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.

Impact of febuxostat on visit-to-visit blood pressure variability: insights from the randomised PRIZE Study.

OBJECTIVES: Although uric acid lowering therapies, including xanthine oxidase (XO) inhibition, may reduce the absolute level of blood pressure (BP), the effect of XO inhibition on BP variability is largely unknown. The aim of the present analysis was to evaluate the impact of febuxostat, an XO inhibitor, on BP variability in a randomised trial setting. METHODS: This was a subanalysis of the PRIZE Study, a randomised trial to evaluate the potential effect of febuxostat on carotid intima-media thickness progression. Patients with hyperuricemia and carotid plaques were randomly assigned to the febuxostat or control group. During a 24-month period, office BP and pulse rate (PR) were measured ≥3 times. BP and PR variabilities were assessed with SD and coefficient of variation (CV). The effect of febuxostat on BP and PR variabilities was adjusted with age, sex and baseline BP or PR, expressed with 95% CIs. RESULTS: A total of 472 patients were included into the present subanalysis. During the 24-month follow-up period, the febuxostat group had a significantly lower adjusted mean systolic BP (128.4 (126.8-130.0) vs 130.7 (129.1-132.2) mm Hg, p=0.04) and CV of systolic BP (7.4 (6.7-8.0) vs 8.2 (7.6-8.8), p=0.04) than the control group. Adjusted SD of PR was also lower in the febuxostat group than their counterpart (5.95 (4.93-6.97) vs 7.33 (6.32-8.33), p=0.04). CONCLUSION: XO inhibition with febuxostat was associated with reduced visit-to-visit BP variability as well as reduced PR variability in patients with hyperuricemia and carotid plaques. TRIAL REGISTRATION NUMBERS: University Hospital Medical Information Network Clinical Trial Registry (UMIN000012911 and UMIN000041322).

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.

Microsatellite instability-high endocervical serous carcinoma manifesting as pulmonary thromboembolism: A case report and review of the literature.

A 53-year-old obese woman was referred because of sudden onset of dyspnea and chronic vaginal bleeding. In addition to severe anemia, multiple pulmonary emboli were identified. Pelvic imaging showed an irregular-shaped mass in the region of the endocervix extending to the lower uterine segment. After successful anticoagulant therapy, followed by placement of an inferior vena cava filter, transabdominal hysterectomy and bilateral salpingo-oophorectomy were performed. An immunopathological study resulted in the diagnosis of endocervical serous carcinoma. After the identification of a high level of microsatellite instability (MSI), an immunohistochemical analysis of mismatch repair (MMR) proteins showed the isolated loss of PMS2. Germline testing of MMR genes showed no mutations, indicating that the high MSI had occurred as a result of sporadic isolated loss of the PMS2 gene expression.

Association of smoking with prevalence of common diseases and metabolic abnormalities in community-dwelling Japanese individuals.

Smoking is a significant risk factor for cardiovascular diseases (CVDs). Given that certain common pathologies, including hypertension, dyslipidemia and type 2 diabetes mellitus, are major risk factors for CVDs, the association of smoking with CVDs may be attributable, at least in part, to its effects on common diseases. The aim of the present study was to determine the association of smoking with the prevalence of common diseases and metabolic abnormalities in community-dwelling Japanese individuals. The study included 5,959 subjects (1,302 current smokers, 1,418 past smokers and 3,239 nonsmokers) recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. Various metabolic parameters and prevalence of common diseases were compared between smokers and nonsmokers using multivariable regression or logistic regression analysis with adjustments for age. Analysis indicated significantly higher serum concentrations of triglycerides and lower concentrations of high-density lipoprotein (HDL)-cholesterol in current smokers compared with nonsmokers in men and women. Serum concentrations of creatinine and systolic blood pressure were significantly lower and estimated glomerular filtration rate was higher in male current smokers. In addition, body weight was higher in female current smokers. In multivariable logistic regression analysis, smoking was significantly associated with the prevalence of dyslipidemia [P=6.3×10-10; odds ratio (OR), 1.81], hypertriglyceridemia (P=2.3×10-20; OR, 2.39), hypo-HDL-cholesterolemia (P=2.0×10-9; OR, 2.14), metabolic syndrome (P=0.0003; OR, 1.61) and chronic kidney disease (P=4.4×10-15; OR, 0.54) in men, but not in women. The results indicated that smoking is significantly associated with various metabolic abnormalities and prevalence of common diseases in Japanese individuals, with certain sex differences, which may lead to accelerated development of CVDs.

Association of genetic variants with atrial fibrillation.

Recent genome-wide association studies (GWASs) identified various genes and loci that confer susceptibility to coronary artery disease or myocardial infarction among Caucasian populations. As myocardial ischemia is an important risk factor for atrial fibrillation, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to atrial fibrillation through affecting the susceptibility to coronary artery disease. The aim of the present study was to examine the possible association of atrial fibrillation in Japanese individuals with 29 polymorphisms identified as susceptibility loci for coronary artery disease or myocardial infarction in the meta-analyses of GWASs in Caucasian populations. The study subjects comprised 5,470 Japanese individuals (305 subjects with atrial fibrillation and 5,165 controls). Genotypes for 29 polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test revealed that rs599839 (G→A) of the proline/serine-rich coiled-coil 1 gene (PSRC1, P=0.0084) and rs11556924 (C→T, Arg363His) of the zinc finger, C3HC-type containing 1 gene (ZC3HC1, P=0.0076) were significantly (P<0.01) associated with atrial fibrillation. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, estimated glomerular filtration rate, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidemia revealed that rs599839 (P=0.0043; odds ratio, 1.56; dominant model) and rs11556924 (P=0.0043; odds ratio, 1.93; dominant model) were significantly associated with atrial fibrillation, with the minor G and T alleles, respectively, representing risk factors for this condition. PSRC1 and ZC3HC1 may thus be susceptibility loci for atrial fibrillation in Japanese individuals.

Association of FURIN and ZPR1 polymorphisms with metabolic syndrome.

Although genome-wide association studies (GWASs) have identified various genes and loci in predisposition to metabolic syndrome (MetS) or each component of this condition, the genetic basis of MetS in individuals remains to be identified definitively. The aim of the present study was to examine the possible association of MetS in individuals with 29 polymorphisms that were previously identified as susceptibility loci for coronary artery disease or myocardial infarction by meta-analyses of GWASs. The study population comprised 1,822 subjects with MetS and 1,096 controls. Subjects with MetS had ≥3 of the 5 components of the diagnostic criteria for MetS, whereas control individuals had 0-1 of the 5 components. The genotypes for the 29 polymorphisms were determined by the multiplex bead-based Luminex assay. Comparisons of allele frequencies by the χ2 test revealed that rs17514846 (A→C) of the furin (paired basic amino acid-cleaving enzyme) gene (FURIN; P=0.0006), rs964184 (C→G) of the ZPR1 zinc finger gene (ZPR1; P=0.0078) and rs599839 (G→A) of the proline/serine-rich coiled-coil 1 gene (P=0.0486) were significantly (P<0.05) associated with the prevalence of MetS. Multivariable logistic regression analysis with adjustment for age, gender and smoking status revealed that rs17514846 of FURIN (P=0.0016; odds ratio, 0.76; dominant model) and rs964184 of ZPR1 (P=0.0164; odds ratio, 1.21; dominant model) were significantly associated with MetS. The minor A allele of rs17514846 of FURIN was significantly associated with a decrease in the serum concentration of triglycerides (P=0.0293) and to an increase in the serum concentration of high-density lipoprotein (HDL) cholesterol (P=0.0460). The minor G allele of rs964184 of ZPR1 was significantly associated with increases in the serum concentration of triglycerides (P=6.2×10-9) and fasting plasma glucose level (P=0.0028) and to a decrease in the serum concentration of HDL cholesterol (P=0.0105). FURIN and ZPR1 may thus be susceptibility loci for MetS.

Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke.

Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single-nucleotide polymorphisms (SNPs) previously identified by the meta-analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms-related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 of TOMM40 (P=0.0443; recessive model; odds ratio=0.50) and rs273909 of SLC22A4 (P=0.0123; dominant model; odds ratio=0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition. TOMM40 and SLC22A4 may thus be susceptibility loci for ischemic stroke in Japanese individuals.

Association of a polymorphism of BTN2A1 with dyslipidemia in community-dwelling individuals.

We have previously shown that the C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) was significantly associated with myocardial infarction. Considering that dyslipidemia is a significant risk factor for coronary heart disease, it was hypothesized that the association between rs6929846 of BTN2A1 and myocardial infarction may be attributable, at least in part, to its effect on the susceptibility to dyslipidemia. The purpose of the present study was to examine a possible association of rs6929846 of BTN2A1 with dyslipidemia in community­dwelling individuals. The study subjects were comprised of 5,958 community­dwelling individuals (2,909 subjects with dyslipidemia and 3,049 controls) who were recruited into a population­based cohort study in Inabe, Japan. Dyslipidemia was defined by a serum concentration of triglycerides of ≥1.65 mmol/l, a serum high­density lipoprotein­cholesterol concentration of <1.04 mmol/l or a serum low­density lipoprotein (LDL)­cholesterol concentration of ≥3.64 mmol/l. A comparison of the allele frequencies or genotype distributions by the χ2 test revealed that rs6929846 of BTN2A1 was significantly associated with dyslipidemia (P<0.05). A multivariable logistic regression analysis adjusted for age, gender, body mass index, smoking status and the prevalence of diabetes mellitus revealed that rs6929846 of BTN2A1 was significantly (dominant model; P=2.4x10-4; odds ratio, 1.29) associated with dyslipidemia, with the minor T allele representing a risk for this condition. Among all the individuals, the serum concentrations of total cholesterol, triglycerides and LDL­cholesterol were significantly greater for individuals in the combined CT and TT genotype groups than for those with the CC genotype. BTN2A1 may thus be a susceptibility gene for dyslipidemia in community­dwelling individuals.

Association of genetic variants of CELSR1 and 3q28 with hypertension in community-dwelling individuals.

Findings of previous studies demonstrated that rs6007897 (C→T, Ala2268Thr) of the cadherin, epidermal growth factor (EGF) laminin A G-type repeats (LAG) seven-pass G-type receptor 1 gene (CELSR1) and rs9846911 (A→G) at chromosome 3q28 were significantly associated with ischemic stroke and chronic kidney disease, respectively. Given that hypertension is a risk factor for both ischemic stroke and chronic kidney disease, it was hypothesized that the association of rs6007897 with ischemic stroke or of rs9846911 with chronic kidney disease might be attributable, at least in part, to their effects on genetic susceptibility to hypertension. The purpose of the present study was to examine a possible association of rs6007897 of CELSR1 or rs9846911 at 3q28 with hypertension in community-dwelling individuals. Study subjects comprised 5,959 community-dwelling individuals (1,670 subjects with hypertension and 4,289 controls) who were recruited to a population-based cohort study. Comparisons of allele frequencies by the Chi-square test revealed that rs6007897 of CELSR1 (P=0.0280) and rs9846911 at 3q28 (P=0.0171) were significantly associated with the prevalence of hypertension. Multivariate logistic regression analysis with adjustment for age, gender, body mass index (BMI), smoking status, the serum concentration of creatinine and the prevalence of dyslipidemia and diabetes mellitus revealed that rs6007897 (P=0.0308; recessive model; odds ratio, 1.56) and rs9846911 (P=0.0353; dominant model; odds ratio, 1.22) were significantly associated with hypertension with the T allele rs6007897 and the G allele rs984691 representing risk factors for this condition. CELSR1 and 3q28 may thus be susceptibility loci for hypertension.