-positive cells, leading to the diagnosis of IgG4-related lymphadenopathy with pericardial and periarterial involvement.

Circulating Fibroblast Growth Factor 23 Has a U-Shaped Association With Atrial Fibrillation Prevalence.

BACKGROUND: Atrial fibrillation (AF) occurs more frequently among patients with renal dysfunction. We investigated the possible association between prevalence of AF and serum fibroblast growth factor 23 (FGF23), which has been shown to be increased in subjects with renal dysfunction. METHODS AND RESULTS: Among the total enrollment of 851 cardiac patients, 188 patients had AF (paroxysmal AF, 95; non-paroxysmal AF, 93). Prevalence of AF for FGF23 octile had a U-shaped relationship with the lowest prevalence at the fifth octile. On logistic regression analysis, when the third FGF23 quartile was used as the reference, the first and fourth FGF23 quartiles were associated with prevalence of AF with an odds ratio (OR) of 3.34 (95% confidence interval [CI]: 1.89-5.88) and 2.58 (95% CI: 1.45-4.58), respectively, after adjusting for confounding factors including estimated glomerular filtration rate (eGFR). Among the subgroup of 416 patients for whom serum parathyroid hormone and 25-hydroxy vitamin D data were available, OR of the first and the fourth FGF23 quartile were calculated to be 3.52 and 2.97, respectively, when further adjusted for these two variables in the statistical model. CONCLUSIONS: Serum FGF23 had a U-shaped relationship with prevalence of AF among Japanese cardiac patients, which was independent of other calcium/phosphate metabolism-related parameters and eGFR. Pathophysiology underlying the observed link, if at all, awaits further investigation.

Analysis of individual matrix particles in the Allende meteorite by high-resolution FIB-TOF-SIMS.

The matrix in the "Allende meteorite" was analyzed by high-spatial-resolution focused ion beam time-of-flight secondary ion mass spectrometry (FIB-TOF-SIMS), and consisted of fine grains with sizes of several micrometers. It is difficult to analyze the matrix particles individually. As FIB-TOF-SIMS has a high spatial resolution, it can analyze the matrix individually. In addition, if the sample can be smoothed, no other pretreatment is required. By this method, it was clarified that Al, Cr, etc., which were conventionally detected as trace components in mass spectra, existed as fine particles between the matrix particles, rather than as impurities within them. The Al-rich particles did not match the minerals already found in the Allende meteorite matrix. Although the identity of the aluminum-rich particles has not been clarified, the abundance and localization could be observed correctly. Al-rich particles are likely to be affected by metamorphism and have important information to clarify the metamorphism process.

Inhalation of hydrogen gas attenuates left ventricular remodeling induced by intermittent hypoxia in mice.

Sleep apnea syndrome increases the risk of cardiovascular morbidity and mortality. We previously reported that intermittent hypoxia increases superoxide production in a manner dependent on nicotinamide adenine dinucleotide phosphate and accelerates adverse left ventricular (LV) remodeling. Recent studies have suggested that hydrogen (H(2)) may have an antioxidant effect by reducing hydroxyl radicals. In this study, we investigated the effects of H(2) gas inhalation on lipid metabolism and LV remodeling induced by intermittent hypoxia in mice. Male C57BL/6J mice (n = 62) were exposed to intermittent hypoxia (repetitive cycle of 1-min periods of 5 and 21% oxygen for 8 h during daytime) for 7 days. H(2) gas (1.3 vol/100 vol) was given either at the time of reoxygenation, during hypoxic conditions, or throughout the experimental period. Mice kept under normoxic conditions served as controls (n = 13). Intermittent hypoxia significantly increased plasma levels of low- and very low-density cholesterol and the amount of 4-hydroxy-2-nonenal-modified protein adducts in the LV myocardium. It also upregulated mRNA expression of tissue necrosis factor-α, interleukin-6, and brain natriuretic peptide, increased production of superoxide, and induced cardiomyocyte hypertrophy, nuclear deformity, mitochondrial degeneration, and interstitial fibrosis. H(2) gas inhalation significantly suppressed these changes induced by intermittent hypoxia. In particular, H(2) gas inhaled at the timing of reoxygenation or throughout the experiment was effective in preventing dyslipidemia and suppressing superoxide production in the LV myocardium. These results suggest that inhalation of H(2) gas was effective for reducing oxidative stress and preventing LV remodeling induced by intermittent hypoxia relevant to sleep apnea.

Hypoplastic Left Atrial Appendage: A Case Report and Literature Review.

BACKGROUND The left atrial appendage (LAA) has considerable variations in its size, shape, and spatial relationship with other cardiac structures. Absence of the LAA is a congenital cardiac condition usually identified by an imaging modality intended for other purposes. Absence of the LAA has been described in a total of 19 case reports so far; however, no cases of "hypoplastic" LAA in a real sense have ever been reported. CASE REPORT We herein report a case of hypoplastic, but not truly absent, LAA in a 76-year-old man scheduled for catheter ablation against atrial flutter. Preprocedural transesophageal echocardiography (TEE) performed in this patient to exclude intracardiac thrombosis failed to detect the LAA, although Doppler color-flow mapping revealed a jet signal spewed out into the main LA around where the LAA would be located. The LAA was also not detectable by routinely developed tomographic images from computed tomography (CT) angiography. Eventually, however, the multiplanar reconstruction into 3-dimensional volume rendering via the CT angiography identified a very small LAA. Those findings by TEE and CT led to a diagnosis of hypoplastic LAA. CONCLUSIONS Hypoplastic LAA should be kept in mind when considering LAA interventions as well as anticoagulation treatment. Multiple imaging modalities are necessary to recognize morphological aberration of the LAA.

Effects of acarbose on the acceleration of postprandial hyperglycemia-induced pathological changes induced by intermittent hypoxia in lean mice.

Postprandial hyperglycemia (PPH) and intermittent hypoxia related to the sleep apnea syndrome are important predictors of cardiovascular disease. We investigated the effects of intermittent hypoxia on pathological changes in the left ventricular (LV) myocardium caused by PPH in lean mice and evaluated the influence of acarbose, an α-glucosidase inhibitor. Male C57BL/6J mice aged 8 weeks were exposed to intermittent hypoxia (8 h/day during the daytime) or kept under normoxia. PPH was induced by restriction of feeding to 1-h periods twice a day, with the restricted diet (RD) mice receiving either standard chow or chow containing 0.02% acarbose. Another group of mice were fed standard chow ad libitum (AL). Plasma glucose levels after food intake were significantly elevated in RD but not in AL mice, and glucose levels were suppressed by acarbose. Intermittent hypoxia exacerbated cardiomyocyte hypertrophy and interstitial fibrosis in the LV myocardium of RD mice. Superoxide production and expression of 4-hydroxy-2-nonenal in the LV myocardium with intermittent hypoxia were increased in RD mice, but not AL mice. In addition, expression of tumor necrosis factor α (TNF-α) mRNA was increased in hypoxic RD mice. Treatment with acarbose inhibited oxidative stress and TNF-α mRNA expression and preserved the histological architecture of the LV myocardium.

A Patient with Cardiac Sarcoidosis in Whom an Abnormal Myocardial Uptake of Fluorine-18 Fluorodeoxyglucose and Sustained Ventricular Tachycardia Recurred 3.5 Years after Discontinuing Oral Corticosteroid Therapy.

We herein report a woman diagnosed with cardiac sarcoidosis (CS) based on the presence of epithelioid granulomas in non-cardiac organs and clinical findings including sustained ventricular tachycardia (VT) and cardiac dysfunction. She stopped oral corticosteroid after 4 years of treatment, and an abnormal myocardial uptake of fluorine-18 fluorodeoxyglucose and sustained VT recurred 3.5 years later. There is no consensus concerning whether or not corticosteroid therapy should be discontinued in the treatment of CS. As a relapse of sarcoidosis-related inflammation may be associated with life-threatening arrhythmia, some patients should continue corticosteroid therapy, even at low doses.

Case of isolated cardiac sarcoidosis diagnosed by newly developed abnormal uptake during serial follow-up fluorine-18 fluorodeoxyglucose positron emission tomography.

Cardiac sarcoidosis (CS) causes lethal arrhythmia and heart failure and has a poor prognosis; therefore, early detection and early stage treatment are important. However, diagnosis of isolated CS may be difficult in some cases owing to the low sensitivity of myocardial biopsy. Herein, we describe the case of a patient with isolated CS, showing change from negative to positive fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) uptake results within 9 months. The patient showed rapid reduction in left ventricular systolic function with sustained ventricular tachycardia. The diagnosis of isolated CS is often under-recognized in clinical practice because it commonly requires the diagnosis of extracardiac disease in the absence of a positive endomyocardial biopsy. The Japanese Circulation Society recently published guidelines for CS diagnosis stating that isolated CS can be clinically diagnosed with positive 18 F-FDG PET or 67 Gallium result. In this case, serial follow-up 18 F-FDG PET was useful for diagnosing isolated CS.

Chronic Kidney Disease as a Possible Predictor of Left Atrial Thrombogenic Milieu Among Patients with Nonvalvular Atrial Fibrillation.

Patients with chronic kidney disease (CKD) experiencing atrial arrhythmia are hypothesized to have elevated CHADS2 and CHA2DS2-VASc scores, thereby predisposed to left atrial (LA) thrombus formation and subsequent thromboembolism. We examined possible association of LA thrombogenic milieu (TM) with CKD in patients with nonvalvular atrial fibrillation. A total of 581 patients (181 women; mean age, 67 years) who underwent transesophageal echocardiography were examined. Patients were divided into 4 groups based on the estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2): eGFR ≥90 (n = 29), 60≤ eGFR <90 (n = 329), 30≤ eGFR <60 (n = 209), and eGFR <30 (n = 14). TM was defined as the presence of LA thrombus, dense spontaneous echo contrast, or LA appendage velocity ≤25 cm/s. Of 581 patients, 147 (25%) had TM. The prevalence of TM increased with decreasing eGFR (4%, 18%, 36%, and 86% for each group, p <0.001). Similar trends were observed for some of the clinical and echocardiographic variables including CHA2DS2-VASc score and LA size. Multivariate logistic regression analysis revealed that every 10 ml/min/1.73 m2 decrement in eGFR was a significant independent correlate of TM (odds ratio 0.80, p = 0.005), along with nonparoxysmal atrial fibrillation (AF) (odds ratio 0.45, p = 0.004), higher CHA2DS2-VASc score (odds ratio 1.24, p = 0.012), every 5 ml/m2 increment in LA volume index (odds ratio 1.57, p <0.001), and every 10% decrement in left ventricular ejection fraction (odds ratio 0.51, p <0.001). In conclusion, CKD may be a significant risk factor for LA thrombus formation in patients with nonvalvular atrial fibrillation.

High serum bilirubin is associated with lower prevalence of peripheral arterial disease among cardiac patients.

Several studies have shown that subjects with higher serum bilirubin may have a lower risk of cardiovascular disorders. We herein investigated whether serum bilirubin concentration is associated with lower extremity ischemia among cardiology patients. In total, 935 patients without a history of angioplasty or bypass surgery of the lower limb arteries and who had bilateral ankle-brachial index measurements were included in the study. Peripheral arterial disease (PAD) was defined to be present when ABI of either or both sides was <0.9. Overall, the serum total bilirubin concentration ranged between 0.1 and 2.7mg/dL (normal range, 0.1-1.0mg/dL). Across the bilirubin tertiles, age did not differ significantly. On the other hand, male patients (median 0.6mg/dL, interquartile range (IQR) 0.4-0.7mg/dL) had significantly higher bilirubin levels than female patients (median 0.5mg/dL, IQR 0.4-0.7mg/dL, P=0.014). Logistic regression analysis showed that, as compared with the lowest bilirubin tertile (0.1-0.4mg/dL), the highest tertile (0.7-2.7mg/dL) was significantly negatively associated with prevalent PAD after adjusting for sex, age, eGFR, white blood cell count, inorganic phosphate, HbA1C, total and HDL cholesterol, triglycerides, current smoking, diabetic medication, and statin use. This association remained significant when only those with serum bilirubin in the normal range were included in the analysis. Among cardiology patients, serum bilirubin concentration was significantly negatively associated with prevalence of PAD. The underlying mechanism and therapeutic indications should be investigated in further investigations.

Association between serum soluble urokinase-type plasminogen activator receptor and atrial fibrillation.

BACKGROUND: Circulating soluble urokinase-type plasminogen activator receptor (suPAR), which can reflect immune activation and low-grade inflammation, may be a novel biomarker of cardiovascular disease. METHODS: We investigated the potential association between suPAR and the prevalence of atrial fibrillation (AF) by analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either permanent or persistent AF. RESULTS: Among 426 patients enrolled (mean age 71.4±9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm, PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR quartile (<1802 pg/mL; 3 (2.8%) of 107 patients). Logistic regression analysis showed that, as compared with the lowest suPAR quartile, the highest suPAR quartile was associated with NPAF with an odds ratio of 6.48 (95% confidence interval, 1.71-24.5) after adjustment for sex, age, log(eGFR), C-reactive protein, and systolic blood pressure. In multivariate receiver operating characteristic analysis to predict NPAF, the area under the curve (AUC) for the combination of age, sex, log(eGFR), and C-reactive protein was 0.777 (standard error [SE], 0.036); the addition of log(suPAR) slightly improved the prediction (AUC, 0.812; SE, 0.034, P=0.084). CONCLUSIONS: Serum suPAR was associated with AF, particularly NPAF, as demonstrated by multivariate logistic regression analysis. Whether suPAR promotes or maintains AF should be investigated in further studies.

Acute cholecystitis mimicking or accompanying cardiovascular disease among Japanese patients hospitalized in a Cardiology Department.

BACKGROUND: Acute cholecystitis sometimes displays symptoms and electrocardiographic changes mimicking cardiovascular problems. It may also coexist with cardiovascular disorders. We analyzed the clinical characteristic of the cardiac patients who were diagnosed with acute cholecystitis during hospitalization in the cardiology department. METHODS: Using the department database, we identified 16 patients who were diagnosed with acute cholecystitis during the hospitalization in the cardiology department between June 2010 and June 2014. RESULTS: Five patients who were initially suspected to have cardiac problems (acute coronary syndrome, four patients; Adams-Stokes syndrome, one patient) owing to their symptoms were subsequently diagnosed with acute cholecystitis. Two of these patients showed electrocardiographic changes mimicking myocardial ischemia, and three tested positive for a biomarker (heart-type fatty acid binding protein) of acute myocardial injury. The 11 remaining cardiac patients were diagnosed with acute cholecystitis during their hospitalization or at the time of admission. Prolonged fasting and/or staying in an intensive care unit (ICU) may have contributed to their condition. Among these 11 patients, aortic dissection was the most prevalent underlying cardiac condition, affecting 5 patients. CONCLUSIONS: Although it is a rare condition, acute cholecystitis may coexist with or be misdiagnosed as a cardiovascular disorder. This possibility should not be overlooked in cardiac patients because a delay in treatment may result in critical complications.

Cardiovascular protection by ezetimibe and influence on oxidative stress in mice exposed to intermittent hypoxia.

Ezetimibe is as an inhibitor of NPC1L1 protein, which has a key role in cholesterol absorption. The aim of this study was to evaluate the influence of ezetimibe on the plasma lipid profile, atherosclerotic lesions, and cardiomyocyte ultrastructure in an animal model of atherosclerosis with intermittent hypoxia. Apolipoprotein E-knockout mice received a high-fat diet for 30 days. Then animals were exposed to intermittent hypoxia for 10 days or were maintained under normoxic conditions. In the ezetimibe group, ezetimibe (5 mg/kg/day) was added to the diet. Under normoxic conditions, the total cholesterol level was significantly lower in the ezetimibe group (63.6±6.6 mg/dl) than in the control group (116.3±16.9 mg/dl, P<0.001). Intermittent hypoxia accelerated atherosclerosis associated with increased superoxide production, which also caused degeneration of cardiomyocytes, mitochondrial abnormalities, and interstitial fibrosis. Compared with the control group, the ezetimibe group showed significantly less advanced atherosclerotic lesions and lower superoxide production in the thoracic aorta, as well as reduced oxidative stress, preservation of cardiomyocyte ultrastructure, and reduced interstitial fibrosis in the left ventricular myocardium. In conclusion, ezetimibe not only reduces total cholesterol, but also prevents the development of atherosclerosis and cardiovascular events due to intermittent hypoxia at least partly through suppression of oxidative stress.

Celiprolol reduces oxidative stress and attenuates left ventricular remodeling induced by hypoxic stress in mice.

We have previously reported that intermittent hypoxic stress, which is relevant to sleep apnea syndrome (SAS), increases oxidative stress and induces left ventricular (LV) remodeling. Celiprolol, a ß1-selective adrenoreceptor blocker, is known to have not only an antihypertensive effect but also an antioxidant effect through releasing nitric oxide. The aim of this study was to examine the hypothesis that celiprolol might ameliorate the LV remodeling induced by intermittent hypoxia through its antioxidant effect. Male C57BL/6J mice (8 weeks old) were exposed to intermittent hypoxia (30 s of 5% oxygen followed by 30 s of 21% oxygen) for 8 h day(-1) during the daytime for 10 consecutive days or were maintained under normoxic conditions. Animals were treated with either celiprolol (100 mg kg(-1) day(-1) by gavage) or vehicle. Hypoxic stress caused fluctuations in blood pressure (BP), an increase in the mean cardiomyocyte diameter, perivascular fibrosis and a decrease in endothelial nitric oxide synthase (eNOS) expression. These changes were associated with increased levels of 4-hydroxy-2-nonenal protein, superoxide, tumor necrosis factor-α mRNA and brain natriuretic peptide mRNA in the LV myocardium. Celiprolol significantly suppressed BP fluctuation, restored eNOS expression and reduced oxidative stress and superoxide production, thus ameliorating hypoxia-induced LV remodeling in mice. These findings suggest that treatment with celiprolol might prevent cardiovascular events in borderline hypertensive patients with SAS.

Familial hypercholesterolemia with multiple large tendinous xanthomas and advanced coronary artery atherosclerosis.

We herein report the case of a 53-year-old man with severe coronary ischemia who underwent successful coronary artery bypass surgery. Of note, he had hypercholesterolemia and presented with multiple large tendinous xanthomas and thickened Achilles tendons that had been present for more than two decades. Together with a family history of dyslipidemia, the patient was diagnosed as having familial hypercholesterolemia. Irrespective of an extensive search for possible mutations in the genes presumably involved in the patient's pathophysiology, including low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), autosomal recessive hypercholesterolemia (ARH) and apolipoprotein B (APOB), we were not able to identify the gene mutations responsible for the phenotype observed in the present case.