Comorbidity and Special Issues That Influence Interpretation of BNP

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Renal Insufficiency

The Breathing Not Properly Multinational Study and other observational studies have demonstrated a correlation between estimated glomerular filtration rate (eGFR) and BNP in patients with and without heart failure (22). Findings from this study indicated that the concentration of BNP should not be interpreted in isolation but should be integrated with other findings in the diagnostic evaluation. Chronic kidney disease influences the optimal threshold for BNP in the diagnosis of heart failure. In general, as the stage of chronic kidney disease advances, a higher cut point of BNP is required to maintain specificity. For example, a cut point of200 pg/mL is reasonable for those with an eGFR <60 mL/(min. 1.73 m2). Despite the presence of renal dysfunction, BNP maintains a high level of diagnostic utility with an area under the ROC curve of >0.80 across all chronic kidney disease groups (Table 2).

The mechanism(s) underlying the higher concentration of BNP in patients with chronic kidney disease are not yet completely elucidated. It is possible that reduced renal blood flow in acute heart failure can result in increases in serum creatinine and, hence, a falsely lower eGFR. In addition, chronic volume overload owing to chronic kidney disease with or without heart failure can increase left ventricular (LV) hypertrophy and wall tension, thus stimulating secretion of BNP. In fact, multiple studies of systolic heart failure have demonstrated a decreased survival with reduced baseline eGFR (23).

Pulmonary Disease

The presence of concomitant pulmonary disease does not diminish the utility of the BNP test in distinguishing patients with heart failure from those without heart failure. Morrison et al. (24) showed that rapid testing of BNP could differentiate pulmonary from cardiac etiologies of dyspnea. Some types of pulmonary disease that provoke significant increases in wall stress in the right heart, such as cor pulmonale, lung cancer, and pulmonary embolism (PE), are associated with elevated levels of BNP. However, the magnitude

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