Mid-regional Pro-atrial Natriuretic Peptide Research Articles

Prognostic and diagnostic significance of mid-regional pro-atrial natriuretic peptide in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 Study

Purpose: To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea.Methods: MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n = 313), on day 2 (n = 234), and before discharge (n = 91) and compared for diagnosing acute heart failure (HF; n = 143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n = 84) separately.Results: The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p < 0.001) and the receiver-operating area under the curve (AUC) was 0.85 (95% CI 0.81–0.89) for MR-proANP and 0.86 (0.82–0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816 days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio (lnMR-proANP) 1.98 (95% CI 1.17–3.34).Conclusion: MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.

Abstract P379: Paradoxical Natriuretic Peptide Resetting in Astronauts

Human studies in space provide unique and often unexpected findings regarding the role of terrestrial gravity for human cardiovascular and renal regulation. While vascular volume is shifted towards the head, which would be expected to increase natriuretic peptide (NP) release, preliminary observations suggested the opposite. Therefore, we assessed natriuretic peptide regulation on different controlled sodium diets in space and on Earth. Eight male astronauts (50±2.8 yrs.) ingested higher (5.5 g/day) and low sodium (2g/day) diets for five days each on Earth and on the International Space Station (ISS) in alternating order. Dietary nutrient intake was individually tailored and kept constant. At day five of each intervention, midregional-pro atrial NP (MRproANP), N-terminal pro B-type NP (NTproBNP), and aldosterone in blood, urinary sodium excretion, and body mass were measured. On Earth, MRproANP was 71.86±4.39 pmol/L on moderately high and 65.13±6.71 pmol/L on low sodium intake. In space, MRproANP was 44.61±4.26 pmol/L on high and 31.37±4.02 pmol/L on low sodium intake (p&lt;0.001 between sodium intakes, p&lt;0.01 between Earth and space). Similarly, NTproBNP responded to changes in sodium intake (p&lt;0.001) and was regulated at lower levels in space (p=0.008). Serum aldosterone concentrations decreased on higher sodium intake but did not differ between space and Earth (p&lt;0.001 between sodium intakes, p=0.95 between Earth and space). Body mass did not differ between low and high sodium intake, either on Earth or in space (space: low sodium 83.7±3.1 kg, higher sodium 84.4±3.1 kg, Earth: low sodium 87.1±3.6 kg, higher sodium 87.2±3.2 kg). In conclusion, NP release while responding to changes in sodium intake is paradoxically reset to lower levels in space. The mechanisms may have implications for volume regulation and cardiovascular health during long-term space travel.

Pilot Trial Evaluating Mid-Regional Pro-Atrial Natriuretic Peptide as a Marker of Sepsis after Abdominal Surgery

Mid-regional pro-atrial natriuretic peptide (MR pro-ANP) has been shown to be a diagnostic marker for sepsis. The objective of this pilot study was to evaluate the potential of MR pro-ANP in the diagnosis of postoperative sepsis. We enrolled 18 patients with postoperative sepsis, 19 patients who underwent major abdominal surgery without sepsis and 9 healthy individuals as control subjects. MR pro-ANP, interleukin-6 (IL-6) and procalcitonin (PCT) were measured on the day of inclusion in the study, and at days 3, 7 and 10. The mean levels of MR pro-ANP were significantly higher in patients with postoperative sepsis than in patients without sepsis (two-way ANOVA p <0.0001). The best cut-off level for MR pro-ANP was determined to be 162.5 pmol/l, with a sensitivity of 100% and specificity of 68%. On the day of inclusion in the study, MR pro-ANP detected postoperative sepsis equally as well as PCT (Youden test P = 0.17). MR pro-ANP levels in patients with postoperative sepsis remained significantly elevated for 10 days, regardless of the clinical state, whereas falling levels of IL-6 and PCT indicated improvement of sepsis. The overall correlation of MR pro-ANP with IL-6 and PCT was therefore low (Pearson´s r 0.15 and 0.36, respectively). MR pro-ANP may contribute to the diagnosis of postoperative sepsis, as its level can differentiate between elevation of other inflammatory markers due to abdominal surgery alone or postoperative sepsis.

Independent effect of atrial fibrillation on natriuretic peptide release.

We investigated whether the increase of plasma natriuretic peptides (NPs) in atrial fibrillation (AF) is independent of the effect of AF on the left atrial (LA) hemodynamics. Hemodynamically stable patients scheduled for AF ablation underwent assessment of B-type natriuretic peptide (BNP) and mid-regional pro-atrial natriuretic peptide (MR-proANP), echocardiography, and direct measurement of left atrial (LA) pressure. Concentrations of the NPs were compared between patients in AF (n = 31) and controls in sinus rhythm (SR; n = 31) who were matched for age, gender, heart rate, left ventricular ejection fraction, LA volume index, and directly measured mean LA pressure. Eighteen patients underwent serial measurement of NPs and LA pressure during native SR and after 20min of pacing-induced AF. Compared to the patients in SR, the patients in AF had 2.6 times higher unadjusted BNP [median (inter-quartile range), 101 (63, 129) vs. 38 (26, 79) ng/L] and two times higher unadjusted MR-proANP [183 (140, 230) vs. 91 (67, 135) pmol/L; both p < 0.001]. Concentrations of both NPs correlated with mean LA pressure in the patients in SR (r = 0.75 for BNP and 0.62 for MR-proANP, both p < 0.001) but not in the patients in AF (r = 0.18 and 0.04, respectively, both p > 0.3). Both NPs increased significantly during induced AF [adjusted median (IQR) relative change, BNP: 27 (22; 40)%, MR-proANP: 75 (64; 99)%, both p < 0.001] without a significant change in the LA pressure. The increase of NPs in AF was independent of its effect on the LA hemodynamics.

Midregional pro-atrial natriuretic peptide, an important member of the natriuretic peptide family: potential role in diagnosis and prognosis of cardiovascular disease.

Midregional pro-atrial natriuretic peptide (MR-proANP), first isolated in 1981, is a novel peptide with multiple biological functions, especially within the cardiovascular system. This peptide plays an important role in many processes, including natriuresis, diuresis, and other physiological and pathophysiological pathways in the human body. Several electronic databases (PubMed, EBSCO, Scopus, and ScienceDirect) were analyzed in the present literature review. The aim of this study was to elucidate the wide roles of MR-proANP, which can be analyzed because of the development of a new sandwich immunoassay, and to determine the possible diagnostic and prognostic implications of MR-proANP on cardiovascular disease and other disorders. The studies discussed in this literature review provide valuable data on the role of ANP in the pathogenesis, diagnostic process, prognosis, and potential therapeutic strategies for disease. Although ANP is mainly associated with cardiovascular disease, it may be used as a biomarker in diabetology, neurology, and metabolic disorders.

Biomarkers for heart failure: small molecules with high clinical relevance.

Heart failure (HF) is a rising epidemic due to the ageing population and progress in all areas of medicine. Thus, research efforts are made to ensure a timely diagnosis, to improve prognosis and treatment of the disease and to facilitate risk prediction at the population level. Because of their noninvasive determination with mostly high sensitivity and accuracy, circulating blood biomarkers are becoming increasingly important for daily clinical practice. Natriuretic peptides, especially B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) and cardiac troponins are established blood biomarkers in HF diagnosis and prognosis of HF-related outcomes. Inflammatory molecules as C-reactive protein (CRP) may have added value in anti-inflammatory therapy guidance. Next-generation biomarkers including soluble source of tumorigenicity 2 (sST2), growth differentiation factor-15 (GDF-15), galectin-3 (Gal-3) and diverse microribonucleic acids (miRNAs) may have additional benefit in assessment of cardiac remodeling or differentiation of HF subtypes. Multimarker approaches containing different combinations of established and novel biomarkers might improve HF risk prediction at the population level once they are used on top of clinical variables.

Serum proatrial natriuretic peptide concentrations during oral glucose-induced acute hyperinsulinemia in lean and obese men

Atrial natriuretic peptide (ANP) is primarily seen as a hormone involved in salt and water homeostasis and blood pressure regulation. Evidence supports a link between metabolism and ANP. Circulating ANP concentrations are low in obese individuals with insulin resistance and hyperinsulinemia. The dynamic relationship between insulin and ANP has been sparsely studied. We therefore measured circulating concentrations of midregional proatrial natriuretic peptide (MR-proANP), a stable marker of ANP secretion, and insulin in lean and obese men during an oral glucose challenge. One hundred and three obese men (body mass index (BMI) ≥30.0 kg/m2) were compared with 27 lean men (BMI = 20.0–24.9 kg/m2). During a 75 g oral glucose challenge, circulating concentrations of MR-proANP and insulin were measured at baseline and every half hour for 2 h. Fasting MR-proANP concentrations were lower in the obese men as compared with the lean men (median (interquartile range): 51.2 (38.7–64.7) pmol/L vs. 69.3 (54.3–82.9) pmol/L, P = 0.002). During the oral glucose challenge, serum MR-proANP concentrations fell steadily in the obese men (P < 0.0001), whereas there was no significant fall in the lean men (P = 0.14). However, the time-course curves of MR-proANP did not display a clear reciprocal relation to the time-course curves of insulin. Adjusted for age, the area under curve (AUC) for MR-proANP was inversely correlated with AUC for insulin (r = −0.38, P < 0.0001). In conclusion, during an oral glucose challenge, serum MR-proANP concentrations drop significantly in obese individuals, but the time-course curves of MR-proANP do not display a reciprocal relationship to the time-course curves of insulin.

Obese Hypertensive Men Have Lower Circulating Proatrial Natriuretic Peptide Concentrations Despite Greater Left Atrial Size.

Obese persons have lower circulating natriuretic peptide (NP) concentrations. It has been proposed that this natriuretic handicap plays a role in obesity-related hypertension. In contrast, hypertensive patients with left atrial enlargement have higher circulating NP concentrations. On this background, we investigated whether obese hypertensive men could have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size. We examined 98 obese men (body mass index [BMI] ≥ 30.0 kg/m2) and 27 lean normotensive men (BMI 20.0-24.9 kg/m2). All men were healthy, medication free, with normal left ventricular ejection fraction. We measured blood pressure using 24-hour ambulatory blood pressure (ABP) recordings. Hypertension was defined as 24-hour ABP ≥ 130/80 mm Hg, and normotension was defined as 24-hour ABP < 130/80 mm Hg. We determined left atrial size using echocardiography, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP). Of the 98 obese men, 62 had hypertension and 36 were normotensive. The obese hypertensive men had greater left atrial size (mean ± SD: 28.7 ± 6.0 ml/m2) compared with the lean normotensive men (23.5 ± 4.5 ml/m2) and the obese normotensive men (22.7 ± 5.1 ml/m2), P < 0.01. Nevertheless, despite evidence of pressure-induced greater left atrial size, the obese hypertensive men had lower serum MR-proANP concentrations (median [interquartile range]: 48.5 [37.0-64.7] pmol/l) compared with the lean normotensive men (69.3 [54.3-82.9] pmol/l), P < 0.01, whereas the obese normotensive men had serum MR-proANP concentrations in between the 2 other groups (54.1 [43.6-62.9] pmol/l). Despite greater left atrial size, obese hypertensive men have lower circulating MR-proANP concentrations compared with lean normotensive men.

Increased blood pressure and aortic stiffness among abusers of anabolic androgenic steroids: potential effect of suppressed natriuretic peptides in plasma?

Abuse of anabolic androgenic steroids (AAS) is prevalent among recreational athletes and adverse effects on blood pressure (BP) and arterial stiffness could be substantial. Testosterone decreases natriuretic peptides which are key components in BP-regulation and may impair BP-homeostasis in AAS abusers. To investigate BP and aortic stiffness in relation to natriuretic peptides among current AAS abusers, former AAS abusers and controls. In this cross-sectional study, 37 current AAS abusers, 33 former AAS abusers and 30 controls were included. All participants were men involved in recreational strength training. We used 24-h BP monitoring, assessed proximal aorta distensibility index (ADI) by MRI and obtained overnight fasting blood samples to measure: midregional proatrial natriuretic peptide (MR-proANP), aldosterone, noradrenaline and copeptin. Current AAS abusers exhibited higher mean (95% confidence interval) 24-h systolic BP than controls [132 (129; 135) versus 124 (120; 128) mmHg, P = 0.005] and systolic hypertension was more frequent among current AAS abusers than controls (51 versus 17%, P = 0.009). ADI was lower among both current and former AAS abusers suggesting higher aortic stiffness; %-difference (95% confidence interval) from controls: -21% (-35; -5) and -21% (-36; -4), P < 0.05. Plasma MR-proANP was decreased, whereas aldosterone and noradrenaline were increased among current AAS abusers compared with former AAS abusers and controls. Decreased MR-proANP was independently associated with increased systolic BP and reduced ADI in multivariate linear regressions. Current AAS abusers displayed increased 24-h systolic BP and decreased plasma MR-proANP. Both current and former AAS abusers exhibited higher aortic stiffness.

B-type natriuretic peptide for prediction of incident clinically significant abdominal aortic aneurysm: A population-based prospective study.

Pathogenesis of abdominal aortic aneurysm (AAA) is unclear. The aim of this study was to evaluate inflammatory and hemodynamic plasma biomarkers as predictors for AAA in the prospective longitudinal cohort of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer Study ( n=5551; 1991-94). C-reactive protein, cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional pro-atrial natriuretic peptide (MR-proANP) and conventional risk factors at baseline were measured in patients with incident AAA during follow-up and compared to individuals without a diagnosis of AAA. Subjects were followed until 31 December 2013. Multivariable analyses were expressed in terms of hazard ratios (HR) per 1 standard deviation increment of each respective log-transformed plasma biomarker in the Cox proportional hazard models. Mean follow-up time was 20.7 years. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry and AAA was diagnosed on average 14 years later. Adjusting for age, sex, smoking, body mass index, hypertension and diabetes mellitus, N-BNP (HR 1.29; 95% CI 1.03-1.62), but not MR-proANP (HR 1.20; 95% CI 0.95-1.50), was independently associated with incident AAA. In conclusion, the plasma biomarker N-BNP was associated with future development of AAA, which implies that this marker is a sensitive indicator of early subclinical cardiovascular disease.

Midregional proatrial natriuretic peptide improves risk stratification after ischemic stroke.

To validate midregional proatrial natriuretic peptide (MR-proANP) for outcome prediction and diagnosis of cardioembolic stroke etiology compared to established clinical variables. In this prospective multicenter cohort study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours of onset. Primary outcome measures were 90-day mortality, unfavorable functional outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology diagnosed during hospitalization. Of 788 included patients, 783 completed their 90-day follow-up, and 118 patients (15%) died. After full adjustment, MR-proANP levels were associated with 90-day mortality (adjusted hazard ratio 6.12, 95% confidence interval [CI] 2.36-15.84, p = 0.01) and functional outcome (adjusted odds ratio [aOR] 2.46, 95% CI 1.05-5.74, p = 0.038). For mortality prediction, adding MR-proANP to the regression model increased its discriminatory accuracy, and the continuous net reclassification index (cNRI) was 49% (95% CI 26%-78%, p < 0.001). For functional outcome, there was no significant improvement in discrimination or reclassification. Cardioembolic stroke etiology and the diagnosis of atrial fibrillation at hospital discharge were associated with MR-proANP with an aOR of 2.10 (95% CI 1.11-3.97, p = 0.02) and 18.35 (95% CI 7.94-42.45, p < 0.001), respectively. The cNRI of MR-proANP for cardioembolic stroke etiology was not significant, as opposed to atrial fibrillation (78%, 95% CI 60%-89%, p < 0.001). MR-proANP levels ≥289 pmol/L had a specificity of 86% and sensitivity of 48% for the diagnosis of atrial fibrillation. MR-proANP is a newly validated blood biomarker providing additional prognostic information for mortality after stroke. Higher MR-proANP levels were associated with cardioembolic stroke etiology and, even more strongly, atrial fibrillation.

Diagnostic Utility of Mid-Regional Pro–Atrial Natriuretic Peptide in Patients with Heart Failure with Preserved Ejection Fraction

Diagnostic Utility of Mid-Regional Pro–Atrial Natriuretic Peptide in Patients with Heart Failure with Preserved Ejection Fraction

Acutely decompensated heart failure with preserved and reduced ejection fraction present with comparable haemodynamic congestion.

Congestion is a central feature of acute heart failure (HF) and its assessment is important for clinical decisions (e.g. tailoring decongestive treatments). It remains uncertain whether patients with acute HF with preserved ejection fraction (HFpEF) are comparably congested as in acute HF with reduced EF (HFrEF). This study assessed congestion, right ventricular (RV) and renal dysfunction in acute HFpEF, HFrEF and non-cardiac dyspnoea. We compared echocardiographic and circulating biomarkers of congestion in 146 patients from the MEDIA-DHF study: 101 with acute HF (38 HFpEF, 41 HFrEF, 22 HF with mid-range ejection fraction) and 45 with non-cardiac dyspnoea. Compared with non-cardiac dyspnoea, patients with acute HF had larger left and right atria, higher E/e', pulmonary artery systolic pressure and inferior vena cava (IVC) diameter at rest, and lower IVC variability (all P < 0.05). Mid-regional pro-atrial natriuretic peptide (MR-proANP) and soluble CD146 (sCD146), but not B-type natriuretic peptide (BNP), correlated with echocardiographic markers of venous congestion. Despite a lower BNP level, patients with HFpEF had similar evidence of venous congestion (enlarged IVC, left and right atria), RV dysfunction (tricuspid annular plane systolic excursion), elevated MR-proANP and sCD146, and renal impairment (estimated glomerular filtration rate; all P > 0.05) compared with HFrEF. In acute conditions, HFpEF and HFrEF presented in a comparable state of venous congestion, with similarly altered RV and kidney function, despite higher BNP in HFrEF.

Transient cardiac dysfunction but elevated cardiac and kidney biomarkers 24\xa0h following an ultra-distance running event in Mexican Tarahumara

BackgroundThe Mexican Tarahumara are accustomed to running ultra-distance races. No data exist on the acute physiological changes following ultra-distance running and physiological-biomarker associations in this population. Thus, we aimed to investigate the acute impact (≤ 24 h) on functional and biochemical changes of the cardiac muscle and biochemical changes associated with kidney function following a 63-km ultra-distance race with an altitude difference of 1800 m in Mexican Tarahumara athletes.MethodsTen Tarahumara male athletes (mean ± SD age = 29.9 ± 6.6 years) volunteered to participate in the study. VO2max was assessed by a sub-maximal step test individually calibrated combining heart rate and accelerometry. Standard transthoracic echocardiography methodology and venipuncture blood tests were carried out at four time points: pre-race, immediately post-race, 6 h, and 24 h post-race.ResultsEstimated mean VO2max was 54.5 (± 8.8) mL O2 min−1 kg−1 and average physiological activity intensity was 746 (± 143) J min−1 kg −1 (~ 11.5 METs). When compared to pre-race values, significant changes in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (− 15%, p < 0.001 for both parameters), cardiac output (39%, p < 0.001), and maximal longitudinal velocity (− 13%, p < 0.009) were seen post-race with LVEF also being decreased at < 6 h post-race (− 8%, p < 0.014). Plasma biomarkers mid-regional pro-atrial natriuretic peptide, copeptin-ultra sensitive, and high-sensitivity cardiac troponin T remained significantly elevated at 24 h post-race, and the two latter were inversely associated with LVEF (p < 0.04). Kidney dysfunction was indicated by increased post-race copeptin-ultra sensitive.ConclusionsThe athletes participating in this study had acute transient cardiac dysfunction as assessed by echocardiography but elevated cardiac and kidney biomarkers at 24 h following a 63-km race with extreme altitude variation.

Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS.

ContextWomen with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP.ObjectiveTo investigate if treatment with liraglutide in women with PCOS reduces levels of the cardiovascular biomarkers MR-proADM, MR-proANP and copeptin.MethodsSeventy-two overweight women with PCOS were treated with 1.8 mg/day liraglutide or placebo for 26 weeks in a placebo-controlled RCT. Biomarkers, anthropometrics, insulin resistance, body composition (DXA) and visceral fat (MRI) were examined.ResultsBaseline median (IQR) levels were as follows: MR-proADM 0.52 (0.45–0.56) nmol/L, MR-proANP 44.8 (34.6–56.7) pmol/L and copeptin 4.95 (3.50–6.50) pmol/L. Mean percentage differences (95% CI) between liraglutide and placebo group after treatment were as follows: MR-proADM −6% (−11 to 2, P = 0.058), MR-proANP −25% (−37 to −11, P = 0.001) and copeptin +4% (−13 to 25, P = 0.64). Reduction in MR-proANP concentration correlated with both increased heart rate and diastolic blood pressure in the liraglutide group. Multiple regression analyses with adjustment for BMI, free testosterone, insulin resistance, visceral fat, heart rate and eGFR showed reductions in MR-proANP to be independently correlated with an increase in the heart rate.ConclusionIn an RCT, liraglutide treatment in women with PCOS reduced levels of the cardiovascular risk biomarkers MR-proANP with 25% and MR-proADM with 6% (borderline significance) compared with placebo. The decrease in MR-proANP was independently associated with an increase in the heart rate.

Percutaneous Closure of Left Atrial Appendage affects Mid-Term Release of MR-proANP

The left atrial appendage (LAA) represents both a predisposing source of thrombus formation and of neuro-humoral haemostasis. This study aims to evaluate changes of biomarker expression before and after successful percutaneous closure of the LAA. Patients with atrial fibrillation and contraindication for oral anticoagulant therapy were enrolled. Blood samples were taken within 24 hours before (T1) and at least 6 months (mid-term) (T2) after successful implantation of LAA occlusion devices. Blood levels of high sensitivity troponin I and T (hsTnI, hsTnT), aminoterminal pro-brain natriuretic peptide (NT-proBNP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) were evaluated at both time points. A total of 42 patients with successful percutaneous LAA closure were included. Median mid-term follow-up was of 183 days. HsTnT, hsTnI and NT-proBNP did not show any significant differences over time. Serum levels of MR-proANP increased significantly between immediate pre-intervention (T1: median = 245.7 pmol/l, IQR 155.8–361.3 pmol/l) and at mid-term follow-up (T2: median = 254 pmol/l, IQR 183.4–396.4 pmol/l) (p = 0.037). These results indicate, that percutaneous LAA closure affects neuro-humoral haemostasis by increasing MR-proANP serum levels at mid-term follow-up.

Clinically Relevant Biomarkers in Acute Heart Failure: An Update.

Acute Heart Failure (AHF), owing to the difficulties in diagnosis, prognostic stratification and patient-related management, is still associated with unusually high morbidity and mortality. The advent of novel biomarkers apart from natriuretic peptides involved in myocardial injury, neuro-hormonal activation, and ventricular remodeling augurs immense hope in redefining the biomarker-based approach towards AHF. A thorough review of the available literature including latest review articles from distinguished experts, textbook references and guidelines from leading cardiological societies worldwide as well as the latest trials, encompassing various biomarkers known in AHF was conducted. The most relevant ones were chosen as references for the current review article. Biomarkers such as midregional proatrial natriuretic peptide, soluble ST2, highly-sensitive troponin, and midregional proadrenomedullin are some such examples that have passed various stages of substantiation while there is an array of potential biomarkers innascent stages like osteopontin, CTGF, GDF-15 and TGF beta-1 awaiting further reiteration. Not only the diagnosis of AHF itself but the evaluation of co-morbidities using markers like PCT, hematologic markers or acute kidney injury markers like NGAL present a new perspective to the management of AHF. This review article outlines the current status of the most relevant cardiac biomarkers related to AHF.

Relationships between Novel Biomarkers and Hemodynamics during Exercise in Heart Failure with Preserved Ejection Fraction

Introduction: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) develop pathologic hemodynamic responses during exercise. Biomarkers that reflect specific pathophysiological pathways might help to understand mechanisms in HFpEF. We hypothesized that novel biomarkers reflect hemodynamic abnormalities at rest and during exercise. Methods: Subjects with invasively-diagnosed HFpEF (n = 38) and controls free of HF (n = 20) underwent invasive catheterization at rest and during exercise with blood sample collection for assessment of novel biomarkers: hs troponin T, copeptin, NT-proBNP, mid regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), and mid regional pro-adrenomedullin (MR-proADM). Results: Compared to controls, subjects with HFpEF displayed elevations in biomarkers of myocardial injury/stress (troponin T, copeptin), myocyte stretch (NT-proBNP, MR-proANP), and neurohormonal activation (CT-proET-1, MR-proADM) both at rest and during exercise (Table 1). As compared to controls, HFpEF subjects displayed greater increases in troponin T, copeptin and NT-proBNP during exercise (Fig. A), and the increase in troponin T varied directly with changes in left filling pressures (r = 0.27, P = .04). CT-proET-1 and MR-proADM levels were highly correlated with PA mean pressures (r = 0.73 and r = 0.65, both P < .0001)(Fig. B), which were driven by both increases in left heart filling pressure (r = 0.67 and r = 0.62, both P < .0001) and pulmonary vascular resistance (r = 0.32, P = .02 and r = 0.26, P = .05). Conclusions: Biomarkers might reflect specific pathophysiology of HFpEF, including pulmonary vascular disease and an increase in filling pressure during exercise.Table 1Biomarker levels at rest and exerciseControl (n = 20)HFpEF (n = 38)PBaselinehs troponin T (pg/mL)5.2 (4.2, 8.6)12.4 (7.8, 22.3)<0.0001Copeptin (pmol/L)5.3 (3.4, 12.8)11.0 (6.0, 20.8)0.04NT-proBNP (pg/mL)100 (54, 236)436 (147, 978)0.0002MR-proANP (pmol/L)128 (90, 147)239 (139, 300)0.001CT-proET-1 (pmol/L)69 (56, 74)105 (83, 130)<0.0001MR-proADM (nmol/L)0.6 (0.5, 0.7)1.0 (0.8, 1.4)<0.0001Peak Exercisehs troponin T (pg/mL)6.3 (4.8, 9.7)13.8 (8.9, 26.2)0.0002Copeptin (pmol/L)5.8 (3.4, 9.3)14.5 (8.4, 35.1)0.001NT-proBNP (pg/mL)122 (47, 279)484 (155, 1133)0.0009MR-proANP (pmol/L)174 (128, 226)267 (184, 359)0.007CT-proET-1 (pmol/L)73 (62, 85)118 (87, 138)<0.0001MR-proADM (nmol/L)0.6 (0.5, 0.7)1.0 (0.8, 1.3)<0.0001 Open table in a new tab

Natriuretic Propeptides as Markers of Atrial Fibrillation Burden and Recurrence (from the AMIO-CAT Trial)

Natriuretic peptides are established plasma markers of systolic heart failure, but their usefulness for the evaluation of atrial fibrillation (AF) is unknown. We examined mid-regional pro-atrial natriuretic peptide (MR-proANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing ablation for AF. A subpopulation of 102 patients (median age 60 [52;65], 82% male) from the AMIO-CAT trial (Recurrence of arrhythmia following short-term oral AMIOdarone after CATheter ablation for atrial fibrillation: a double-blind, randomized, placebo-controlled study) undergoing ablation for paroxysmal (n = 55) or persistent (n = 47) AF was studied. MR-proANP and NT-proBNP were measured before ablation and at 1, 3, and 6 months' follow-up. Three-day Holter monitoring was performed before ablation, and 6 to 8 weeks and 6 months after ablation. Plasma MR-proANP and NT-proBNP concentrations were higher during AF than during sinus rhythm before ablation (188 pmol/L [131;260] vs 94 pmol/L [64;125], p <0.001; 78 pmol/L [43;121] vs 10.3 pmol/L [5.9;121], p <0.001) and at 1, 3, and 6 months' follow-up. Categories of AF burden on 3-day Holter monitoring (0%, 0% to 99%, and 99% to 100%) were associated with plasma concentrations of both MR-proANP (94 pmol/L [55;127] vs 117 pmol/L [88;185] vs 192 pmol/L [127;261], p <0.001) and NT-proBNP (10 pmol/L [5.9;22] vs 22 pmol/L [8.9;53] vs 81 pmol/L [45;116], p <0.001). In a multivariate regression analysis, however, there was no significant association between baseline propeptide concentrations and recurrence of AF at 6 months' follow-up. In conclusion, AF was associated with higher plasma concentrations of MR-proANP and NT-proBNP than sinus rhythm. Moreover, AF burden was associated with subsequent concentrations of both MR-proANP and NT-proBNP. The results suggest that natriuretic propeptide measurement reflects functional cardiac dysfunction during AF, and that AF burden should be included in biochemical assessment of left ventricular dysfunction.

Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population-based prospective study.

Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults. A population-based cohort of 5347 individuals (men, 70%; age, 69±6years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6±1.3years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis. Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P=0.002, and 1.52; 1.21-1.89; P<0.001, respectively). Risk of all-cause dementia increased across the quartiles of MR-proANP (p for linear trend= 0.004; Q4, 145-1681pmolL-1 vs. Q1, 22-77 pmolL-1 : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend=0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmolL-1 (Q3-Q4, 68-432pmolL-1 vs. Q1-Q2,4-68pmolL-1 ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors. Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia.