Michio Inukai

Visit-to-visit variability in blood pressure over a 1-year period is a marker of left ventricular diastolic dysfunction in treated hypertensive patients.

Although visit-to-visit variability in systolic blood pressure (SBP) has recently been demonstrated to be a strong predictor of stroke, there are no data about relationships between SBP variability and cardiac damage in hypertensive patients. We compared relationships between visit-to-visit variability in SBP and left ventricular (LV) diastolic dysfunction with the relationships between the mean SBP value and cardiac parameters in treated patients. Forty treated hypertensive patients (69±9 years of age) had their blood pressure measured at outpatient clinics every 1 or 2 months over a 1-year period. The standard deviation (s.d.) of SBP and the difference between the maximum and minimum SBPs during this year were calculated to assess visit-to-visit variability. The mean SBP during the year was also calculated. LV diastolic function was assessed by the ratio (E/A) of early (E) and late (A) diastolic transmitral flows, early diastolic mitral annular velocity (e′) and the ratio (E/e′) of E to e′ using Doppler echocardiography. E/A only correlated with the s.d. of SBP (r=−0.327, P=0.040), whereas e′ correlated with s.d. of SBP (r=−0.496, P=0.001) and maximum–minimum SBP difference (r=−0.490, P=0.001). E/e′ correlated with s.d. of SBP (r=0.384, P=0.014), maximum–minimum SBP difference (r=0.410, P=0.009), and the mean value of SBP (r=0.349, P=0.028). Multiple regression analysis demonstrated only the maximum–minimum SBP difference independently associated with E/e′ (β=0.410, P=0.009). Thus, the visit-to-visit variability of SBP showed better correlation with LV diastolic dysfunction than mean values of SBP. High visit-to-visit variability of SBP was associated with LV diastolic dysfunction and may constitute a high risk for diastolic heart failure in hypertensive patients.

Comparison of central blood pressure and cardio-ankle vascular index for association with cardiac function in treated hypertensive patients

Recent automated applanation tonometry can measure radial pulse wave-derived central blood pressure (CBP), which has shown a prognostic value independently of peripheral blood pressure. However, CBPs clinical significance has not been fully established. We examined the associations between CBP and cardiac structure and function by comparing them with those of arterial stiffness assessed by cardio-ankle vascular index (CAVI) in treated hypertensive patients. Enrolled in the study were 102 patients (71±7 years) with treated hypertension. The transmitral early-to-atrial velocity ratio (E/A), peak systolic (S′), early diastolic (E′) mitral annular velocities and the Tei index were measured as indexes of cardiac function derived from conventional and tissue Doppler echocardiography. Left ventricular mass index (LVMI) was measured as an index of LV hypertrophy. CBP and CAVI were measured just after echocardiographic examination. CBP, but not CAVI, correlated with LVMI (r=0.306, P<0.01). Although CBP correlated only with the Tei index (r=0.201, P<0.05), CAVI correlated with E/A (r=−0.387, P<0.001), S′ (r=−0.270, P<0.01), E′ (r=−0.362, P<0.01) and the Tei index (r=0.339, P<0.01). Stepwise regression analysis revealed that neither CBP nor CAVI was independently associated with E/A, S′ or E′. However, CAVI, but not CBP, was independently associated with the Tei index (β coefficient=0.311, P<0.001), reflecting both LV systolic and diastolic function. In conclusion, CBP may be suitable for detecting LV hypertrophy. In contrast, CAVI may be suitable for detecting LV dysfunction. This difference, suggesting the clinical value of each parameter, should be kept in mind when we use CBP and CAVI for assessing arteriosclerosis in treated hypertension.

Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus–related chronic liver disease

The relationship between selenium (Se) deficiency and insulin resistance has not much been established in persistent hepatitis C virus (HCV) infection, although Se deficiency is often observed in patients with liver cirrhosis. We hypothesized that the decreased serum Se levels were associated with the severity of hepatic fibrosis or insulin resistance in patients with HCV-related chronic liver disease (CLD). To test the hypothesis, 52 patients with HCV-related CLD including chronic hepatitis and liver cirrhosis were enrolled in this study. The severity of hepatic fibrosis was divided into 4 categories (F(1) through F(4)) according to the new Inuyama classification. Insulin resistance was defined by the homeostasis model for assessment of insulin resistance value. Serum Se levels significantly declined in proportion to the severity of hepatic fibrosis and were positively correlated with serum albumin (r = 0.372, P = .0065) and zinc (r = 0.403, P = .0081) concentrations. Serum Se levels were also linked to glutathione peroxidase activities in the sera of the enrolled patients (r = 0.374, P = .0148). By contrast, serum Se levels were inversely correlated with the homeostasis model for assessment of insulin resistance values (r = -0.304, P = .0338). However, serum Se levels were independent of HCV genotype and loads of HCV-RNA. These findings suggest that Se deficiency was associated with the severity of hepatic fibrosis in patients with HCV-related CLD and that Se deficiency was likely to be one of the factors contributing to insulin resistance in those patients.

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study

EAGLE was a randomized, multicenter phase III study which evaluated the superiority of bevacizumab 10 mg/kg plus FOLFIRI compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC previously treated with first-line bevacizumab plus an oxaliplatin-based regimen. The results suggest that the higher 10 mg/kg dose offers no clear clinical benefit compared with bevacizumab 5 mg/kg in this setting.

Aortic root dilatation as a marker of subclinical left ventricular diastolic dysfunction in patients with cardiovascular risk factors.

Consensus is lacking about the clinical importance of aortic root dilatation in assessment of the risk of cardiovascular disease. In this study, correlations between aortic root diameter and echocardiographic features of left ventricular (LV) diastolic function were investigated in 333 patients with at least one cardiovascular risk factor (hypertension, diabetes or dyslipidaemia) and preserved LV systolic function. Aortic root diameter was measured by M-mode echocardiography, and LV diastolic function was evaluated by measuring the peak velocity of early (E) and late (A) diastolic transmitral blood flow and peak early diastolic mitral annular velocity (E′) by Doppler echocardiography. Linear regression analysis showed that, in men, age was no related to aortic root diameter but hypertension and LV hypertrophy were, whereas the converse was true in women. The parameters E, E/A ratio and E′, were related to aortic root diameter in both sexes. Stepwise multiple regression analysis confirmed that E in women and E′ in men were independently associated with aortic root diameter. It is concluded that aortic root dilatation might be a useful marker of subclinical LV diastolic dysfunction. Patients with preserved systolic function showing aortic root dilatation should, therefore, be given preventative therapy against LV diastolic heart failure.

Clinical Significance of Autoantibodies to P53 Protein in Patients with Autoimmune Liver Diseases

BACKGROUND Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies. OBJECTIVE To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH⁄PBC overlap syndrome (AIH⁄PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases. METHODS Forty patients with AIH, 41 patients with PBC, eight patients with AIH⁄PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53. RESULTS Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH⁄PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH⁄PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH⁄PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213). CONCLUSION The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH⁄PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH⁄PBC OS.

Clinical Relevance of Antibodies to Cardiolipin in Patients with Chronic Hepatitis C

The significance of antibodies to cardiolipin (anti‐CL) remains uncertain in patients with chronic hepatitis C (CH‐C). The main purpose of this study was to elucidate the clinical characteristics of patients with CH‐C seropositive for anti‐CL. The prevalence of anti‐CL and clinical parameters associated with anti‐CL in those patients were examined. Six of the 45 (13%) patients with CH‐C had anti‐CL. However, none of these six CH‐C patients fulfilled the criteria for antiphospholipid syndrome. Serum triglyceride and apolipoprotein B (ApoB) levels in CH‐C patients with anti‐CL were significantly higher than those in CH‐C patients without anti‐CL. Serum triglyceride levels positively correlated with serum ApoB levels. CH‐C patients with anti‐CL had significantly more progressive hepatic fibrosis than those without anti‐CL. The degree of 8‐hydroxy 2′‐deoxyguanosine (8‐OHdG) expression in the liver tissue was more severe in CH‐C patients with anti‐CL than in those without it. However, the emergence of anti‐CL in CH‐C patients was independent of insulin resistance, hepatic steatosis, and iron overload. These findings suggest that the emergence of anti‐CL is associated with oxidative stress and that CH‐C patients seropositive for anti‐CL have clinical characteristics of hypertriglyceridemia, which derives from the facilitation of ApoB synthesis, and progressive hepatic fibrosis. J. Clin. Lab. Anal. 26:342‐348, 2012.

Differences in left ventricular diastolic dysfunction between eccentric and concentric left ventricular hypertrophy in hypertensive patients with preserved systolic function.

Left ventricular (LV) hypertrophy (LVH) may be eccentric or concentric (2 × LV posterior wall thickness relative to LV end-diastolic dimension ≤ 0.42 or > 0.42, respectively). The LV diastolic function between age-matched hypertensive patients with eccentric and concentric LVH was compared in the present study. Echocardiography was used to measure LV mass index (LV mass/body surface area; LVMI) as an index of LVH. LV diastolic function was assessed by measurements of peak early transmitral flow velocity (E)/peak late transmitral flow velocity (A) (the E/A ratio), peak early diastolic mitral annular velocity (e′) and the E/e′ ratio. Although LVMI, E/A and e′ did not differ between the two groups, E/e′ was significantly higher (worse) in patients with concentric LVH (13.4 ± 5.4) than in those with eccentric LVH (11.1 ± 3.6). Among hypertensive patients with LVH, those with concentric LVH may, therefore, have more severe LV diastolic dysfunction than those with eccentric LVH even if their LVMIs, which reflect the degree of LVH, are similar.

Relationship between arterial stiffness and variability in systolic blood pressure during a single clinic visit in patients with hypertension

Objective To examine factors affecting systolic blood pressure (SBP) variability during a single clinic visit, in treated hypertensive patients. Methods Hypertensive patients were recruited to this observational study. Blood pressure was measured using an automated blood pressure monitor when each patient arrived at the outpatient clinic and again when they saw the physician. Mean SBP and SBP variability during a single clinic visit were calculated. The cardio–ankle vascular index (CAVI), as a marker of arterial stiffness, was also measured. Results A total of 57 treated hypertensive patients (mean age 71 years) were included in the study. The mean SBP was positively correlated with age (r = 0.457), while SBP variability was positively correlated with age (r = 0.383), CAVI (r = 0.330), and glycosylated haemoglobin (r = 0.345) and triglyceride levels (r = 0.299). Conclusion Variability in SBP during a single clinic visit showed better correlations with arterial stiffness and risk factors for atherosclerosis than did mean SBP. Large SBP variability during a single clinic visit may reflect progression of atherosclerosis, in treated hypertensive patients.

Contribution of Zinc Deficiency to Insulin Resistance in Patients with Primary Biliary Cirrhosis

The relationship between metabolic abnormalities of trace elements and insulin resistance has been established. Recent studies have revealed that insulin resistance is associated with autoimmune responses. The purpose of this study was to examine the correlation between zinc or copper metabolism and insulin resistance in patients with primary biliary cirrhosis (PBC). Sixteen patients with PBC were divided into two groups: early and advanced stage disease. The overall value of the homeostasis model assessment of insulin resistance (HOMA-IR) in patients with advanced stage PBC was significantly higher than that in patients with early stage PBC, although the mean value in advanced stage PBC was significantly lower than that in hepatitis C virus (HCV)-related liver cirrhosis. There was an inverse correlation between serum zinc concentrations and HOMA-IR values in patients with PBC, while we found no correlation between serum copper levels and HOMA-IR values. HOMA-IR values were inversely associated with peripheral platelet counts, indicating the relationship between insulin resistance and hepatic fibrosis. These results suggest that zinc deficiency plays important roles of insulin resistance and subsequent hepatic fibrosis in patients with PBC, although insulin resistance in advanced stage PBC was significantly milder than that in HCV-related liver cirrhosis.