We have previously reported that BMI has an effect on plasma NT-proBNP concentrations in CHF
. In the current study we extended these findings on NPs to include MR-proANP, reporting that concentrations of both NT-proBNP and MR-proANP are negatively associated with BMI. After adjusting for parameters with known impact on concentrations of NPs, levels of NT-proBNP remained independently associated with BMI. By contrast, the other biomarkers examined reflecting neurohormonal stimulation, inflammation and endothelial dysfunctions were not related to BMI in the present CHF population.
Low BMI is associated with an unfavourable survival in CHF and accordingly it may be hypothesized that biomarkers significantly associated with BMI are mechanistically linked to the weight loss. In line with this the interest in the lipolytic role of natriuretic peptides is expanding. Recently, NPs have been shown to enhance lipolysis of adipose tissue though activation of the hormone sensitive lipase
. Furthermore, in experimental studies of ANP and BNP, an increase in energy utilization and thermogenesis by enhancing ‘browning’ of white adipocytes has recently been reported
, hence, suggesting a pathophysiological explanation of the inverse relationship between BMI and NPs. We found a gradual decline in plasma MR-proANP levels corresponding to an increase in BMI, which is in accordance with findings of a previous study by Masson et al.
. We did not however, observe an independent association between MR-proANP and BMI, after adjustment for age, gender and kidney function. This observation is in accordance with a study in healthy subjects, in whom kidney function and age appeared to be the primary predictors of MR-proANP
. Clearance mechanisms of MR-proANP and NT-proBNP are presumably not identical. Therefore, these findings support that secretion from the myocytes of A and B-type NPs are blunted in obesity
In the present study decreasing BMI was associated with advanced age and when eliminating age from the base model, MR-proANP became independently related to BMI. A recent post hoc analysis from The BACH trial reported significant differences in MR-proANP levels between acute HF patients with highest vs. lowest BMI
Atrial NP promotes adiponectin release in healthy subject
. This association is corroborated by the current study. More knowledge on this cross-talk between the heart and adipose tissue may be of importance in CHF.
The inverse association between adiponectin levels and BMI found in this study has been documented in both healthy populations and in cohort of CHF patients. Increased levels of adiponectin have been identified in patients with extremely low BMI as in cardiac cachexia
, a syndrome present in approximately 10% of a CHF population
. In this context, it is interesting that high plasma concentrations of adiponectin in the more advanced state of CHF are independent of BMI
. On this basis it has been suggest that adiponectin contributes to weight loss in cardiac cachexia by increasing energy expenditure
Chronic low grade inflammation is involved in the pathophysiology of CHF. We have recently reported that elevated levels of the novel biomarker α-defensins, reflecting the innate immune system, have prognostic implications in CHF patients
. Plasma levels of α-defensins were not affected by BMI in the present study and this finding indicate that the innate immune system is not directly linked to the progressive weight loss observed in CHF with cachexia.
Circulating concentrations of biomarkers reflecting low-grade inflammation and hsCRP, endothelial dysfunction, MR-proADM, and water homeostasis copeptin were not associated with BMI in the present study, even though hsCRP concentrations were increased by a factor 2 in CHF with BMI < 21 kg/m2. In contrast to our findings, recent data on MR-proADM levels in lean as well as obese individuals demonstrated a positive correlation to BMI, with a progressive decrease in plasma levels during weight reduction after gastric by-pass surgery
[14, 28]. None of the novel biomarkers affected the association between BMI and outcome.
There are some limitations to this study. First, there are a limited number of patients enrolled in the current study, which might diminish the statistical power of detecting associations between BMI and biomarkers. Second, this study was monocentric and only BMI and no other anthropometric data were available in this CHF cohort. Finally, it should be noted that the present analyses are post hoc analyses on data collected for other purposes
. This may increase the risk for a Type I error. Whether we have overlooked a small effect of BMI on α-defensins due to a low sample size (a Type II error) can neither be excluded and our findings should be confirmed in larger cohorts.