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Background Currently, there is limited research on the prognostic value of NT-proBNP (N-terminal pro-B-type natriuretic peptide) as a biomarker in COVID-19. We proposed the a priori hypothesis that an elevated NT-proBNP concentration at admission is associated with increased in-hospital mortality. Methods and Results In this prospective, observational cohort study of the American Heart Association's COVID-19 Cardiovascular Disease Registry, 4675 patients hospitalized with COVID-19 were divided into normal and elevated NT-proBNP cohorts by standard age-adjusted heart failure thresholds, as well as separated by quintiles. Patients with elevated NT-proBNP (n=1344; 28.7%) were older, with more cardiovascular risk factors, and had a significantly higher rate of in-hospital mortality (37% versus 16%; P <0.001) and shorter median time to death (7 versus 9 days; P <0.001) than those with normal values. Analysis by quintile of NT-proBNP revealed a steep graded relationship with mortality (7.1%-40.2%; P <0.001). NT-proBNP was also associated with major adverse cardiac events, intensive care unit admission, intubation, shock, and cardiac arrest ( P <0.001 for each). In subgroup analyses, NT-proBNP, but not prior heart failure, was associated with increased risk of in-hospital mortality. Adjusting for cardiovascular risk factors with presenting vital signs, an elevated NT-proBNP was associated with 2-fold higher adjusted odds of death (adjusted odds ratio [OR], 2.23; 95% CI, 1.80-2.76), and the log-transformed NT-proBNP with other biomarkers projected a 21% increased risk of death for each 2-fold increase (adjusted OR, 1.21; 95% CI, 1.08-1.34). Conclusions Elevated NT-proBNP levels on admission for COVID-19 are associated with an increased risk of in-hospital mortality and other complications in patients with and without heart failure.

Cross-sectionally measured NT-proBNP (N-terminal pro-B-type natriuretic peptide) is related to incident dementia. However, data linking changes in NT-proBNP to risk of future dementia are lacking. We aimed to examine the association of change in NT-proBNP over 3.2 years with incident dementia. We included 4563 participants in MESA (Multi-Ethnic Study of Atherosclerosis) prospective cohort who were free of cardiovascular disease at enrollment, had NT-proBNP level measured at MESA exams 1 (baseline, 2000-2002) and 3 (2004-2005), and had no diagnosis of dementia before exam 3. The association of change in NT-proBNP level between MESA exams 1 through 3 and all-cause hospitalized dementia (by International Classification of Diseases, Ninth Revision , codes) after MESA exam 3 (2004-2005) through 2015 was assessed using competing-risks Cox proportional hazard regression analysis. During 45 522 person-years of follow-up, 223 dementia cases were documented. Increase in log-NT-proBNP from MESA exams 1 through 3 was positively associated with incidence of dementia (multivariable hazard ratio, 1.28 [95% CI, 1.001-1.64]; P =0.049). An increase of at least 25% in NT-proBNP level from MESA exam 1 through 3 was associated with a 55% ( P =0.02) increase in the risk of dementia in multivariable analysis. Addition of temporal NT-proBNP change to a model including risk factors and baseline NT-proBNP improved the prediction of dementia (Harrell C statistic from 0.85 to 0.87, P =0.049). Increase in NT-proBNP is independently associated with future all-cause hospitalized dementia and offers a moderately better predictive performance for risk of dementia compared with risk factors and baseline NT-proBNP. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Objective: Natriuretic peptides (NPs) are hormones with cardioprotective effects. NP levels vary by race; however, the pathophysiological consequences of lower NP levels are not well understood. We aimed to quantify the association between NPs and endothelial function as measured by flow-mediated dilation (FMD) and the contribution of NP levels to racial differences in endothelial function., Methods: In this cross-sectional study of 2938 Multi-Ethnic Study of Atherosclerosis participants (34% Caucasian, 20% African-American, 20% Asian-American and 26% Hispanic) without cardiovascular disease at baseline, multivariable linear regression models were used to examine the association between serum N-terminal pro-B-type NP (NT-proBNP) and natural log-transformed FMD. We also tested whether NT-proBNP mediated the relationship between race and FMD using the product of coefficients method., Results: Among African-American and Chinese-American individuals, lower NT-proBNP levels were associated with lower FMD, β=0.06 (95% CI: 0.03 to 0.09; p<0.001) and β=0.06 (95% CI: 0.02 to 0.09; p=0.002), respectively. Non-significant associations between NT-proBNP and FMD were found in Hispanic and Caucasian individuals. In multivariable models, endothelial function differed by race, with African-American individuals having the lowest FMD compared with Caucasians, p<0.001. Racial differences in FMD among African-Americans and Chinese-Americans were mediated in part by NT-proBNP levels (African-Americans, mediation effect: -0.03(95% CI: -0.05 to -0.01); Chinese-Americans, mediation effect: -0.03(95% CI: -0.05 to -0.01))., Conclusions: Lower NP levels are associated with worse endothelial function among African-Americans and Chinese-Americans. A relative NP deficiency in some racial/ethnic groups may contribute to differences in vascular function., Competing Interests: Competing interests: LBD has received speaking fees from Roche and Critical Diagnostics, and consulting honoraria from Roche Diagnostics and Siemens Healthcare., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal fragment of its prohormone (NT-proBNP), are well-established biomarkers for patients with heart failure (HF). Although these biomarkers have consistently demonstrated their value in the diagnosis and prognostication of HF, their ability to help clinicians in making treatment decisions remains debated. Moreover, some new HF drugs can affect concentrations of NPs, such as the prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors (ARNIs), and may present a challenge in the interpretation of levels of BNP. Use of NT-proBNP measurement has been suggested in the context of ARNI therapy because its concentrations are not affected by neprilysin inhibition. As biomarkers are reconsidered in the context of ARNI therapy, cutoff levels and the effects of individual patient characteristics, such as renal function and age, on biomarker concentrations should be reassessed.

Natriuretic peptides (NP) are cardiac-derived hormones with favorable cardiometabolic actions. Low NP levels are associated with increased risks of hypertension and diabetes mellitus, conditions with variable prevalence by race and ethnicity. Heritable factors underlie a significant proportion of the interindividual variation in NP concentrations, but the specific influences of race and ancestry are unknown. In 5597 individuals (40% white, 24% black, 23% Hispanic, and 13% Chinese) without prevalent cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis, multivariable linear regression and restricted cubic splines were used to estimate differences in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels according to, ethnicity, and ancestry. Ancestry was determined using genetic ancestry informative markers. NT-proBNP concentrations differed significantly by race and ethnicity (black, median 43 pg/ml [interquartile range 17 to 94], Chinese 43 [17 to 90], Hispanic 53 [23 to 107], white 68 [34 to 136]; p = 0.0001). In multivariable models, NT-proBNP was 44% lower (95% confidence interval -48 to -40) in black and 46% lower (-50 to -41) in Chinese, compared with white individuals. Hispanic individuals had intermediate concentrations. Self-identified blacks and Hispanics were the most genetically admixed. Among self-identified black individuals, a 20% increase in genetic European ancestry was associated with 12% higher (1% to 23%) NT-proBNP. Among Hispanic individuals, genetic European and African ancestry were positively and negatively associated with NT-proBNP levels, respectively. In conclusion, NT-proBNP levels differ according to race and ethnicity, with the lowest concentrations in black and Chinese individuals. Racial and ethnic differences in NT-proBNP may have a genetic basis, with European and African ancestry associated with higher and lower NT-proBNP concentrations, respectively., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment., Methods: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure., Findings: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure., Interpretation: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention., Funding: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: N-terminal pro B-type natriuretic peptide (NT-proBNP) is inversely associated with diabetes mellitus, obesity and metabolic syndrome. We aim to characterize the association between NT-proBNP and nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with metabolic syndrome., Methods: 4529 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) free of cardiovascular disease, without self-reported liver disease and not diabetic at their baseline visit in 2000-2002 were included in this analysis. NAFLD was defined by a liver attenuation <40 HU. Relative prevalence (RP) for NAFLD was assessed adjusted for age, race, and sex, percentage of dietary calories derived from fat, total intentional exercise, alcoholic drinks per week, and interleukin-6 by quintiles of NT-proBNP. Adjusted linear spline model was used to characterize a non-linear association between NT-proBNP and liver fat. The inflection point (IP) was the NT-proBNP concentration where there was a change in slope in the association between liver attenuation and NT-proBNP., Results: RP for NAFLD decreased by 30% from the lowest to the highest quintile of NT-proBNP, p=0.01. We observed an inverse linear association between NT-proBNP and liver fat, which plateaued (IP) at an NT-proBNP concentration of 45pg/mL. Linear regression coefficient (SE) per unit of NT-proBNP less than and greater than or equal to IP was of 0.05 (0.02), p=0.001 and 0.0006 (0.0008), p=0.5, respectively; differences between slopes, p<0.0001., Conclusions: In this cross-sectional study of a community based multiethnic sample of non-diabetic adults, low levels of NT-proBNP are associated with greater prevalence of NAFLD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (TnT) predict cardiovascular disease (CVD) risk in a variety of populations. Whether their predictive value varies by ethnicity is unknown. We sought to determine whether NT-proBNP and TnT improve prediction of incident coronary heart disease (CHD) and CVD, independent of CVD risk factors, in a multiethnic population; whether NT-proBNP improves prediction compared with the Framingham Risk Score or the Pooled Cohort Risk Equation; and whether a second NT-proBNP further improves prediction., Methods: Both NT-proBNP and TnT were measured in 5,592 MESA white, black, Hispanic, and Chinese participants (60% nonwhite; mean age 62.3 ± 10.3 years) in 2000 to 2002 and 2004 to 2005. We evaluated adjusted risk of incident CHD and CVD based on baseline and change in biomarker concentration., Results: Participants were followed up through 2011 and incurred 370 CVD events (232 CHD). Concentrations of NT-proBNP and TnT varied by ethnicity. Both NT-proBNP and TnT were associated with an increased risk of events (adjusted hazard ratio [HR] for CHD [95% CI] for fifth quintile vs other 4 quintiles of NT-proBNP, 2.03 [1.50-2.76]; HR for CHD for detectable vs undetectable TnT, 3.95 [2.29-6.81]). N-terminal-pro-B-type natriuretic peptide improved risk prediction and classification compared with the Framingham Risk Score and the Pooled Cohort Risk Equation. Change in NT-proBNP was independently associated with events (HR for CHD per unit increase in ΔlogNT-proBNP, 1.95 [1.16-3.26]). None of the observed associations varied by ethnicity., Conclusions: Both NT-proBNP and TnT are predictors of incident CHD, independent of established risk factors and ethnicity, in a multiethnic population without known CVD. Change in NT-proBNP may add additional prognostic information., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels., Methods: Plasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA). ΔNT-proBNP was calculated as NT-proBNP visit3-NT-proBNP baseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n=3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1)<54.4 pg/mL; (2) 54.4-85.9 pg/mL; and (3) 86-54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) -6.2 (-131-11.7) pg/mL; (2) 19.8 (11.8-30.1) pg/mL; (3) 44.0 (30.2-67.9) pg/mL; and (4) 111.2 (68.0-3749.9) pg/mL., Results: The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P=0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP., Conclusion: This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a 'physiological range' of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2015. Published by Elsevier Inc.)

Background and Aims: To investigate the associations between selected adipokines and the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP)., Methods and Results: As many as 1489 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis were evaluated at 4 clinic visits about every 2 years. The evaluation included fasting venous blood, which was analyzed for NT-proBNP (at visits 1 and 3) and the adipokines adiponectin and leptin (at visits 2 and 3). The mean age was 64.8 ± 9.6 years and 48% were female. After multivariable adjustment, a 1-SD increment in adiponectin was associated with a 14 pg/ml higher NT-proBNP level (p < 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles had 28, 45 and 67% higher NT-proBNP levels (p < 0.01 for all). For changes in NT-proBNP over the follow-up period, and after multivariable adjustment including baseline NT-proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml absolute increase in NT-proBNP (p < 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated with increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and <0.01, respectively). There was a significant interaction between adiponectin and sex for visit 3 NT-proBNP (p-interaction < 0.01), with significantly stronger associations in men. Leptin was not associated with NT-proBNP., Conclusion: Higher adiponectin, but not leptin, is significantly associated with higher levels of NT-proBNP, as well as with greater longitudinal increases in NT-proBNP. The associations were stronger in men., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Longitudinal associations between the aminoterminal pro-B-type natriuretic peptide (NT-proBNP) and incident hypertension are lacking., Methods: We tested associations between baseline NT-proBNP (bNT-proBNP) and change in NT-proBNP (ΔNT-proBNP) (visit 3 NT-proBNP - bNT-proBNP, 3.2 years apart) with incident hypertension (SBP ≥ 140 and/or DBP ≥90 mmHg or taking antihypertensive medications). Incident hypertension was evaluated in 5596 individuals in the Multi-Ethnic Study of Atherosclerosis without hypertension at baseline (53% women, age range 45-84 years without overt cardiovascular disease) and follow-up for 9.5 years and in a subgroup (1550) who had bNT-proBNP less than 100 pg/ml and no hypertension at visit 3. Incident hypertension was regressed (proportional hazards) on quintiles of bNT-proBNP (range) (reference <19.2, 19.3-40.8, 40.9-70.9, 71-135.2, and >135.5) and also on ΔNT-proBNP categories (reference <-10, -10 to 10, >10 to 50, and >50 pg/ml). Hazard ratios were adjusted for age, race, sex, education, diabetes, obesity, left ventricle mass/height, SBP and DBP, interleukin-6, salt intake, estimated glomerular filtration rate, and exercise., Results: Compared with the reference category, hazard ratios (95% confidence interval) for incident hypertension compared with the first quintile of bNT-proBNP were 1.47 (1.13-1.93), 1.57 (1.18-2.09), 1.52 (1.12-2.06), and 2.36 (1.62-3.41). Hazard ratios for incident hypertension by categories of ΔNT-proBNP from 3.2 to 9.5 years follow-up were 0.98 (0.62-1.56), 1.13 (0.72-1.79), and 1.82 (1.07-3.12)., Conclusion: The development of hypertension tended to be preceded by elevated levels of bNT-proBNP or a substantial positive ΔNT-proBNP.

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), 45-84years 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

Background: Elevated 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 Results: A 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)., Conclusions: Plasma 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 Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Since the initial studies showing the usefulness of B-type natriuretic peptide for aiding in heart failure diagnosis, a vast number of other clinical applications for this neurohormone have emerged. In addition to refining our capabilities to diagnose and prognosticate in acute heart failure, natriuretic peptides are now being used in outpatient heart failure clinics, in screening programs, and in risk prediction algorithms in various settings. In just 10 years, B-type natriuretic peptide has gone from being an unknown biomarker to being one of the most useful in cardiology and beyond. In this perspective piece, the investigators review what we have learned about using natriuretic peptides over the past 10 years and the anticipated advances in their use over the next decade., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Few tools exist that provide objective accurate prediction of short-term mortality risk in patients presenting with acute heart failure (AHF). The purpose was to describe the accuracy of several biomarkers for predicting short-term death rates in patients diagnosed with AHF in the emergency department (ED)., Methods: The Biomarkers in ACute Heart failure (BACH) trial was a prospective, 15-center, international study of patients presenting to the ED with nontraumatic dyspnea. Clinicians were blinded to all investigational markers, except troponin and natriuretic peptides, which used the local hospital reference range. For this secondary analysis, a core lab was used for all markers except troponin. This study evaluated patients diagnosed with AHF by the on-site emergency physician (EP)., Results: In the 1,641 BACH patients, 466 (28.4%) had an ED diagnosis of AHF, of whom 411 (88.2%) had a final diagnosis of AHF. In the ED-diagnosed HF patients, 59% were male, 69% had a HF history, and 19 (4.1%) died within 14 days of their ED visit. The area under the curve (AUC) for the 14-day mortality receiver operating characteristic (ROC) curve was 0.484 for brain natriuretic peptide (BNP), 0.586 for N-terminal pro-B-type natriuretic peptide (NT-proBNP), 0.755 for troponin (I or T), 0.742 for adrenomedullin (MR-proADM), and 0.803 for copeptin. In combination, MR-proADM and copeptin had the best 14-day mortality prediction (AUC = 0.818), versus all other markers., Conclusions: MR-proADM and copeptin, alone or in combination, may provide superior short-term mortality prediction compared to natriuretic peptides and troponin. Presented results are explorative due to the limited number of events, but validation in larger trials seems promising., (© 2011 by the Society for Academic Emergency Medicine.)

Background: Natriuretic peptides have prognostic value across a wide spectrum of cardiovascular diseases and may predict cognitive dysfunction in patients with cardiovascular disease, even in the absence of previous stroke. Little is known about the association of natriuretic peptides with cognitive function in community-dwelling adults. We assessed the association between N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and cognitive function in community-dwelling ambulatory older adults in the Rancho Bernardo Study., Methods: We studied 950 men and women, aged 60 years and older, who attended a research clinic visit where a medical history and examination were performed, and blood for cardiovascular disease risk factors and NT-proBNP levels were obtained. Three cognitive function tests were administered: the Mini Mental State Examination (MMSE), Trail-Making Test B (Trails B), and Category Fluency., Results: Participants with high NT-proBNP levels (≥450 pg/mL; n=198) were older and had a higher prevalence of coronary heart disease (12% vs 30%), and stroke (5% vs 11%; P≤.001 for both). In unadjusted analyses, all 3 cognitive function test scores were significantly associated with NT-proBNP levels (P<.001). After adjusting for age, sex, education, hypertension, body mass index, exercise, alcohol use, smoking, low density lipoprotein cholesterol, creatinine clearance, and previous cardiovascular disease, elevated NT-proBNP levels remained independently associated with poor cognitive performance on MMSE (odds ratio [OR] 2.0; 95% confidence interval [CI], 1.1-3.6; P=.02) and Trails B (OR 1.7; 95% CI, 1.2-2.7; P=.01), but not Category Fluency (OR 1.4; 95% CI, 0.9-2.2; P=.19). Results were unchanged after excluding the 6% of participants with a history of stroke., Conclusions: NT-proBNP levels were strongly and independently associated with poor cognitive function in community-dwelling older adults., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) patients have a poor prognosis, yet outcomes might be improved by early identification of risk. We investigated the prognostic value of B-type natriuretic peptide (BNP) in patients at risk for HF (American College of Cardiology [ACC]/American Heart Association [AHA] HF Stages A and B), and compared prognosis with Stage C/D patients., Methods and Results: Outpatients referred for echocardiogram (n=829) were stratified by ACC/AHA HF stage and BNP levels (cutpoint of 100pg/mL). Primary outcome was death or cardiac hospitalization at 1 year. BNP levels increased with increasing numbers of cardiovascular risk factors and with HF stage. Stage A/B patients with high BNP had a similar or worse prognosis than Stage C/D patients with low BNP. In fact, the prognosis of Stage C/D patients with low BNP did not significantly differ from the prognosis of Stage A/B patients with low BNP (adjusted HR 1.21, 95% CI 0.62-2.37), whereas Stage A/B patients with high BNP did have a significantly worse prognosis (adjusted HR 1.91, 95% CI 1.11-3.28)., Conclusions: Individuals without any history of HF but with BNP >or=100pg/mL are at equal or higher risk than those with a HF history whose BNP is <100pg/mL. BNP may be useful to identify asymptomatic individuals at high risk for future cardiovascular events., (Copyright 2010 Elsevier Inc. All rights reserved.)

Pulmonary congestion can be challenging to diagnose because of nonspecific symptoms and the blunt nature of physical examination and radiographic findings. Assessing for euvolemia following treatment of congestion also can be difficult but can improve both the inpatient and outpatient care of patients who have heart failure. Tools such as the natriuretic peptides are important adjuncts to the physical examination and chest radiographs and often obviate the need for invasive hemodynamic assessment.

Background: Detection of heart failure (HF) in stable outpatients can be difficult until an overt event occurs. This study sought to determine whether the combination of B-type natriuretic peptide (BNP) and impedance cardiography (ICG) could be used in a nonacute clinical setting to risk stratify and predict HF-related events in stable outpatients., Methods and Results: Patients undergoing routine outpatient echocardiography underwent ICG and BNP testing and were followed for one year for HF-related events (Emergency Department [ED] visit or hospitalization due to HF or all-cause death). A total of 524 patients were analyzed, resulting in 57 HF-related events; 16 ED visits, 17 hospitalizations, and 24 all-cause deaths. Using Cox regression analyses, BNP and systolic time ratio index (STRI) by ICG proved to be the strongest predictors of future HF-related events. Patients with a BNP >100 pg/ml and STRI >0.45 sec(-1) had a significantly lower event-free survival rate than those with a high BNP and low STRI (67% versus 89%, P=.001). In patients with LV dysfunction only, if both BNP and STRI values were high, the relative risk of a HF-related event increased by 12.5 (95 % C.I. 4.2-36.7), when compared with patients with a low BNP and low STRI (P<.001)., Conclusions: In a nonacute clinical setting, both BNP and ICG testing can provide unique predictive power of long-term HF-related events in a stable cohort of patients with and without LV dysfunction.

Objectives: This study investigated the prognostic value of detectable cardiac troponin T (TnT) and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in a population of community-dwelling older adults., Background: Minimally elevated levels of TnT, a marker of cardiomyocyte injury, have been found in small subsets of the general population, with uncertain implications. A marker of ventricular stretch, NT-proBNP has clinical utility in many venues, but its long-term prognostic value in apparently healthy older adults and in conjunction with TnT is unknown., Methods: Participants were 957 older adults from the Rancho Bernardo Study with plasma NT-proBNP and TnT measured at baseline (1997 to 1999) and followed up for mortality through July 2006., Results: Participants with detectable TnT (>/=0.01 ng/ml, n = 39) had an increased risk of all-cause and cardiovascular death (adjusted hazard ratio [HR] by Cox proportional hazards analysis: 2.06; 95% confidence interval [CI]: 1.29 to 3.28, p = 0.003 for all-cause mortality; HR: 2.06, 95% CI: 1.03 to 4.12, p = 0.040 for cardiovascular mortality); elevated NT-proBNP also predicted an increased risk of all-cause and cardiovascular mortality (adjusted HR per unit-log increase in NT-proBNP: 1.85, 95% CI: 1.36 to 2.52, p < 0.001 for all-cause mortality; HR: 2.51, 95% CI: 1.55 to 4.08, p < 0.001 for cardiovascular mortality). Those with both elevated NT-proBNP and detectable TnT had poorer survival (HR for high NT-proBNP and detectable TnT vs. low NT-proBNP and any TnT: 3.20, 95% CI: 1.91 to 5.38, p < 0.001). Exclusion of the 152 participants with heart disease at baseline did not materially change the TnT mortality or NT-proBNP mortality associations., Conclusions: Apparently healthy adults with detectable TnT or elevated NT-proBNP levels are at increased risk of death. Those with both TnT and NT-proBNP elevations are at even higher risk, and the increased risk persists for years.

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Background: Previous studies have shown that in patients presenting to the emergency department (ED) with heart failure, there is a disconnect between the perceived severity of congestive heart failure (CHF) by physicians and the severity as determined by B-type natriuretic peptide (BNP) levels. Whether ethnicity plays a role in this discrepancy is unknown., Methods and Results: The Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) was a 10-center trial of 464 patients seen in the ED with acute dyspnea and BNP level higher than 100 pg/mL on arrival. Physicians were blinded to BNP levels. Patients were followed for 90 days after discharge. A total of 151 patients identified themselves as white (32.5%) and 294 as black (63.4%). Of these, 90% were hospitalized. African Americans were more likely to be perceived as New York Heart Association class I or II than whites (P = .01). Blacks who were discharged from the ED had higher median BNP levels than whites who were discharged (1293 vs. 533, P = .004). The median BNP of blacks who were discharged was actually higher than the median BNP of blacks who were admitted (1293 vs. 769, P = .04); the same did not hold true for whites. BNP was predictive of 90-day outcome in both blacks and whites; however, perceived severity of CHF, race, and ED disposition did not contribute to the prediction of events., Conclusion: In patients presenting to the ED with heart failure, the disconnect between perceived severity of CHF and severity as determined by BNP levels is most pronounced in African Americans.

Background: B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis., Methods: The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results., Results: Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively (P < .05 for all comparisons except 35 vs 25). B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients., Conclusions: Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP > or = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP > or = 170 pg/mL) could be used to increase specificity.