title: The associations between metabolic variables and NT-proBNP are blunted at pathological ranges: the Multi-Ethnic Study of Atherosclerosis.
abstract: OBJECTIVE
  Under physiological conditions brain natriuretic peptide (BNP) is inversely associated with metabolic risk factors, but under pathological conditions these associations may tend to plateau.
  
  
  METHODS
  5597 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA), 45-84years of age, free of overt cardiovascular disease in 2000-02 and then again in 2003-05 participated in this study. Associations between NT-proBNP and BMI, blood lipids, homeostasis model of insulin resistance (HOMA-IR) using linear regression models were adjusted for age, race, sex, BMI, % of energy from saturated fats, intentional exercise, statin use, antihypertensive medication use, diabetes and glomerular filtration rate. The inflection points (IP) at which these associations became nonlinear were determined using linear splines with knots at different levels of NT-proBNP.
  
  
  RESULTS
  Participants with NT-proBNP ≥100pg/mL (29%) tended to be older, on statins and anti-hypertensive medications vs. those with NT-proBNP <100pg/mL. The IP point varies among variables and ranged from 50-120pg/mL. NT-proBNP<IP, associated inversely with BMI, total cholesterol (TC), LDL-C, triglycerides (TG) and HOMA-IR, but positively with HDL-C. A higher proportion of participants with NT-proBNP ≥100pg/mL had subclinical CVD. All associations with NT-proBNP plateaued when NT-proBNP≥IP. Baseline level in NT-proBNP was not associated with 3-year change in BMI, TG, HDL-C or fasting glucose.
  
  
  CONCLUSIONS
  In a large cardiovascular disease-free cohort, NT-proBNP within the lower (physiological) range was inversely associated with TC, LDL-C, TG and insulin resistance with different inflection points, but at higher (pathological) levels these associations were blunted.
authors.affiliation: School of Public Health, Division of Epidemiology & Community Health, University of Minnesota. Electronic address: sanc0050@umn.edu.
authors.forename: Otto A
authors.initials: OA
authors.lastname: Sanchez
authors.affiliation: Division of Cardiology, University of Minnesota.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Duprez
authors.affiliation: Stanford University.
authors.forename: Hossein
authors.initials: H
authors.lastname: Bahrami
authors.affiliation: School of Medicine, University of California, San Diego.
authors.forename: Lori B
authors.initials: LB
authors.lastname: Daniels
authors.affiliation: School of Public Health, Division of Epidemiology & Community Health, University of Minnesota.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: Division of Cardiology, Johns Hopkins Bayview Medical Center.
authors.forename: Joao A
authors.initials: JA
authors.lastname: Lima
authors.affiliation: School of Medicine, University of California, San Diego.
authors.forename: Alan
authors.initials: A
authors.lastname: Maisel
authors.affiliation: School of Medicine, University of California San Francisco.
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Peralta
authors.affiliation: School of Public Health, Division of Epidemiology & Community Health, University of Minnesota and University of Oslo.
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000208:ethnology / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D005006:Ethnicity; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: BMI; HOMA; Inflammatory markers; Lipids; NT-proBNP