Circulating BNP/NT-proBNP concentrations should not be considered an indicator of a specific cardiac disease (such as heart failure) nor, even less, a surrogate for echocardio graphic examination. On the contrary, it is important to understand how the results of their determination must always be evaluated, keeping in mind the state of activation of the neurohormonal system and the general clinical state of the patient, especially in consideration of concomitant mor bid conditions and the pharmacological therapy. BNP, a hormone produced and secreted by the heart, must be considered, above all, an index of the state of activation of the neuro- immune- hormonal system; this, among other, explains why circulating levels of BNP/NT-proBNP are influenced by therapy in heart failure. The most widely used and effective drugs (β-blockers, ACE inhibitors, specific angiotensin II receptor blockers, and diuretics) act by inhibiting the neuro- immune- hormonal system (including the adrenergic system, the renin–angiotensin–aldosterone system, the arginine- vasopressin system, the endothelin system, and the cytokine system). The response to drug treatment is clinically significant as it is the factor that most affects mortality.

Another essential aspect to consider when evaluating and, more importantly, comparing BNP and NT-proBNP values to each other is that the results are strictly method dependent. Indeed, there are differences between the circulating levels of the various peptides (BNP vs. NT-proBNP) and the different methods specific for a single peptide (Fig. 1). In particular, the methods for determining BNP currently on the market are sandwich-type solid-phase dual-antibody immunoassay systems, which use different calibrators and anti bodies. Generally, one of the two antibodies is specific for the part of the peptide chain with the ring shape, which binds to specific biological receptors, while the other is specific for the NH2 or COOH-terminal part. Since BNP is degraded in vivo and in vitro by various enzyme systems attacking the peptide chain at different positions, there are several degradation products and many potential interferent peptide molecules in plasma. Currently available commercial methods use different antibodies specific for different epitopes of the BNP peptide chain, as well as different calibration materials, resulting in different values and strictly method-dependent reference ranges and decision limits (Fig. 1).

Fig1. Systematic differences between commercially available BNP assay methods. Results of external quality control CardioOrmocheck in the cycles from 2005 to 2008: 112 participating laboratories, 28 control samples, and 2354 determinations. The 10^th, 25^th, 50^th (median), 75^th, and 90^th percentiles are shown in the box plots. The results obtained by all the methods show significant differences between them. In particular, the AIA and ADVIA methods measure BNP values that are approximately half of the TRIAGE Access and POCT methods. (Copyright EDISES 2021. Reproduced with permission)

As previously noted, from a strictly diagnostic point of view, determining BNP/NT-proBNP peptides should be used to exclude heart failure (HF). Many studies indicate that the most appropriate decision level for this differential diagnosis may correspond to the 97.5^th (or 99^th) percentile of the distribution of BNP/NT-proBNP values in the healthy population, preferably divided into groups concerning age and sex. Although this value is different for each measurement method, the distribution of peptide values in each method is relatively constant for the various populations studied. Thus, it seems reasonable to use in clinical practice the corresponding value indicated by scientific studies or by the manufacturing companies if calculated on a numerically significant population.

From a strictly clinical point of view, the information provided by ANP and BNP and their related peptides, MR-proANP or NT-proBNP, is not substantially different. From an analytical point of view, however, it is essential to note that active hormones (ANP and BNP) are less stable in vitro than their respective nonactive peptides, such as pro hormones (proANP and proBNP) or N-terminal peptides (such as NT-proANP, MR-proANP, and NT-proBNP). Active hormones should only be measured in plasma-EDTA sam ples (which partially inhibits enzymes that degrade hormones in plasma), whereas NT-proANP, MR-proANP, and NT-proBNP peptides can be assayed in either plasma-EDTA or lithium-heparin plasma or serum.

Although BNP and NT-proBNP values are closely correlated in most clinical conditions, recent studies in patients with chronic heart failure treated with a new drug called LCZ696 (Entresto) have shown conflicting results. This pharmacological combination consists of two substances: a specific competitor of the angiotensin II receptor (valsartan) and an inhibitor of the enzyme neprilysin (sacubitril). A recent multicenter study, called PARADIGM-HF, showed that plasma BNP levels were higher in patients treated with LCZ696 than in those treated with enalapril. In contrast, cir culating levels of NT-proBNP were lower during treatment with LCZ696 than with enalapril. Thus, for the first time, an opposed behavior between the levels of active BNP hormone and inactive NT-proBNP peptide in patients undergoing pharmacological treatment for heart failure has been described in the literature. These data, therefore, require an ad hoc physiopathological interpretation that takes into account the dual action of the drug: inhibition of the peripheral degradation of BNP (with a consequent increase in the circulating levels of the active hormone) and of the renin angiotensin system with a decreased production of cardiac natriuretic peptides by the myocardial cells (Fig. 2). Consequently, the clinician’s interpretation of natriuretic peptide changes during treatment with this pharmaceutical combination requires special attention. In particular, all cases of increased plasma levels of BNP not linked to the inhibition effects of the drug on the degradation of the hormone but secondary to a worsening of the patient’s clinical conditions must be recognized.

Fig2. Interrelationship between the renin-angiotensin system and the B-type natriuretic peptide system with plasma proteolytic enzymes ACE (angiotensin I converting enzyme) and NEP (neprilysin). The NEP enzyme degrades natriuretic peptides (including BNP), bradykinin, and angiotensins, transforming them into shorter and inactive pep tides. The ACE enzyme acts on bradykinin, inactivating it, and on angiotensin I (angio I), transforming it into the much more active pep tide angiotensin II (angio II). The inhibition of the NEP enzyme, there fore, causes high levels of bradykinin, angiotensin II, and natriuretic peptides (ANP, BNP, and CNP), which have contrasting effects on the cardiovascular system. (Copyright EDISES 2021. Reproduced with permission)

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية يعلن مشاركة ممثلين من 18 دولة إفريقية في خدمة زائري الإمام العسكري (عليه السلام)

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المزيد

الآخبار الصحية

دون آثار جانبية.. زيت عشبة طبيعية قد يعالج القلق

"ليكانيماب".. علاج الزهايمر يطرح رسميا في السوق الألمانية

متى يجب تنظيف الأسنان في الصباح.. قبل أم بعد الإفطار؟

ارتفاع الوفيات.. منظمة الصحة تدق جرس الإنذار بشأن الكوليرا

المزيد

الآخبار التكنلوجية

أكبر مشروع طاقة رياح في نصف الكرة الجنوبي يحقق إنجازين جديدين

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"واتساب" يطلق خاصية جديدة لكتابة الرسائل بالذكاء الاصطناعي

المزيد

مواضيع ذات صلة

Biomarkers of Myocardial Remodeling and Fibrosis

sputum cytology

sodium (Na), urine

Sims-Huhner test (Postcoital test, Postcoital cervical mucus test, Cervical mucus sperm penetration test)

Quality Specifications of Troponin Measurement Methods

Clinical Relevance of Troponins Measurement

Hyperkalemia

sickle cell screen (Sickledex, Hemoglobin [Hgb] S test)

sexually transmitted disease testing (STD testing)

serotonin (5-hydroxytryptamine, 5-HT) and chromogranin A

Hypokalemia

Hypernatremia