Minna Ala-Kopsala

Cardiovascular hemodynamics and umbilical artery N-terminal peptide of proB-type natriuretic peptide in human fetuses with growth restriction.

To test our hypothesis that human fetal N‐terminal peptide of proB‐type natriuretic peptide (NT‐proBNP) secretion is increased in proportion to the severity of fetal cardiovascular compromise in intrauterine growth restriction.

BNP as A Biomarker in Heart Disease

Heart ventricles produce B-type natriuretic peptide (BNP) in response to increased mechanical load and wall stretch. BNP protects the heart from adverse consequences of overload by increasing natriuresis and diuresis, relaxing vascular smooth muscle, inhibiting the renin-angiotensin-aldosterone system, and by counteracting cardiac hypertrophy and fibrosis. BNP is synthesized by human cardiac myocytes as a 108-amino acid prohormone (proBNP), which is cleaved to the 32-residue BNP and the 76-residue N-terminal fragment of proBNP (NT-proBNP). Both can be used as sensitive biomarkers of cardiac dysfunction and well-characterized commercial assays have recently become available. In acute coronary syndromes increased concentrations are strong predictors of recurring myocardial infarction, heart failure, and death. In acute dyspnea, high BNP and NT-proBNP point to a cardiac rather than a pulmonary origin of the symptoms. BNP and NT-proBNP help in the assessment of the severity of ventricular dysfunction and heart failure and as a prognostic predictor, regardless of the primary cause of the condition. They can be used to guide the therapy of heart failure and left ventricular dysfunction. BNP and NT-proBNP work better when they are used for specific clinical purposes, rather than for screening in the general population. Their main strength is the excellent negative predictive value with regard to left ventricular dysfunction and heart failure. BNP and NT-proBNP are nonspecific biomarkers of cardiac dysfunction. Specific diagnostic tools, such as echocardiography, are required to define the actual abnormality.

Plasma N-Terminal Fragments of Natriuretic Peptides Predict the Risk of Stroke and Atrial Fibrillation in Men

Background: Risk stratification for cardiovascular outcomes is gaining importance in general population. Prognostic value of natriuretic peptides has been established in patients with heart failure. However, the prognostic significance of natriuretic peptides with respect to stroke is not well known in general populations. Methods: Plasma natriuretic peptides were measured in a representative population-based sample of 958 men (age 46–65 years) from Eastern Finland. There were 46 cases of stroke, 74 of atrial fibrillation and 31 cases of ischaemic strokes during a follow-up of 9.6 years. Results: The multivariable adjusted risk was 1.35-fold (95% CI 1.01 to 1.84, p = 0.049) for any stroke and 1.30-fold (95% CI 0.90 to 1.91, p = 0.0150) for ischaemic stroke for each log-transformed SD (0.240 pmol/l) increment in N-terminal fragment of proA-type natriuretic peptide. The respective risks were 1.36-fold (95% CI 1.05 to 1.76, p = 0.010) and 1.50-fold (95% CI 1.12 to 2.02, p = 0.007) for each log-transformed SD (0.237 pmol/l) increment in N-terminal fragment of proB-type natriuretic peptide. The multivariate adjusted risks for future atrial fibrillation were 1.71 (95% CI 1.32 to 2.22, p<0.001) and 1.68-fold (95% CI 1.38 to 2.07, p<0.001) for each log-transformed SD increment in N-terminal fragments of proA- and proB-type natriuretic peptides, respectively. Conclusions: N-terminal fragments of pro-atrial natriuretic peptide and pro-brain natriuretic peptide are new additional predictors of any stroke and atrial fibrillation. Natriuretic peptides provide prognostic information for stroke and atrial fibrillation and may help in identifying subjects at risk for stroke and atrial fibrillation.

Increased fetal cardiac natriuretic peptide secretion in type-1 diabetic pregnancies

Background. We hypothesised that human fetal cardiac natriuretic peptide secretion is increased in type‐1 diabetic pregnancies with normal placental hemodynamics, and this increase is related to the first trimester maternal glycemic control. Methods. Thirty‐two neonates of type‐1 diabetic mothers and 60 neonates born after uncomplicated pregnancy and labour (control group) were included in this study. Diabetic pregnancies were divided into two subgroups based on the first trimester HbA1c value. Group 1 pregnancies (n =22) had a good glycemic control (HbA1c <7.5%) and Group 2 pregnancies (n =10) had a poor glycemic control (HbA1c ≥7.5%). At delivery, an umbilical artery (UA) blood sample was obtained for assessment of N‐terminal peptide of proatrial (NT‐proANP) and proB‐type (NT‐proBNP) natriuretic peptide levels. In diabetic pregnancies, each fetus had normal UA Doppler velocimetry for gestational age. Results. The newborn UA NT‐proANP and NT‐proBNP concentrations were significantly higher in type‐1 diabetic pregnancies than in the control group. Group 2 fetuses with poor glycemic control showed significantly higher UA NT‐proANP levels than Group 1 fetuses. UA NT‐proANP levels correlated significantly with maternal HbA1c values in the first, second and third trimesters, while UA NT‐proBNP levels did not correlate with maternal HbA1c values. Conclusions. In type‐1 diabetic pregnancies, fetal cardiac natriuretic peptide secretion is increased, even in the presence of good glycemic control and normal placental hemodynamics. In addition, fetal NT‐proANP levels are already related to maternal glycemic control in the first trimester of pregnancy.

Characterization of Molecular Forms of N-Terminal B-Type Natriuretic Peptide In Vitro

BACKGROUND The heterogeneity of circulating peptides may influence the interpretation of results from N-terminal profragment of BNP (NT-proBNP) assays. Our objective was to characterize the heterogeneity for better usability of the assays. METHODS Endogenous proBNP was purified from patient samples and treated with trifluoromethanesulfonic acid (chemical deglycosylation). The human proBNP gene was introduced into rat hearts by adenoviral transfer. Cell lysates and plasma samples containing proBNP-derived peptides were analyzed by chromatography. The fate of exogenous recombinant NT-proBNP added to fresh whole blood samples was followed by immunoassays and chromatography. The main NT-proBNP components were isolated and identified by mass spectrometry. RESULTS Immunoreactive NT-proBNP in human plasma comprised several molecular forms, as did circulating immunoreactive human NT-proBNP after adenoviral transfer of human proBNP cDNA into rat ventricular myocardium. Incubation of recombinant NT-proBNP(1-76) in human plasma or serum resulted in multiple components with the 2 major components identified as NT-proBNP(1-36) and NT-proBNP(1-62/64). Profiling by different antisera and chromatography indicated masking of the non-mid-region epitopes likely due to formation of oligomers. More than 75% of the original immunoreactivity in the mid-region epitope was retained after 3-week storage of plasma samples at room temperature. CONCLUSIONS There is marked heterogeneity in immunoreactive NT-proBNP in plasma not related to glycosylation. The mid-region epitope of NT-proBNP is stable even in harsh storage conditions. Careful choice of antibody epitopes can yield extraordinarily robust assays.

N-terminal probrain natriuretic peptide level inversely correlates with cardiac index after arterial switch operation in neonates

Background:  Natriuretic peptide levels are associated with cardiac output and ventricular function. We hypothesized that concomitant measurement of the peptide fragments and the hemodynamic parameters could elucidate the associations of these parameters after pediatric cardiac surgery.

Strong relationship between NT-proXNP levels and cardiac output following cardiac surgery in neonates and infants

Background: NT‐proXNP, a new natriuretic peptide analyte, incorporates information about the concentrations of both N‐terminal pro‐atrial and pro‐brain natriuretic peptides (NT‐proANP, NT‐proBNP). We aimed to investigate whether NT‐proXNP is a reliable indicator of the cardiac index (CI) and the hemodynamic state in neonates and infants undergoing an open heart surgery.