BNP

**Physiology** - Synthesized as preproBNP, then cleaved to proBNP. ProBNP is cleaved into active BNP (32 aa) and inactive NT-proBNP. Both are released from ventricular cardiomyocytes in response to increased wall stress/stretch. ANP is the atrial counterpart. - Mechanism of action: binds natriuretic peptide receptor-A (NPR-A), which is guanylyl cyclase-linked, so it increases cGMP. Effects: - Dilates afferent arterioles and constricts efferent arterioles, which raises GFR. - Increases natriuresis and diuresis. - Causes vasodilation (arterial and venous), which decreases preload and afterload. - Inhibits renin, aldosterone, and ADH release, and inhibits the sympathetic system. - Clearance: neprilysin (neutral endopeptidase) degrades BNP, along with NPR-C receptor clearance and renal excretion. NT-proBNP is cleared mainly by the kidneys.

**Clinical use** - Diagnosis of acute HF in a dyspneic patient: - BNP <100 pg/mL: HF unlikely (high NPV, so it is good for ruling out). - BNP >400 pg/mL: HF likely. - 100–400 pg/mL is a gray zone. - NT-proBNP cutoffs are age-adjusted (e.g., >450 if <50 y, >900 if 50–75 y, >1800 if >75 y; <300 rules out). - Prognosis and monitoring: higher levels predict worse outcomes. Serial measurements can guide therapy. - Also elevated in: acute coronary syndrome, pulmonary embolism, cor pulmonale/pulmonary hypertension, atrial fibrillation, left ventricular hypertrophy, valvular disease, sepsis, renal failure (decreased clearance), advanced age, and female sex. - Falsely low in: obesity (adipose tissue expresses NPR-C and clears BNP) and flash pulmonary edema (e.g., acute mitral regurgitation, which may not give time for BNP to rise).

**Pharmacology pearls** - Sacubitril/valsartan (Entresto): sacubitril inhibits neprilysin, so it increases BNP, ANP, and bradykinin. Valsartan is an ARB. It is used for HFrEF and is superior to enalapril (PARADIGM-HF). Neprilysin inhibition raises bradykinin, so combining it with an ACE inhibitor risks angioedema. It is contraindicated within 36 hours of an ACE inhibitor and in patients with a history of angioedema. - Because neprilysin inhibitors raise BNP (but not NT-proBNP), NT-proBNP is the preferred marker for monitoring patients on sacubitril/valsartan. - Nesiritide is recombinant human BNP. It was used for acute decompensated HF but is not routinely used because it has not shown a mortality benefit.

**Board tip** - Dyspnea + elevated BNP + S3, JVD, pulmonary edema, and bibasilar crackles points to HF. - Low BNP in a dyspneic patient suggests a pulmonary cause (COPD, asthma, pneumonia).