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Pro-B-type natriuretic peptide(1-108) circulates in the general community: plasma determinants and detection of left ventricular dysfunction.

ABSTRACT: The purpose of this study was to investigate circulating pro-B-type natriuretic peptide (proBNP(1-108)) in the general community and evaluate its ability to detect left ventricular (LV) dysfunction.The current concept for cardiac endocrine function is that, in response to cardiac stress, the heart secretes B-type natriuretic peptide (BNP(1-32)) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP(1-76)) after intracardiac cleavage of their molecular precursor, proBNP(1-108). We hypothesized that proBNP(1-108) circulates in normal human subjects and that it is a useful biomarker for LV dysfunction.Our population-based study included a cohort of 1,939 adults (age ?45 years) from Olmsted County, Minnesota, with 672 participants defined as healthy. Subjects underwent in-depth clinical characterization, detailed echocardiography, and measurement of proBNP(1-108). Independent factors associated with proBNP(1-108) and test characteristics for the detection of LV dysfunction were determined.ProBNP(1-108) in normal humans was strongly influenced by sex, age, heart rate, and body mass index. The median concentration was 20 ng/l with a mean proBNP(1-108) to NT-proBNP(1-76) ratio of 0.366, which decreased with heart failure stage. ProBNP(1-108) was a sensitive (78.8%) and specific (86.1%) biomarker for detecting LV systolic dysfunction, which was comparable to BNP(1-32), but less than NT-proBNP(1-76), in several subsets of the population.ProBNP(1-108) circulates in the majority of healthy humans in the general population and is a sensitive and specific biomarker for the detection of systolic dysfunction. The proBNP(1-108) to NT-proBNP(1-76) ratio may provide insights into altered proBNP(1-108) processing during heart failure progression. Thus, this highly specific assay for proBNP(1-108) provides important new insights into the biology of the BNP system.

SUBMITTER: Macheret F

PROVIDER: S-EPMC3927966 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Pro-B-type natriuretic peptide(1-108) circulates in the general community: plasma determinants and detection of left ventricular dysfunction.

Macheret Fima F Boerrigter Guido G McKie Paul P Costello-Boerrigter Lisa L Lahr Brian B Heublein Denise D Sandberg Sharon S Ikeda Yasuhiro Y Cataliotti Alessandro A Bailey Kent K Rodeheffer Richard R Burnett John C JC

Journal of the American College of Cardiology 20110301 12

<h4>Objectives</h4>The purpose of this study was to investigate circulating pro-B-type natriuretic peptide (proBNP(1-108)) in the general community and evaluate its ability to detect left ventricular (LV) dysfunction.<h4>Background</h4>The current concept for cardiac endocrine function is that, in response to cardiac stress, the heart secretes B-type natriuretic peptide (BNP(1-32)) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP(1-76)) after intracardiac cleavage of their molecular ...[more]

PMID: 21414536

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Project description:BackgroundElevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population.Methods and resultsA total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54-2.46, P<0.001). This relationship held among different ethnic groups, non-Hispanic whites, African-Americans, and Hispanics. Most importantly, NT-proBNP provided additive prognostic value beyond both traditional risk factors and LV mass index for predicting incident HF (integrated discrimination index=0.046, P<0.001; net reclassification index; 6-year risk probability categorized by <3%, 3-10%, >10% =0.175, P=0.019; category-less net reclassification index=0.561, P<0.001).ConclusionsPlasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Project description:AimsNatriuretic peptides have reportedly been associated with cardiac hypertrophy and insulin resistance; however, it has not been established if B-type natriuretic peptide (BNP) is associated with either insulin resistance or cardiac remodelling in a population with normal plasma BNP levels. We investigated the relationship among plasma BNP levels, insulin resistance, and left ventricular (LV) remodelling in a population with normal physiological plasma BNP levels.Methods and resultsAmong 1632 individuals who participated in annual health checks between 2005 and 2008 in Arita-cho, Saga, Japan, 675 individuals [median (interquartile range) for age 62 (51-69) years; 227 men (34%)] with LV ejection fraction 50% and BNP level <35 pg/mL were enrolled in this study. Insulin resistance was assessed using homeostatic model assessment of insulin resistance (HOMA-IR). LV geometry, including LV concentric remodelling, was classified based on relative wall thickness (RWT) and LV mass index values derived from echocardiographic findings. Factors associated with insulin resistance and LV geometry were investigated using multiple logistic regression analysis. Tertiles of BNP were inversely associated with HOMA-IR [1st tertile, 1.33 (0.76-1.74); 2nd tertile, 1.05 (0.72-1.59); 3rd tertile, 0.95 (0.66-1.58), P = 0.005]. Lower BNP was associated with the prevalence of insulin resistance, defined as HOMA-IR ≥1.37, even after full multivariate adjustment [1 SD increment in BNP = adjusted odds ratio (aOR) 0.740; 95% confidence interval (CI) 0.601-0.912; P = 0.005]. LV concentric remodelling (RWT >0.42; LV mass index ≤115 g/m2 in men and ≤95 g/m2 in women) was observed in 107 (16%) participants, while normal LV geometry (RWT ≤0.42; LV mass index ≤115 g/m2 in men and ≤95 g/m2 in women) was seen in 423 (63%), and LV hypertrophy (LV mass index >115 g/m2 in men and >95 g/m2 in women) in 145 (21%). Both low BNP level and higher insulin resistance were independently linked to LV concentric remodelling after multivariate adjustment (1 SD increment in BNP = aOR 0.714, 95% CI 0.544-0.938, P = 0.015; HOMA-IR ≥ 1.37 vs. <1.37: aOR 1.694, 95% CI 1.004-2.857, P = 0.048, respectively).ConclusionsLower BNP levels are linked to either insulin resistance or LV concentric remodelling in a population with normal plasma BNP levels, suggesting that participants with lower natriuretic peptide level might be vulnerable to the development of metabolic disorders and LV morphological abnormalities.

Project description:Background Elevated levels of N-terminal pro-B natriuretic peptide (NT-proBNP) and left ventricular hypertrophy (LVH) are independent risk factors for heart failure (HF). In addition, right ventricular pacing (RVP) is an effective treatment strategy for bradyarrhythmia, but long-term RVP is associated with HF. However, there is limited evidence on the independent and combined association of NT-proBNP and left ventricular mass index (LVMI) with HF risk in elderly diabetic patients with long-term RVP. Methods Between January 2017 and January 2018, a total of 224 elderly diabetic patients with RVP at Fuwai Hospital were consecutively included in the study, with a 5-year follow-up period. The study endpoint was the first HF readmission during follow-up. This study aimed to explore the independent and joint relationship of NT-proBNP and LVMI with HF readmission in elderly diabetic patients with long-term RVP, using a multivariate Cox proportional hazards regression model. Results A total of 224 (11.56%) elderly diabetic patients with RVP were included in the study. During the 5-year follow-up period, a total of 46 (20.54%) patients suffered HF readmission events. Multivariate Cox proportional hazards regression analysis showed that higher levels of NT-proBNP and LVMI were independent risk factors for HF readmission [NT-proBNP: hazard risk (HR) = 1.05, 95% confidence interval (CI): 1.01–1.10; LVMI: HR = 1.14, 95% CI: 1.02–1.27]. The optimal cut-off point of NT-proBNP was determined to be 330 pg/ml by receiver operating characteristic (ROC) curve analysis. Patients with NT-proBNP > 330 pg/ml and LVH had a higher risk of HF readmission compared to those with NT-proBNP ≤ 330 pg/ml and non-LVH (39.02% vs. 6.17%; HR = 7.72, 95% CI: 1.34–9.31, P < 0.001). Conclusion In elderly diabetic patients with long-term RVP, NT-proBNP and LVMI were associated with the risk of HF readmission. Elevated NT-proBNP combined with LVH resulted in a significantly higher risk of HF readmission.

Dataset Information

Pro-B-type natriuretic peptide(1-108) circulates in the general community: plasma determinants and detection of left ventricular dysfunction.

Publications

Pro-B-type natriuretic peptide(1-108) circulates in the general community: plasma determinants and detection of left ventricular dysfunction.

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