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. Material and methods 5597 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA), 45-84 years 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 ≥ 100 pg/mL (29%) tended to be older, on statins and anti-hypertensive medications vs. those with NT-proBNP < 100 pg/mL. The IP point varies among variables and ranged from 50-120 pg/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 ≥ 100 pg/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.
Bibliographical noteFunding Information:
This research was supported by contracts N01-HC-95159 through N01-HC-95165, N01-HC-95169 grants R01-HL 66075, N01-HC-95168, N01-HC 9808, and N01-HC 95168 from the National Heart, Lung, and Blood Institute. The authors also thank the investigators and staff 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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