The association of serum adiponectin level with activities of daily living in hospitalized elderly patients with heart failure.

BACKGROUND: Several studies have reported a relationship between elevated serum adiponectin levels and poor outcomes in patients with heart failure (HF). However, data on the activities of daily living (ADL) in elderly patients with HF are limited. METHODS: We evaluated 218 hospitalized elderly (≥65 years) patients with HF who underwent a comprehensive cardiac rehabilitation (CR) program during hospitalization. Serum adiponectin levels were measured before discharge. The Barthel index (BI) score was evaluated at discharge. Low ADL was defined as a BI score < 85. RESULTS: Serum adiponectin levels were significantly associated with low ADL [p = 0.03; odds ratio (OR), 1.024, per 1.0 µg/mL increase]. In logistic or regression analyses adjusted for age, sex, body mass index, and estimated glomerular filtration rate, high adiponectin levels (≥16.2 µg/mL) were significantly associated with low ADL (p = 0.04; OR, 2.53), malnutrition (p < 0.01; OR, 2.88), and 6-min walk distance (p = 0.04; ß = -17.5). In the multivariate analysis adjusted for conventional risk factors of low ADL, high adiponectin levels were also significantly associated with low ADL (p = 0.03; OR, 2.68). In the stepwise forward selection procedure, a high adiponectin level was an independent determinant of low ADL (p = 0.02; R2 = 0.0262). Both net reclassification improvement (0.53; p < 0.01) and integrated discrimination improvement (0.02; p = 0.01) improved significantly after the addition of high adiponectin level to conventional risk factors. In the regression analysis adjusted for age and sex, serum adiponectin levels were significantly (p < 0.0025) negatively associated with abdominal visceral and subcutaneous adipose tissue areas, body weight, body mass index, and serum triglyceride levels. CONCLUSIONS: High serum adiponectin levels were not only significantly associated with an increased risk of low ADL, but also with an increased risk of malnutrition and low physical activity in elderly patients with HF after the in-hospital CR program.

Predictive value of abdominal aortic calcification index for mid-term cardiovascular events in patients with acute coronary syndrome.

The utility of abdominal aortic calcification (AAC) for prediction of cardiovascular events (CVEs) in patients with acute coronary syndrome (ACS) remains to be determined. The aim of this prospective study was to determine the predictive value of the abdominal aortic calcification index (ACI), a semi-quantitative measure of AAC, for CVEs in patients with ACS. We evaluated 314 patients with ACS. All patients underwent successful percutaneous coronary intervention to the culprit coronary vessel without in-hospital adverse events. ACI was calculated on non-contrast computed tomography images. CVEs were defined as a composite of cardiovascular death, ACS recurrence, and stroke. During a median follow-up period of 19.1 months, CVEs occurred in 29 patients (9.2%). Multivariable regression analysis after adjustment for age and gender showed a significantly higher baseline ACI in patients with CVEs than in those without [median (interquartile ranges), 42.1 (25.9-60.2) vs. 20.8 (8.8-38.6) %; P = 0.021]. The cutoff value of ACI for prediction of CVEs, estimated by receiver-operating characteristic analysis, was 29.2%, with sensitivity of 76% and specificity of 64% (area under the curve, 0.69). After adjustment for conventional cardiovascular risk factors, Cox analysis showed high ACI (≥29.2%) to be significantly associated with increased risk of CVEs (P = 0.011; hazard ratio, 1.82). Multivariate analysis identified high ACI as an independent predictor of CVEs (P = 0.012; hazard ratio, 1.80). Stepwise forward selection procedure also showed that high ACI was a significant independent determinant of CVEs (P = 0.004; R2, 0.089). Both net reclassification improvement (0.64; P = 0.001) and integrated discrimination improvement (0.04; P < 0.001) improved significantly after the addition of high ACI to conventional risk factors. Evaluation of ACI using CT seems to provide valuable clinical information for proper assessment of mid-term CVEs in patients with ACS after percutaneous coronary intervention.

A case of floating thrombus in the ascending aorta that caused recurrent peripheral arterial embolic events.

We report the case of a 62-year-old man with recurrent arterial embolisms to his arms caused by a thrombosis of the ascending aorta. He had developed a left brachial artery embolism 8 years previously, but presented with a right brachial artery embolus on this occasion. A clot-like mass was seen in the ascending aorta on computed tomography without significant atherosclerosis. Magnetic resonance imaging identified multiple asymptomatic cerebral infarctions. Therefore, we surgically removed the thrombus in the ascending aorta, which was an organized fibrin clot. Pathologically, atherosclerosis and plaque formation were evident at the intima where the clot attached. Clot formation was considered to be due to local arteriosclerosis. We report a case of thrombosis of the ascending aorta causing multiple and recurrent arterial embolisms. The patient had no evidence of coagulation disorders, and arteriosclerotic risk factors such as hypertension, diabetes mellitus, and dyslipidemia were absent. Thus, thrombosis may develop in patients without traditional risk factors. .

Compound heterozygotes for a novel mutation, apo E1 Nagoya (Arg142Ser) and Apo E2 (Arg158Cys), with severe type III hyperlipoproteinemia and familial hypercholesterolemia.

AIM: A patient with severe type III hyperlipoproteinemia and familial hypercholesterolemia (FH) was previously reported (Metabolism, 44,1995:460-465). In the current study, the patient's apolipoprotein (apo) E gene was analyzed. METHODS: An apo E isoform analysis was performed using isoelectric focusing and immunoblotting. In addition, after DNA preparation, a restriction fragment length polymorphism analysis and DNA sequence analysis were performed. RESULTS: The patient's apo E phenotype was E2/E1, and the genotype was ε2/ε2. The sequence analysis of the patient's DNA revealed a new variant of apo E, which involves a single substitution of one serine (AGC) for one arginine (CGC) at position 142, thereby adding one negatively charged unit to apo E2. Therefore, the patient was compound heterozygous for apo E1 (Arg142Ser) and apo E2 (Arg158Cys). CONCLUSIONS: A novel mutation, apo E1 Nagoya (Arg142Ser) in a patient with severe type III hyperlipoproteinemia with heterozygous FH was characterized. Since the presence of arginine at the amino acid residue 142 of apo E is considered to play an important role in binding to LDL receptors, the mutation apo E1 Nagoya (Arg142Ser) likely contributed to the expression of severe type III hyperlipoproteinemia in this patient.

Association of a matrix metallopeptidase 1 gene polymorphism with long-term outcome of thoracic aortic aneurysm.

Although genetic variants are thought to contribute to the development of thoracic aortic aneurysm including dissection (TAA), it remains unclear whether gene polymorphisms are associated with the long-term outcome of TAA. The purpose of the present study was to identify genetic variants associated with the long-term outcome of medically treated patients with TAA. A total of 103 medically-treated patients with TAA (13 aneurysms and 90 dissections) were retrospectively studied for their outcomes (mean follow-up period, 24 months). The genotypes for 95 polymorphisms of 89 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the Chi-square test and subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the -340A→G polymorphism (rs514921) of the matrix metallopeptidase 1 gene (MMP1) was significantly (P=0.0288) associated with the outcome of TAA, with the minor G allele being related to a favorable outcome. The aneurysm diameter was significantly (P=0.0167) smaller in the combined group of the AG and GG genotypes for this polymorphism than in subjects with the AA genotype. Kaplan-Meier survival curves constructed according to MMP1 genotypes showed a more favorable outcome of TAA (log-rank P=0.0146) in subjects with the G allele of rs514921. Determination of genotype for this polymorphism may prove informative for assessment of the long-term outcome of TAA.

Acute interstitial pneumonitis after implantation of paclitaxel-eluting stents: a report of two fatal cases.

Paclitaxel is an anti-neoplastic agent widely used as a coating substance for coronary stents to reduce the rate of restenosis. Although the release rate of paclitaxel from stents is quite slow and the dose of paclitaxel is extremely small, long-term safety and avoidance of potentially lethal pulmonary damage is not well established. We report two cases of paclitaxel-eluting stent implantation in ischemic heart disease patients who developed acute interstitial pneumonitis a few days afterward, and who succumbed to fatal respiratory dysfunction despite corticosteroid therapy. Based upon the clinical course and autopsy findings in these two patients, paclitaxel eluted from the stent may have played a causal role in the development of acute interstitial pneumonitis. Physicians should bear in mind that paclitaxel has the potential of causing acute interstitial pneumonitis not only when used for anti-neoplastic therapy, but also following stent implantation, where the objective is to inhibit coronary neointimal proliferation.

HDL2 can inhibit further oxidative modification of partially oxidized LDL.

AIM: To investigate whether HDL(2) can inhibit further oxidative modification of partially oxidized LDL (ox-LDL) by interrupting the chain oxidation reaction after lipid hydroperoxides (LOOH) formation. METHODS: Following incubation of LDL 400 microg protein/mL phosphate-buffered saline with Cu(2+) for 1.75 h (defined as 0 min), incubation was continued after adding HDL(2) 200 microg protein/mL or HDL(2) 800 microg protein/mL to give both ox-LDL+HDL(2) 200 microg protein/mL or ox-LDL+HDL(2) 800 microg protein/mL. As a control, ox-LDL 200 microg protein/mL and native LDL were prepared. Each sample was subjected to agarose gel electrophoresis and the LOOH in each sample was measured. RESULTS: When the electrophoretic mobility of native LDL was designated 1, the relative electrophoretic mobility (REM) of ox-LDL increased significantly over time. The REMs of ox-LDL+HDL(2) 800 microg protein/mL from 10 min to 9 h were significantly lower than the REM of ox-LDL at the respective times (p<0.01). LOOH of ox-LDL+HDL(2) 800 microg protein/mL at 1, 3, 6 and 9 h was significantly higher than LOOH in ox-LDL at the respective times (p<0.01). The results of ox-LDL+HDL(2) 200 microg protein/mL were almost the same but to a lesser extent than the results of ox-LDL+HDL(2) 800 microg protein/mL. CONCLUSION: The present findings suggest that HDL(2) can inhibit further oxidative modification of partially oxidized LDL by interrupting the chain oxidation reaction after LOOH formation in a concentration-dependent manner.

Impact of matrix metalloproteinase-2 levels on long-term outcome following pharmacological or electrical cardioversion in patients with atrial fibrillation.

AIMS: The aim of this study was to evaluate the role of matrix metalloproteinases (MMPs) for the prediction of long-term maintenance of sinus rhythm (SR) after cardioversion in atrial fibrillation (AF). METHODS AND RESULTS: The study comprised 102 patients with AF. Pharmacological cardioversion was attempted for a 4-week period with anti-arrhythmic drugs in all patients. Those who failed medication underwent electrical cardioversion. Blood samples for biomarkers and echocardiographic data were obtained at baseline. Thirty-four patients (33.3%) converted to SR by pharmacological (n = 22) and electrical (n = 12) cardioversion and maintained it (SR group). The remaining 68 patients were refractory to the AF (RAF) group including recurrence (n = 22) and unsuccessful treatment (n = 46) after electrical/pharmacological cardioversion. Refractory AF was significantly associated with the duration of AF, hypertension, left atrial diameter, brain natriuretic peptide, MMP-2, and tissue inhibitor of MMP-2. For both multivariable logistic regression analysis and stepwise forward selection procedure, the duration of AF >5 months [odds ratio (OR) 15.32] and MMP-2 >767.0 ng/mL (OR 4.84) were significantly associated with RAF. CONCLUSION: Our study suggests that elevated MMP-2 and longer AF duration increased the risk for difficulty in restoring SR in AF patients. Stratification of subjects according to the MMP-2 level may therefore be important for the effective management of AF.

A rare case of tako-tsubo cardiomyopathy documented during Holter monitoring.

We report a rare case of Holter monitoring documenting the onset of tako-tsubo cardiomyopathy in a 70-year-old woman. The patient experienced sudden chest discomfort after a quarrel in her hospital stay. Follow-up echocardiography on day 22 revealed a marked improvement of left ventricular apical akinesis. Angiographic examination at discharge showed neither coronary artery disease nor left ventricular asynergy.

Tako-tsubo cardiomyopathy complicated by apical thrombus formation: a case report.

Tako-tsubo cardiomyopathy is a rare, stress-related cardiomyopathy that occurs in postmenopausal women after emotional or physiological stressors. The prognosis is favorable with normalization of wall motion abnormalities within weeks. We report a rare case of tako-tsubo cardiomyopathy complicated by a left thrombus. Coronary angiography showed normal coronary arteries, although the echocardiography demonstrated the ballooning of the apex with hyperkinesis of the base in addition to a left ventricular thrombus. It is thought that this thrombus may have been caused by left ventricular dyskinesis. After short-term anticoagulant therapy, echocardiography revealed complete resolution of the left ventricular thrombus.

A rare case of tako-tsubo cardiomyopathy with variable forms of left ventricular dysfunction: a new entity.

We report a rare case of an 83-year-old woman with tako-tsubo cardiomyopathy, who presented with variable forms of left ventricular dysfunction during her clinical course. The distribution regional wall-motion abnormalities of the left ventricle on echocardiography had changed from a mid-ventricular ballooning type to the apical ballooning type 3 days from the onset. We suggest that these findings may indicate a new or variant entity of tako-tsubo cardiomyopathy.

Transient mid-ventricular ballooning syndrome complicated by syncope: a variant of tako-tsubo cardiomyopathy.

Tako-tsubo cardiomyopathy, also called transient left ventricular apical ballooning, is a clinical entity first described in Japan. This syndrome is triggered by emotional or physical stress and mimics an acute coronary syndrome, although the coronary arteries are essentially normal. Recently, several reports have described variant forms of tako-tsubo cardiomyopathy, such as inverted tako-tsubo and mid-ventricular ballooning cardiomyopathy. We describe a case herein of an 87-year-old woman who presented a variant form of tako-tsubo cardiomyopathy complicated by syncope. Our findings may contribute to an elucidation of the mechanism underlying tako-tsubo cardiomyopathy.

The recurrence of tako-tsubo cardiomyopathy complicated by cardiogenic shock: a case report.

Tako-tsubo cardiomyopathy is a stress-related cardiomyopathy which occurs in postmenopausal women after severe emotional stress. Although no evidence supporting specific treatment with tako-tsubo cardiomyopathy has been established, the prognosis is considered favorable with normalization of wall motion abnormalities within weeks. In addition, recurrence of this syndrome seems to be rare. Now, we report a recurrent case of tako-tsubo cardiomyopathy complicated by cardiogenic shock after repeated emotional stress.

Assessment of genetic risk factors for thoracic aortic aneurysm in hypertensive patients.

BACKGROUND: Conventional risk factors for thoracic aortic aneurysm including dissection (TAA) are thought to include age, arteriosclerosis, and hypertension. In addition, evidence suggests that genetic factors play a role in the development of this condition. The purpose of the present study was to identify genetic variants that confer susceptibility to TAA in hypertensive subjects. METHODS: Study subjects comprised 1,351 hypertensive individuals: 88 patients with TAA and 1,263 subjects without this condition. The genotypes for 142 polymorphisms of 119 candidate genes were determined by a method that combines the PCR and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: Evaluation of genotype distributions by the chi2-test and subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the 3949T-->G (3' untranslated region) polymorphism of the thrombospondin-2 gene (THBS2; odds ratio, 4.6), the -110A-->C polymorphism of the heat shock 70-kDa protein 8 gene (HSPA8; odds ratio, 0.4), the C-->T (Pro198Leu) polymorphism of the glutathione peroxidase 1 gene (GPX1; odds ratio, 0.3), the -6G-->A polymorphism of the angiotensinogen gene (AGT; odds ratio, 0.3), and the -850C-->T polymorphism of the tumor necrosis factor gene (TNF; odds ratio, 0.5) were significantly (P < 0.05) associated with TAA. CONCLUSIONS: The variant allele of THBS2 is a risk factor for TAA in hypertensive patients, whereas the variant alleles of HSPA8, GPX1, AGT, and TNF are protective against this condition. Determination of genotypes for these polymorphisms may prove informative for assessment of the genetic risk for TAA.

Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals.

BACKGROUND AND PURPOSE: Although genetic epidemiologic studies have implicated several genetic variants as risk factors for ischemic or hemorrhagic stroke, the genetic determinants of these conditions remain largely unknown. We performed an association study to identify gene polymorphisms that confer susceptibility to atherothrombotic cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage. METHODS: The study population comprised 3432 unrelated Japanese individuals: 1362 stroke patients (822 with atherothrombotic cerebral infarction, 333 with intracerebral hemorrhage, and 207 with subarachnoid hemorrhage) and 2070 controls. The genotypes for 50 polymorphisms of 38 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: An initial chi(2) test (false discovery rate <0.05) and subsequent multivariable logistic-regression analysis with adjustment for conventional risk factors (P<0.05) revealed that the -14C-->T polymorphism (rs1800977) of ABCA1, the A-->C (rs3027898) and C-->T (Ser532Leu, rs1059703) polymorphisms of IRAK1, and the G-->C (Cys2229Ser) polymorphism (rs619203) of ROS1 were significantly associated with atherothrombotic cerebral infarction; that the -428G-->A polymorphism (rs710968) of LIMK1 was significantly associated with intracerebral hemorrhage; and that the 13989A-->G (Ile118Val) polymorphism (NC_000007.12) of CYP3A4 was significantly associated with subarachnoid hemorrhage. CONCLUSIONS: Genotypes for ABCA1, IRAK1, and ROS1 may prove useful for assessment of the genetic risk for atherothrombotic cerebral infarction, whereas those for LIMK1 and CYP3A4 may be similarly beneficial in assessment of the genetic risk for intracerebral hemorrhage and subarachnoid hemorrhage, respectively. Validation of these findings will require additional studies with independent subject panels.

Association of a polymorphism of ABCB1 with obesity in Japanese individuals.

The aim of the present study was to identify gene polymorphisms that confer susceptibility to obesity. A total of 5448 unrelated Japanese individuals from two independent populations were examined: subject panel A comprised 4252 individuals who visited participating hospitals; subject panel B comprised 1196 community-dwelling elderly individuals. The genotypes for 95 polymorphisms of 67 candidate genes were determined. The chi(2) test revealed that six polymorphisms were related (p<0.05) to the prevalence of obesity in subject panel A; after application of Bonferroni's correction, however, only the 2677G --> A/T polymorphism (rs2032582) of the ATP-binding cassette, subfamily B, member 1 gene (ABCB1) was significantly associated (p=0.0003) with obesity. Subsequent multivariable logistic regression analysis also revealed that the 2677G --> A/T polymorphism of ABCB1 was significantly associated with obesity. For validation of this association, the 2677G --> A/T polymorphism of ABCB1 was examined in subject panel B and again found to be significantly associated with obesity. Body mass index was significantly (p=0.01) greater for individuals with the variant T allele of this polymorphism than for those with the GG genotype in the combined subject panels A and B. Our results suggest that the ABCB1 genotype may prove informative for assessment of genetic risk for obesity in Japanese individuals.

A failed case to diagnose cardiac sarcoidosis presenting advanced atrioventricular block.

A 53-year-old-male developed atrioventricular block in January 2001. A chest X-ray and laboratory tests, including serum angiotensin converting enzyme, were normal. The patient underwent permanent pacemaker implantation and attended for semiannual follow-up after discharge since the etiology of advanced atrioventricular block remains unknown. One year later, the patient was diagnosed with uveitis related to sarcoidosis. No clinical finding specific to cardiac sarcoidosis was notable at that time. Four years after onset, the patient developed congestive heart failure. An echocardiogram revealed diffuse LV hypokinesis, but no asymmetric interventricular septal thinning. Laboratory tests showed normal angiotensin converting enzyme. Noncaseating granuloma was not confirmed by transbronchial biopsy. Despite normal myocardial uptake of gallium-67, uptake of (18)F-Fluorodeoxyglucose increased in the myocardium. Nevertheless, clinical manifestations did not match the criteria for cardiac sarcoidosis. Prednisolone was administered daily. Two months after tapering dosage, the patient developed multiple organ failure and died. Post mortem histological findings were consistent with cardiac sarcoidosis. We experienced great difficulty in detecting cardiac involvement in the early stage of sarcoidosis. A specific method with greater sensitivity is required to diagnose cardiac involvement in the early stages of sarcoidosis.

Association of a polymorphism of CYP3A4 with type 2 diabetes mellitus.

Although several environmental factors, including a high-calorie diet and physical inactivity, influence the development of type 2 diabetes mellitus, genetic factors have been shown to contribute to individual susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to type 2 diabetes mellitus, and thereby to contribute to assessment of the genetic risk for this condition. The study population comprised 5259 unrelated Japanese individuals (2980 men, 2279 women), including 1640 subjects with type 2 diabetes mellitus (1071 men, 569 women) and 3619 controls (1909 men, 1710 women). The genotypes for 94 polymorphisms of 67 genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the chi-square test revealed that the 13989-->G (Ile118Val) polymorphism of the cytochrome P450, subfamily IIIA, polypeptide 4 gene (CYP3A4) was significantly (false discovery rate, 0.000009) associated with the prevalence of type 2 diabetes mellitus. Multivariable logistic regression analysis with adjustment for age and sex also revealed that the 13989-->G (Ile118Val) polymorphism of CYP3A4 was significantly (P=0.00002) associated with the prevalence of type 2 diabetes mellitus, with the AG genotype being protective against this condition. Genotyping for CYP3A4 may thus prove informative for assessment of the genetic risk for type 2 diabetes mellitus.

A pathophysiologic study of tako-tsubo cardiomyopathy with F-18 fluorodeoxyglucose positron emission tomography.

UNLABELLED: AIMS; Our study aims to investigate the pathophysiologic mechanism underlying tako-tsubo cardiomyopathy using F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). METHODS AND RESULTS: Fifteen patients with tako-tsubo cardiomyopathy were enrolled in this study. Plasma catecholamines, cardiac troponin T (cTnT), and D-dimer were serially evaluated in all patients. Thallium-201 ((201)Tl) single-photon emission computed tomography (SPECT) and F-18 FDG PET were performed in 10 and eight patients, respectively. Emotional or physical stress occurred in 12 (80.0%) patients. ST-T segment abnormalities existed in all patients. Thirteen patients exhibited mildly elevated cTnT, although coronary angiography did not reveal significant stenosis in any patient. Endomyocardial biopsy specimens (n = 9) demonstrated contraction-band necrosis (n = 4) and mononuclear cell infiltration (n = 3). The levels of norepinephrine and epinephrine peaked on admission (744 +/- 452 and 140 +/- 166 pg/mL, respectively). There was severely reduced uptake at the apex on F-18 FDG PET image, despite slightly reduced uptake of (201)Tl. Elevation of D-dimer was observed in nine patients. CONCLUSION: The extent of metabolic defect involving apical akinetic area was more severe than perfusion abnormality. Our data suggest that sudden emotional or physical stress may cause a catecholamine-induced metabolic disorder in the myocardium, which is probably central to this syndrome.