Brief ReportThe 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
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.
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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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Computerized tomography measured liver fat is associated with low levels of N-terminal pro-brain natriuretic protein (NT-proBNP). Multi-Ethnic Study of Atherosclerosis
2016, Metabolism: Clinical and ExperimentalCitation Excerpt :Furthermore, natriuretic peptides have been shown to be inversely associated with incident diabetes [8,9]. These observations may stem from the metabolic effects of natriuretic peptides on lipoproteins [10], lipolysis, mitochondrial density and fat oxidation [11]. Given the common pathophysiological mechanisms of NAFLD with diabetes and other metabolic disorders, it is possible that natriuretic peptides have an effect on liver fat.
Metabolomic profiling implicates adiponectin as mediator of a favorable lipoprotein profile associated with NT-proBNP
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