brain-natriuretic-peptide--porcine and Ventricular-Dysfunction--Left

To test the hypothesis that elevated plasma levels of natriuretic peptides may serve to identify patients with left ventricular (LV) dysfunction, we assessed the predictive diagnostic value of natriuretic peptide levels, in addition to clinical and electro-cardiographic risk factors, as noninvasive indicators of cardiac dysfunction. Plasma levels of atrial natriuretic peptide (cANP) (99-126), N-terminal fragment of proANP (nANP) (26-55), nANP(80-96), brain natriuretic peptide (BNP-32), proBNP(22-46), and C-type natriuretic peptide (CNP-22) were measured in 211 subjects before cardiac catheterization. The strongest correlations with parameters of LV function were found for nANP(80-96) (up to r = -0.55, p < 0.0001), whereas there was no significant correlation with proBNP(22-46) or CNP-22. In patients with LV ejection fractions (LVEF) < or = 45% (n = 38) nANP(26-55), nANP(80-96), cANP(99-126), and BNP-32 were significantly increased (p < 0.001). Partition values for elevated versus normal natriuretic peptide levels were obtained from normal controls and used to separate subjects with and without LV dysfunction. Receiver operating characteristic analysis for LVEF < or = 45% indicated a significantly better diagnostic accuracy for high levels of nANP(80-96), nANP(22-56), cANP(99-126), and BNP-32 than for proBNP and CNP-22. Multivariate analysis by logistic regression identified Q waves and bundle branch block in the electrocardiogram as well as elevated plasma levels of cANP, nANP(80-96), and nANP(26-55) as the strongest independent predictors of low ejection fractions. The relative risk of LV dysfunction was raised up to tenfold in subjects with high natriuretic peptide levels (p < 0.001). The addition of nANP(80-96) and nANP(26-55) to the combination of clinical and electrocardiographic risk factors did not further improve the diagnostic sensitivity for the detection of LVEF < or = 45%, but it markedly increased the overall accuracy (59% to 81%, p < 0.001) and specificity (55% to 81%, p < 0.001). Among natriuretic peptides, elevated nANP(80-96) and nANP(26-55) levels have the strongest impact on the detection of LV dysfunction. They add to the diagnostic information contained in clinical and electrocardiographic factors. Plasma levels alone or in combination with clinical factors seem to be of value for a refined identification of abnormal LV function in the individual patient.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Evaluation Studies as Topic; Female; Hemodynamics; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins; Risk Factors; ROC Curve; Ventricular Dysfunction, Left

Human brain natriuretic peptide-32 (BNP) (i.e. proBNP(77-108)), the mature form of BNP and secreted predominantly by the cardiac ventricle, is formed from a high molecular weight precursor, proBNP(1-108). We have recently identified the aminoterminal form proBNP(1-76) (NT-proBNP) in human plasma but its source, metabolism and production in circulatory disorders are unknown. We have investigated the relationship between immunoreactive (IR) NT-proBNP and BNP-32 in normal and hypertensive subjects and in patients with cardiac impairment, as well as the regional plasma concentrations in patients undergoing routine cardiac catheterization.. Plasma hormone measurements were made in 26 normal subjects, 20 subjects with untreated mild hypertension and 111 treated patients with a history of coronary heart disease and documented cardiac impairment (left ventricular election fraction (LVEF) < 45% (mean 29%); 25 NYHA Class I, 65 Class II and 21 Class III). Regional blood sampling from the femoral artery, femoral vein, renal vein and coronary sinus was undertaken in 14 patients presenting for left and right cardiac catheterization studies in the course of standard investigation for a range of cardiac disorders.. Plasma samples were assayed for IR NT-proBNP and IR BNP-32 (and atrial natriuretic peptide (ANP) in the regional blood samples). In the patients with cardiac impairment, LVEF was determined by gated radionuclide ventriculography, exercise capacity was measured using a modified Naughton multistage protocol and creatinine clearance was calculated from plasma creatinine, age and weight. In the regional study, extraction ratios across the kidney and lower limb (and step-ups across the heart) were calculated from plasma peptide concentrations.. In normal subjects mean IR NT-proBNP levels (10.8 +/- 1.3 pmol/L) were similar to levels of IR BNP-32 (9.7 +/- 0.5 pmol/L). In hypertensive patients the levels of IR NT-proBNP and IR BNP-32 tended to be higher than but were not significantly different from normal subjects. Both IR NT-proBNP and IR BNP-32 were raised in NYHA Classes I, II and III compared with normals (P < 0.001 for all) with higher levels of both BNP forms seen with increasing cardiac impairment. The levels of IR NT-proBNP were greater than IR BNP-32 in all NYHA Classes (P < 0.001) for all). Overall, the levels of IR NT-proBNP (129 +/- 12 pmol/L) were 4-fold higher than concomitant BNP-32 levels (29 +/- 2 pmol/L). Multivariate analysis showed that LVEF, exercise test time and creatinine clearance were independent predictors of IR NT-proBNP. In all study groups, the levels of IR NT-proBNP and IR BNP-32 levels were highly correlated. Regional plasma sampling showed similar step-ups in IR NT-proBNP and IR BNP-32 levels across the heart, together with similar extraction of both BNP forms across the kidney and lower limb. For both BNP forms, these changes across tissues were significantly less than for ANP.. Plasma levels of immunoreactive amino terminal-proBNP are raised in cardiac impairment, including NYHA Class I, and rise with increasing cardiac decompensation. Metabolism and tissue uptake of immunoreactive amino terminal-proBNP and immunoreactive BNP-32 appear similar. In cardiac impairment the proportional and absolute increment above normal levels of the aminoterminal BNP peptide exceeds that for BNP-32 and suggest that amino terminal-proBNP may be a more discerning marker of early cardiac dysfunction than BNP-32.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiac Catheterization; Coronary Disease; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Reference Values; Regression Analysis; Statistics, Nonparametric; Ventricular Dysfunction, Left