Shinji Maeda

The longitudinal quantitative assessment by transient elastography of chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin

The aim of this study was to assess the association between liver stiffness measured by transient elastography (FibroScan) and the efficacy of pegylated interferon alpha-2b plus ribavirin combination treatment for patients with chronic hepatitis C virus (HCV) infection. We prospectively studied 145 Japanese patients with chronic HCV infection. FibroScan was done at baseline, at the end of treatment, and at 48 and 96 weeks after the end of treatment. The FibroScan values were significantly decreased for sustained virological response (SVR) patients (the mean rate of change; -16.2%, -32.2% and -43.5%) in comparison with non-SVR patients (-7.2%, -2.1% and +17.3%) at the end of treatment (P=0.0127), and 48 weeks (P<0.0001) and 96 weeks (P<0.0001) after the end of treatment. Among the non-SVR patients, the FibroScan values were significantly decreased for patients with biochemical response (BR) (-17.9%, -30.0% and -27.1%) in comparison with non-BR (-4.1%, +6.4% and +30.6%) at the end of treatment (P=0.0270), and 48 weeks (P<0.0001) and 96 weeks (P<0.0001) after the end of treatment. The FibroScan values may predict a progressively better clinical outcome for patients with successful virological and biochemical responses.

Chronic Helicobacter pylori infection is associated with peripheral arterial disease

It is reported that Helicobacter pylori infection is associated with coronary atherosclerosis both epidemiologically and pathogenetically, but no conclusions have yet been reached. Therefore, we investigated the relationship between H. pylori infection and peripheral arterial disease (PAD). Sixty-nine patients with PAD attending Harasanshin General Hospital (Fukuoka, Japan) were compared with 143 controls (age-matched asymptomatic outpatients with hyperlipidemia). H. pylori infection was diagnosed by the detection of IgG antibodies, the 13C-urea breath test, and histological examination. Multiple logistic regression analysis was used to assess the data. The 69 PAD patients and 143 controls were aged from 50 to 92 years. According to the Fontaine classification, 43/69 PAD patients (62.3%) were grade I, 25 (36.2%) were grade II, and 1 (0.14%) was grade III. The prevalence of H. pylori infection was higher in the PAD patients than in the controls (79.7% versus 44.8%; P < 0.01). Stepwise logistic regression analysis revealed that H. pylori infection and hypertension had a significant influence on the occurrence of PAD. Our results suggest that chronic H. pylori infection may be one of the risk factors for PAD.

Both hepatitis C virus and Chlamydia pneumoniae infection are related to the progression of carotid atherosclerosis in patients undergoing lipid lowering therapy.

Recent experimental and epidemiological findings suggest that infectious agents may play a role in the development and progression of atherosclerosis. We previously reported that Chlamydia pneumoniae (C. pneumoniae) infection reduces the effectiveness of lipid-lowering therapy for carotid atherosclerosis and that this micro-organism may play a role in the progression of atherosclerosis. In this study, we investigated the possible association between hepatitis C virus (HCV) infection and carotid arteriosclerosis. A total of 165 asymptomatic hypercholesterolemic patients were randomized to receive probucol (500 mg/day, n=82) or pravastatin (10 mg/day, n=83) and were followed for 2 years. The 2-year change of the maximum common carotid artery intima-media thickness (Max-IMT) was the primary endpoint, while the Max-IMT and the incidence of major cardiovascular events were secondary endpoint. All serum samples were tested for antibody to HCV (anti-HCV) by enzyme-linked immunosorbent assay (ELISA), and all anti-HCV-positive samples were assayed for HCV RNA. Patients without HCV infection (n=25) showed a significant reduction of Max-IMT (-10.9%) (p<0.0001), while a small decrease of Max-IMT was noted in the patients with HCV infection (n=25) (-0. 3%). Significant differences in the reduction of serum total cholesterol and LDL cholesterol were found between patients with and without HCV infection (both p<0.0001). No significant difference in therapeutic effect was noted between the probucol and the pravastatin groups. After adjustment for confounding risk factors, both C. pneumoniae infection and anti-HCV positivity were associated with a greater risk of an increase in Max-IMT (8.5635 [1.3738-15.7532], p<0.05, 9.5040 [0.2886-18.7194], p<0.05, respectively). These findings suggest that both chronic HCV infection and C. pneumoniae infection can reduce the effectiveness of lipid-lowering therapy for carotid atherosclerosis, and that the HCV may play a role in the progression of atherosclerosis in HCV infected patients.

The association between fatal vascular events and risk factors for carotid atherosclerosis in patients on maintenance hemodialysis: Plaque number of dialytic atherosclerosis study

Atherosclerotic vascular diseases are a major cause of morbidity and mortality for end-stage renal disease patients. We followed prospectively 226 hemodialysis patients by carotid ultrasonography to determine if ultrasonographic markers are predictive of the prognosis of these patients. The end-point was death or completion of the five-year follow-up period. Fatal cerebrovascular and cardiovascular events were the most common cause of death. By multivariate analysis, diabetes mellitus (DM) (P=0.005), plaque number (PN) by ultrasonography (P=0.023), age (P=0.001), calcium-phosphate product (P=0.049), and serum albumin (P=0.009) were extracted as independent risk factors. The five-year increase of PN was significantly greater for DM patients than for non-DM patients. Moreover, PN was an independent marker of a fatal event, irrespective of DM status. Our results suggest that PN may be a useful predictor of the long-term prognosis of hemodialysis patients.

Association of hyperhomocysteinemia and Chlamydia pneumoniae infection with carotid atherosclerosis and coronary artery disease in Japanese patients

An elevated plasma level of homocysteine (Hcy) and infection by Chlamydia pneumoniae (C. pneumoniae) have been suggested as independent risk factors for carotid atherosclerosis (CA) and coronary artery disease (CAD), but the mechanisms involved are unclear. We investigated the correlation between positivity for antibody to C. pneumonia (anti-C. pneumoniae) and the Hcy level in patients with CA and CAD. The total plasma homocysteine (tHcy) concentration was determined in 99 patients with CA and 31 patients with CAD, as well as 119 controls with matched risk factors for atherosclerosis. The tHcy level was measured with a Bio-Rad microplate enzyme immunoassay. In the CAD group, the tHcy level (13.67 μmol/l) was significantly higher than that in other groups (CA group, 10.96 μmol/l; control group, 9.95 μmol/l; ANOVA, P = 0.0006). Positivity for anti-C. pneumoniae IgG was significantly more common in the CAD group (77.4%) than in the other groups (CA group, 53.5%; control group, 54.6%; ANOVA, P = 0.0490). There was no association between anti-C. pneumoniae IgA positivity or tHcy and conventional risk factors. However, anti-C. pneumoniae IgG positivity was significantly more common in subjects with higher tHcy levels than in those with low tHcy levels from each of the 3 groups. The CAD group had significantly higher tHcy levels, and tHcy was significantly associated with anti-C. pneumoniae IgG positivity. These findings indicate that elevation of tHcy is related to positivity for anti-C. pneumoniae IgG in patients with CAD.

High molecular weight form of adiponectin levels of Japanese patients with chronic hepatitis C virus infection

Aim:  The aim of the present study was to clarify the correlation between serum adiponectin level and the properties of hepatitis C virus (HCV).

Impact of peripheral arterial disease and acute ischemic stroke.

Peripheral arterial disease (PAD) is associated with coronary artery disease (CAD) and stroke, but data on the relationship between PAD and acute ischemic stroke are lacking. Therefore, we investigated this relationship. A total of 101 patients were enrolled on admission to Harasanshin General Hospital (Fukuoka, Japan) with their first ischemic stroke. All 101 patients underwent cranial CT and/or brain magnetic resonance imaging, duplex ultrasonography of the extracranial carotid arteries, and transthoracic echocardiography. The subjects were aged 41 to 92 years. PAD was present in 81/101 patients (80.2%), including 57/73 (78.1%) with small artery occlusion, 11/13 (84.6%) with large artery occlusion, and 13/15 (86.7%) with cardiogenic embolism. In 42 of these 81 patients (51.9%), PAD was asymptomatic. Serum apoprotein A1 levels were significantly higher and the intima-media thickness was significantly greater in the patients with PAD than in those without PAD. The modified Rankin scale score was significantly higher on admission in patients with PAD than in those without PAD. Stepwise logistic regression analysis revealed that the apoprotein A1 level and the modified Rankin scale score on admission were strongly associated with the occurrence of stroke in patients with PAD. Our results suggest that PAD is frequently associated with acute ischemic stroke. It may be important to perform screening for PAD in patients who have suffered an ischemic stroke.

Efficacy and safety of ezetimibe for Japanese patients with dyslipidaemia: The ESSENTIAL Study.

AbstractBackground: There are insufficient data available on the efficacy and safety of lipid-lowering therapy for patients with dyslipidaemia complicated by multiple metabolic abnormalities. Objective: This study aimed to examine the efficacy and safety of ezetimibe 10mg/day administered to Japanese patients with dyslipidaemia. Methods: This was a prospective study carried out at Kyushu University Hospital, Fukuoka, Japan. In one group, ezetimibe 10mg/day alone was given to 33 patients for 12 weeks. In the other two groups, ezetimibe was given with an HMG-CoA reductase inhibitor (statin) to 13 patients for 12 weeks: pravastatin 10mg/day (n = 7) or rosuvastatin 2.5mg/day (n = 6). The main outcome measure was the effect of ezetimibe on low-density lipoprotein cholesterol (LDL-C) and other lipid levels from baseline to 12 weeks. Results: After 12 weeks of treatment, all groups showed marked reductions in mean ± SD LDL-C level (from 155.4±22.0 mg/dL at baseline to 118.0 ± 28.1 mg/dL, i.e. −37.4 mg/dL; p< 0.001). The mean reduction in LDL-C level with ezetimibe monotherapy was significantly greater in patients with impaired LDL-C metabolism, glucose metabolism or hypertension than in those without such abnormalities (−21.0% vs −8.4%, p<0.01; −22.7% vs −9.5%, p < 0.05; and −22.5% vs −5.9%, p < 0.05; respectively). The reduction in LDL-C levels with ezetimibe monotherapy was also correlated with the number of metabolic abnormalities (r = 0.426, p = 0.013). Conclusions: Both ezetimibe monotherapy and combination therapy with ezetimibe and a statin were able to safely and effectively control LDL-C levels in Japanese patients with dyslipidaemia, including those with metabolic abnormalities.