Hiroo Sonoda

Uric Acid Levels Predict Future Development of Chronic Kidney Disease

Aims: Increased uric acid levels are associated with kidney dysfunction. We tested the hypothesis that uric acid level predicts future development of chronic kidney disease (CKD) in the general population. Methods: For this study, we enrolled 7,078 consecutive subjects with normal estimated glomerular filtration rates (eGFR; ≧60 ml/min/1.73 m2) who visited our hospital for a yearly health checkup (age: 52.8 ± 10.7 years; female: 35.8%). Subjects underwent a routine physical examination and laboratory assessment of cardiovascular disease risk factors at enrollment, and were followed up for 1,694 days (median) with the endpoint being the development of CKD (eGFR <60 ml/min/1.73 m2). The impact of uric acid and other cardiovascular risk factors at baseline on the future development of CKD were assessed. Results: During the follow-up period, 417 male (9.2%) and 151 female subjects (6.0%) developed CKD. Univariate logistic regression analysis revealed a significant association between the onset of CKD and age, male gender, body mass index, blood pressure, fasting plasma glucose, dyslipidemia and uric acid. Multiple logistic regression analysis revealed that new-onset CKD was independently correlated with the baseline uric acid level after adjustment for possible factors. Subanalysis showed similar results in subjects with normal uric acid levels (male: ≤7.0 mg/dl; female: ≤6.0 mg/dl; n = 6,223). Conclusion: Uric acid is an independent predictor of future development of CKD. Whether preventing an increase in uric acid levels reduces the incidence of CKD must be clarified by prospective follow-up studies.

Brachial-ankle pulse wave velocity predicts increase in blood pressure and onset of hypertension.

BACKGROUND The present study was designed to test the hypothesis that brachial-ankle pulse wave velocity (baPWV) predicts longitudinal increases in blood pressure (BP) and new onset of hypertension in individuals with normal BP. METHODS baPWV was measured using a semiautomated device in 2,496 participants (27-84 years) without hypertension who visited our hospital for a yearly health check-up. They were followed up for 4 years with the endpoint being development of hypertension. RESULTS During the follow-up period (median, 733 days; actual follow-up, 5,215 person-years), hypertension developed in 698 participants (133.8/1,000 person-years). Kaplan-Meier analysis revealed that risk for hypertension was increased across the tertiles of baseline baPWV. The hazard ratio (first tertile as reference) was 2.02 (95% confidence interval (CI) 1.55-2.64) and 3.49 (95% CI 2.66-4.57) in the second and third tertiles, respectively, after adjustment for possible risk factors. Multivariate Cox proportional hazard regression analysis adjusted for known risk factors, where baPWV was used as a continuous variable, also indicated that the baseline value of baPWV independently predicted new onset of hypertension (P < 0.001). Furthermore, baseline baPWV was significantly associated with a longitudinal increase in BP after adjustment for known risk factors in multiple regression analysis (P < 0.001). CONCLUSION This study provides the first evidence that baPWV is an independent predictor of longitudinal increases in BP as well as of new onset of hypertension.

Evaluation of risk for incident hypertension using glomerular filtration rate in the normotensive general population.

Objectives: The present study tested the hypothesis that glomerular filtration rate can predict the onset of hypertension in individuals with normal blood pressure in the general population. Methods: Normotensive individuals (n = 7684) who visited our hospital for a routine physical examination were enrolled in the study (4907 men; mean age 52.1 ± 11.1 years) and were followed up with the endpoint being the development of hypertension. The relationship between estimated glomerular filtration rate at baseline and the incidence of hypertension was evaluated. Results: During the follow-up period (median 4.0 years; actual follow-up 30 624 person-years), hypertension developed in 2031 participants (66.3 per 1000 person-years). After adjustment for possible risk factors, the hazard ratio of incident hypertension (first tertile as reference) in the second and third tertiles was 1.03 (95% confidence interval 0.92–1.16) and 1.40 (95% confidence interval 1.26–1.57), respectively. Multivariate Cox proportional hazard regression analysis, in which estimated glomerular filtration rate was taken as a continuous variable and adjustments were made for known risk factors, also indicated that baseline estimated glomerular filtration rate independently predicted the onset of hypertension (P < 0.0001). Furthermore, multiple regression analysis revealed that a longitudinal increase in SBP was significantly associated with baseline estimated glomerular filtration rate after adjustment for known risk factors (P < 0.01). Conclusion: Estimated glomerular filtration rate in normotensive individuals is a good predictor of the onset of hypertension in the general population.

Elevation of arginine vasopressin levels following loop diuretic therapy as a prognostic indicator in heart failure

Objective To investigate the association between arginine vasopressin (AVP) levels and loop diuretic (LD) therapy in patients with heart failure and to determine if AVP levels are a prognostic indicator of treatment failure. Methods Patients with stable heart failure and reduced (< 40%) left ventricular ejection fraction (LVEF) were divided into those treated with (LD) or without LD (NLD). The LD group was separated into subgroups of high (> 6.5 pg/dl) and low (≤ 6.5 pg/dl) AVP levels. The clinical and biochemical characteristics of the two groups were compared and the prognostic value of AVP levels in heart failure evaluated. Results Of the 63 patients enrolled into the study, 41 (65.1%) were in the LD group and 22 (34.9%) were in the NLD group. Despite no differences between groups in LVEF, creatinine clearance, or brain natriuretic peptide, the LD group had significantly higher AVP levels compared with the NLD group. A Cox proportional-hazards model showed that AVP was an independent predictor of adverse events. In addition, the elevation in AVP in the LD group was inversely correlated with an increase in free water clearance but not serum osmolality and was related to poor outcome. Conclusions Elevated AVP levels in patients with heart failure who received LD therapy were associated with a poor prognosis. Loop diuretics may induce non-osmolar AVP release, which can worsen heart failure.

AN INCREASE IN BLOOD PRESSURE PREDICTS FUTURE DEVELOPMENT OF TYPE 2 DIABETES MELLITUS IN SUBJECTS WITH NORMAL FASTING PLASMA GLUCOSE LEVEL: PP.17.136

Objective: The prevalence of diabetes mellitus is higher in patients with hypertension than in normotensive subjects. Diabetes mellitus and hypertension may not be coincidently overlapped, but may be related factors tending to co-occur in the same individual. We tested the hypothesis that the risk of new diabetes mellitus increases with increasing blood pressure. Design and Method: Among 10,618 participants who visited our hospital for a physical check-up from July 2001 to December 2008, 9,413 subjects with normal fasting plasma glucose were enrolled in this study (male 60.0%, 51.9 ± 12.5 years old) and followed up for the median of 1,674 days, with the endpoint being the development of type 2 diabetes mellitus. The ESH2007 guideline was used for classifications of blood pressure levels. The relationship between the blood pressure category at baseline and the incidence of diabetes mellitus during the follow-up was evaluated. Diabetes mellitus was defined as fasting plasma glucose > = 126 mg/dl or use of anti-diabetic medications. Results: During the follow-up, diabetes mellitus developed in 254 subjects (6.11 per 1000 person-year), with the incidence being more frequent in male than in female subjects (7.41 vs 4.02 per 1000 person-year). The incidence (per 1000 person-year) and relative risk of the onset of new diabetes mellitus in each blood pressure category were as follows: optimal, 3.88 and 1 (reference); normal, 5.83 and 1.467; high normal, 5.71 and 1.445; hypertension, 10.43 and 2.562. Multiple logistic regression analysis adjusted for age, gender, body mass index, the presence of dyslipidemia, and current smoking status revealed that hypertension was the significant predictor of new diabetes mellitus (p = 0.0032). Conclusions: The risk of new onset of diabetes mellitus increases with increasing blood pressure levels in subjects with normal fasting glucose levels.

USEFULNESS OF 75G GLUCOSE TOLERANCE TEST FOR DETECTION OF IMPAIRED GLUCOSE TOLERANCE IN HYPERTENSIVE PATIENTS: PP.17.148

Objective: Diagnosis of impaired glucose tolerance (IGT) is important in patients with hypertension, because IGT often coexists with hypertension and markedly increases cardiovascular risk in hypertensive individuals. The present study was designed to investigate usefulness of glucose tolerance test (GTT), as compared to fasting plasma glucose (FPG) levels, in the evaluation of glucose metabolism in hypertensive patients. Design and Method: We enrolled consecutive 7,012 participants in our physical check-up program without anti-diabetic medications (1,957 hypertension; 5,055 normotension). First, glucose metabolism was assessed using FPG. Second, among participants who had normal FPG levels, 333 participants were randomly selected and underwent 75 g GTT. Results: The results are shown in the Table. The prevalence of IGT or diabetes mellitus (DM) was about double in participants with hypertension as compared to normotensive participants. Strikingly, about 30% and 20% of hypertensive and normotensive participants, respectively, with normal FPG showed disorder of glucose metabolism in GTT. Figure 1. No caption available. Conclusions: GTT is a useful and sensitive method to identify IGT or DM, while FPG may not be adequate for this purpose. GTT should be used for accurate detection of IGT or DM, especially in high risk population such as hypertension.