Naoko Nakanishi

Visit-to-visit variability in systolic blood pressure is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes

OBJECTIVE Recent studies make remarks on the effect of variability in systolic blood pressure (SBP) on the development of cardiovascular disease. The aim of this study was to investigate the relationship between the variability in SBP and the degree of diabetic nephropathy and atherosclerosis in patients with type 2 diabetes. METHODS We measured SBP in 422 consecutive patients with type 2 diabetes at every visit during a year, and we calculated the coefficient of variation (CV) of SBP. Then, we evaluated relationships of variability of SBP to degree of urinary albumin excretion (UAE), which is a useful marker for cardiovascular disease as well as diabetic nephropathy, ankle-brachial index (ABI) and pulse wave velocity (PWV). RESULTS CV of SBP positively correlated with logUAE (r=0.210, P<0.0001) or PWV (r=0.409, P<0.0001), whereas CV of SBP inversely correlated with ABI (r=-0.098, P=0.0463). Multiple regression analysis demonstrated that CV of SBP independently correlated with logUAE (β=0.149, P=0.0072), PWV (β=0.337, P<0.0001) or ABI (β=-0.162, P=0.0101). CONCLUSIONS Not only average SBP but also variability in SBP is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.

Visit-to-Visit Blood Pressure Variability Is a Novel Risk Factor for the Development and Progression of Diabetic Nephropathy in Patients With Type 2 Diabetes

OBJECTIVE Recent study has suggested that not only the presence of hypertension but also the variability in systolic blood pressure (SBP) are risk factors for vascular disease and organ damage. The aim of this study was to investigate the relationship between visit-to-visit variability in SBP and change in urinary albumin excretion (UAE) or development of albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We measured SBP in 354 consecutive patients at every visit during 1 year and calculated the coefficient of variation (CV) of SBP. We performed a follow-up study to assess change in UAE or development of albuminuria, the mean interval of which was 3.76 ± 0.71 years. Then, we evaluated relationships of variability of SBP to diabetic nephropathy using multiple regression analysis and multiple Cox regression model. RESULTS Multiple regression analysis demonstrated that CV of SBP was independently associated with change in UAE (β = 0.1758; P = 0.0108). Adjusted Cox regression analyses demonstrated that CV of SBP was associated with an increased hazard of development of albuminuria; hazard ratio was 1.143 (95% CI 1.008–1.302). CONCLUSIONS Visit-to-visit variability in SBP could be a novel risk factor for the development and progression of diabetic nephropathy in patients with type 2 diabetes.

Low Urine pH Is a Predictor of Chronic Kidney Disease

Background/Aims: A variety of risk factors for chronic kidney disease (CKD), including the metabolic syndrome, were recently reported. It has been suggested that a low urine pH is another characteristic of the metabolic syndrome. However, the relationship between urine pH and CKD remains to be elucidated. Methods: A cohort study was performed on 1,811 subjects who underwent a health check-up, and we examined whether low urine pH could be a predictor of CKD. The following risk factors for CKD were evaluated: age, gender, history of alcohol intake and smoking, BMI, systolic blood pressure, fasting plasma glucose, total cholesterol, uric acid, total leukocyte count, CKD stage, fasting urine pH, and protein at baseline. Results: We followed 1,811 subjects for a median period of 7.7 years. Three hundred and thirty-nine subjects developed stage 3 CKD defined as progression to estimated glomerular filtration rate <60 ml/min/1.73 m2. Multiple Cox regression analysis revealed that the adjusted HR (95% CI) for stage 3 CKD was 1.32 (1.06–1.65; p = 0.0129) in subjects with fasting urine pH 5.0–5.5 compared to subjects with pH 6.5–7.0. Conclusion: Our study suggests that low urine pH is an independent predictor of stage 3 CKD.

Visit-to-visit variability in systolic blood pressure is a novel risk factor for the progression of coronary artery calcification

Recent studies have suggested that variability in the systolic blood pressure (SBP) is a risk factor for cardiovascular disease (CVD). The aim of this study was to investigate the relationship between variability in the SBP and the progression of coronary artery calcification (CAC), which is a useful marker for CVD. We measured SBP in 164 consecutive patients at every visit over the course of a year and calculated the coefficient of variation and s.d. of the SBP. We performed a follow-up study using multislice computed tomography to assess the progression of the CAC score, the mean interval of which was 3.93±1.36 years. We then evaluated the relationship between variability in the SBP and progression of the CAC score. The coefficient of variation for the SBP correlated positively with the progression of the CAC score (r=0.4382, P<0.0001). Multiple regression analysis demonstrated that the coefficient of variation of the SBP (β=0.3826, P<0.0001) was independently associated with the progression of the CAC score. The visit-to-visit variability in SBP could be a novel risk factor for the progression of CAC.

A difference in systolic blood pressure between arms and between lower limbs is a novel risk marker for diabetic nephropathy in patients with type 2 diabetes.

Recent studies have demonstrated that a difference in systolic blood pressure (SBP) between arms is associated with both vascular disease and mortality. The aim of this study was to investigate the relationship between a difference in SBP between arms and between lower limbs and the degree of albuminuria, which is an established marker for cardiovascular disease and diabetic nephropathy in patients with Type 2 diabetes. We measured blood pressure in the arms and lower limbs of 314 consecutive patients with Type 2 diabetes, and we calculated a difference in SBP between arms and between lower limbs. We then evaluated the relationship of the difference in SBP between arms and between lower limbs to the degree of urinary albumin excretion (UAE). The average difference in SBP between arms and between lower limbs was 3.52±3.94 and 9.66±14.1 mm Hg, respectively. Multiple regression analyses demonstrated that a difference in SBP between arms (β=0.172, P=0.0239) and between lower limbs (β=0.238, P=0.0033) independently correlated with the logarithm of the UAE. Multiple logistic regression analyses showed that a difference in SBP of ⩾10 mm Hg between arms (odds ratio 12.23 (95% CI 1.130–132.35), P<0.0393) and a difference in SBP of ⩾15 mm Hg between lower limbs (odds ratio 4.291 (95% CI 1.403–13.123), P<0.0106) correlated with the risk of albuminuria. A difference in SBP between arms and between lower limbs, therefore, could be a novel risk marker for diabetic nephropathy in patients with Type 2 diabetes.

Various patterns of disrupted daily rest-activity rhythmicity associated with diabetes.

Disruptions to sleep and circadian rhythms have now been recognized as common comorbidities in patients with medical illnesses. We aimed to determine if the diurnal rhythms for rest and activity were disrupted in parallel with the development of diabetic complications. Ninety outpatients in our diabetes clinic who had a body mass index <25 kg m2 wore an actigraph for 7 consecutive days (42 men; mean age 68.7 ± 8.2 years). Patients with neuropsychiatric diseases, liver cirrhosis, renal failure, chronic obstructive pulmonary disease or blindness, or those who performed shiftwork were excluded. We grouped the actigraph recordings into 1‐h periods and counted the number of minutes that showed activity. Stepwise regression analysis showed an association between a diabetic clinical background and measurements of circadian rhythms such as daytime activity, night‐time activity, phase, interdaily stability, intradaily variability and relative amplitude. Higher age, body mass index, total cholesterol levels and insulin usage were associated with lower daytime activity and higher intradaily variability, whereas higher haemoglobin A1c levels and the presence of neuropathy were associated with greater daytime activity. The presence of proliferative retinopathy and increased levels of microalbuminuria were associated with higher intradaily variability and lower interdaily stability and amplitude. The presence of cardiovascular disease was associated with advanced phase, whereas painful neuropathy was associated with delayed phase. Our study demonstrated that different diabetic complications were associated independently with a variety of alterations in the circadian rest and activity rhythms. Our findings have provided novel insights that may be helpful in developing interventions for sleep–wake disorders associated with diabetes.

Morning pulse pressure is associated more strongly with elevated albuminuria than systolic blood pressure in patients with type 2 diabetes mellitus: Post hoc analysis of a cross-sectional multicenter study

AIMS Recently, focus has been directed toward pulse pressure as a potentially independent risk factor for micro- and macrovascular disease. This study was designed to examine the relationship between pulse pressure taken at home and elevated albuminuria in patients with type 2 diabetes. METHODS This study is a post hoc analysis of a cross-sectional multicenter study. Home blood pressure measurements were performed for 14 consecutive days in 858 patients with type 2 diabetes. We investigated the relationship between systolic blood pressure or pulse pressure in the morning or in the evening and urinary albumin excretion using univariate and multivariate analyses. Furthermore, we measured area under the receiver-operating characteristic curve (AUC) to compare the ability to identify elevated albuminuria, defined as urinary albumin excretion equal to or more than 30 mg/g creatinine, of systolic blood pressure or pulse pressure. RESULTS Morning systolic blood pressure (β=0.339, P<0.001) and morning pulse pressure (β=0.378, P<0.001) were significantly associated with logarithm of urinary albumin excretion independent of other potential co-factors. AUC for elevated albuminuria in morning systolic blood pressure and morning pulse pressure were 0.668 (0.632-0.705; P<0.001) and 0.694 (0.659-0.730; P<0.001), respectively. AUC of morning pulse pressure was significantly greater than that of morning systolic blood pressure (P=0.040). CONCLUSIONS Our findings implicate that morning pulse pressure is associated with elevated albuminuria in patients with type 2 diabetes, which suggests that lowering morning pulse pressure could prevent the development and progression of diabetic nephropathy.

E-012 UNCONTROLLED HOME BLOOD PRESSURE IN THE MORNING IS ASSOCIATED WITH NEPHROPATHY IN JAPANESE PATIENTS WITH TYPE 2 DIABETES

Backgrounds Nephropathy in diabetic patients is the leading cause of end-stage renal failure. The significance of home blood pressure measurement has been widely recognized. In this study, we have investigated the state of blood pressure control level by measuring clinic and home blood pressure, and investigated the relationship between blood pressure control and nephropathy in Japanese patients with type 2 diabetes. Methods We measured clinic and home blood pressure in 923 patients with type 2 diabetes. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH). Results Of all patients, 13.9%, 12.6%, 13.3% and 60.2% were identified as having CH, WCH, MH and SH, respectively. The average number of drugs prescribed was 1.8. Degree of urinary albumin excretion and the prevalence of nephropathy in diabetic patients were higher in MH and SH groups than those in CH group. The majority of patients had poor blood pressure control, regardless of ongoing conventional antihypertensive therapy, and diabetic patients with MH and SH were associated with nephropathy in diabetic patients. Conclusions More aggressive antihypertensive treatment is recommended to prevent nephropathy in patients with type 2 diabetes.

E-009 THE COEFFICIENT VARIATION OF HOME BLOOD PRESSURE IS A NOVEL FACTOR ASSOCIATED WITH MACROALBUMINURIA IN TYPE 2 DIABETES MELLITUS

Backgrounds Home blood pressure (HBP) measurement has been found to have a stronger relationship with target organ damage. Recent studies have explored the association between variabilities of BP and target organ damage. Therefore, we investigated the relationship between day-by-day variabilities of HBP and diabetic nephropathy in Japanese patients with type 2 diabetes. Methods We compared the coefficient variation (CV) of HBP in 858 Japanese patients withand withoutmacroalbuminuria. Next, we analyzed the relationship between logarithm of urinary albumin excretion and the CV of HBP using linear regression analysis. Then, we evaluated the association of the CV of HBP with macroalbuminuria using logistic regression analysis. Results The CV of morning systolic blood pressure in patients with macroalbuminuria was significantly greater than that without (8.08 ± 3.35% vs. 7.19 ± 2.25%, p < 0.05). Multivariate linear regression analyses indicated that CV of morning systolic (P < 0.05) was the independent explanatory variables for logarithm of urinary albumin excretion. Multivariate logistic regression analysis demonstrated that the odds ratio of the CV of morning systolic blood pressure for macroalbuminuria was 1.35 (P < 0.05). Conclusions The CV of HBP correlated with macroalbuminuria independent of the known risk factors in Japanese patients with type 2 diabetes.

B-008 N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE COULD BE A MARKER OF SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH TYPE 2 DIABETES

Background Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in patients with type 2 diabetes. N-terminal pro-brain natriuretic peptide (NT-proBNP), which is a useful biomarker of chronic heart failure, has been shown to be a strong predictor of cardiovascular mortality. Furthermore, alterations in vascular structure and function are also recognized increasingly as significant independent predictors of adverse cardiovascularoutcomes. In this study, we investigated the relationships between NT-proBNP and markers of subclinical atherosclerosis in patients with type 2 diabetes. Methods Relationships of NT-proBNP to pulse wave velocity (PWV) or ankle-brachial index (ABI) as wellas to major metabolic risk parameters, including body mass index, blood pressure, serum lipid concentration, serum uric acid concentration,and glycemic control (hemoglobinA1c), age, hemoglobin, serum creatinine concentration, severity of diabetic nephropathy orretinopathy, current treatment of diabetes, smoking status, and presence of CVD were investigated in 323 consecutive patients with type 2 diabetes. Results Log (NT-proBNP) correlated positively with PWV (r = 0.283, p < 0.0001) and correlated negatively with ABI (r = −0.144, p = 0.0094). Multiple regression analysis demonstrated that age (&bgr; = 0.267, p < 0.0001), systolic blood pressure (&bgr; = 0.249, p < 0.0001), uric acid (&bgr; = 0.121, p = 0.0383), creatinine (&bgr; = −0.139, p = 0.0239) and log (NT-proBNP) (&bgr; = 0.173, p = 0.0043) were independent determinants of PWV and that log triglyceride (&bgr; = −0.130, p = 0.0390) andlog (NT-proBNP) (&bgr; = −0.153 p = 0.0256) were independent determinants of ABI. Conclusions NT-proBNP was associated with PWV and ABI in patients with type 2 diabetes. NT-proBNP could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.