Elsevier

Metabolism

Volume 64, Issue 8, August 2015, Pages 857-861
Metabolism

Brief Report
The association between N-terminal pro B-type natriuretic peptide and lipoprotein particle concentration plateaus at higher N-terminal pro B-type natriuretic peptide values: Multi-Ethnic Study on Atherosclerosis

https://doi.org/10.1016/j.metabol.2015.04.001Get rights and content

Abstract

Background

The association between N-terminal pro B-type natriuretic peptide (NT-proBNP) and blood levels of small and large LDL- and HDL- particle (P) concentration may not be linear throughout the whole range of NT-proBNP values.

Methods

Linear spline regression analysis between NT-proBNP and lipoprotein particle concentrations was performed cross-sectionally in 5597 individuals from the Multi-Ethnic Study of Atherosclerosis adjusted for age, race, sex, body mass index, % of energy from saturated fats, intentional exercise, statin use, antihypertensive medication use, diabetes, IL-6 and estimated glomerular filtration rate. Spline knots were selected as the point at which the linear slope changed in these associations.

Results

NT-proBNP was positively associated with large LDL-P and HDL-P, but inversely associated with small LDL-P and HDL-P, but only for NT-proBNP values below the knot (range: 100–200 pg/mL).

Conclusion

These results suggest the presence of two distinct biological mechanisms above and below the knot determining the association between NT-proBNP and lipoprotein particle concentrations.

Introduction

B-type natriuretic peptide (BNP), which is associated with an increased risk of morbidity and mortality from cardiovascular disease [1], could potentially be involved in modifying lipoprotein particle concentration because of its effect on lipid oxidation and lipolysis [2], [3]. This is important because prospective cohort studies and clinical trials have shown that low density lipoprotein particle (LDL-P) and small high density lipoprotein particle (HDL-P) concentrations are positively associated with an increased risk of cardiovascular disease (CVD) [4], [5] and coronary heart disease (CHD) events [6].

The association between blood lipids concentrations and glucose with NT-proBNP does not follow a linear association throughout the whole range of NT-proBNP values [7]. For NT-proBNP levels < 100 pg/mL, we suggested that variations in NT-proBNP occur in response to physiological events. However, within the range in which pathophysiology presumably plays a primary role in determining BNP levels (≥ 100 pg/mL) the influence of pathological factors (subclinical CVD and inflammation) becomes progressively more important leading to substantial elevations in NT-proBNP and blunting of the physiological effects of natriuretic peptides on lipid metabolism [7].

We hypothesized that NT-proBNP is inversely associated with small LDL-P and HDL-P, but positively associated with large LDL-P and HDL-P. We also hypothesized that this effect does not follow a linear association throughout the whole range of NT-proBNP, but that plateaus occur at presumably pathophysiological levels of NT-proBNP.

Section snippets

Study Subjects

Participants eligible for this study were 5597 of the 6814 from the Multi-Ethnic Study of Atherosclerosis (MESA) in whom NT-proBNP and concentrations of lipoprotein particles were measured at their baseline visit in 2000–2002. They were men and women ages 45–84 years, of white, black, Chinese, and Hispanic race/ethnicity, initially free of overt CVD. Details of study recruitment and design have been published [8]. The institutional review boards at all participating centers approved the study

Results and Discussion

This sample has been described previously. In brief, about one third of the sample had NT-proBNP values > 100 pg/mL and were more likely to be females, have lower BMI, and have a greater proportion with subclinical CVD [7]. Table 1 shows the adjusted regression coefficients using linear splines and Fig. 1 (A–C) shows the plots of the adjusted lipoprotein particle concentration by deciles of NT-proBNP at MESA baseline. Regression coefficients of the slopes below the knot are on average 4

Strength and Limitations

The use of a well-validated technique with low intra-assay coefficient of variation to measure lipoprotein particle size concentrations [12] and the large multiethnic cohort free of cardiovascular disease in this cross-sectional study are factors that strongly support our results. Although choosing a cutoff value to differentiate the two phases of the association between NT-proBNP and lipoproteins is based on well-established statistical methods it should be carefully considered and we are not

Conclusions

This study shows that the associations between NT-proBNP and lipoprotein particle concentrations do not follow a linear response throughout the whole range of NT-proBNP values, consistent with the idea that two distinct biological mechanisms are in play above vs below the knot.

Authors’ Contribution

OAS performed the statistical analysis and prepared the manuscript. AM, CAP and LBD provided critical discussion of the results and interpretation. JDO performed the analysis to measure lipoprotein particles and also provided comments on the methods used in this manuscript. DAD and HB provided important clinical comments for this manuscript. DRJ Jr. contributed with his expertise in statistical analysis.

Funding

This research was supported by contract N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from NCRR.

Disclosures

Otto A. Sanchez, no disclosures. Daniel Duprez MD, PhD, consultant to Novartis Astra Zeneca. Lori B Daniels, consultant to Singlulex and Alere, Inc; speaking fees from Critical Diagnostics. Alan Maisel, consultant to Alere, BG Medicine, Brahms, Critical Diagnostics, EFG diagnostics, Novartis, Abbott. James D. Otvos, Chief Scientific Officer of Liposcience. Carmen A. Peralta, no disclosures. Joao A. Lima, consultant to Toshiba Medical Systems, Bracco. Hossein Bahrami, no disclosures. David R

Acknowledgements

The authors also thank the investigators staff and the participants of the Multi-Ethnic Study of Atherosclerosis (MESA) for their valuable contributions. A full list of MESA investigators and institutions can be found at http://www.mesa-nhlbi.org/.

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