心力衰竭患者血尿酸与有创血液动力学监测指标、血浆N末端B型利钠肽原和高敏C反应蛋白的相关研究

目的 评价心力衰竭(心衰)患者血尿酸与有创血液动力学监测指标、血浆N末端B型利钠肽原(NT-proBNP)和高敏C反应蛋白(Hs-CRP)的相关性.方法 选择141例NYHA Ⅱ～Ⅳ级心衰患者,在入院12 h内行漂浮导管监测和血尿酸等常规检查,同时检测血浆NT-proBNP和Hs-ClIP.结果 高尿酸血症的比率为55.30%,肺毛细血管楔压(PCWP)在高尿酸血症总组及高尿酸血症A、B、C组均较正常血尿酸组显著增高(P<0.01,P=0.01,P<0.01,P<0.01).血浆NT-proBNP在高尿酸血症总组和高尿酸血症C组较正常血尿酸组显著增高(P=0.02,P<0.01).与PCWP<18mm Hg(1 mm Hg=0.133 kPa)组比较,高NT-proBNP和高尿酸血症比率在PCWP≥18 mm Hg、<28mm Hg组和PCWP≥28 mm Hg组均显著增高(P=0.01,P=0.02;P<0.01,P<0.01).偏相关分析表明,血尿酸分别与右房压、右室压、肺动脉压和PCWP相关(r=0.19,P=0.03;r:0.45,P<0.01;r=0.23,P=0.01;r=0.24,P=0.01).多元回归分析表明,血尿酸和血浆NT-proBNP分别与PC:WP独立相关(β=0.24,P=0.01;β=0.47,P<0.01).血浆Hs-CRP以及左室射血分数与血尿酸及PCWP均不相关.结论 心衰患者血尿酸水平与PCWP等有创血液动力学指标独立相关,与血浆NT-proBNP结合可能更有利于心衰患者的临床评价.     

Serum uric acid is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus

Hyperuricemia has been reported to be associated with increased risk of renal insufficiency as well as cardiovascular events. The aim of this study was to evaluate the relationships between serum uric acid concentration and degree of urinary albumin excretion as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Serum uric acid concentrations were measured in 343 men with type 2 diabetes mellitus. We then evaluated relationships of serum uric acid concentrations to degree of urinary albumin excretion as well as to major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, and glycemic control (hemoglobin A1c). The relationships between serum uric acid concentration and pulse wave velocity or ankle-brachial index (n=236) and between serum uric acid concentration and carotid intima-media thickness or plaque score (n=125) were investigated additionally in a subgroup of patients. Serum uric acid concentration correlated positively with logarithm of urinary albumin excretion (r=0.302, P<.0001). Positive correlation was found between serum uric acid concentration and intima-media thickness (r=0.233, P=.0087), whereas inverse correlation was found between serum uric acid concentration and ankle-brachial index (r=-0.150, P=.0207). Multiple regression analysis demonstrated that serum uric acid concentration (beta=.281, P<.0001), duration of diabetes (beta=.253, P<.0001), hemoglobin A1c (beta=.166, P=.0034), serum triglyceride concentration (beta=.125, P=.0472), and systolic blood pressure (beta=.275, P=.0013) were independent determinants of logarithm of urinary albumin excretion. In conclusion, serum uric acid concentration is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus.     

Relationships between serum levels of thyroid hormones and serum concentrations of asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) in patients with Graves' disease

Endothelial dysfunction as well as abnormal thyroid hormone levels may be responsible for increased cardiovascular risk in Graves' disease (GD). Asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) are new markers of endothelial and myocardial dysfunction, respectively. The purpose of this study was to investigate the relationship among the serum levels of ADMA, NT-proBNP, and thyroid hormones in GD patients. This was a cross-sectional investigation conducted in a university teaching hospital. Two hundred and thirty-nine GD (Female: 182, Male: 57) patients and 81 normal controls were enrolled in this study. Serum levels of ADMA were positively related with FT3 (r = 0.584, P < 0.001), FT4 (r = 0.551, P < 0.001), and TRAb levels (r = 0.502, P < 0.001). Serum NT-proBNP levels were positively associated with FT3 (r = 0.243, P < 0.001) and FT4 levels (r = 0.274, P < 0.001), as well as heart rate (r = 0.271, P < 0.03). The elevation of serum ADMA and NT-proBNP levels were also observed in patients with controlled hyperthyroidism. It is thus concluded that serum ADMA and NT-proBNP levels were increased in GD patients. Future studies may determine the usefulness of these two biomarkers to detect early signs of endothelial dysfunction, vascular stiffness, and fluid volume in GD patients.     

Association of serum uric acid level and coronary blood flow

OBJECTIVES: Slow coronary flow (SCF) has long since been identified and endothelial dysfunction and atherosclerosis of the epicardial coronary arteries and microvasculature are reported to be associated with SCF. Serum uric acid is an independent biochemical marker of atherosclerosis, oxidative stress and endothelial dysfunction. Consequently, we aimed to investigate the association between coronary blood flow and serum uric acid level by means of thrombolysis in myocardial infarction frame count (TFC) and other laboratory parameters, in patients with SCF compared with control participants. METHODS: Sixty-four patients with SCF and 369 control participants with normal coronary flow were studied after quantifying coronary blood flow according to TFC. Serum uric acid levels were determined using commercially available assay kits. The association between TFC and serum uric acid level and other clinical and laboratory parameters were evaluated. RESULTS: Statistically significant differences were present between SCF and control groups with respect to serum uric acid, and hemoglobin levels, heart rate, cigarette smoking and sex (P<0.05 for all). The mean TFC was significantly correlated with serum uric acid, urea, creatinine, high-density lipoprotein-cholesterol and hemoglobin levels, platelet count, male gender, cigarette smoking, heart rate and systolic blood pressure (P<0.05 for all). Serum uric acid level (chi(2)=22.86, beta=0.54, P<0.001), heart rate (chi(2)=7.42, beta=-0.034, P=0.032) and cigarette smoking (chi(2)=12.343, beta=0.969, P=0.025) were independent predictors of SCF, whereas serum uric acid level was the only independent predictor of the mean TFC (beta=0.298, P<0.001). CONCLUSIONS: These findings have shown that serum uric acid level is significantly associated with coronary blood flow and that elevated uric acid might be an independent predictor for the presence of SCF.     

Uric acid, heart failure survival, and the impact of xanthine oxidase inhibition

Increasing evidence suggests that serum uric acid (UA), a product of xanthine oxidase (XO), may be a useful marker for metabolic, hemodynamic, and functional staging in heart failure (HF) and a valid predictor of survival in HF patients. Recent data support an expanded role for UA and the XO pathway in the pathogenesis of HF, as studies have shown that an elevation in the enzymatic activity of XO can lead to increases in oxidative stress, endothelial dysfunction, and reduced myocardial function. Numerous population studies have previously reported that elevated UA levels are an independent predictor of cardiovascular mortality, and recent evidence suggests that lowering serum levels of UA may lead to improved outcomes in HF patients. The question of whether UA is only a marker rather than a causal factor in the pathogenesis of HF remains. Regardless of whether UA levels are ready for routine clinical use, either as a prognostic factor or novel therapeutic target, further prospective studies are necessary to demonstrate that routine measurement or reduction of UA levels improves outcomes in HF patients.     

Influence of ramipril on the course of plasma thrombomodulin in patients with diabetes mellitus.

BACKGROUND: In diabetic patients endothelial dysfunction is reflected by an increased urinary albumine excretion, which can be reduced by ACE-inhibitors. No data are available showing a endothelial-protective effect by determining a marker reflecting endothelial cell-damage. PATIENTS AND METHODS: The effect of angiotensin converting enzyme inhibitor (ACEI) (ramipril) treatment on the progression of endothelial cell damage,--assessed by measurement of plasma-thrombomodulin (TM),--was investigated in an open, non randomized, prospective pilot study over a period of 18 months in diabetic patients. 87 patients with an urinary albumin concentration (UAC) below 100 mg/l at baseline were included. 46 patients were treated without ACEI and served as a control group, 41 patients were treated with ACEI. Participation in this study did not affect intensity in the treatment of blood glucose, blood pressure or diet. At study entry both groups were comparable with respect to duration of diabetes, diabetic complications, vascular risk factors, body mass index, medications used to treat diabetes, presence of hypertension, glycemic control, tryglycerides, HDL cholesterol, creatinine, UAC and plasma-TM. Age, blood pressure, and total cholesterol were significantly higher in the ACEI group, compared with the control group. RESULTS: After a follow up of 18 months a significant increase in UAC (delta UAC = 10.48 mg/l, p = 0.03) and plasma-TM (delta TM = 3.06 ng/l, p = 0.009) was observed in the control group, while in the ACEI treated group a decrease in albuminuria (delta UAC = -7.44 mg/l, p = 0.01) and plasma-TM (delta TM = -4.78 ng/l, p = 0.001) was seen. Despite a similar approach in hypertension and diabetes control in both groups, UAC and plasma-TM decreased after 18 months only in the ACEI treated group. Treatment with ACEI was the strongest predictor (p = 0.0001) indicating decrease of UAC and plasma-TM (multi regression analysis). CONCLUSION: Plasma-thrombomodulin might be a useful marker for assessing the efficacy of drugs potentially protecting the vessel wall. While the present study was a open, non randomized study, further investigation is necessary to proof the hypothesis in a randomized, placebo-controlled, double-blind study.     

Elevated serum uric acid levels impair coronary microvascular function in patients with idiopathic dilated cardiomyopathy

In patients with idiopathic dilated cardiomyopathy (IDC), attenuated coronary flow reserve (CFR) and elevated serum uric acid levels have been reported. In this study, we investigated whether increased uric acid levels correlate with the degree of coronary microvascular dysfunction. Serum uric acid levels were measured in 29 patients with IDC (mean age: 57.0+/-10.8 years, 10 female), and each patient also underwent transthoracic echocardiographic examination including CFR measurement. The study population was divided into two groups according to the median CFR value (lower CFR group and higher CFR group). Uric acid levels were significantly higher in the lower CFR group than in the higher CFR group (7.59+/-2.56 vs 4.80+/-0.80 mg/dL, P=0.000). CFR correlated significantly and inversely to serum uric acid (r=-0.570, P=0.001). Logistic regression analysis revealed that uric acid level was the only independent predictor of CFR (B=-1080, P=0.015). We found a possibly clinically important negative association between serum uric acid levels and CFR in patients with IDC.     

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

BACKGROUND: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. METHODS: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. RESULTS: One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.     

The relation between serum erythropoietin level and severity of disease and mortality in patients with chronic heart failure

OBJECTIVE: We evaluated the relation between serum erithropoietin level and the severity of disease and mortality in patients with chronic heart failure (CHF). METHODS: We enrolled 96 CHF patients and 50 age- and sex-matched control subjects. Haemoglobin, haemotocrit, N terminal pro-B type natriuretic peptide (NT-proBNP) and erythropoietin levels and echocardiographic parameters were measured. The patients were contacted 1 year after the evaluations to determine survival. RESULTS: The patients had lower haemoglobin and haematocrit but higher serum erythropoietin and NT-proBNP levels than the control subjects. Serum erythropoietin and NT-proBNP levels increased with worsening functional class. The serum erythropoietin level correlated negatively with left ventricular ejection fraction (r = -0.404, P < 0.001), haemoglobin (r = -0.530, P < 0.001) and haematocrit (r = -0.496, P < 0.001) levels. The patients who died (n = 17) had lower haemoglobin and haematocrit levels and significantly higher erythropoietin and NT-proBNP levels. However, multivariate logistic regression analysis showed that only NT-proBNP level was an independent predictor of mortality (P = 0.002). CONCLUSION: Anaemia and resistance to erythropoietin develop proportionately to disease severity and left ventricular systolic dysfunction in patients with CHF. Although serum erythropoietin level seems related with mortality, this observation needs to be confirmed by studies with more patients and longer follow-up.     

N-terminal pro-brain natriuretic peptide (NT-proBNP) in Type 2 diabetes with left ventricular dysfunction

Plasma N-terminal proBNP (NT-proBNP) is released in response to pressure overload, intravascular volume expansion and myocardial ischemia from cardiac ventricles. We studied the relationship between NT-proBNP levels and left ventricular dysfunction and urinary albumin excretion in Type 2 diabetes. The study group consisted of 130 diabetic patients referred for echocardiography. They were divided into four groups according to echocardiographic finding and into three groups according to urinary albumin excretion. NT-proBNP levels were measured by electrochemiluminescence. There were significant differences in NT-proBNP levels among four groups (P=0.012), with a highly significant difference between normal and other groups with left ventricular dysfunction. NT-proBNP levels in diastolic dysfunction were significantly higher than normal group (1491.1 pg/mL versus 232.3 pg/mL, P=0.01), even though there was no difference in ejection fraction (EF) (61.2+/-7.9% versus 60+/-8.4%, P=0.773). NT-proBNP levels showed positive correlation with age (Rs=0.37, P<0.001), creatinine (Rs=0.38, P=0.001), LVIDS (Rs=0.56, P=0.001) and LVIDD (Rs=0.34, P=0.04) and negative correlation with EF (Rs=-0.66, P=0.001). NT-proBNP levels significantly differed among three groups according to urinary albumin excretion (P=0.031). These results suggest that NT-proBNP could be used to identify any impairment of left ventricular function in diabetes.     

Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in Type 2 diabetes mellitus.

AIMS: Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetes mellitus. We determined whether alterations of plasma and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic patients. METHODS: One hundred and seven patients and 47 healthy controls were studied. Study subjects were divided into four groups using urinary albumin-to-creatinine ratio (ACR): a non-diabetic healthy control group (n = 47), a normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n = 37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary VEGF concentrations were significantly higher in the diabetic groups, even at the normoalbuminuric stage (log VEGF/Cr, normoalbuminuria; 4.33 +/- 1.06 vs. control; 3.53 +/- 0.79, P = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced. (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients than in the normotensive individuals with diabetes. (iii) In those with diabetes, plasma VEGF levels were found to be positively correlated with plasma urea (r = 0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be positively correlated with urinary ACR (r = 0.645, P < 0.001), and creatinine (r = 0.336, P = 0.009), and to be negatively correlated with serum albumin (r = -0.557, P < 0.001). Urinary VEGF and serum creatinine were independently correlated with urinary ACR. CONCLUSIONS: Urinary excretion of VEGF increased during the earlier stage of diabetic nephropathy and was significantly correlated with urinary albumin excretion. This suggests that urinary VEGF might be used as a sensitive marker of diabetic nephropathy and for predicting disease progression.     

Tissue Doppler velocities of mitral annulus and NT-proBNP in patients with heart failure

BACKGROUND: It has been shown that pulsed wave tissue Doppler velocities of mitral annulus correlate well with left ventricular (LV) diastolic and systolic functions. It is not yet clear whether these velocities can be used to estimate left ventricular dysfunction in an unselected population of patients with clinical signs and symptoms of heart failure (HF). AIM: To determine whether LV mitral annulus velocities measured by tissue Doppler imaging (TDI) correlate with plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF. METHODS AND RESULTS: Early diastolic (E(m)) and systolic (S(m)) TDI velocities of septal and lateral mitral annulus were measured in 50 patients with HF together with other conventional echocardiographic parameters, and compared with plasma NT-proBNP levels. Significant correlations were found between NT-proBNP level and E(m) velocity (r=-0.79), S(m) velocity (r=-0.43), early transmitral to E(m) velocity ratio (r=0.38), LV end diastolic diameter (r=0.29), LV ejection fraction (r=-0.44) and tricuspid regurgitant velocity (r=0.31). In multiple regression model (R(2)=0.733), the E(m) velocity was the most important predictor of NT-proBNP level. CONCLUSIONS: Early diastolic mitral annulus velocity measured by TDI correlates strongly with plasma NT-proBNP levels, and provides a simple, accurate and reproducible echocardiographic index of heart failure.     

Impact of kidney dysfunction on plasma and urinary N-terminal pro-B-type natriuretic peptide in patients with acute heart failure

The precise mechanism explaining the increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among patients with concomitant acute heart failure (AHF) and kidney dysfunction is not fully understood. The aim of this study was to assess the impact of kidney dysfunction on simultaneous measures of plasma and urinary NT-proBNP in an unselected cohort of patients with AHF. One hundred thirty-eight consecutive hospitalized patients (median age: 74 years; interquartile range: 67-80 years; 54% male) with a diagnosis of AHF were prospectively studied. Blood and urine samples were collected on hospital arrival to determine NT-proBNP concentrations. Both plasma and urinary NT-proBNP concentrations increased with declining estimated glomerular filtration rate (eGFR; P<.001 for both). However, after multivariate adjustment, eGFR was found to be an independent predictor of plasma (but not urinary) NT-proBNP concentration (eGFR: β=-0.19; P=.016). Indeed, plasma NT-proBNP was the main independent determinant of its urinary concentration (β=0.42; P<.001), and the ratio of urine/plasma NT-proBNP was independent of kidney function and similar across the range of eGFR examined (P=.368). In patients with AHF and concomitant kidney dysfunction, the increased circulating NT-proBNP may be mainly related to increased cardiac secretion and not decreased renal clearance.     

Relation between serum uric acid and lower limb blood flow in patients with chronic heart failure.

OBJECTIVE: To determine whether lower limb blood flow is related to serum uric acid concentrations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic treatment and insulin resistance. DESIGN: Lower limb blood flow was measured at rest and after maximum exercise followed by a five minute period of ischaemia (maximum blood flow) using strain gauge venous occlusion plethysmography. All patients underwent a metabolic assessment, which included an intravenous glucose tolerance test (IVGTT)-to obtain an index of insulin sensitivity- and measurement of serum uric acid. SETTING: University and hospital departments specialising in cardiology and metabolic medicine. SUBJECTS: 22 patients with chronic heart failure. RESULTS: Mean (SEM) resting and maximum blood flow values were 2.87 (0.23) and 24.00 (1.83) ml/100 ml/min, respectively. Patients in the upper tertile of serum uric acid had lower maximum blood flow than those in the lowest tertile (15.6 (2.2) v 31.0 (2.1) ml/100 ml/min, P = 0.003). Serum uric acid correlated with maximum blood flow (r = -0.86, P < 0.001), but not with resting blood flow. In stepwise regression analysis, uric acid emerged as the only predictor of maximum blood flow (standardised coefficient = -0.83 (P < 0.001), R2 = 0.68 (P < 0.001)), independently of diuretic dose, age, body mass index, plasma creatinine, fasting and IVGTT glucose and insulin, insulin sensitivity, maximum oxygen uptake and exercise time during the treadmill exercise test, and alcohol intake. CONCLUSIONS: There is a strong inverse relation between serum uric acid concentrations and maximum leg blood flow in patients with chronic heart failure. Further studies are needed to determine whether serum uric acid can be used as an index of vascular function in cardiovascular diseases.     

Diagnostic and prognostic value of urine NT-proBNP levels in heart failure patients

BACKGROUND: Plasma NT-proBNP levels are sensitive markers of ventricular dysfunction. However, studies of natriuretic peptides in urine are limited. AIMS: To compare urine and plasma NT-proBNP levels and to investigate the diagnostic and prognostic value of urine levels in heart failure (HF). METHODS: Urinary and plasma NT-proBNP levels were measured in 96 HF patients and 20 control subjects. The patients were functionally classified according to the NYHA criteria. RESULTS: Urine NT-proBNP was higher in HF patients than in control subjects (94+/-31 pg/ml vs. 67+/-6 pg/ml, p<0.0001), correlating with plasma NT-proBNP levels (r=0.78, p<0.0001). Urinary levels were elevated in the more severe functional classes and diminished in obese patients. Urine NT-proBNP was a good tool for diagnosis of HF, the area under the curve (AUC) being 0.96+/-0.02 (p<0.0001), and for predicting 12-month cardiac events (p=0.011). To determine the prognostic power of urinary NT-proBNP in detecting 12-month cardiac mortality, we obtained an AUC of 0.75+/-0.10 (p=0.015). CONCLUSION: Urinary NT-proBNP, a relatively simple non-invasive test, is a new candidate marker for the diagnosis and evaluation of prognosis in HF and for the characterization of functional status in these patients.     

Neurohormonal activation and diagnostic value of cardiac peptides in patients with suspected mild heart failure

BACKGROUND: Data describing activation of brain natriuretic peptide (BNP) system relative to the renin-angiotensin-aldosterone system (RAAS) are sparse in the early phase of heart failure (HF). AIMS: To compare activation of BNP system relative to RAAS hyperactivity and to assess diagnostic accuracy of cardiac peptides to detect any left ventricular dysfunction (LVD) in patients referred from primary care with suspected HF before institution of medical therapy. METHODS: Of 166 referred patients 150 were consecutively included (14 were excluded and two refused consent). Echocardiography and measurements of neurohormonal activity were performed. Systolic dysfunction (LVSD) was defined as an ejection fraction相似文献   

尿白蛋白水平升高预测不合并糖尿病的射血分数降低的心力衰竭患者预后的价值

目的:分析入院时尿白蛋白水平(UAC)升高对不合并糖尿病的射血分数降低的心力衰竭(HFrEF)患者预后的评价价值.方法:入选2013年1月至2017年12月期间于北京水利医院内科住院的不合并糖尿病的HFrEF患者212例.留取患者入院后次日晨起首次中段尿检测UAC,以≥30 mg/L定义为UAC升高.出院后通过电话或门...     

Uric acid excretion in healthy subjects: a nomogram to assess the mechanisms underlying purine metabolic disorders

The reference range for urinary uric acid excretion has not been precisely defined. Different urinary variables have been proposed to determine the renal contribution to increased or decreased serum urate concentrations. We examined which urinary variable best indicates uric acid excretion over a wide range of serum urate concentrations. Purine metabolism was studied in 10 healthy male subjects (aged 26-58 years) both at their endogenous normal serum urate levels (normouricemic state) and after the oral administration of allopurinol (300 mg/24 h for 5 days) and ribonucleic acid (4 g/8 h for 4 days) to decrease (hypouricemic state) and increase (hyperuricemic state) serum urate concentrations, respectively. The results from patients with several conditions known to affect uric acid synthesis and/or the renal excretion of uric acid were used to validate a constructed nomogram. Over a wide range of mean serum urate levels (from 2.7 to 9.5 mg/dL) and mean 24-hour urinary uric acid excretion (171 to 1368 mg/[24 h 1.73 m(2)]), the highest correlation coefficient between serum urate and uric acid excretion was obtained for the 24-hour uric acid determination (r = 0.928; P < .001). The constructed nomogram allowed the definition of the mechanism underlying hyperuricemia and hypouricemia in patients with a myriad of diseases known to affect purine metabolism. The urinary variable that best correlates with a wide range of serum urate concentrations is 24-hour urinary uric acid excretion. The constructed nomogram allows the identification of the kidney contribution to a given purine metabolic abnormality.     

Relationship between low T3 syndrome and NT-proBNP levels in non-cardiac patients

OBJECTIVES: A low T3 syndrome was described in patients with heart failure (HF), and it appears to be associated with adverse outcome, representing an independent predictor of mortality. However, it is not known if low T3 levels contribute to the pathophysiology of HF. On the other hand, it has been seen that an elevation of brain natriuretic peptides (BNP and NT-proBNP) may represent a warning signal for future cardiovascular disease and may be an early marker of diastolic dysfunction. Therefore we tested the hypothesis that low levels of free-triiodothyronine (FT3) are sufficient to determine an increased concentration of the amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), as the result of an initial and asymptomatic cardiac impairment. METHODS: A total of 52 consecutive non-cardiac patients underwent thyroid function profile evaluation and NT-proBNP determination. On the basis of FT3 values they were divided in two subgroups: a low T3 group (19 patients) and a normal T3 group (33 patients). RESULTS: The median NT-proBNP concentration of patients with low T3 syndrome was significantly higher than in those with normal FT3 (370 vs. 120 pg/ml, P = 0.002). There is a strong and inverse correlation between FT3 and Log NT-proBNP (R = -0.47, P < 0.001); this relation persists in a multivariable regression analysis, after adjustment for other potentially confounding variables (P = 0.008). CONCLUSION: In absence of overt cardiovascular disease, patients with low T3 syndrome present an increased concentration of NT-proBNP. These data suggest that low FT3 levels may be a contributing factor for the development of cardiac dysfunction.     

The serum concentration of allograft inflammatory factor-1 is correlated with metabolic parameters in healthy subjects

Obesity is associated with low-grade chronic inflammation characterized by inflamed adipose tissue with increased infiltration of macrophages. The aim of this study was to investigate the correlations between the serum concentration of allograft inflammatory factor-1 (AIF-1), which is a marker of activated macrophages, and metabolic parameters. The serum AIF-1 concentrations were measured in 303 healthy subjects (163 men and 140 women). We then evaluated the relationships between the serum AIF-1 concentrations and metabolic parameters, including fasting plasma glucose levels, serum lipid concentration, uric acid concentration, and waist circumference. The serum AIF-1 concentrations positively correlated with levels of fasting plasma glucose (r = 0.159, P =.0056), hemoglobin A(1c) (r = 0.169, P = .0032), triglycerides (r = 0.137, P = .0172), and uric acid (r = 0.146, P = .0108) and with waist circumference (r = 0.221, P = .0001) and body mass index (r = 0.185, P = .0012), whereas the serum AIF-1 concentrations inversely correlated with high-density lipoprotein cholesterol level (r = -0.178, P = .0019). Stepwise multiple regression analysis demonstrated that hemoglobin A(1c) level (β = .133, F = 5.490, P < .05) and waist circumference (β = .197, F = 11.954, P < .05) were independent predictors of the serum AIF-1 concentrations. The serum AIF-1 concentrations correlated with clinical and biochemical metabolic parameters. Allograft inflammatory factor-1 may be a significant predictor of activated macrophages as well as cardiovascular disease in humans.