Ki-ichiro Tomiyasu

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.

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.

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.

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.

Visit-to-visit variability in systolic blood pressure is a novel risk factor for the progression of coronary artery calcification

Recent studies have suggested that variability in the systolic blood pressure (SBP) is a risk factor for cardiovascular disease (CVD). The aim of this study was to investigate the relationship between variability in the SBP and the progression of coronary artery calcification (CAC), which is a useful marker for CVD. We measured SBP in 164 consecutive patients at every visit over the course of a year and calculated the coefficient of variation and s.d. of the SBP. We performed a follow-up study using multislice computed tomography to assess the progression of the CAC score, the mean interval of which was 3.93±1.36 years. We then evaluated the relationship between variability in the SBP and progression of the CAC score. The coefficient of variation for the SBP correlated positively with the progression of the CAC score (r=0.4382, P<0.0001). Multiple regression analysis demonstrated that the coefficient of variation of the SBP (β=0.3826, P<0.0001) was independently associated with the progression of the CAC score. The visit-to-visit variability in SBP could be a novel risk factor for the progression of CAC.

Low serum bilirubin concentration is a novel risk factor for the development of albuminuria in patients with type 2 diabetes

OBJECTIVE Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes. MATERIALS AND METHODS We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2±0.9years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria. RESULTS During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93). CONCLUSIONS Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.

Low insulin level is associated with aortic stiffness

Recent studies have demonstrated that hyperinsulinemia is a risk factor for cardiovascular disease. The aim of this study was to evaluate the relationship between serum insulin level and the cardio-ankle vascular index (CAVI), which was developed as a marker of arterial stiffness. We performed a cross-sectional study of 260 consecutive and nondiabetic subjects with clinical suspicion of coronary heart disease. We measured CAVI in all subjects. A standard 75-g oral glucose tolerance test was performed, and plasma glucose and serum insulin levels were measured in venous blood collected at 0, 30, 60 and 120 min after the test. Statistical analyses were conducted for four subgroups according to the insulin area under the concentration time curve (InsAUC). Mean CAVI and InsAUC were 8.7 and 109.5 μIU ml–1 h–1, respectively. Unadjusted analysis demonstrated that the InsAUC quartiles were significantly associated with CAVI (P<0.0001), and the lowest InsAUC quartile (P=0.001) had a lower glucose AUC. Analysis of covariance demonstrated that the lowest InsAUC quartile had the highest CAVI, and, after adjusting for several coronary risk factors, the highest InsAUC quartile had a higher CAVI than the second and third InsAUC quartiles (P<0.0001). In conclusion, the lowest InsAUC quartile was related to CAVI, although the lowest InsAUC quartile maintained glucose homeostasis in this study population. Both hyperinsulinemia and low insulin level are independently associated with CAVI.

Association of coronary artery calcification with liver fibrosis in Japanese patients with NAFLD

Cardiovascular events are the leading cause of death among patients with non‐alcoholic fatty liver disease (NAFLD), but their relationship remains unclear. This study examined the association between coronary atherosclerosis and liver fibrosis, represented by the coronary artery calcification (CAC) score and non‐invasive fibrosis markers, respectively.

High-sensitivity cardiac troponin T is associated with coronary artery calcification

OBJECTIVE Recent studies have suggested that high-sensitivity cardiac troponin T (hs-cTnT) may be useful for detecting subclinical atherosclerosis and assessing cardiovascular disease risk. The aim of this study was to investigate whether serum hs-cTnT is associated with the degree of coronary artery calcification. METHODS We measured serum hs-cTnT concentrations and performed multidetector row coronary CT in 215 consecutive, stable patients with clinical suspicion of coronary artery disease. Nonenhanced coronary CT was performed to determine the coronary calcium score, and contrast-enhanced coronary CT was performed to identify obstructive coronary artery disease. We then evaluated the relationship between serum hs-cTnT concentrations and the degree of coronary calcium or obstructive coronary artery disease using multiple regression analysis and logistic regression models. RESULTS Multiple regression analysis demonstrated that serum hs-cTnT concentrations and calcium score were independently associated after logarithmic transformation (β = 0.348; P < .0001). Logistic regression analyses demonstrated that serum hs-cTnT concentration was associated with an increased odds of an Agatston score >10 (odds ratio, 1.250; 95% confidence interval [CI], 1.150-1.378), an Agatston Score >400 (odds ratio, 1.101; 95% CI, 1.054-1.157), and obstructive coronary artery disease (odds ratio, 1.119; 95% CI, 1.066-1.185). CONCLUSION Serum hs-cTnT is associated with coronary calcium in individuals with suspected coronary disease and may therefore be a marker to detect subclinical atherosclerosis.

Association of coronary artery calcification with liver fibrosis in Japanese patients with non-alcoholic fatty liver disease.

Cardiovascular events are the leading cause of death among patients with non‐alcoholic fatty liver disease (NAFLD), but their relationship remains unclear. This study examined the association between coronary atherosclerosis and liver fibrosis, represented by the coronary artery calcification (CAC) score and non‐invasive fibrosis markers, respectively.