Predictive power of isolated high home systolic blood pressure for cardiovascular outcomes in individuals with type 2 diabetes mellitus: KAMOGAWA-HBP study.

AIMS/INTRODUCTION: Isolated high home systolic blood pressure (IHHSBP) is a risk for cardiovascular disease (CVD). However, no study has shown an association between IHHSBP and CVD in diabetes. We examined the association between IHHSBP and CVD in type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study included 1082 individuals with type 2 diabetes, aged 20 to 90 years, without a history of macrovascular complications. Home blood pressure (HBP) was measured three times every morning and evening for 14 days. Cox proportional hazards models were used to examine the relationship between IHHSBP and CVD incidence. RESULTS: With the normal HBP group as the reference, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for CVD was 1.58 (1.02-2.43) in the IHHSBP group. Correcting for antihypertensive medication use did not change HR. Based on sex, the adjusted HR (95% CI) for CVD was 1.25 (0.74-2.13) in males and 2.28 (1.01-5.15) in females. CONCLUSIONS: In individuals with type 2 diabetes, those with IHHSBP had a higher HR for cardiovascular disease than those with normal HBP. But, Isolated high home diastolic blood pressure and high HBP were not. The association between IHHSBP and CVD was stronger in females than in males.

Impact of continued high blood pressure on the progression of diabetic nephropathy after 10 years: KAMOGAWA-HBP study.

Albuminuria is a prognostic marker of worsening renal outcomes in people with hypertension and type 2 diabetes. High home systolic blood pressure is associated with the development of diabetic nephropathy. We assessed the impact of chronic high home blood pressure on diabetic nephropathy progression 10 years after study entry. The participants measured their blood pressure three times in the morning for 14 days at study entry and 10 years after study entry. A retrospective cohort of 165 people with type 2 diabetes at a single hospital was classified into four groups (good control maintenance, improvement, deterioration, and continuous high blood pressure groups) according to a morning home systolic blood pressure ≥125 mmHg at study entry and 10 years after study entry. Logistic regression analysis was performed to determine the association between home blood pressure control and the progression of diabetic nephropathy. After 10 years of entry, the status of nephropathy improved for 5.5% of the participants, remained unchanged for 72.1%, and progressed for 22.4%. The odds ratio of the continuous high blood pressure group versus that of the good control maintenance group for the progression of diabetic nephropathy was 10.41 (95% CI, 1.26-86.15). After adjusting for the introduction of renin-angiotensin-aldosterone system inhibitors during the follow-up period, there was no significant difference in the odds ratio of worsening nephropathy between these groups. The deterioration and improvement groups did not have significant diabetic nephropathy progression compared to the good control maintenance group. Chronic high home blood pressure was associated with the progression of diabetic nephropathy, and RAAS inhibitors could attenuate the negative effect. We demonstrated that chronic home blood pressure was associated with the progression of diabetic nephropathy.

Impact of sustained hypertension on new cardiovascular events in patients with type 2 diabetes: KAMOGAWA-HBP study.

We have previously shown that masked hypertension (MH) and sustained hypertension (SH) contribute to the progression of diabetic nephropathy. Although the risk of target organ damage and cardiovascular events in MH and SH is significantly higher than that in normotension and white coat hypertension, the role of MH or SH in cardiovascular events has never been reported in studies specific to diabetic patients. Therefore, in this study, we aimed to determine whether blood pressure control status contributes to the development of new cardiovascular events. A longitudinal study of 1082 patients with type 2 diabetes mellitus and no history of cardiovascular events was conducted. Patients were instructed to have their blood pressure measured three times, every morning and evening, for 14 consecutive days. Hypertension status was classified into four groups based on the systolic blood pressure measurements in the clinic and at home. The primary endpoint was the first cardiovascular event. After a median follow-up of 7.0 (interquartile range, 4.0-9.0) years, 119 patients developed cardiovascular events. The hazard ratio (95% confidence interval) for the risk of developing cardiovascular events was significantly higher in the SH group than in the controlled blood pressure group (1.63 [1.02-2.59]). SH is a useful predictor of cardiovascular events. Both at home and in the clinic, blood pressure monitoring should be assessed in routine clinical practice to predict future cardiovascular events in patients with type 2 diabetes.

Home-measured pulse pressure is a predictor of cardiovascular disease in type 2 diabetes: The KAMOGAWA-HBP study.

BACKGROUND AND AIMS: Pulse pressure (PP) is a prognostic predictor of cardiovascular mortality. This retrospective cohort study aimed to investigate the association between home PP measurements and cardiovascular disease in patients with type 2 diabetes. METHODS AND RESULTS: Home blood pressure was measured for 14 consecutive days in 1082 patients with type 2 diabetes, and pulse pressure was calculated. A 10 mmHg increase in morning PP was associated with a 1.30-fold increase in the risk of cardiovascular disease. The risk of cardiovascular disease was 1.88 times higher in the morning in the higher PP group than in the lower PP group. In the receiver operating characteristic analysis, the areas under the curve (95% confidence interval) corresponding to the PP (morning, evening, and clinic) for new-onset cardiovascular disease were 0.63 (0.58-0.69), 0.62 (0.57-0.67), and 0.59 (0.54-0.64), respectively. The area under the curve for PP measured in the morning was significantly greater than that for PP measured in the clinic (P = 0.032). CONCLUSION: Home-measured PP is a better predictor of new-onset cardiovascular disease than clinic-measured PP, in patients with type 2 diabetes.

Maximum home blood pressure and cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study.

OBJECTIVE: The maximum blood pressure was reported as a possible marker of organ damage. We previously showed that maximum home blood pressure was significantly associated with development of diabetic nephropathy. In the same cohort of patients with diabetes as in the previous study, this study aimed to evaluate the prognostic blood pressure values for the onset of first cardiovascular events. METHODS: This retrospective cohort study included 1082 patients with type 2 diabetes (47.0% female, median age 65.0) without a history of macrovascular complications. Blood pressure measurements were performed in triplicates every morning and evening for 14 consecutive days from the start of the study. Cox hazards model was used to evaluate the risk of primary endpoint, which was defined as the onset of first major cardiovascular event. RESULTS: The primary endpoint occurred in 119 patients (incidence rate, 15.7/1000 person-years) during an average of 7.0-year follow-up. The adjusted hazard ratios (95% confidence interval [CI]) of maximum morning systolic blood pressure (SBP) and maximum evening SBP for cardiovascular events were 1.12 (1.01-1.24) and 1.19 (1.07-1.31), respectively, adjusted by sex, duration of diabetes, body mass index, hemoglobin A1c, low density lipoprotein cholesterol, smoking status, and use of antihypertensive medications. The cutoff values of maximum blood pressure for the events were 150 mmHg in the morning (hazard ratio, 1.73; 95% CI, 1.07-2.81) and 157 mmHg in the evening (hazard ratio, 2.30; 95% CI, 1.46-3.61), using the Youden's index. CONCLUSION: Maximum home blood pressure is a predictor of subsequent cardiovascular events in patients with type 2 diabetes.

Predictive power of home blood pressure measurement for cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study.

Our previous study showed that the morning systolic blood pressure target should be <120 mmHg to prevent the onset or progression of diabetic nephropathy in patients with type 2 diabetes. In this study, we examined the prognostic values of home and clinical blood pressure for first cardiovascular events in the same cohort. Morning and evening home blood pressure measurements were obtained in triplicate for 14 consecutive days from the beginning of the study in a retrospective cohort of 1081 type 2 diabetes patients (44.5% women; median age 66.0 years) with no history of macrovascular complications. The first major cardiovascular event was the primary endpoint; the risk was examined by the Cox proportional hazards model. After a mean follow-up of 6.63 years, first-time cardiovascular events occurred in 119 patients (incidence, 16.6/1000 patient-years). Baseline morning systolic blood pressure (hazard ratio: 1.14, 95% CI 1.01-1.28) significantly predicted cardiovascular events, whereas clinical blood pressure did not. The adjusted hazard ratio (95% CI) for the incidence of cardiovascular events in patients with morning systolic blood pressure ≥135 mmHg tended to be higher than that in those with morning systolic blood pressure <125 mmHg [1.67 (0.94-2.97)]. Elevated home blood pressure measurement is a predictor of future cardiovascular events in type 2 diabetes patients and may be superior to clinical blood pressure measurement in this regard.

Isolated pulmonary valvular stenosis with equilateral triangle orifice.

Isolated congenital pulmonary valvular stenosis is a relatively common abnormality. A 52-year-old woman with an asymptomatic cardiac murmur since her childhood visited our hospital. The peak pressure gradient across the pulmonary valve (PV) was calculated 25 mmHg by Doppler velocity during the transthoracic echocardiography, the severity was graded into mild. The cardiac computed tomography indicated a dome-shaped PV with an equilateral triangle orifice without commissural fusion. No case has been described in a triangle orifice, it will be necessary to follow up carefully. .

Isolated high home systolic blood pressure in patients with type 2 diabetes is a prognostic factor for the development of diabetic nephropathy: KAMOGAWA-HBP study.

BACKGROUND: Isolated high home systolic blood pressure (IH-HSBP) has been revealed to be correlated with cardiovascular disease and diabetic nephropathy, however, the prognostic significance of IH-HSBP with the development of diabetic nephropathy is unclear. METHODS: In this prospective 2-year cohort study of 477 patients with normoalbuminuria, we investigated the effect of IH-HSBP on the development of diabetic nephropathy defined by diabetic nephropathy advanced from normoalbuminuira to micro or macroalbuminuria. RESULTS: Among 477 patients, 67 patients showed the development of diabetic nephropathy. In the multivariate logistic regression analyses, IH-HSBP was prognostic factor for the development of nephropathy after adjusting for sex, age, duration of diabetes mellitus, body mass index, total cholesterol, hemoglobin A1c, creatinine, smoking habits and use of renin-angiotensin-aldosterone system inhibitors (odds ratio: 2.53, 95% confidence interval: 1.16-5.56, p = 0.020). CONCLUSION: IH-HSBP in patients with type 2 diabetes with normoalbuminuria was prognostic factor for the development of diabetic nephropathy. We should pay more attention to IH-HSBP to prevent the development of diabetic nephropathy.

Maximum morning home systolic blood pressure is an indicator of the development of diabetic nephropathy: The KAMOGAWA-HBP study.

AIMS/INTRODUCTION: The maximum value of home systolic blood pressure is correlated with damage to target organs, including diabetic nephropathy. However, the precise relationship between the development of diabetic nephropathy and maximum home systolic blood pressure has not been elucidated. MATERIALS AND METHODS: In this prospective 2-year cohort subanalysis of the KAMOGAWA-HBP study, the patient population was 477 Japanese patients with normoalbuminuria. We investigated the effects of mean and maximum home blood pressure on the development of diabetic nephropathy, which we defined as a urinary albumin excretion value ≥30 mg/g creatinine. Among the 477 patients, 67 developed diabetic nephropathy. RESULTS: In our multivariate logistic regression analyses, the maximum morning home systolic blood pressure was significantly positively associated with the development of diabetic nephropathy after adjusting for patient sex and age, smoking status, the diabetes mellitus duration, body mass index, creatinine, total cholesterol, hemoglobin A1c, and antihypertensive medication use (odds ratio 1.21, 95% confidence interval 1.03-1.42, P = 0.021). CONCLUSIONS: Maximum home blood pressure can be identified at a glance, and its measurement would thus be helpful to healthcare providers who treat patients with diabetes and normoalbuminuria.

Impact of masked hypertension on diabetic nephropathy in patients with type II diabetes: a KAMOGAWA-HBP study.

The prognostic significance of masked hypertension (MH) on the progression of diabetic nephropathy among patients with type II diabetes is not well documented. We examined the relationship between clinic systolic blood pressure (SBP) and morning home SBP measurements and progression to macroalbuminuria in patients with type II diabetes. We analyzed prospective cohort study data from 712 patients with type II diabetes. We classified the patients into the following four groups according to their clinic (130 mm Hg) and home (125 mm Hg) SBP measurements: controlled blood pressure group, white-coat hypertension group, MH group, and sustained hypertension (SH) group. The patients were instructed to perform triplicate morning and evening blood pressure measurements for 14 consecutive days. During the 2-year follow-up period, 23 patients progressed to macroalbuminuria. The unadjusted odds ratio (95% confidence interval) for progression to macroalbuminuria among the patients with MH was significantly higher than that among the patients with controlled blood pressure (8.89 [1.06-74.88]). No significant relationship was observed between white-coat hypertension or SH and progression to macroalbuminuria. In analyses adjusted for various potential confounders, the adjusted odds ratio for progression to macroalbuminuria in the MH group was more than 8-fold higher than that in the controlled blood pressure group. MH might be a predictor of progression to macroalbuminuria among patients with type II diabetes. This rate of progression is comparable with or greater than the results reported for patients with SH.

Prognostic significance of day-by-day variability of home blood pressure on progression to macroalbuminuria in patients with diabetes.

OBJECTIVES: Previously, we have shown in cross-sectional analysis of patients with type 2 diabetes mellitus that the presence of diabetic nephropathy is associated with increased home blood pressure (HBP) variability. We now examine the prognostic significance of HBP variability in substantially the same cohort. METHODS: We performed a prospective cohort study of type 2 diabetes patients. We analyzed 714 patients. Major exclusion criteria are missing data of urinary albumin excretion and newly prescribed or stopped renin-angiotensin system inhibitors during 2-year follow-up. Patients were instructed to perform triplicate morning and evening HBP measurements for 14 consecutive days. We computed day-by-day HBP variability as within-patient standard deviation (SD) and coefficient of variation (CV) of measurements. RESULTS: During the follow-up period of 2 years, 23 patients progressed to macroalbuminuria. The changing risk of progression to macroalbuminuria with increasing day-by-day variability of morning SBP was better depicted using smoothing spline analyses. Patients with greater SD of morning SBP tended to significantly progress to macroalbuminuria [odds ratio: 5.24 (95% confidence interval: 2.10-13.03; P > 0.001)]. Patients with greater CV of morning SBP also tended to significantly progress to macroalbuminuria [odds ratio: 3.36 (95% confidence interval: 1.39-8.12; P = 0.007)]. CONCLUSION: Day-by-day variability of morning SBP was proven as an independent predictor for progression to macroalbuminuria in patients with type 2 diabetes.

Maximum home blood pressure is a useful indicator of diabetic nephropathy in patients with type 2 diabetes mellitus: KAMOGAWA-HBP study.

OBJECTIVE: Maximum home systolic blood pressure has been shown to predict target organ damage. We aimed to clarify the association between maximum home systolic blood pressure and urine albumin to creatinine ratio, an indicator of early-phase diabetic nephropathy in patients with type 2 diabetes. METHODS: In 1040 patients, we assessed the relationship of mean or maximum home systolic blood pressure and urine albumin to creatinine ratio, and compared the area under the receiver operating characteristic curve of mean or maximum home systolic blood pressure for diabetic nephropathy (urine albumin to creatinine ratio ⩾30 mg/g Cr). RESULTS: Multivariate linear regression analyses indicated that mean morning systolic blood pressure ( ß = 0.010, p < 0.001) and maximum morning systolic blood pressure ( ß = 0.008, p < 0.001) were significantly associated with urine albumin to creatinine ratio. Area under the receiver operating characteristic curve (95% confidence interval) for diabetic nephropathy in mean and maximum morning systolic blood pressure was 0.667 (0.634-0.700; p < 0.001) and 0.671 (0.638-0.703; p < 0.001), respectively. CONCLUSION: Maximum home systolic blood pressure, as well as mean home systolic blood pressure, was significantly associated with diabetic nephropathy in patients with type 2 diabetes.

Optimal home SBP targets for preventing the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

OBJECTIVES: Home blood pressure control can reduce the risk of increased urinary albumin excretion in patients with diabetes mellitus. However, the optimal home blood pressure targets to prevent the onset or progression of diabetic nephropathy are not well defined. METHODS: We performed a retrospective cohort study of 851 patients with type 2 diabetes mellitus. Logistic regression models were used to evaluate the correlations of home SBP levels with progression of diabetic nephropathy. RESULTS: During the follow-up of 2 years, 86 patients had progression of diabetic nephropathy. Adjusted odds ratios (95% confidence interval) for progression of diabetic nephropathy in patients with morning SBP of 120-129  mmHg [2.725 (1.074-6.917), P = 0.035], 130-139  mmHg [3.703 (1.519-9.031), P = 0.004] and in those with morning SBP equal or more than 140  mmHg [2.994 (1.182-7.581), P = 0.021] were significantly higher than that in those with morning SBP less than 120  mmHg in multiple logistic analyses. CONCLUSION: The preferable morning SBP targets might be less than 120  mmHg for preventing the onset or progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

Maximum home systolic blood pressure is a useful indicator of arterial stiffness in patients with type 2 diabetes mellitus: post hoc analysis of a cross-sectional multicenter study.

AIMS: Maximum (max) home systolic blood pressure (HSBP) as well as mean HSBP or HSBP variability was reported to increase the predictive value of target organ damage. Yet, the association between max HSBP and target organ damage in patients with type 2 diabetes has never been reported. The aim of this study was to investigate the association between max HSBP and pulse wave velocity (PWV), a marker of arterial stiffness which in turn is a marker of target organ damage, in patients with type 2 diabetes. METHODS: We assessed the relationship of mean HSBP or max HSBP to PWV, and compared area under the receiver-operating characteristic curve (AUC) of mean HSBP or max HSBP for arterial stiffness in 758 patients with type 2 diabetes. RESULTS: In the univariate analyses, age, duration of diabetes mellitus, body mass index, mean clinic systolic blood pressure (SBP), mean HSBP and max HSBP were associated with PWV. Multivariate linear regression analyses indicated that mean morning SBP (ß=0.156, P=0.001) or max morning SBP (ß=0.146, P=0.001) were significantly associated with PWV. AUC (95% CI) for arterial stiffness, defined as PWV equal to or more than 1800 cm per second, in mean morning SBP and max morning SBP were 0.622 (0.582-0.662; P<0.001) and 0.631 (0.591-0.670; P<0.001), respectively. CONCLUSIONS: Our findings implicate that max HSBP as well as mean HSBP was significantly associated with arterial stiffness in patients with type 2 diabetes.

Home-measured heart rate is associated with albuminuria in patients with type 2 diabetes mellitus: a post-hoc analysis of a cross-sectional multicenter study.

Epidemiological studies have shown that elevated heart rate (HR) is associated with an increased risk of diabetic nephropathy, as well as cardiovascular events and mortality, in patients with type 2 diabetes mellitus. Recently, the advantages of the self-measurement of blood pressure (BP) at home have been recognized. The aim of this study was to investigate the relationship between home-measured HR and albuminuria in patients with type 2 diabetes mellitus. We designed a cross-sectional multicenter analysis of 1245 patients with type 2 diabetes mellitus. We investigated the relationship between the logarithm of urinary albumin excretion (log UAE) and home-measured HR or other factors that may be related to nephropathy using univariate and multivariate analyses. Multivariate linear regression analysis indicated that age, duration of diabetes mellitus, morning HR (ß=0.131, P<0.001), morning systolic BP (ß=0.311, P<0.001), hemoglobin A1C, triglycerides, daily consumption of alcohol, use of angiotensin II receptor blockers and use of beta-blockers were independently associated with the log UAE. Multivariate logistic regression analysis indicated that the odds ratio (95% confidence interval) associated with 1 beat per min and 1 mm Hg increases in the morning HR and morning systolic BP for albuminuria were 1.024 ((1.008-1.040), P=0.004) and 1.039 ((1.029-1.048), P<0.001), respectively. In conclusion, home-measured HR was significantly associated with albuminuria independent of the known risk factors for nephropathy, including home-measured systolic BP, in patients with type 2 diabetes mellitus.

Left ventricular free wall rupture associated with a combination of acute myocardial infarction and stress-provoked cardiomyopathy: An autopsy case.

A 74-year-old female was admitted to our hospital due to prolonged chest pain that had lasted about 2 h. An electrocardiogram revealed ST-elevation in leads I, aVL, and V3-6, with an increase in myocardial necrosis markers. Emergency coronary angiography was performed, and left ventriculography showed the typical features of apical ballooning, and so a diagnosis of Takotsubo cardiomyopathy (TC) was made. On the 10th day after admission, the patient suddenly went into cardiopulmonary arrest because of a blow-out type left ventricular (LV) free wall rupture. Despite extensive cardiopulmonary resuscitation, the patient died. The autopsy revealed hemopericardium and a perforating wound located in the anterior wall of the LV. It was revealed that the diagonal branch of the coronary artery was occluded, and so a diagnosis of TC coexisting with acute myocardial infarction (AMI) was made. No previous case of TC accompanied by AMI has been reported. We present its clinical course during hospitalization and the result of a histopathologic examination.

Comparison of human herpes virus 8 related primary effusion lymphoma with human herpes virus 8 unrelated primary effusion lymphoma-like lymphoma on the basis of HIV: report of 2 cases and review of 212 cases in the literature.

BACKGROUND: Primary lymphomatous effusion is a rare lymphoma that arises in the body cavity and has a peculiar proliferative form, lacking a tumor. This primary lymphomatous effusion includes human herpes virus 8 (HHV8)-related primary effusion lymphoma (PEL) and HHV8-unrelated PEL-like lymphoma. We attempted to clarify the nature of the primary lymphomatous effusion. METHODS: Using 'PEL' and 'body cavity-based lymphoma' (BCBL) as key words, reports written in English were collected from PubMed. Primary lymphomatous effusion was defined as BCBL with primary effusion and without tumor at onset. Adding our 2 PEL-like lymphoma cases, each case was studied as to the patients' and lymphomas' characteristics, therapy and survival time. Moreover, each item was compared among four groups according to the presence of HHV8 and HIV. RESULTS: In 214 cases investigated, there was no difference in proliferation, but an apparent difference in age, gender, phenotype, effectiveness and prognosis among the four groups. CONCLUSIONS: Both PEL and PEL-like lymphoma are thought to be characterized by a peculiar proliferation, regardless of the presence of HHV8. Dividing PEL or PEL-like lymphoma into two subgroups on the basis of HIV presentation might also be appropriate.

Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart.

Naked plasmid DNA (pDNA) and short interfering RNA (siRNA) duplexes were transduced into adult murine heart by means of sonoporation using the third-generation microbubble, BR14. Plasmid DNAs carrying luciferase, beta-galactosidase (beta-gal), or enhanced green fluorescent protein (EGFP) reporter genes were mixed with BR14 and injected percutaneously into the left ventricular (LV) cavity of C57BL/6 mice while exposed to transthoracic ultrasound at 1MHz for 60s. Sonoporation at an output intensity of 2.0W/cm(2) and a 50% pulse duty ratio resulted in the highest luciferase expression in the heart. Histological examinations revealed significant expression of the beta-gal and EGFP reporters in the subendocardial myocardium of LV. Intraventricular co-injection of siRNA-GFP and BR14 with concomitant ultrasonic exposure resulted in substantial reduction in EGFP expression in the coronary artery in EGFP transgenic mice. The present method may be applicable to gain-of-function and loss-of-function genetic engineering in vivo of adult murine heart.