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.

Clinical significance of abnormal relaxation pattern of the transmitral flow velocity waveform in older patients with preserved left ventricular ejection fraction.

BACKGROUND: The pathophysiology of abnormal relaxation pattern in the transmitral flow (TMF) velocity waveform has not been fully elucidated. METHODS AND RESULTS: A total of 173 patients who underwent comprehensive Doppler echocardiography and diagnostic cardiac catheterization for coronary artery disease were enrolled in the study. Peak early and late diastolic TMF velocities (E and A, respectively) were measured. Minimum left ventricular (LV) pressure; LV pre-A wave pressure (surrogate of mean left atrial [LA] pressure); time constant (τ) of LV pressure decay; and LV ejection fraction (LVEF) were calculated. Patients with E/A ratio <1.0 and LVEF ≥ 50% were enrolled. Patients with τ ≥ 48 ms and those with τ <48 ms were compared. The 2 groups had no significant differences in E or E/A. Minimum LV pressure (6.9 ± 2.2 mmHg vs. 3.6 ± 2.9 mmHg, P<0.0001) and LV pre-A wave pressure (9.5 ± 2.4 mmHg vs. 6.1 ± 3.0 mmHg, P<0.0001) were significantly higher in patients with τ ≥ 48 ms compared to those with τ <48 ms, but the difference between the LV pre-A and minimum LV pressures was similar between the groups (2.6 ± 1.4 mmHg vs. 2.5 ± 1.5 mmHg, P=0.89). CONCLUSIONS: Proportional elevations in minimum LV and pre-A pressures, due to deteriorated LV relaxation, resulted in no changes in the pressure gradient between the LA and LV in early diastole, E, or E/A.

Prediction of Atrial Fibrillation by B-type Natriuretic Peptide.

Background: Although several conditions have been proposed as risk factors contributing to the incidence of atrial fibrillation, many individuals without such 'risk factors' also suffer from atrial fibrillation. The present study tested the hypothesis that the risk of new-onset atrial fibrillation increases with increasing circulating levels of B-type natriuretic peptide in the general population. Methods: Participants in our health checkup program without atrial fibrillation or a history of atrial fibrillation were enrolled (n=10,058, 54.3±11.3 years old). After baseline evaluation, subjects were followed up for the median of 1,791 days with the endpoint being the new onset of atrial fibrillation. Results: Atrial fibrillation occurred in 53 subjects during the follow-up period (1.16 per 1,000 person-year). The risk of new-onset atrial fibrillation increased across the gender-specific quartiles of B-type natriuretic peptide levels at baseline. In multivariate Cox proportional hazard regression analysis where B-type natriuretic peptide concentrations were taken as a continuous variable, B-type natriuretic peptide was a significant predictor of new onset of atrial fibrillation after adjustment for possible factors (hazard ratio 5.65 [95% CI 2.63-12.41]). Conclusions: The risk of new onset of atrial fibrillation increases with increasing B-type natriuretic peptide levels in the general population. Measurement of B-type natriuretic peptide may improve the prediction of incident atrial fibrillation.

Plasma N-terminal pro-brain natriuretic peptide levels identifying left ventricular diastolic dysfunction in patients with preserved ejection fraction.

BACKGROUND: Diagnosis of left ventricular (LV) diastolic dysfunction by blood testing is expedient in the clinical setting. METHODS AND RESULTS: In 98 patients with LV ejection fraction ≥50% who underwent cardiac catheterization for evaluation of coronary artery disease, LV pressure (LVP) was measured using a catheter-tipped micromanometer. A time constant, τ, of LV relaxation was computed from LVP decay; the inertia force (IF) of late systolic aortic flow, a surrogate index of LV elastic recoil, was also computed from the LVP-dP/dt relation (phase loop). Patients were classified into 2 groups: those with impaired LV relaxation (τ ≥48 ms) and those with preserved LV relaxation (τ <48 ms). Patients were also classified into another 2 groups: those with IF (≥0.5 mmHg) and those without (<0.5 mmHg). Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥56.5 pg/ml had a sensitivity of 100%, specificity of 52.5%, and negative predictive value of 100% for identifying impaired LV relaxation. NT-proBNP ≥244.5 pg/ml had a sensitivity of 62.5% and specificity of 93.9% for detecting lack of IF. CONCLUSIONS: NT-proBNP level <56.5 pg/ml could be used as a value to sensitively identify patients with preserved LV systolic and diastolic function among those with coronary artery disease. NT-proBNP level ≥244.5 pg/ml is able to specifically detect a lack of IF and has potential for specifically diagnosing LV isolated diastolic dysfunction.

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 ±â€Š11.1 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.

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 m(2)) 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 m(2)). 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.