Author + information
- Roland van Kimmenade, MD,
- François van Dielen, MD, PhD,
- Jaap Bakker, MSc,
- Jeroen Nijhuis, MD,
- Harry Crijns, MD, PhD,
- Wim Buurman, PhD,
- Marja van Dieijen-Visser, PhD,
- Jan-Willem Greve, MD, PhD and
- Yigal Pinto, MD, PhD⁎ ()
- ↵⁎Department of Cardiology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands
To the Editor: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) >25 kg/m2(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 = 6), hypertension (n = 4), and myocardial infarction (n = 1). No patient was known to have HF or be using diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or spironolactone during the study. Four patients were using beta-blockers with no alternations during the study.
We confirm the correlation between BNP and NT-proBNP versus BMI in the combined consecutive measurements (r = −0.30, p < 0.05; r = −0.41, p < 0.01, respectively). Body mass index decreased drastically after three months (p < 0.001) and six months (p < 0.001), whereas BNP and NT-proBNP concentrations significantly increased after three months (p < 0.01 for both) and six months (p < 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.
The negative correlation between BNP and BMI was already known from large observational studies (5–7). However, these results left room for different explanations. It has, for instance, been hypothesized that obesity leads to an increase in NPR-C activity (4) or that obesity causes a decrease in BNP production (9,10).
The finding that BNP and NT-proBNP increase simultaneously after weight loss suggests that obesity suppresses their common production. This finding raises the question whether their suppression is caused by hindered production or reflects truly lower wall stress. As both peptides are powerful predictors of outcome (11,12), the evidence suggests the counterintuitive notion that lower (NT-pro)BNP concentrations herald a better prognosis for obese subjects. Mehra et al. (6) found lower BNP levels in obese versus non-obese HF patients with a non-significant tendency toward a lower one-year event rate in the obese patients. Other studies show a significantly better prognosis in obese HF patients (3), suggesting that lowered (NT-pro)BNP levels indeed reflect a more advantageous cardiac status.
Our data support findings by others concerning the regulation of natriuretic peptides secretion in obesity. Morabito et al. (10) show a decreased messenger ribonucleic acid expression of atrial natriuretic peptide (ANP) in hearts of obese rats. Licata et al. (9) found a lack of ANP response and a reduced suppression of renine and aldosterone after saline load in obese subjects. We therefore speculate that neurohumoral interactions are altered and decrease natriuretic peptide production in obese subjects.
Our study is the first interventional study to show that a decrease in BMI is accompanied by an increase not only in BNP but also in NT-proBNP. This implies that there is a relationship between adipose tissue and the production of these peptides. It has been suggested that lower BNP concentrations in obese subjects are caused by an increased clearance. If this were true, we would have expected only BNP to rise after weight loss. However, NT-proBNP also rose after surgery. Taken together with the fact that both peptides derive simultaneously from their joint predecessor proBNP, the parallel increase suggests that production of BNP increaseswith decreasing weight.
This somewhat counterintuitive conclusion is in line with previous studies and suggests that the previously reported negative correlation between BMI and (NT-pro)BNP cannot be explained by inappropriate inclusion of severely obese subjects as having HF. Our data are also congruent with the notion that obese HF patients have a better prognosis, as lower BNP and NT-proBNP concentrations are powerful predictors of better outcome (11,12). 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.
Please note: Drs. van Kimmenade and Pinto have received consulting fees from Roche Diagnostics.
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