Taro Minagawa

Risk stratification using serum concentrations of cardiac troponin T in patients with end-stage renal disease on chronic maintenance dialysis.

BACKGROUND It has been recently suggested that cardiac troponin T (cTnT) may be more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in patients on chronic dialysis. METHODS We prospectively compared the predictive value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100 consecutive outpatients on chronic dialysis without acute coronary syndromes over a period of 3 months, and assessed whether the combination of cTnT with clinical information including age, duration of dialysis, and medical histories was useful for risk stratification of these patients. During the 2-year follow-up period, 19 patients died, mostly due to cardiac causes (53%). RESULTS The area under the receiver operator characteristic (ROC) curve for the cTnT as predictor of both overall and cardiac death was significantly greater than the area under the cTnI curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l and/or history of heart failure, the overall and cardiac mortality rate for the low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9). CONCLUSION cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP and BNP in patients on chronic dialysis. The combination of elevated cTnT and a history of heart failure may be a highly effective means of risk stratification of these patients.

C-reactive protein, lipoprotein(a), homocysteine, and male sex contribute to carotid atherosclerosis in peritoneal dialysis patients

BACKGROUND In patients with end-stage renal disease, the morbidity and mortality of cardiovascular disease are substantially greater than in the general population. Advancement in understanding the pathogenesis of atherosclerotic vascular disease suggests a central role of inflammation in atherogenesis. However, clinical data evaluating the role of inflammation in atherogenesis are sparse in peritoneal dialysis (PD) patients. METHODS We measured serum C-reactive protein (CRP), intact parathyroid hormone, lipoprotein(a) [Lp(a)], interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor soluble receptor (TNF-sR), fibrinogen, and plasma homocysteine (Hcy), as well as intima-media thickness (IMT) and number of atherosclerotic plaques (plaque score [PS]) in the carotid arteries by means of carotid B-mode ultrasonography in 59 PD patients (35 men, 24 women; mean age, 52.4 years; average dialysis period, 36 months). All patients had chronic glomerulonephritis. RESULTS Sixty-eight percent of PD patients had at least 1 plaque. Serum CRP level was greater than the upper limit of the normal range in 52.5% of patients. Compared with PD patients with normal CRP levels, concentrations of such proinflammatory cytokines as IL-1Ra and TNF-sR, Lp(a), and Hcy were increased in PD patients with elevated CRP levels. However, no differences in plasma fibrinogen and intact parathyroid hormone levels were found between PD patients with increased and normal CRP levels. In a multiple regression model, age, male sex, CRP level, and Lp(a) level were independent predictors of IMT. Similarly, male sex, CRP level, Lp(a) level, and Hcy level were independent correlates of PS. CONCLUSION This study suggests that Lp(a) and Hcy levels and male sex, and especially CRP level, have an important role in carotid atherosclerosis in PD patients.

Renoprotective Effect of the Addition of Losartan to Ongoing Treatment with an Angiotensin Converting Enzyme Inhibitor in Type-2 Diabetic Patients with Nephropathy

Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria- or proteinuria-reducing effects. To many patients who are nonresponsive to monotherapy with these agents, combination therapy appears to be a good treatment option. In the present study, we examined the effects of the addition of an ARB (losartan) followed by titration upon addition and at 3 and 6 months (n=14) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months (n=20) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure (BP) of 130/80 mmHg and to reduce urinary albumin to <30 mg/day. During the 12-month treatment, addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline value, respectively. However, the effects on both BP and urinary albumin were not significantly different between the two therapies. In conclusion, addition of losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP, and provided renal protection in patients with type-2 diabetic nephropathy.

Relation between functional stenosis and tissue characterization of intermediate coronary plaques in patients with stable coronary heart disease

BACKGROUND Tissue characteristics of coronary plaques can be evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), while fractional flow reserve (FFRmyo) is an index of functional coronary stenosis. We assessed the relation between functional stenosis and the characteristics of plaque tissue using FFRmyo and IB-IVUS. METHODS AND RESULTS A total of 17 lesions with 75%-stenosis assessed visually by coronary angiography from 17 stable angina patients (64.2+/-9.1 years old, 11 males) were studied. IB-IVUS was evaluated in the most stenotic cross-sectional area. Using commercially available software, coronary plaques were assessed for calcification (CA), fibrosis (F), and lipid pool (LP). Lesions were localized in the left anterior descending artery in 11 patients, the left circumflex in 3, and the right coronary artery in 3. On quantitative coronary angiography, the percent diameter stenosis (%DS) was 60.5+/-7.3%. Plaque burden was 71.4+/-9.1%, FFRmyo was 0.74+/-0.13. The tissue component of the plaques was: CA(%), 3.0+/-2.4%; F(%), 60.5+/-9.6%; LP(%), 37.2+/-11.0%. Significant correlation was not observed between %DS or plaque burden and FFRmyo, structural stenosis and plaque characterization, nor between CA(%) and FFRmyo. There was a positive correlation between F(%) and FFRmyo (r=0.62, p<0.01) and a negative correlation between LP(%) and FFRmyo (r=-0.52, p<0.05). CONCLUSION Our findings indicate that the tissue characteristics of coronary plaques in intermediate lesion affect functional stenosis.

Impact of tissue characteristics on luminal narrowing of mild angiographic coronary stenosis: assessment of integrated backscatter intravascular ultrasound.

Integrated backscatter intravascular ultrasound (IB-IVUS) is a useful method for analyzing coronary plaque tissue. We evaluated whether tissue composition determined using IB-IVUS is associated with the progression of stenosis in coronary angiography. Sixty-three nontarget coronary lesions in 63 patients with stable angina were evaluated using conventional IVUS and IB-IVUS. IB-IVUS images were analyzed at 1-mm intervals for a length of 10 mm. After calculating the relative areas of the tissue components using the IB-IVUS system, fibrous volume (FV) and lipid volume (LV) were calculated through integration of the slices, after which percentages of per-plaque volume (%FV/PV, %LV/PV) and per-vessel volume (%FV/VV, %LV/VV) were calculated. Progression of coronary stenosis was interpreted from the increase in percent diameter stenosis (%DS) from baseline to the follow-up period (6–9 months) using quantitative coronary angiography. %DS was 24.1 ± 12.8 % at baseline and 23.2 ± 13.7 % at follow-up. Using IB-IVUS, LV was 31.7 ± 10.5 mm3, and %LV/PV and %LV/VV were 45.6 ± 10.3 % and 20.2 ± 6.0 %, respectively. FV, %FV/PV, and %FV/VV were 35.5 ± 12.1 mm3, 52.1 ± 9.5 %, and 23.4 ± 7.1 %, respectively. The change in %DS was −0.88 ± 7.25 % and correlated closely with %LV/VV (r = 0.27, P = 0.03) on simple regression. Multivariate regression after adjustment for potentially confounding risk factors showed %LV/VV to be correlated independently with changes in %DS (r = 0.42, P = 0.02). Logistic regression analysis after adjusting for confounding coronary risk factors showed LV (odds ratio 1.08; 95 % confidence interval 1.01–1.16; P = 0.03) and %LV/VV (odds ratio 1.13; 95 % confidence interval 1.01–1.28; P = 0.03) to be independent predictors of the progression of angiographic coronary stenosis. Our findings suggest that angiographic luminal narrowing of the coronary artery is likely associated with tissue characteristics. IB-IVUS may provide information about the natural progression of luminal narrowing in coronary stenosis.

Comparative effect of candesartan and amlodipine, and effect of switching from valsartan, losartan, telmisartan and olmesartan to candesartan, on early morning hypertension and heart rate

Abstract Early morning hypertension and a high heart rate are risk factors for cardiovascular disease. The DOHSAM study was designed to evaluate the effect of candesartan on early morning blood pressure (BP) and heart rate in hypertensives. We used a prospective, randomized, open-label design. Protocol 1: Patients with early morning BP more than 135/85 mmHg who were not on any antihypertensive drug or on candesartan were given amlodipine 2.5 mg/day (amlodipine group, n = 22) or added candesartan 4 mg/day (candesartan group, n = 36). Candesartan or amlodipine was added when BP did not fall lower than 135/85 mmHg. Protocol 2: Early morning hypertensives who were on other angiotensin receptor blockers (ARBs) (n = 50) such as valsartan, losartan, telmisartan and olmesartan were switched to candesartan. Early morning BP significantly decreased in the candesartan group compared with the amlodipine group 9 and 12 months after treatment. Switching other ARBs except for olmesartan to candesartan significantly decreased early morning systolic and diastolic BP 3, 6, 9 and 12 months after treatment. Heart rate in the office significantly decreased by switching to candesartan 6, 9 and 12 months after treatment. In conclusion, candesartan significantly decreased early morning hypertension more than amlodipine or other ARBs except olmesartan in early morning hypertensives.

Long-term effects of the alpha, beta-blocker arotinolol on stable effort angina pectoris using 24-hour ambulatory electrocardiographic monitoring: an open-label, pilot study

Abstract Background: Beta-blockers are effective in patients with effort angina pectoris. However, there have been no previous reports on the long-term effects of beta-blocker therapy using ambulatory electrocardiographic (AECG) monitoring according to a MEDLINE ® search. Objective: This study was undertaken to assess the long-term effects of the alpha, beta-blocker arotinolol in patients with stable effort angina pectoris using AECG monitoring. Methods: This pilot study involved patients with Canadian Cardiovascular Society class I or II stable effort angina pectoris and left ventricular ejection fraction >40% assessed using 2-dimensional echocardiography in whom percutaneous transluminal coronary angioplasty and coronary artery bypass grafting had not been performed. Patients were excluded if they were >75 years of age, had congestive heart failure of New York Heart Association class III or IV, or had a confirmed diagnosis of an illness likely to shorten their life span (eg, cancer, cirrhosis). Effort angina pectoris was diagnosed based on chest pain on effort and myocardial ischemia as demonstrated by stress thallium-201 myocardial perfusion scintigraphy and significant ST-segment depression on exercise electrocardiogram. The alpha, beta-blocker arotinolol 20 mg/d, divided into 2 doses of 10 mg each, was administered orally for 2 years. Patients were seen by the same physician at 2-week intervals during the first 6 weeks of treatment and at 4-week intervals thereafter, at which times chest pain, nitrate consumption, blood pressure, and heart rate were assessed. AECG monitoring was performed before treatment, at 6 weeks, and after 2 years of treatment. Results: Results were assessable in 12 of 18 patients at 4 institutions (6 withdrew from the study within 4 weeks of treatment) with a mean (±SD) age of 65 ± 3 years. The number of episodes per day of chest pain decreased significantly ( P P P P P Conclusions: Arotinolol improved the incidence and duration of ST-segment depression in patients with stable effort angina pectoris on AECG monitoring by decreasing heart rate. Because the improvement was more marked after 2 years than after 6 weeks, we concluded that arotinolol is beneficial in the long-term treatment of patients with stable effort angina pectoris, although a larger study using a control group is needed to confirm our results.