Body Mass Index and NT-pro-BNP in High-Risk Cardiac Patients

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is released in the heart when it faces increased pressure and is among the most important biomarkers of heart failure, (1). Its release is affected by other factors as well, including the body mass index (BMI): a high BMI is associated with lower NT-pro-BNP levels in both healthy and sick persons (2). NT-pro-BNP is now being used to monitor the course of heart failure, but the relationship between NT-pro-BNP and BMI among high-risk cardiac patients, many of whom are overweight, has not yet been adequately investigated. This was the aim of the present study.

Methods

CONSIDER-AF is an observational study of patients aged 18 to 85 who have coronary heart disease and an indication for elective bypass grafting. Its exclusion criteria were severe obstructive lung disease and nocturnal home oxygen therapy. The patients underwent echocardiography and blood drawing preoperatively. They were divided into three categories depending on their BMI: normal weight (< 25 kg/m²), overweight (25–30  kg/m²), and obesity (≥ 30 kg/m²). The characteristics of the patient groups are given as mean ± standard deviation and as numbers and percentages. Comparisons across BMI classes were made with ANOVA for continuous variables and with the χ² test for dichotomous variables. The relation of BMI to the NT-pro-BNP level was examined with uni- and multivariate regression analysis; important clinical cofactors were considered as potential confounders.

Results

770 patients were studied. Their mean age was 66.4 ± 8.3 years, 86% were male, the mean BMI was 28.3 ± 4.3 kg/m², the mean left ventricular ejection fraction (LVEF) was 55.4 % ± 10.7 %, and 15% had atrial fibrillation. The BMI groups did not differ with respect to sex distribution, LVEF, or the frequency of preoperative atrial fibrillation.

The NT-pro-BNP level of patients of normal weight (<25 kg/m²) was approximately twice that of the overweight and obese patients (Figure). Linear regression analysis revealed an inverse correlation of BMI and NT-pro-BNP (351 patients with complete data sets, r² = 0.009, B = –71.1, p = 0.007).

Figure

The NT-pro-BNP level in three BMI categories (means and 95% confidence intervals, ANOVA p < 0.001, with the Holm-Sidak correction for multiple tests).

Patients with higher BMI were younger ([years] 67.7 ± 8.7; 66.4 ± 8.4; 65.6 ± 8.2; p = 0.031); they suffered more commonly from arterial hypertension (70.5%; 81.3%; 89.5%; p<0.001) and diabetes mellitus (21.7%; 35.5%; 41.6%; p<0.001) and had a higher left ventricular mass index (LVMi, [g/m²] 217.7 ± 69.5; 230.3 ± 72.6; 254.1 ± 75.1; p<0.001). These are all risk factors for heart failure with preserved ejection fraction (HFpEF) (1).

Multivariate regression analysis showed that high BMI was independently associated with lower NT-pro-BNP levels after adjustment for potential confounders. Male sex, higher LVEF, and higher glomerular filtration rate were also associated with lower NT-pro-BNP (Table). The findings of regression analysis must be interpreted with caution in relation to clinical practice, as there are complex pathophysiological relationships among the cofactors that can lead to very different results in individual cases.

Table

Uni- and multivariate regression analysis of predictors of the NT-pro-BNP value

Discussion

In our group of high-risk cardiac patients, there was an inverse correlation between the BMI and the NT-pro-BNP level, even though high BMI was associated with a higher frequency of major risk factors for heart failure (arterial hypertension, diabetes mellitus, high LVMi). The inverse correlation between BMI and NT-pro-BNP has been reported before, but its pathophysiological mechanism is not well understood. There is evidence linking high BMI with insulin-dependent reduced production of NT-pro-BNP, as well as with altered metabolism of natriuretic peptides and their increased clearance by adipocytes (3). Increased epicardial fat may also lower ventricular wall tension, which is the most important stimulus for the release of natriuretic peptides (2). The inverse correlation between BMI and natriuretic peptides has been studied to date only in healthy persons or in patients who were markedly less ill than the subjects in our study. Our findings show that this correlation is particularly strong among high-risk cardiac patients, for whom the regular measurement of regular NT-pro-BNP is very important.

In view of the important role of NT-pro-BNP in the diagnosis and treatment of heart failure, this correlation is highly relevant in routine clinical practice. As stated in the guideline of the European Society of Cardiology, an NT-pro-BNP level below cutoff has a high negative predictive value for chronic (NT-pro-BNP < 125 pg/mL) or acute (pro-BNP < 300 pg/mL) heart failure. An elevated NT-pro-BNP level (> 125 pg/mL) is a criterion for the diagnosis of HFpEF, but HFpEF has also been demonstrated by invasive means in 18% of patients with normal NT-pro-BNP levels (4). In the multivariate regression model, only a small fraction of the variance (r²) of NT-pro-BNP was explained: this clearly implies that there are further important factors affecting the NT-pro-BNP level. Nevertheless, the multivariate model still revealed a clinically relevant effect, with a lowering of the NT-pro-BNP value by an average of 123 pg/mL per point of BMI. More research will be needed to define more reliable thresholds here, or to identify new biomarkers that are not affected by an elevated BMI.

In summary, in our group of high-risk cardiac patients, BMI and NT-pro-BNP were inversely correlated, independently of potential clinical confounders. A limitation of this study is that certain data points (in particular, echocardiographic measurements) were not available for all patients. In conclusion, when HFpEF is clinically suspected, particularly in overweight patients, a stress test or right heart catheterization should be performed for liberal indications. In the routine interpretation of NT-pro-BNP values, it should be borne in mind that a BMI of 25 kg/m² or more can lower the value of NT-pro-BNP.

Michael Wester, Philipp Hegner, Maria Tafelmeier, Leopold Rupprecht, Christof Schmid, Lars S. Maier, Stefan Wagner, Michael Arzt, and Simon Lebek

Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg (Wester, Hegner, Tafelmeier, Maier, Wagner, Arzt, Lebek), [e-mail]

Klinik und Poliklinik für Herz-, Thorax- und Herznahe Gefäßchirurgie, Universitätsklinikum Regensburg, Regensburg (Rupprecht, Schmid)

Conflict of interest statement
The authors state that they have no conflict of interest.

Manuscript submitted on 7 May 2024, revised version accepted on 19 September 2024.

Cite this as:
Wester M, Hegner P, Tafelmeier M, Rupprecht L, Schmid C, Maier LS, Wagner S, Arzt M, Lebek S: Body mass index and NT-pro-BNP in high-risk cardiac patients. Dtsch Arztebl Int 2025; 122: 57–8. DOI: 10.3238/arztebl.m2024.0197

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4. Obokata M, et al:Circulation 2017; 135: 825–38

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