Is Brain Natriuretic Peptide Production Decreased in Obese Subjects?

Abstract

Both obesity and heart failure (HF) are highly prevalent syndromes in modern Western society. Nearly 60% of the U.S. population has a body mass index (BMI) Ͼ25 kg/m 2 (1). The incidence of HF approaches 10 per 1,000 among persons older than 65 years (2). Because both syndromes are highly prevalent, patients are likely to have both simultaneously.Surprisingly, obese HF patients have a better prognosis than normal-weight HF patients, giving rise to the so-called obesity paradox (3).Brain natriuretic peptide (BNP) and aminoterminal proBNP (NT-proBNP) are established diagnostic markers in HF. However, it is unclear how to interpret the levels of BNP in overweight patients, as BNP is cleared by the natriuretic peptide receptor type-C (NPR-C), which is abundantly expressed in adipocytes (4). Indeed, a negative correlation has been described between BNP and BMI (5-7). Interestingly, a similar correlation was recently described for NT-proBNP (8), which is not cleared by NPR-C. To reliably address these relationships, we investigated the effect of a decrease in BMI following bariatric surgery on the concentrations of BNP and NT-proBNP.We studied 22 patients (5 men,17 women; median age 38 years) referred to our general surgery department for surgical treatment of obesity. Blood samples were collected one day before surgery, three months after surgery, and six months after surgery.The medical history of the patients showed diabetes (n ϭ 6), hypertension (n ϭ 4), and myocardial infarction (n ϭ 1). No patient was known to have HF or be using diuretics, angiotensinconverting enzyme inhibitors, angiotensin receptor blockers, or spironolactone during the study. Four patients were using betablockers with no alternations during the study.We confirm the correlation between BNP and NT-proBNP versus BMI in the combined consecutive measurements (r ϭ Ϫ0.30, p Ͻ 0.05; r ϭ Ϫ0.41, p Ͻ 0.01, respectively). Body mass index decreased drastically after three months (p Ͻ 0.001) and six months (p Ͻ 0.001), whereas BNP and NT-proBNP concentrations significantly increased after three months (p Ͻ 0.01 for both) and six months (p Ͻ 0.01 for both) (Table 1).Our study rejects the hypothesis that the negative correlation between BNP and BMI is due to an upregulation of NPR-C because the NPR-C does not clear NT-proBNP. Given that both peptides derive simultaneously from the cleavage of their common predecessor proBNP, but are cleared via different mechanisms, the parallel associations between peptide concentrations and BMI suggest a relationship between adipose tissue and production.Taken together, our findings show that BNP and NT-proBNP concentrations increase with decreasing weight. This is likely to be due to decreased cardiac production of BNP, suggesting some yet undefined beneficial effects of obesity in HF that clearly warrant further study.

Impact of Increased Body Mass Index on Accuracy of B-Type Natriuretic Peptide (BNP) and N-Terminal proBNP for Diagnosis of Decompensated Heart Failure and Prediction of All-Cause Mortality

“…To our knowledge, 14 studies have investigated the effect of obesity on BNP and NT-proBNP concentrations. Six studies investigated the relationship between BNP and BMI (12)(13)(14)(15)(16)(17), 2 studies correlated obesity with NT-proBNP (18 -20 ), and 6 others included both BNP and NT-proBNP (7,18,(21)(22)(23)(24). Of the 12 studies that assessed BNP concentrations, 11 found reduced concentrations in obese and overweight patients; a single study showed that BNP concentrations were unaffected by BMI (21 ).…”

“…A problem with this hypothesis, however, is that NTproBNP concentrations are also reduced in obesity, although this inactive cometabolite is not cleared by the NPR-C mechanism (12,18,20,22,23 ). Further, van Kimmenade et al (24 ) showed in an interventional study of 22 patients who had undergone surgical treatment for obesity that a decrease in BMI is accompanied by increased concentrations of both BNP and NTproBNP. These data suggest a relationship between adipose tissue and the production of both peptides.…”

Obesity paradox in heart failure: a heavy matter

“…After 52 weeks, BMI had decreased by 20% and BNP levels had nearly doubled 59. The exact mechanism for this is unclear, but recent studies suggest decreased production is the cause 60. Despite lower levels of natriuretic peptides in the obese patient, circulating levels can still be used for prognosis 61…”

Plasma cBIN1 Score (CS) Identifies HFrEF and Can Predict Cardiac Hospitalization in Stable Ambulatory Patients

“…Furthermore, renal dysfunction is associated with elevated concentrations of BNP markers [17] and BNP also has a negative correlation with body mass index (BMI) [18,19]. Taken together, these data suggest that HF management could benefit from additional assessment of cardiac muscle health independent of volume status.…”

“…In this manner, CS could assist with management of complex, multi-organ disease syndromes. Conversely, patients with obesity may have false negative BNP, yet with failing heart muscle [19]. CS in this instance would help identify the failing heart muscle.…”