[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to compare the effects of the aldosterone blocker eplerenone and thiazide-like diuretic indapamide on blood pressure (BP) and target organs with reference to salt intake in hypertensive outpatients. Twenty hypertensive patients (nine women and 11 men, mean age 71 ± 13 years) with inadequate BP control despite taking calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) were administered eplerenone (50 mg/day) or indapamide (1 mg/day) for 3 months each in a randomized crossover manner. Salt intake, BP and indices of organ damage were assessed at baseline and at the end of each treatment period. Eplerenone and indapamide were similarly effective in lowering office and home BPs. Both the treatments significantly reduced the estimated glomerular filtration rate (eGFR) and increased serum uric acid levels. The treatment with eplerenone significantly increased serum potassium levels, whereas the treatment with indapamide significantly decreased them. The treatment with eplerenone significantly decreased pulse wave velocity and urinary 8-hydroxydeoxyguanosine levels. These changes were not significantly affected by the treatment with indapamide. In conclusion, eplerenone and indapamide were similarly effective in lowering office and home BPs in hypertensive patients treated with CCBs and ARBs. Eplerenone may exert more favorable effects on arterial stiffness and oxidative stress.
No preview · Article · May 2015 · Clinical and Experimental Hypertension
[Show abstract][Hide abstract] ABSTRACT: To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA.
We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA.
A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055).
Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.
No preview · Article · Apr 2015 · Clinical and Experimental Hypertension
[Show abstract][Hide abstract] ABSTRACT: Risk stratification of acute kidney injury (AKI) is important for acute decompensated heart failure (ADHF). The aim of this study was to determine whether clinical markers, such as the blood urea nitrogen/creatinine ratio (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for mortality.Methods and Results:In all, 371 consecutive ADHF patients were enrolled in the study. AKI was defined as serum creatinine ≥0.3 mg/dl or a 1.5-fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI occurred in 99 patients; 55 patients died during the 12-month follow-up period. Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non-AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups) revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001). Cox's proportional hazard analysis revealed an association between AKI+high BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach statistical significance. When patients were grouped according to AKI and median BUN or creatinine values at admission, AKI was associated with mortality, regardless of BUN or creatinine.
The combination of AKI and elevated BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk stratification of AKI.
No preview · Article · Apr 2015 · Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: Aerobic exercise has been recommended in the management of hypertension. However, few studies have examined the effect of walking on ambulatory blood pressure (BP), and no studies have employed home BP monitoring. We investigated the effects of daily walking on office, home, and 24-h ambulatory BP in hypertensive patients. Sixty-five treated or untreated patients with essential hypertension (39 women and 26 men, 60 ± 9 years) were examined in a randomized cross-over design. The patients were asked to take a daily walk of 30–60 min to achieve 10 000 steps/d for 4 weeks, and to maintain usual activities for another 4 weeks. The number of steps taken and home BP were recorded everyday. Measurement of office and ambulatory BP, and sampling of blood and urine were performed at the end of each period. The average number of steps were 5349 ± 2267/d and 10 049 ± 3403/d in the control and walking period, respectively. Body weight and urinary sodium excretion did not change. Office, home, and 24-h BP in the walking period were lower compared to the control period by 2.6 ± 9.4/1.3 ± 4.9 mmHg (p < 0.05), 1.6 ± 6.8/1.5 ± 3.7 mmHg (p < 0.01), and 2.4 ± 7.6/1.8 ± 5.3 mmHg (p < 0.01), respectively. Average 24-h heart rate and serum triglyceride also decreased significantly. The changes in 24-h BP with walking significantly correlated with the average 24-h BP in the control period. In conclusion, daily walking lowered office, home, and 24-h BP, and improved 24-h heart rate and lipid metabolism in hypertensive patients. However, the small changes in BP may limit the value of walking as a non-pharmacologic therapy for hypertension.
No preview · Article · Mar 2015 · Clinical and Experimental Hypertension
[Show abstract][Hide abstract] ABSTRACT: Abstract The purpose of the present study was to investigate awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic. Subjects included 330 patients, with a mean age of 69 ± 12 years, who were followed at a hypertension clinic and 200 patients, with a mean age of 67 ± 11 years, who were followed at a general clinic. We estimated 24-h salt excretion using spot urine samples and checked the awareness of salt intake using a self-description questionnaire. The number of antihypertensive drugs available at the hypertension clinic was significantly higher than that at the general clinic (2.2 ± 1.1 versus 1.6 ± 0.9, p < 0.01); however, no significant difference was observed in office systolic blood pressure between the two groups. Urinary salt excretion was significantly lower at the hypertension clinic than at the general clinic (8.7 ± 2.5 versus 9.3 ± 2.5 g/d, p < 0.01). The rate of achievement of salt intake <6 g/d was 15% at the hypertension clinic and 6% at the general clinic. In patients with excessive salt intake (≥10 g/d), 28% of patients at the hypertensive clinic and 23% at the general clinic thought that their salt intake was low. Urinary salt excretion in hypertensive patients was lower at a hypertensive clinic than at a general clinic. This may be due to the professional nutritional guidance at the hypertension clinic. However, most patients could not comply with the guidelines, and the awareness of salt restriction in patients with excessive salt intake was low.
No preview · Article · Dec 2014 · Clinical and Experimental Hypertension
[Show abstract][Hide abstract] ABSTRACT: Since acute kidney injury (AKI) is not always related to mortality in patients with acute decompensated heart failure (ADHF), the aim of this study was to focus on onset time of AKI and its clinical importance. A total of 371 ADHF patients were included. The impact of AKI (≥0.3 mg/dl or 1.5-fold increase in serum creatinine level within 48 h) with early onset (≤4 days from admission) or late onset (≥5 days from admission) was assessed. AKI occurred in 99 patients, who were divided into two groups according to the median onset time of AKI: 50 with early onset of AKI and 49 with late onset of AKI. The maximum increase in serum creatinine level from admission was greater in patients with late onset of AKI than in patients with early onset of AKI (p = 0.012). Patients with late onset of AKI had a higher 12-month mortality rate than that in patients with early onset of AKI (log-rank test, p = 0.014). Late onset of AKI was an independent predictor of mortality (hazard ratio: 3.39, 95 % confidence interval: 1.84-6.18, p < 0.001). Late onset of AKI was associated with high blood urea nitrogen level at admission and intravenous administration of dobutamine. In conclusion, late onset of AKI related to high blood urea nitrogen level and intravenous administration of dobutamine, but not early onset of AKI, is linked to high mortality rate. Onset time of AKI may be useful for risk stratification of mortality in ADHF patients developing AKI.
No preview · Article · Aug 2014 · Heart and Vessels
[Show abstract][Hide abstract] ABSTRACT: Background and aim:
The infusion of chronic angiotensin II (Ang II) has been shown to promote renal interstitial fibrosis. To evaluate the pathophysiological significance of the natriuretic peptide-GC-A system, we infused Ang II (1.0 mg/kg/day) in GC-A-deficient mice (GC-A-KO).
We used 5 groups (Wild-Saline n = 12, Wild-Ang II n = 14, GC-A-KO-Saline n = 11, GC-A-KO-Ang II n = 13, and GC-A-KO-Ang II-Hydralazine n = 10). Saline or Ang II was infused subcutaneously using an osmotic minipump for 3 weeks. Hydralazine was administered orally (0.05 g/L in drinking water).
Systolic blood pressure was significantly higher in the GC-A-KO-Saline group (130 ± 12 mmHg) than in the Wild-Saline group (105 ± 30 mmHg), and was similar to that in the Wild-Ang II (141 ± 17 mmHg) and GC-A-KO-Ang II-Hydralazine (140 ± 20 mmHg) groups. Systolic blood pressure was significantly higher in the GC-A-KO-Ang II group (159 ± 21 mmHg) than in the 4 other groups. Renal tubular atrophy and interstitial fibrosis were significantly more severe in the GC-A-KO-Ang II group (atrophy 13.4 %, fibrosis 12.0 %) than in the Wild-Saline (0, 2.0 %), Wild-Ang II (2.9, 4.4 %), and GC-A-KO-Saline (0, 2.6 %) groups. Hydralazine could not inhibit this aggravation (GC-A-KO-Ang II-Hydralazine 13.5, 11.3 %). The expression of monocyte chemotactic protein-1 in tubular cells, and F4/80 and alpha-smooth muscle actin in the interstitium was clearly detected in the Ang II-infused wild and GC-A-KO groups and was associated with renal tubular atrophy and interstitial fibrosis. The expression of E-cadherin in tubular cells was absent in the Ang II-infused wild and GC-A-KO groups and was associated with renal tubular atrophy.
The natriuretic peptide-GC-A system may play an inhibitory role in Ang II-induced renal tubular atrophy, interstitial fibrosis, and phenotypic transformation in renal tubular cells and fibroblasts.
No preview · Article · May 2014 · Clinical and Experimental Nephrology
[Show abstract][Hide abstract] ABSTRACT: Abstract Blood pressure (BP) control in hypertensives has improved in recent years; however, it remains insufficient. We investigated the trend of BP control status in hypertensive patients with antihypertensive medication and salt intake. Two hundred and eight treated hypertensive patients were prospectively followed between 2007 and 2012. During this period, average clinic BP significantly decreased from 137 ± 12/80 ± 9 to 133 ± 11/76 ± 8 mmHg, and the achievement rate of BP control defined as <140/90 mmHg increased from 58% to 71% (p < 0.01). Morning home BP also significantly decreased from 132 ± 8/80 ± 8 to 130 ± 8/76 ± 7 mmHg, and the percentage of patients with sustained hypertension (CBP ≥140/90 mmHg and HBP ≥135/85 mmHg) decreased from 27% to 16% (p < 0.05). The number of antihypertensive drugs increased significantly from 2.1 ± 1.2 to 2.3 ± 1.1 (p < 0.01), while no differences were observed in urinary salt excretion (9.0 ± 2.4 g/day in 2007, 9.0 ± 2.6 g/day in 2012). Office and home BP decreased and the rate of BP control increased in treated hypertensive patients in the past 5 years. Intensive pharmacological therapy, but not a reduction in salt intake appears to have contributed to improved BP control.
No preview · Article · Apr 2014 · Clinical and Experimental Hypertension
[Show abstract][Hide abstract] ABSTRACT: Carotid artery intima-media thickness (IMT) has emerged as a predictor of cardiovascular events. Home blood pressure (BP) is more closely associated with cardiovascular prognosis than clinic BP. The aim of this study was to compare the progression of carotid IMT with respect to strict and mild control of morning home systolic BP (SBP) and amlodipine- and losartan-based antihypertensive therapy in hypertensive patients. Subjects included 80 hypertensive outpatients who participated in the Hypertension Control Based on Home Systolic Pressure (HOSP) pilot study. After a 1-month drug-free period, the patients were randomly assigned to either the strict control group (target SBP <130 mm Hg) or the mild control group (130-139 mm Hg) and to either the amlodipine group or the losartan group. Additional antihypertensive drugs were added if target BP was not achieved with monotherapy. Morning SBP achieved target levels during 5 years in the strict control group and in the mild control group, while it was comparable between amlodipine and losartan groups. In all patients, mean and maximum carotid IMT increased significantly. Changes in carotid IMT did not differ between strict and mild control groups. Changes in mean carotid IMT in amlodipine group were smaller than those in losartan group at year 1, but were not different between the two groups at year 5. In conclusion, carotid IMT increased over time in hypertensive patients in spite of the strict control of home BP. Amlodipine may slow the progression of IMT more than losartan, although a difference was not obvious after 5 years.
No preview · Article · Mar 2013 · Clinical and Experimental Hypertension
[Show abstract][Hide abstract] ABSTRACT: It has been suggested that fibrates, lipid-lowering agents with a peroxisome proliferator-activated receptor-α agonistic property, lower blood pressure (BP) in some experimental models of hypertension. However, the effect of fibrates on BP in humans has been inconsistent, and there are few studies using home or ambulatory BP monitoring. We investigated the effects of bezafibrate on office, home and ambulatory BP in hypertensive patients with dyslipidemia. Thirty-two essential hypertensive patients with dyslipidemia (6 men and 26 women, mean age 65±8 years old) were assigned to a control period and a bezafibrate period (200 mg twice daily) for 8 weeks each in a randomized crossover manner. Bezafibrate significantly reduced serum triglyceride, total and low-density lipoprotein-cholesterol, blood glucose, plasma insulin, the homeostasis model assessment ratio and increased high-density lipoprotein-cholesterol. Compared with the control period, changes in office, home and 24-h BP with bezafibrate were -0.7±2.1/-1.6±1.2 mm Hg, +0.9±1.0/-0.5±0.6 and +0.8±1.4/-0.6±0.9 mm Hg, respectively. None of these differences in BP was significant. In conclusion, bezafibrate improved lipid metabolism and insulin sensitivity but did not affect office, home or ambulatory BP in hypertensive patients with dyslipidemia. Fibrates do not appear to lower BP in patients with essential hypertension.Journal of Human Hypertension advance online publication, 20 December 2012; doi:10.1038/jhh.2012.64.
No preview · Article · Dec 2012 · Journal of human hypertension
[Show abstract][Hide abstract] ABSTRACT: Objectives: Salt intake is still high and many hypertensive patients do not follow guidelines in Japan. We evaluated the feasibility of self-measurement of salt intake at home using an electronic device in hypertensive patients. We also studied changes in salt intake and blood pressure with self-measurement of salt intake. Design and methods: Eighty treated hypertensive patients (mean age 67) were randomly assigned to salt intake self-measurement group (Salt group, n = 40) or control group (n = 40). Electronic monitors that estimate daily salt intake from overnight urine were provided to Salt group. They were asked to measure salt intake everyday for the first month, then once a week for the next 11 months. Salt intake from 24-hour urine was determined and office and home blood pressure were measured in both groups during the study period. Results: At baseline, average salt intake from 24-hour urine was 9.9 g/day in the whole patients. Ninety percent of the Salt group patients were able to measure salt intake as instructed. Average estimated daily salt intake during the first week was 9.8 g, and that during the fourth week and after 12 months were 9.6 g and 9.2 g, respectively. The amount of self-measured salt intake did not change significantly. Blood pressure and 24-hour urinary Na excretion also did not change significantly in either group. Conclusions: Self-measurement of daily salt intake from overnight urine using an electronic device is feasible. However, amount of salt intake and BP did not change significantly with introduction of the self-measurement.
No preview · Article · Sep 2012 · Journal of Hypertension
[Show abstract][Hide abstract] ABSTRACT: Background
The renal resistive index (RI) measured using Doppler ultrasonography has been used as a diagnostic tool in the daily work-up of kidney diseases. A better understanding of its relationship with preclinical organ damage may help in determining overall cardiovascular risk in hypertensive patients.Methods
We evaluated the association between RI and the presence and degree of target organ damage (TOD) in 288 (130 male) essential hypertensive patients. RI, carotid intima-media thickness (IMT), and left ventricular (LV) mass index were assessed by ultrasound scan. Albuminuria was measured as the albumin-to-creatinine ratio (ACR) in three consecutive first morning urine samples.ResultsIn univariate analysis, patients with TOD showed significantly higher RI as compared with those without TOD (presence vs. absence of carotid wall thickening, LV hypertrophy, and albuminuria, P < 0.01, respectively). The severity of each TOD increased progressively from the lower to the upper RI tertile. Multiple logistic regression analysis found that each standard deviation increase in RI gave a 47% higher odds of having LV hypertrophy, and a 70% higher odds of having albuminuria (P < 0.05, respectively). The occurrence of at least two signs of TOD also significantly increased in parallel with elevation of RI (odds ratio (OR): 1.89 for 1 s.d. increase, P < 0.01).Conclusions
These results suggest that increased RI may be a marker of subclinical TOD in patients with essential hypertension.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.113.
No preview · Article · Aug 2012 · American Journal of Hypertension
[Show abstract][Hide abstract] ABSTRACT: Increased renal restive index (RI) measured using Doppler ultrasonography has been shown to correlate with the degree of renal impairment in hypertensive patients. We investigated the prognostic role of RI in cardiovascular and renal outcomes. A total of 426 essential hypertensive subjects (mean age, 63 years; 50% female) with no previous cardiovascular disease were included in this study. Renal segmental arterial RI was measured by duplex Doppler ultrasonography. During follow-up (mean, 3.1 years), 57 participants developed the primary composite end points including cardiovascular and renal outcomes. In multivariate Cox regression analysis, RI was an independent predictor of worse outcome in total subjects (hazard ratio, 1.71 for 1 SD increase), as well as in patients with estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m(2) (hazard ratio, 2.11 for 1 SD increase; P<0.01, respectively). When divided into 4 groups based on the respective sex-specific median levels of RI in the eGFR ≥60 and eGFR <60 mL/min per 1.73 m(2) groups, the group with eGFR <60 and high RI (male ≥0.73, female ≥0.72) had a significantly poorer event-free survival rate (χ(2)=126.4; P<0.01), and the adjusted hazard ratio by multivariate Cox regression analysis was 9.58 (95% CI, 3.26-32.89; P<0.01). In conclusion, impairment of renal hemodynamics evaluated by increased RI is associated with an increased risk of primary composite end points, and the combination of high RI and low eGFR is a powerful predictor of these diseases in essential hypertension. In hypertensive patients with chronic kidney disease, RI evaluation may complement predictors of cardiovascular and renal outcomes.
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease (CVD). We previously reported renal parenchymal damage in autopsy subjects with stroke or abdominal aortic aneurysm. The aim of this study is to evaluate the relationship between renal histology and clinical characteristics of patients with myocardial infarction (MI).
A total of 699 subjects were autopsied at the National Cerebral and Cardiovascular Center Hospital. We retrospectively evaluated all autopsy cases with MI (n = 123). Estimated glomerular filtration rate (eGFR) was calculated using the Japanese formula. Subjects were classified into four groups: 25 subjects with eGFR ≥ 60 mL/min/1.73 m(2) and no proteinuria (no CKD), 10 subjects with eGFR ≥ 60 and proteinuria (CKD1/2), 65 subjects with 60 > eGFR ≥ 30 (CKD3), and 23 subjects with eGFR < 30 (CKD4/5). Renal parenchymal damage was evaluated using a semi-quantitative histological score (score 0-3) for glomerulosclerosis, interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, and arteriosclerosis of medium-sized artery (maximum score = 15).
The mean histological score was significantly higher in patients with CKD3 and CKD4/5 and was associated with age, hypertension, diabetes, kidney function, proteinuria, and other CVD.
In patients with MI, renal parenchymal damage and deteriorating kidney function are closely associated.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION AND AIMS: The phosphatonin FGF-23 has recently been associated with structural cardiac disease. Patients with echocardiographically
assessed left-ventricular hypertrophy have higher FGF-23 levels than subjects with normal cardiac geometry. As cardiac remodelling
in patients with left-ventricular hypertrophy often involves left atrial structural changes, we studied a potential association
between atrial fibrillation and elevated FGF-23 levels.
METHODS: 885 patients who underwent elective coronary angiography were included in our prospective HOM SWEET HOMe cohort study. At
study entry, an electrocardiography (ECG) reading was performed in all subjects, and a blood sample was drawn for measurement
of serum phosphate, calcium, creatinine and FGF-23. For the present analysis, we excluded patients with estimated glomerular
filtration rate (eGFR) <60 ml/min/1.73 m². Patients were stratified by the presence or absence of atrial fibrillation (AF).
RESULTS: 714 out of 885 patients had normal eGFR (≥60 ml/min/1.73 m²) and were included in the present analysis. Among these 714 subjects,
46 patients (6.4%) had atrial fibrillation. Patients with AF were older (68.5±8.0 years vs. 63.2±10.1 years; p=0.002) and showed a higher body-mass index (BMI; 29.8±4.7 kg/m2 vs. 28.4±4.6 kg/m2; p=0.03). While patients stratified by prevalent AF did not differ in serum phosphate levels (3.3±0.5 mg/dl vs. 3.2±0.6 mg/dl; p=0.516), subjects with AF had higher FGF-23 levels compared to patients without AF (87.6 rU/ml [IQR 52.0-147.8
rU/ml] vs. 32.3 rU/ml [IQR 12.4-58.0 rU/ml]; p<0.001). Elevated FGF-23 levels remained significantly associated with AF after adjustment
for potential confounders.
CONCLUSIONS: Patients with atrial fibrillation show elevated FGF-23 levels despite normal renal function. This finding supplements earlier
reports which have linked the phosphatonin FGF-23 to structural heart disease.
No preview · Article · Jun 2011 · CKJ: Clinical Kidney Journal
[Show abstract][Hide abstract] ABSTRACT: Inflammation is associated with the development of atherosclerotic vascular lesions and some inflammatory parameters are used as cardiovascular (CV) risk markers. The present study was designed to assess the predictive power of interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C-reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9 years) after the baseline assessment, 50 patients newly experienced CV events such as stroke/transient ischemic attack (n=10), heart failure hospitalization (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6, but not hs-CRP, was significantly higher in patients who had CV events than in event-free subjects (3.9±2.6 and 3.0±2.2 pg/mL, P=0.04). When the patients were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85-3.77, and ≥3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19% in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test, P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine clearance, and serum IL-6 levels were significantly associated with CV events during follow-up. Among these possible predictors, the highest tertile of IL-6 was only an independent determinant for the morbidity in the multivariate analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate that IL-6 is a powerful independent predictor of future CV events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP.