Yohei Oda

Low serum bilirubin concentration is associated with coronary artery calcification (CAC).

BACKGROUND Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis. The purpose of this study was to assess the correlation between serum bilirubin concentration and coronary artery calcification (CAC). METHODS This study consisted of 637 participants and we evaluated the relationship between CAC score determined by multislice computed tomography and serum bilirubin concentration. RESULTS An inverse correlation was found between serum bilirubin concentration and log(CAC+1) (r=-0.361, P<0.0001). Multiple regression analysis also demonstrated that age (beta=0.261, P=0.0125), systolic blood pressure (beta=0.153, P=0.0237), uric acid (beta=0.126, P=0.0441), estimated glomerular filtration rate (beta=-0.139, P=0.0416) and serum bilirubin concentration (beta=-0.281, P<0.0001) were independent determinants of log(CAC+1). An increment of 1 micromol/L in serum bilirubin concentration was associated with 14% decrease in the odds for CAC score > or =400 after adjustment for several risk factors. Both age and SBP were also positively associated with CAC score > or =400, but the odds ratio for CAC score > or =400 was greater for every 1 micromol/L increment in serum bilirubin concentration than for every 1-year increment in age and 1-mmHg increment in SBP. CONCLUSIONS Low serum bilirubin concentration is associated with coronary artery calcification. Serum bilirubin concentration can be measured easily in the clinical laboratory and applied in medical practice, and low serum bilirubin concentration would be useful as a provisional new risk factor of CAC.

Metabolically Healthy Obesity and Risk of Incident CKD

BACKGROUND AND OBJECTIVES Metabolically healthy obesity (MHO) is a unique obesity phenotype that apparently protects people from the metabolic complications of obesity. The association between MHO phenotype and incident CKD is unclear. Thus, this study investigated the association between MHO phenotype and incident CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 3136 Japanese participants were enrolled in an 8-year follow-up cohort study in 2001. Metabolically healthy status was assessed by common clinical markers: BP, triglycerides, HDL cholesterol, and fasting plasma glucose concentrations. Body mass index ≥25.0 kg/m(2) was defined as obesity. CKD was defined by proteinuria or eGFR of <60 ml/min per 1.73 m(2). To calculate the odds ratio for incident CKD, logistic regression analyses were performed. RESULTS The crude incidence proportions of CKD were 2.6% (56 of 2122 participants) in participants with the metabolically healthy nonobesity phenotype, 2.6% (8 of 302) in those with the MHO phenotype, 6.7% (30 of 445) in those with the metabolically abnormal nonobesity phenotype, and 10.9% (29 of 267) in those with the metabolically abnormal obesity phenotype. Compared with metabolically healthy nonobesity phenotype, the odds ratios for incident CKD were 0.83 (95% confidence interval [95% CI], 0.36 to 1.72; P=0.64) for MHO, 1.44 (95% CI, 0.80 to 2.57; P=0.22) for metabolically abnormal nonobesity, and 2.80 (95% CI, 1.45 to 5.35; P=0.02) for metabolically abnormal obesity phenotype after adjustment for confounders, including age, sex, smoking statues, alcohol use, creatinine, uric acid, systolic BP, HDL cholesterol, and impaired fasting glucose or diabetes. CONCLUSION MHO phenotype was not associated with higher risk of incident CKD.

Home blood pressure variability on one occasion is a novel factor associated with arterial stiffness in patients with type 2 diabetes

Recent studies have suggested that not only mean blood pressure but also variability in blood pressure might be related to cardiovascular disease. The aim of this study was to investigate the association between home blood pressure variability on one occasion and markers of arterial stiffness in patients with type 2 diabetes. We investigated the relationship between the s.d. of clinic- or home-measured systolic blood pressure on one occasion and pulse wave velocity (PWV) in 332 patients with type 2 diabetes, and we evaluated whether the SD of clinic- or home-measured systolic blood pressure on one occasion was an independent determinant of PWV by multivariate linear regression analysis, after adjustment for known risk factors for arterial stiffness, including sex, age, duration of diabetes, body mass index, hemoglobin A1c, serum total cholesterol, triglycerides, smoking status, drinking alcohol, presence of antihypertensive medication, average systolic blood pressure and heart rate. Age, average morning home-measured systolic blood pressure, heart rate and PWV (r=0.259, P<0.0001) were positively correlated with the s.d. of morning home blood pressure on one occasion. Multiple regression analysis demonstrated that age, average morning home-measured systolic blood pressure (P=0.0019), heart rate and the s.d. of morning home-measured systolic blood pressure on one occasion (P=0.0159) were independently associated with PWV. In conclusion, home blood pressure variability on one occasion was correlated with PWV, independent of other known risk factors, in Japanese patients with type 2 diabetes.

Low serum bilirubin concentration is a predictor of chronic kidney disease.

OBJECTIVE Chronic kidney disease (CKD) is a worldwide public health problem. It is very important to identify the factors that affect CKD. Previous studies have reported that serum bilirubin concentration was positively correlated with renal function in a cross-sectional study. The aim of this study was to investigate the relationship between serum bilirubin concentration and the progression of CKD. METHODS A cohort study was performed on a consecutive series of 2784 subjects without CKD, defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), at baseline. We analyzed the relationship between serum total bilirubin concentration at baseline and new-onset CKD in the general population. RESULTS We followed the subjects for a median period of 7.7 years. There were 1157 females and 1627 males, and 231 females and 370 males developed CKD during this period. Multiple Cox regression analyses revealed that serum total bilirubin concentration (hazard ratio (HR) per 1.0 μmol/L increase 0.97 (95% CI 0.95-0.99), P = 0.0084) in addition to age, gamma-glutamyl transpeptidase (GGT), uric acid (UA), creatinine and medication for hypertension in men and serum total bilirubin concentration (HR per 1.0 μmol/L increase 0.96 (95% CI 0.93-1.00), P = 0.0309) in addition to age, GGT, alanine aminotransferase, UA, creatinine and medication for dyslipidemia in women were independent predictors of new-onset CKD, after adjusting for confounders. CONCLUSION Our study demonstrated that serum total bilirubin concentration could be a novel risk factor for the progression of CKD, defined as eGFR <60 ml/min/1.73 m(2), in the general population.

Uncontrolled home blood pressure in the morning is associated with nephropathy in Japanese type 2 diabetes

The purposes of this study were to investigate the state of blood pressure control level and to investigate the relationship between blood pressure control level and nephropathy in Japanese type 2 diabetes. We measured clinic and home blood pressure in 923 type 2 diabetic patients. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH). Of all patients, 13.9, 12.6, 13.3, and 60.2% were identified as having CH, WCH, MH, and SH, respectively. The average number of drugs prescribed was 1.8. We assessed the association between blood pressure control level and nephropathy in diabetic patients. The degree of urinary albumin excretion and the prevalence of nephropathy in diabetic patients were higher in MH and SH groups than those in the CH group. The majority of patients had poor blood pressure control, regardless of ongoing conventional antihypertensive therapy, and diabetic patients with MH and SH were associated with nephropathy. It is suggested that more aggressive antihypertensive treatment is recommended to prevent nephropathy in diabetic patients.

Evaluation of characteristics and degree of remodeling in coronary atherosclerotic lesions by 64-detector multislice computed tomography (MSCT)

BACKGROUND Multislice computed tomography (MSCT) permits reliable imaging of not only the coronary artery lumen but also vessel wall. It is assumed that both lipid-rich plaques and those that display positive remodeling are more prone to rupture and erosion with subsequent coronary events. The purpose of this study was to assess the correlation between the characteristics of coronary arteries by MSCT and several measures of coronary heart disease (CHD) risk. METHODS This study consisted of 424 consecutive participants who received MSCT and coronary angiography (CAG). We assessed coronary artery findings including coronary artery calcification (CAC), degree of remodeling and narrowing of lumen and characteristics including uric acid (UA) and high-sensitivity C-reactive protein (hs-CRP). Statistical analyses were conducted for four subgroups classified by the presence of significant stenosis and positive remodeling. RESULTS Hs-CRP was 2.10+/-2.70mg/L in positive remodeling (+) and stenosis (+) group (PS), 1.05+/-0.97mg/L in positive remodeling (-) and stenosis (+) group (nPS), 0.94+/-0.88mg/L in positive remodeling (+) and stenosis (-) group (PnS) and 0.44+/-0.49mg/L in positive remodeling (-) and stenosis (-) group (nPnS). The results of logistic regression analysis showed that hs-CRP was higher in PS compared with the other groups (p<0.001) and higher in nPS and PnS compared with nPnS (p<0.05). CONCLUSIONS Regardless of significant stenosis, positive remodeling by MSCT correlates to the increase of hs-CRP.

Low Urine pH Is a Predictor of Chronic Kidney Disease

Background/Aims: A variety of risk factors for chronic kidney disease (CKD), including the metabolic syndrome, were recently reported. It has been suggested that a low urine pH is another characteristic of the metabolic syndrome. However, the relationship between urine pH and CKD remains to be elucidated. Methods: A cohort study was performed on 1,811 subjects who underwent a health check-up, and we examined whether low urine pH could be a predictor of CKD. The following risk factors for CKD were evaluated: age, gender, history of alcohol intake and smoking, BMI, systolic blood pressure, fasting plasma glucose, total cholesterol, uric acid, total leukocyte count, CKD stage, fasting urine pH, and protein at baseline. Results: We followed 1,811 subjects for a median period of 7.7 years. Three hundred and thirty-nine subjects developed stage 3 CKD defined as progression to estimated glomerular filtration rate <60 ml/min/1.73 m2. Multiple Cox regression analysis revealed that the adjusted HR (95% CI) for stage 3 CKD was 1.32 (1.06–1.65; p = 0.0129) in subjects with fasting urine pH 5.0–5.5 compared to subjects with pH 6.5–7.0. Conclusion: Our study suggests that low urine pH is an independent predictor of stage 3 CKD.

Eosinophil count is positively correlated with coronary artery calcification

Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C-reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log(CAC+1), respectively. Positive correlations were found between log(CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log(CAC+1) and eGFR (r=−0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (β=0.314, P<0.0001), sex (β=0.124, P<0.0001), hypertension (β=0.084, P=0.0008), DM (β=0.108, P<0.0001), eGFR (β=−0.079, P=0.0021) and eosinophil count (β=0.147, P<0.0001) were independent determinants of log(CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD.

Transthoracic direct current shock facilitates intramyocardial transfection of naked plasmid DNA infused via coronary vessels in canines

Catheter-mediated, percutaneous, transluminal delivery of naked plasmid DNA (pDNA) into myocardium may offer a valuable strategy to heart diseases. Here, we examined whether clinically available transthoracic direct current (DC) shock improves intracoronary naked DNA transfection into myocardium. Plasmid vector encoding the GL3 luciferase was infused retrogradely into the coronary veins of beagle dogs, whereas another pDNA solution was infused into the left coronary artery. During and after these procedures, the coronary venous sinus was occluded by balloon, and transthoracic DC shock of 200 J was applied immediately after the infusions. Without DC shock, no remarkable increase in luciferase activity was demonstrated in any part of the left ventricular myocardium. In the presence of DC pulsation, significant luciferase expression was detected in the regions that were supplied by left anterior descending coronary artery (LAD), whereas the gene expression in the right coronary artery (RCA) regions was much less drastic. X-gal (5-bromo-4-chloro-3-indolyl-β-D-galactoside) staining of cardiac cross-sections also revealed regional expression of β-galactosidase. Immunohistochemical examinations of heart cryosections revealed that cardiomyocytes in LAD regions successfully expressed transgene product. The present system may enable a new strategy for myocardial gene therapy, without any special device or technique other than cardiac catheterization and DC cardioversion that are generally performed in ordinary hospitals.

Factors affecting variability in home blood pressure in patients with type 2 diabetes: post hoc analysis of a cross-sectional multicenter study.

Recent studies have shown that variability in home blood pressure has an important role in the progression of organ damage. The objective of this study was to investigate the factors that affect variability in home blood pressure in patients with type 2 diabetes. We assessed the relationship between home blood pressure variability, defined as coefficient of variation of mean of triplicate morning and evening blood pressure for 14 consecutive days, and various factors using univariate and multivariate linear regression analyses in 1114 patients with type 2 diabetes. Age (β=0.149, P<0.001), female sex (β=0.125, P=0.010), duration of diabetes mellitus (β=0.103, P=0.005), heart rate (β=0.136, P<0.001), current smoker (β=0.118, P=0.005), white-coat hypertension (β=0.136, P=0.002) and treatment with calcium channel blockers (β=−0.094, P=0.024) were independently associated with coefficient of variation of morning systolic blood pressure. Our findings implicate that factors that might be intervened such as heart rate, smoking status, use of antihypertensive medication in addition to age, sex and duration of diabetes mellitus are associated with variability in home blood pressure in patients with type 2 diabetes.