Factors for heterogeneous outcomes of angina and myocardial ischemia without obstructive coronary atherosclerosis.

BACKGROUND AND OBJECTIVES: The absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis is debated. We investigated outcomes of such patients to identify predictors of cardiovascular events. METHODS: We selected 1014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exercise test or imaging stress tests, and nonobstructive CAD (absence of lumen diameter reduction ≥50%) at coronary angiography between 1999 and 2015. Note that, 1905 age- and risk factors-matched asymptomatic subjects served as "real-world" comparators. The primary endpoint was the occurrence of all-cause death or myocardial infarction. RESULTS: At 6-years median follow-up (interquartile range, 3-9 years), the primary endpoint occurred in 53 patients (5.5%, 0.92/100 person-years). Besides similar event rates compared with asymptomatic subjects (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.62-1.15, p = 0.28), the index population showed a very heterogeneous prognosis. Patients with nonobstructive CAD (HR 1.85, 95% CI 1.02-3.37, p = 0.04, compared with "normal" coronary arteries) and ischemia at imaging tests (HR 2.11, 95% CI 1.07-4.14, p = 0.03, compared with ischemia detected only at the ECG exercise test) were at higher risk and those with both these components showing even >10-fold event rates as compared with the absence of both. Three-hundred and twenty-five patients (34%) continued to experience angina, 69 (7.2%) underwent repeat coronary angiography, and 14 (1.5%) had consequent coronary revascularization for atherosclerosis progression. CONCLUSION: Apart from the impaired quality of life, angina without obstructive CAD has an overall benign but very heterogeneous prognosis. Nonobstructive CAD and myocardial ischemia at imaging tests both confer a higher risk.

Sympathetic and renin-angiotensin-aldosterone system activation in heart failure with preserved, mid-range and reduced ejection fraction.

BACKGROUND: Evidence of sympathetic and renin-angiotensin-aldosterone system activation provided a rationale for neurohormonal antagonism in heart failure with reduced ejection fraction (HFrEF), while no data are available in patients with milder degree of systolic dysfunction. We aimed to investigate neurohormonal function in HF with preserved and mid-range EF (HFpEF/HFmrEF). METHODS: Three cohorts (n = 189/each) of stable HFpEF, HFmrEF and HFrEF patients were selected (median age 70, 67 and 67 years; male 56%, 73% and 74%, respectively). Patients received a baseline clinical assessment including plasma renin activity (PRA), aldosterone, catecholamines, and N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) assays, and were followed-up for all-cause death. RESULTS: Neuroendocrine profile was similar between HFpEF and HFmrEF, while all neurohormones except epinephrine were higher in HFrEF than in HFmrEF (NT-proBNP 2332 ng/L, IQR 995-5666 vs 575 ng/L, 205-1714; PRA 1.7 ng/mL/h, 0.4-5.6 vs 0.6 ng/mL/h, 0.2-2.6; aldosterone 153 ng/L, 85-246 vs 113 ng/L, 72-177; norepinephrine 517 ng/L, 343-844 vs 430 ng/L, 259-624; all p < 0.001, epinephrine 31 ng/L, 10-63 vs 25 ng/L, 10-44; p = 0.319). These findings were unrelated to treatment heterogeneity. Ten percent of HFpEF patients had elevated PRA, aldosterone and norepinephrine vs. 8% in HFmrEF and 21% in HFrEF. During a 5-year follow-up, survival decreased with the number of neurohormones elevated (HFpEF: log-rank 7.8, p = 0.048; HFmrEF: log-rank 11.8, p = 0.008; HFrEF: log-rank 8.1, p = 0.044). CONCLUSIONS: Neurohormonal activation is present only in a subset of patients with HFpEF and HFmrEF, and may hold clinical significance. Neurohormonal antagonism may be useful in selected HFpEF/HFmrEF population.

NT-proBNP prognostic value is maintained in elderly and very elderly patients with chronic systolic heart failure.

BACKGROUND: Circulating concentrations of N-terminal fragment of the prohormone of brain natriuretic peptide (NT-proBNP) are influenced by age and common age-related comorbidities, such as renal dysfunction. Therefore, utility of NT-proBNP for prediction of prognosis in the aged has been questioned. We aimed to investigate the prognostic value of NT-proBNP across age classes in a cohort of patients with chronic systolic HF. METHODS AND RESULTS: We enrolled 2364 consecutive outpatients with HF and left ventricular ejection fraction ≤50%. Patients were classified according to age quartiles, and a very elderly subgroup was identified, aged ≥85 years. After baseline assessment (including NT-proBNP testing), patients were followed-up for the composite of cardiovascular death, heart transplantation or ventricular assistance device implantation (primary outcome) and for all-cause death (secondary outcome). Patients in the fourth quartile (Q4, age ≥ 77 years, n = 638) and in the very elderly subgroup (age ≥ 85 years, n = 153), had higher NT-proBNP (p < .001 vs Q1). NT-proBNP was independently associated with primary and secondary outcome at 1- and 5-years follow-up in the whole population, as well as in Q4 and in the very elderly subgroup (all p < .05). Compared to the whole population, Q4 and very elderly had higher NT-proBNP cut-off for prediction of 1-year primary (4188 and 9729 ng/l, respectively vs 3710 ng/l) and secondary outcome (4296 and 7634 ng/l, respectively vs 3056 ng/l). CONCLUSIONS: NT-proBNP predicts mortality in elderly and very elderly patients with chronic systolic HF, both at mid- and long-term follow-up. Higher NT-proBNP prognostic cut-off should be considered in the aged HF population.

Significance of the ionized calcium measurement to assess calcium status in osteopenic/osteoporosis postmenopausal outpatients.

INTRODUCTION: Evaluation of calcium status is important in the osteoporotic risk assessment. Although guidelines indicate total calcium (tCa) as first-line measurement, directly measured ionized calcium (m-iCa), considered as the gold standard, is more and more often required. Aim of this study is to evaluate the agreement between m-iCa, tCa and iCa calculated from a formula based on total calcium and albumin (c-iCa) in osteopenic/osteoporotic postmenopausal outpatients. METHODS: A total of 140 postmenopausal outpatients, 41 osteopenic (OPN) and 99 osteoporotic (OP) were enrolled. Levels of tCa, m-iCa, c-iCa, total protein and albumin, vitamin D (25-OHD), parathyroid hormone 1-84 (PTH), bone alkaline phosphatase, osteocalcin and serum collagen type 1 cross-linked C-telopeptide (CTX) were also measured. RESULTS: There were no statistically significant differences between OPN and OP groups regarding values of tCa, m-iCa, and c-iCa, 25-OHD and PTH. However, OP women had lower levels of CTX (p < 0.05). A significant direct correlation between m-iCa and tCa (r = 0.60, p < 0.001) and c-iCa (r = 0.61, p < 0.001) was found. Women with isolated hyper-m-iCa had similar DEXA parameter levels respect to the other patients. However, one patient with confirmed primary hyperparathyroidism presented hyper-m-iCa versus normal tCa and c-iCa values. CONCLUSIONS: The use of tCa could be sufficient to characterize the calcium status in postmenopausal outpatients, but reflexive calcium testing strategy for m-iCa test is necessary to women presenting the low or high extremes of tCa levels, or in women with suspected PHPT.

Prognostic value of plasma renin activity in heart failure patients with chronic kidney disease.

BACKGROUND: Impairment of kidney function is frequently observed in chronic heart failure (CHF). It correlates with clinical and neurohormonal status, and affects prognosis. We aimed to identify the prognostic impact of plasma renin activity (PRA) in patients affected by CHF with chronic kidney disease (CKD). METHODS: We enrolled 996 consecutive CHF patients (age 65 ± 13 years, mean ± SD, left ventricular ejection fraction, LVEF, 33 ± 10%), who underwent a complete clinical and neurohormonal characterization and were then followed-up (median 36 months) for the end point of cardiac death. RESULTS: A stage ≥ 3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) was found in 437 patients. Impaired renal function was associated with worse symptoms, lower LVEF, higher plasma norepinephrine, NT-proBNP and PRA (all p<0.001). As compared to patients with preserved renal function, those with CKD had higher cardiac mortality [106 (24%) vs 53 (9.5%), p<0.001]. In CKD patients, at Cox multivariate analysis, only ejection fraction (HR 0.91, 95% CI 0.84-0.97, p=0.008), NT-proBNP (2.53, 1.45-4.41, p=0.001) and PRA (1.73, 1.16-2.58, p=0.007) were independent predictors of cardiac death. ROC analysis identified a cut-off value for PRA of 3.29 ng/mL/h that predicted prognosis with the greatest accuracy. Finally, the elevation of both NT-proBNP and PRA identified a subset of patients with the highest risk of cardiac death. CONCLUSIONS: PRA has an independent prognostic value in CHF patients with CKD comorbidity. The combination of PRA and NT-proBNP identifies a group of high risk patients, who might benefit of a more intensive care, targeted to enhance renin-angiotensin system antagonism.

Low triiodothyronine and exercise capacity in heart failure.

BACKGROUND: Cardiopulmonary exercise test (CPT) has a prominent value in assessing clinical severity in chronic heart failure (HF) patients. Reduced free triiodothyronine (fT3) plasma level is associated with a more severe disease and prognosis. The aim of this study was to evaluate the relationship between low fT3 plasma level and reduced exercise capacity in chronic HF, and to determine the influence of a low T3 status in subsets of patients with different functional impairment. METHODS AND RESULTS: 240 HF patients (79% males; age 62 ± 12 years, mean ± standard deviation; left ventricular ejection fraction, EF, 30 ± 9%) underwent a CPT, clinical and neurohormonal characterization (assay for plasma brain natriuretic peptide, BNP, norepinephrine, aldosterone, renin activity, fT3, free T4, thyroid-stimulating hormone). At multivariate analysis in the whole population, age, gender and BNP level were independently associated with peak VO2, whereas in patients with severe functional impairment (peak VO2 < 14 ml/min/kg) fT3 resulted independently related to peak VO2, together with gender and BNP. When patients with peak VO2 < 14 ml/min/kg were divided according to fT3 levels, patients with low T3 syndrome showed reduced exercise capacity and worse ventilatory efficiency. CONCLUSIONS: BNP and fT3 are independently associated with exercise capacity in severely compromised HF patients.

Clinical relevance of time course of BNP levels in neonates with congenital heart diseases.

INTRODUCTION: The aim of this study is to better characterize the time courses of BNP levels throughout the first days of life in larger populations of neonate and infant with or without congenital heart diseases (CHD) in order to increase the diagnostic accuracy of BNP assay in pediatric patients with CHD. MATERIALS AND METHODS: BNP was measured by an automated platform (Triage BNP reagents, ACCESS Immunoassay Systems, Beckman Coulter, Inc., Fullerton, CA 92835) in 218 neonates and infants with different CHD; 222 healthy children, matched for age, served as controls. RESULTS: BNP values were significantly higher (P<0.001) in the whole group of CHD patients (median 1029.8 ng/L, range 25-20,152 ng/L) than in controls (median 149.5 ng/L, range 9-866 ng/L). A different trend between BNP values and age was observed in healthy subjects and CHD patients. After an initial increase within the first 4 days of life, BNP values in CHD patients tend to stabilize to high values in the following days. On the contrary, in control subjects a peak of BNP levels was observed in the second or third day, followed by a progressive decrease. Therefore, the diagnostic accuracy of BNP assay, calculated in the samples collected in the first four days of life (AUC of ROC analysis 0.86, 95% CI 0.83-0.90) was significantly lower (P<0.0001) compared to samples collected from 5 days to 30 days of life (AUC 0.97, 95% CI 0.95-0.99). Optimal cut-off values for BNP assay, as calculated by ROC analysis, were also age-dependent (cutoff for the first 4 days of life: 363.5 ng/L; cutoff values from 5 to 30 days of life: 109.5 ng/L). CONCLUSIONS: Our study demonstrates that differences in time-courses of BNP values between newborns with and without CHD throughout the first days of life clearly affect the diagnostic accuracy of BNP assay. Indeed, the diagnostic accuracy of BNP assay in discriminating between healthy newborns and CHD patients progressively increases after the 4th day of life. As a result, also cutoff values of BNP assay greatly change throughout the first days of life. However, decision values of BNP assay are strongly method-dependent, consequently clinicians should give great care to compare results obtained by different laboratories, especially when different methods are used.

Prognostic value of plasma renin activity in heart failure.

The prognostic role of specific biomarkers of the renin-angiotensin-aldosterone system and sympathetic activation pathways in heart failure has never been investigated in populations with current evidence-weighted treatment. To establish whether the plasma renin activity (PRA), among several neurohormonal biomarkers, is able to predict cardiac events in a population of patients with heart failure on up-to-date treatment, we selected 996 consecutive patients with systolic left ventricular dysfunction (ejection fraction <50%, mean age 65 ± 13 years), who underwent a complete clinical and humoral characterization and were then followed up (median 36 months, range 0 to 72) for cardiac death and appropriate implantable cardioverter device shock. We recorded 170 cardiac deaths and 27 shocks. On Cox multivariate analysis, only ejection fraction (hazard ratio 0.962, 95% confidence interval 0.938 to 0.986), N-terminal pro-brain natriuretic peptide (NT-proBNP; hazard ratio 1.729, 95% confidence interval 1.383 to 2.161) and PRA (hazard ratio 1.201, 95% confidence interval 1.024 to 1.408) were independent predictors of cardiac death. Receiver operating characteristic curve analysis identified a cutoff value for PRA of 2.30 ng/ml/hour that best predicted cardiac mortality. Independent predictors of PRA were ejection fraction, functional class, sodium, potassium, NT-proBNP, norepinephrine, aldosterone, C-reactive protein, and medical therapy. The association of high NT-proBNP and high PRA identified a subgroup (22% of the study population) with the greatest risk of cardiac death. In conclusion, PRA resulted an independent prognostic marker in patients with systolic heart failure additive to NT-proBNP level and ejection fraction. PRA might help to select those patients needing an enhanced therapeutic effort, possibly targeting incomplete renin-angiotensin-aldosterone system blockade.

Diagnostic accuracy of B-type natriuretic hormone for congenital heart disease in the first month of life.

BACKGROUND: The goal of the present study was to evaluate the diagnostic accuracy of B-type natriuretic hormone (BNP) assay in children with congenital heart disease (CHD) in the first month of life. METHODS: BNP was measured in 152 neonates with CHD; 154 healthy children matched for age were used as controls. BNP was measured with a fully automated platform (Triage BNP reagents, Access Immunoassay Systems, Beckman Coulter, Inc., Fullerton, CA, USA). RESULTS: BNP values were significantly higher (p<0.0001) in newborns and infants with CHD compared with control (CHD patients: median 1167.5 ng/L, range 25-54,447 ng/L; healthy children: median 150.5 ng/L, range 5-866 ng/L). The diagnostic accuracy of BNP was assessed using the receiver operating characteristic (ROC) analysis, taking into account the three different groups divided according to age. Group 1: all CHD patients and healthy newborns and infants as a whole (i.e., from birth to the 30th day of life); Group 2: from the 1st to 3rd day of life; Group 3: from the 4th to 30th day of life. The area under the curve (AUC) of the ROC curve for Group 3 (0.935) was significantly higher than that for Group 1 (0.843, p=0.009) and Group 2 (0.769, p=0.0003), while the AUC values of Group 1 and Group 2 were not significantly different (p=0.191). CONCLUSIONS: BNP may be considered a useful marker for screening in the integrated approach of newborns, infants and children with suspected CHD. However, the accuracy of the BNP assay varies greatly during the first month of extra-uterine life, showing the lowest diagnostic accuracy in the first 3 days after birth. After the second week of life, the biomarker becomes more accurate in ruling in CHD.

Cardiovascular risk factors and gamma-glutamyltransferase fractions in healthy individuals.

BACKGROUND: Serum gamma-glutamyltransferase activity (GGT), even when within its normal reference range, catalyzes low density lipoprotein oxidation in vitro and predicts cardiovascular events. Of the four GGT fractions (b-GGT, m-GGT, s-GGT, and f-GGT) recently identified in blood, only b-GGT is found within atherosclerotic plaques. Our goal was to identify the determinants of the GGT fractions (b-, m-, s-, and f-GGT) and their association with established cardiovascular risk factors in healthy subjects. METHODS: Multiple linear regression analysis was applied to estimate the association of fractional GGT with gender, age, body mass index, arterial pressure (AP), plasma glucose, alanine aminotransferase (ALT), high and low density lipoproteins (LDL-C) cholesterol (HDL-C), triglycerides (TG) and C-reactive protein (CRP) in 200 healthy subjects. RESULTS: All GGT fractions were associated with ALT; b-GGT with AP, TG, and CRP; m-GGT with LDL-C, TG and CRP; s-GGT with TG and CRP, and f-GGT only with LDL-C, whereas gender was associated with s-GGT and f-GGT only. CONCLUSIONS: In healthy individuals, cardiovascular risk factors are associated with high molecular weight GGT fractions, namely with b-GGT, the only form present within the plaque. This finding adds to the present knowledge concerning the relevance of GGT, within its reference range, for atherosclerosis-related events.

Prognostic value of combined measurement of brain natriuretic peptide and triiodothyronine in heart failure.

BACKGROUND: Both low free triiodothyronine (fT3) and high brain natriuretic peptide (BNP) have been separately described as prognostic predictors for mortality in heart failure (HF). We investigated whether their prognostic value is independent. METHODS AND RESULTS: From January of 2001 to December of 2006, we prospectively evaluated 442 consecutive patients with systolic HF and no thyroid disease or treatment with drugs affecting thyroid function (age 65+/-12 years, mean +/- standard deviation, 75% were male, left ventricular ejection fraction 33% +/- 10%, New York Heart Association (NYHA) class I and II: 63%, NYHA class III and IV: 37%). All patients underwent full clinical and echocardiographic evaluation and assessment of BNP and thyroid function. Both cardiac and all-cause mortality (cumulative) were considered as end points. During a median 36-month follow-up (range 1-86 months), 110 patients (24.8%) died, 64 (14.4%) of cardiac causes. Univariate Cox model predictors of all-cause mortality and cardiac death were age, body mass index, creatinine, hemoglobin, ejection fraction, NYHA class, BNP, fT3, and thyroxine level. Multivariate analysis selected age, NYHA class, hemoglobin, BNP, and fT3 as independent predictors for all-cause mortality and NYHA class, BNP, and fT3 as independent predictors for cardiac mortality. Patients with low fT3 and higher BNP showed the highest risk of all-cause and cardiac death (odds ratio 11.6, confidence interval, 5.8-22.9; odds ratio 13.8, confidence interval, 5.4-35.2, respectively, compared with patients with normal fT3 and low BNP). CONCLUSION: fT3 and BNP hold an independent and additive prognostic value in HF.

Risk factors and prognostic value of daytime Cheyne-Stokes respiration in chronic heart failure patients.

BACKGROUND: Sleep-related Cheyne-Stokes (CS) respiration is a known phenomenon in chronic heart failure (CHF). We aimed to study the prevalence, clinical correlates, risk factors and prognostic relevance of daytime CS, as well as its relation with neurohormonal derangement. METHODS: One hundred forty seven CHF patients with left ventricular systolic dysfunction (age: 64+/-12 years, ejection fraction, EF, 31+/-8%, mean+/-SD) underwent morning polygraphic recording, in addition to comprehensive clinical and neurohormonal evaluation. RESULTS: Daytime CS was detected in 87 patients (59%), and associated with worse NYHA class (2.6+/-0.7 vs 2.2+/-0.8, P<0.05), lower EF (29+/-8 vs 33+/-8%, P<0.05), peak oxygen consumption (11.3+/-8.3 vs 13.4+/-4 mL/min/kg, P<0.05), resting carbon dioxide level (33.1+/-4.2 vs 37.9+/-3.8 mm Hg, P<0.001), higher norepinephrine [588 (395-939) vs (331-681) ng/L, median (interquartile range) P<0.01] and natriuretic peptides [ANP: 136 (57-230) vs 66 (18-103); BNP: 284 (99-510) vs 64 (21-202); NT-proBNP: 2575 (814-3320) vs 448 (147-1599) ng/L, all: P<0.001]. At univariate analysis, CS risk factors were age, EF, carbon dioxide, creatinine, norepinephrine, natriuretic peptides, whereas age and NT-proBNP level were the only multivariate predictors. On a 33-month follow-up, CS resulted among univariate predictors of cardiac death, NT-proBNP emerging as the only variable at multivariate analysis. CONCLUSIONS: Daytime CS is frequent in CHF and is correlated with clinical severity, neurohormonal derangement, particularly of NT-proBNP, and long-term prognosis.

Influence of ScaI and natriuretic peptide (NP) clearance receptor polymorphisms of the NP System on NP concentration in chronic heart failure.

BACKGROUND: Genetic variants related to the natriuretic peptide (NP) system [ScaI mutated allele (A1) of the atrial NP (ANP) gene and the C variant of the natriuretic peptide clearance receptor (NPRC) gene] have been identified as independent risk factors for cardiovascular morbidity and mortality. Despite the importance of NPs in heart failure (HF), the role of these polymorphisms in HF has not been evaluated. METHODS: We screened 124 HF patients [mean (SD), age 66 (12) years, 100 men, ejection fraction 32% (10%), New York Heart Association (NYHA) class I-II 65, III-IV 59] for NP concentrations [ANP, brain NP (BNP) and amino-terminal pro-BNP (NT-proBNP)] and for the ScaI and NPRC variants. RESULTS: ScaI polymorphism had no effect on NP concentration in the NYHA I-II subgroup. Conversely, in severe HF, A1 carriers had higher ANP (P < or =0.05), BNP (P <0.01), and NT-proBNP (P <0.01) than A2A2 patients. After multivariate adjustment, A1 presence remained an independent predictor for increased NP. Regarding NPRC polymorphism in mild HF, higher ANP (P <0.05) and BNP (P <0.05) were observed in CC than A allele carriers. After multivariate adjustment, however, this association did not remain significant. In severe HF, the NPRC polymorphism had no effect on NP. CONCLUSIONS: The ScaI polymorphism of the ANP gene might be an important additive genetic factor influencing neurohormonal activation and disease progression in severe HF. The NPRC polymorphism is not an independent determinant of NP concentration in HF.

Comparison of brain natriuretic peptide (BNP) and amino-terminal ProBNP for early diagnosis of heart failure.

BACKGROUND: We compared the diagnostic accuracy of brain natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) for diagnosis of preclinical and mild heart failure (HF). METHODS: We assayed plasma NT-proBNP and BNP in 182 healthy controls and in a prospective cohort of 820 HF patients divided according to the American Heart Association/American College of Cardiology classification. These included 86 patients in stage A [mean (SE) ejection fraction 61% (1%); mean (SE) age 47 (2) years], 255 in stage B [65% (2%); 62 (1) years], 420 patients in stage C [35% (1%); 68 (1) years] and 59 in stage D [25% (1%); 74 (1) years]. Diagnostic accuracies of BNP and NT-proBNP were evaluated by ROC analysis, and a multivariate linear regression model was applied to predict HF staging. RESULTS: Median BNP and NT-proBNP concentrations increased from stage A to D 57-fold and 107-fold, respectively. Both assays were accurate (P <0.001) in separating stage B from controls or stage A, and stage C from controls or stage A or B. NT-proBNP was more accurate (P <0.001) than BNP in differentiating stage C from stages A and B patients and controls and was a better predictor of HF classification in a model including age, sex, and renal function (P <0.001). CONCLUSIONS: Monitoring BNP or NT-proBNP enabled identification of asymptomatic patients at risk for the development of HF. NT-proBNP showed better accuracy than BNP for identifying mild HF.

Comparison of the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP immunoassays in chronic and acute heart failure: a systematic review.

BACKGROUND: We used evidence-based laboratory medicine principles to compare the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) assays for the diagnosis of heart failure. METHODS: In May 2006, we performed a computerized literature search of the online National Library of Medicine to select studies specifically designed to compare the diagnostic accuracy of BNP and NT-proBNP assays. The comparison took into account the area under the curve and diagnostic odds ratio (DOR) derived from ROC analysis of original studies. RESULTS: Both BNP and NT-proBNP assays were found to be clinically useful for the diagnosis of heart failure. Metaanalysis of these data was difficult because of the heterogeneity of data regarding patient population, diagnostic criteria, end-points, and immunoassay methods for both BNP and NT-proBNP. Separate metaanalyses were performed for acute and chronic heart failure. In chronic heart failure, the diagnostic DOR for BNP (8.44, 95% CI 4.66-15.30) was not significantly different from that of NT-proBNP (23.36, 95% CI 9.38-58.19). In patients with acute heart failure, the mean DOR for BNP (16.46, 95% CI 10.65-25.43) was not significantly different from that of NT-proBNP (18.61, 95% CI 12.99-26.65). CONCLUSION: Our results indicate that both BNP and NT-proBNP assays have a high degree of diagnostic accuracy and clinical relevance for both acute and chronic heart failure.

Analytical performance and clinical results of a fully automated MEIA system for brain natriuretic peptide assay: comparison with a point of care testing method.

The aim of this study was to evaluate the analytical performance of a recently available immunoassay for brain natriuretic peptide (BNP), based on microparticle enzyme immunoassay (MEIA, AxSYM System, Abbott Laboratories), whose analytical characteristics and clinical results were compared with those of a point of care testing (POCT) method (TRIAGE system, Biosite Diagnostics). The within-run and total imprecision of the MEIA system were 18.4% and 19.8% at 21 ng/l, 8.0% and 14.8% at 183 ng/l, and 5.7% and 14.0% at 319 ng/l, respectively. The detection limit of the MEIA system was tested by repeatedly measuring (n=20) the 0 calibrator in four different runs; a mean +3 SD value of 5.6+/-4.8 ng/l (range 1.8-12.6 ng/l) was obtained. A close linear relationship (MEIA= -22.5+/-1.71 POCT method, R=0.950, n=296) was found (BNP concentration: 5-5500 ng/l), with a significant bias (mean difference: 164.8 ng/l, p<0.0001). Mean BNP concentration measured in 94 reference subjects (57 women and 37 men; mean age 43.5+/-14.0 years) was higher with MEIA than POCT, (25.9+/-32.7 ng/l vs. 11.7+/-8.9 ng/l, p<0.0001). The same trend was observed also in 202 cardiac patients (620.6+/-1082.2 ng/l vs. 386.1+/-594.5 ng/l, p<0.0001). Our data suggest that MEIA and POCT have quite similar analytical performance but different clinical results. Then, different reference values, as well as cut-off values, should be taken into account for the clinical use of these two immunoassays.