What can cause an increase in B-type natriuretic peptide (BNP)?

Causes of Elevated BNP

BNP rises primarily in response to myocardial stretch from increased ventricular wall tension due to pressure or volume overload, with cardiac causes being most common but numerous non-cardiac conditions also elevating levels. 1, 2

Primary Cardiac Causes

Heart Failure

• Heart failure is the most common cause of elevated BNP, with levels directly correlating to severity of ventricular dysfunction and wall stress 2
• Systolic dysfunction (HFrEF) produces higher BNP levels than diastolic dysfunction (HFpEF) – mean BNP in left ventricular systolic dysfunction is 516 ± 445 pg/mL versus 115 ± 80 pg/mL in diastolic dysfunction 3
• Diastolic dysfunction alone can elevate BNP even when systolic function remains normal 2, 4
• Right ventricular systolic dysfunction produces intermediate elevations (mean 345 ± 184 pg/mL) 3

Acute Coronary Syndromes

• Acute myocardial infarction increases BNP expression (median ~203 pg/mL) even without overt heart failure, with levels correlating to infarct size 2, 5
• BNP elevation in ACS is a strong predictor of recurrent MI, heart failure development, and death 4

Arrhythmias and Structural Disease

• Atrial fibrillation independently raises BNP by 20-30% regardless of ventricular function 2
• Left ventricular hypertrophy increases wall stress and BNP production 2
• Valvular heart disease, particularly mitral regurgitation, produces elevated BNP levels associated with higher mortality 2
• Restrictive cardiomyopathy and cardiac amyloidosis elevate BNP 5

Pulmonary and Right Heart Causes

• Pulmonary embolism causes marked BNP elevation via right ventricular strain, with NT-proBNP >500 pg/mL identifying high-risk PE 2, 6
• Pulmonary hypertension (primary or secondary) elevates BNP, correlating with mean pulmonary arterial pressure and pulmonary vascular resistance 2, 6
• Chronic obstructive pulmonary disease can increase BNP levels 2, 5
• BNP differentiates breathless patients with pulmonary arterial hypertension from those with primary respiratory disease 6

Renal Dysfunction

• Renal failure elevates BNP due to decreased clearance independent of cardiac status 2, 5
• Even mild renal impairment (creatinine clearance 15-60 mL/min) can raise BNP regardless of cardiac function 2
• In end-stage renal disease, BNP levels are markedly elevated (mean pre-dialysis 556 ± 452 pg/mL) 7
• KDIGO recommends adjusting BNP thresholds upward when eGFR <60 mL/min/1.73 m² (rule-out cutoff raised to ~200-225 pg/mL; rule-in cutoffs ~670 pg/mL for HFpEF and ~1,166 pg/mL for HFrEF) 2

Critical Illness

• Sepsis independently elevates BNP, with levels >210 pg/mL at 24 hours being the strongest predictor of in-hospital mortality 2
• Acute decompensated heart failure produces the highest BNP elevations 5
• Severe neurological insults (subarachnoid hemorrhage, stroke, traumatic brain injury) raise BNP 2

Demographic and Physiologic Factors

Age and Sex

• Advanced age increases normal BNP ranges: young adults <25 pg/mL, ages 45-59 <100 pg/mL (males) or <164 pg/mL (females), ages >60 <98 pg/mL (males) or <225 pg/mL (females) 1, 2
• Females have 20-30% higher baseline BNP than males, likely due to androgen suppression of proBNP synthesis 1, 2

Body Mass Index

• Obesity paradoxically lowers BNP values by 20-30% for any given cardiac condition, possibly related to increased clearance or suppression by sex steroid hormones produced in lean mass 1, 2
• Consider lowering diagnostic thresholds by 20-30% in patients with BMI ≥30 kg/m² 2

Other Non-Cardiac Causes

• Thyroid dysfunction (both hyperthyroidism and hypothyroidism) affects BNP levels 2
• Anemia may be associated with elevated BNP 2
• Liver cirrhosis with ascites can produce markedly high BNP 2
• Cyanotic heart disease can elevate BNP without evidence of heart failure or myocardial dysfunction 2

Medication Effects on BNP

Medications That Lower BNP

• ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists reduce BNP by decreasing wall stress 2
• Diuretics lower BNP by reducing volume overload 2
• Beta-blockers may cause transient elevation followed by long-term reduction 2

Medications That Raise BNP

• Neprilysin inhibitors (sacubitril/valsartan) artificially elevate BNP levels because they block BNP degradation; use NT-proBNP instead for monitoring these patients 2, 8

Critical Clinical Pitfalls

• Do not dismiss elevated BNP in renal failure as "false positive" – it reflects genuine myocardial wall stress requiring cardiac evaluation 2
• The "grey zone" (BNP 100-400 pg/mL or NT-proBNP 300-900 pg/mL) has only 60-76% specificity – many non-cardiac conditions produce values in this range 2
• Interpret BNP as a continuous variable rather than binary positive/negative – risk increases proportionally with concentration 2
• Always consider multiple potential causes when interpreting elevated levels, especially in patients with comorbidities 2, 5