Mid-regional Pro-adrenomedullin Levels Research Articles

Change of mid-regional pro-adrenomedullin level in patients with chronic heart failure and its significance

Objective To study the change of mid-regional pro-adrenomedullin(MR-proADM) level in patients with chronic heart failure and its significance. Methods Randomly selected 330 patients with chronic heart failure, including 120 cases of grade Ⅱ and Ⅲ, 90 cases of grade Ⅳ, 90 cases were selected., Within 24 h after the entry of the group and 7 d after symptom relieved, serum N-terminal pro-B-type natriuretic peptide(NT-proBNP), MR-proADM, cardiac ultrasound(left ventricular diameter(LVEDD) and left ventricular function(LVEF)) were measured.Ninety physical examination in the same period as healthy control during the same period.The change of MR-proADM level in patients with chronic heart failure and its significance were analyze. Results Compared with the healthy control group, the level of MR-proADM in patients with chronic heart failure(grade Ⅱ: (641.55±106.34) pmol/l; grade Ⅲ: (684.46±101.33) pmol/l; grade Ⅳ: (737.81±479.37) pmol/l) was significantly higher than that in the control group(610.22±60.84) pmol/l), the difference was statistically significant(F=5.33, P=0.001). At the same time, the level of MR-proADM was increased with the aggravation of heart failure, after drug treatment will decline((608.09±100.81), (617.64±94.32), (642.22±163.53) pmol/L). And MR-proADM levels were significantly positively correlated with NT-proBNP levels and NYHA classification in patients with heart failure(r=0.194, P=0.003; r=0.206, P=0.000). Conclusion MR-proADM has important guiding significance in the diagnosis, classification of patients with chronic heart failure. Key words: Chronic heart failure; Mid-regional pro-adrenomedullin; Cardiac function classification

Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub-analysis of a randomized, placebo-controlled, double-blind, crossover trial.

We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: tumour necrosis factor (TNF)-α; soluble urokinase plasminogen activator receptor (suPAR); mid-regional pro-adrenomedullin (MR-proADM); mid-regional pro-atrial natriuretic peptide (MR-proANP); and copeptin, in people with type 2 diabetes with albuminuria. In a randomized, double-blind, placebo-controlled, crossover trial we enrolled people with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio [UACR] >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 . Participants received liraglutide (1.8 mg/d) and matched placebo for 12 weeks, in random order. The primary endpoint was change in albuminuria; this was a prespecified sub-study. A total of 32 participants were randomized, of whom 27 completed the study. TNF-α level was 12% (95% confidence interval [CI] 3; 20) lower after liraglutide treatment compared with placebo (P = .012); MR-proADM level was 4% (95% CI 0; 8) lower after liraglutide treatment compared with placebo (P = .038), and MR-proANP level was 13% (95% CI 4; 21) lower after liraglutide treatment compared with placebo (P = .006). In the present study, we showed anti-inflammatory effects of liraglutide treatment, reflected in reductions in levels of TNF-α and MR-proADM, while the reduction in MR-proANP levels may represent a clinically relevant benefit with regard to heart failure.

Mid-regional pro-adrenomedullin and copeptin to predict short-term prognosis of COPD exacerbations: a multicenter prospective blinded study.

BackgroundExacerbations of COPD (ECOPD) are a frequent cause of emergency room (ER) visits. Predictors of early outcome could help clinicians in orientation decisions. In the current study, we investigated whether mid-regional pro-adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation, could predict short-term outcomes.Patients and methodsThis prospective blinded observational study was conducted in 20 French centers. Patients admitted to the ER for an ECOPD were considered for inclusion. A clinical risk score was calculated, and MR-proADM and copeptin levels were determined from a venous blood sample. The composite primary end point comprised 30-day death or transfer to the intensive care unit or a new ER visit.ResultsA total of 379 patients were enrolled in the study, of whom 277 were eventually investigated for the primary end point that occurred in 66 (24%) patients. In those patients, the median (interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77–1.48) versus 0.83 nmol/L (0.63–1.07) in patients who did not meet the primary end point (P=0.0009). In contrast, copeptin levels were similar in patients who met or did not meet the primary end point (P=0.23). MR-proADM levels increased with increasing clinical risk score category: 0.74 nmol/L (0.57–0.89), 0.83 nmol/L (0.62–1.12) and 0.95 nmol/L (0.75–1.29) for the low-, intermediate- and high-risk categories, respectively (P<0.001). MR-proADM was independently associated with the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10–2.48; P=0.015). MR-proADM predicted the occurrence of primary end point with a sensitivity of 46% (95% CI, 33%–58%) and a specificity of 79% (95% CI, 74–84).ConclusionMR-proADM but not copeptin was significantly associated with outcomes at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM, alone or combined with the clinical risk score, was a moderate strong predictor of short-term outcomes.

Biomarcadores cardiacos en el síndrome de bajo gasto cardiaco en el posoperatorio de cirugía de cardiopatías congénitas en niños

Introduction and objectivesTo assess the predictive value of atrial natriuretic peptide, β-type natriuretic peptide, copeptin, mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I) as indicators of low cardiac output syndrome in children with congenital heart disease undergoing cardiopulmonary bypass (CPB). MethodsAfter corrective surgery for congenital heart disease under CPB, 117 children (aged 10 days to 180 months) wereenrolled in a prospective observational pilot study during a 2-year period. The patients were classified according to whetherthey developed low cardiac output syndrome. Biomarker levels weremeasured at 2, 12, 24, and 48hours post-CPB. The clinical data and outcome variables were analyzed by a multiple logistic regression model. ResultsThirty-three (29%) patients developed low cardiac output syndrome (group 1) and the remaining 84 (71%) patients were included in group 2. cTn-I levels>14 ng/mL 2hours after CPB (OR=4.05; 95%CI, 1.29-12.64; P=.016) and MR-proADM levels>1.5 nmol/L 24hours following CPB (OR=15.54; 95%CI, 4.41-54.71; P<.001) were independent predictors of low cardiac output syndrome. ConclusionsOur results suggest that cTn-I at 2hours post-CPB is, by itself, an evident independent early predictor of low cardiac output syndrome. This predictive capacity is, moreover, reinforced when cTn-I is combined with MR-proADM levels at 24hours following CPB. These 2 cardiac biomarkers would aid in therapeutic decision-making in clinical practice and would also enable clinicians to modify the type of support to be used in the pediatric intensive care unit.Full English text available from: www.revespcardiol.org/en

Association between Mid-Regional Proadrenomedullin Levels and Progression of Deep White Matter Lesions in the Brain Accompanying Cognitive Decline.

Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory effects and vasodilative and immunomodulatory actions that is widely distributed throughout the vascular system of the brain. To investigate mid-regional proADM (MR-proADM), a stable fragment of the ADM precursor, and cerebral deep white matter lesions (DWMLs) in association with cognitive decline. The study participants were 288 patients (194 men, 94 women) who gave consent to participate in a 5-year longitudinal survey on arteriosclerosis from 2008 to 2013. The Fazekas classification system (Grade [G] 0 [normal] to G3 [severe]) was used for the evaluation of DWMLs on brain magnetic resonance imaging (MRI). In addition, all participants were asked to undergo cognitive function tests regarding word/letter fluency, the results of which were assessed for correlations with MR-proADM levels. MR-proADM levels significantly increased with DWML grade progression. The odds ratio for high MR-proADM levels was 3.08 (95% confidence interval: 1.49-5.17) in the groups graded G3 on brain MRI, suggesting that a high level of MR-proADM is an independent risk factor for DWMLs. A significant inverse correlation was observed between MR-proADM levels and cognitive test scores. MR-proADM levels were significantly increased in the G3 group in 2013 compared with 2008. MR-proADM levels were significantly different between the DWML groups and inversely correlated with cognitive function test scores, suggesting that high MR-proADM levels and DWMLs are associated with cognitive decline. Therefore, the MR-proADM level may be an effective candidate as a potential diagnostic surrogate marker of cognitive decline.

Adrenomedullin Is Associated With Surgical Trauma and Impaired Renal Function in Vascular Surgery Patients.

Patients undergoing vascular surgery are prone to perioperative organ injury because of both higher prevalence of cardiovascular risk factors and the extent of surgery. Early detection of organ failure is essential to facilitate appropriate medical care. Midregional pro-adrenomedullin (MR-proADM) has been investigated in acute medical care settings to guide clinical decision-making regarding patient pathways and to identify patients prone to imminent cardiovascular or inflammatory complications. In this study, we evaluated the impact of perioperative MR-proADM levels as an early marker of perioperative cardiovascular and inflammatory stress reactions and kidney injury. The study was conducted as a monocentric, prospective, noninterventional trial at Hannover Medical School, Germany. A total of 454 consecutive patients who underwent open vascular surgery were followed from the day prior to until 30 days after surgery. The composite primary end point was defined as the occurrence of major adverse cardiac events (MACEs), acute kidney injury (AKI), or systemic inflammatory response syndrome (SIRS). Measurements were correlated with both medical history and postoperative MACE, AKI, or SIRS using univariate and multivariate regression analysis. One hundred thirty-nine (31%) of the patients reached the primary end point within the study interval. Midregional pro-adrenomedullin change was associated with the combined primary end point and with the intensity of surgical trauma. Midregional pro-adrenomedullin change was increased in patients reaching the secondary end points, SIRS (optimal cutoff: 0.2 nmol/L) and AKI (optimal cutoff: 0.7 nmol/L), but not in patients with MACEs. Increased levels of MR-proADM within the perioperative setting (1) were linked to the invasiveness of surgery and (2) identified patients with ongoing loss of renal function. Increased MR-proADM levels may therefore identify a subgroup of patients prone to excessive cardiovascular stress but did not directly correlate with adverse cardiac events. Consistently low levels of MR-proADM may identify a subgroup of patients with acceptable low risk to guide discharge from high-density care units.

MR-proADM: A New Biomarker for Early Diagnosis of Sepsis in Burned Patients.

Mid regional pro-adrenomedullin (MR-proADM) has been used as a marker of sepsis, but its dynamics and role in a burn injury setting has not been tested. In a prospective observational study, we included 42 consecutive patients with >15% TBSA. Daily blood specimens collected over the initial 20 days of treatment were submitted for laboratory analysis of MR-proADM and procalcitonin (PCT) via immunoluminometric sandwich assay (Kryptor, BRAHMS, Berlin, Germany). In patients with an absence of sepsis, an initial increase in MR-proADM and PCT levels was noted post-burn injury, peaking on the second day postadmission and thereafter demonstrated a continued decline in MR-proADM and PCT levels. In those patients who went on to develop sepsis (n = 27, 64.3%), the levels of MR-proADM and PCT were significantly higher (P < .001) on days categorized as septic, than on days categorized as nonseptic. The increase in PCT levels was noted on the first day to be categorized as septic. In contrast, the MR-proADM levels demonstrated an increase one day earlier. The optimal relationship between the specificity and sensitivity of MR-proADM and PCT for the detection of sepsis was an increase of 31% and at least 0.015 nmol/L (area under curve 0.76) or of >39% and at least 0.15 µg/L (area under the curve 0.83), respectively. Burn injury is associated with increased levels of MR-proADM. Subsequent increases may be considered as diagnostic of sepsis onset. In this context, PCT displayed higher specificity and sensitivity, while MR-proADM may be more suitable for the early recognition of sepsis (ClinicalTrials.gov number, NCT01055587).

Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia.

Study DesignThis study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. Index test results were compared with those derived from routine diagnostic tests, i.e., white blood cell (WBC) counts, neutrophil percentages, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels.MethodsThis prospective, multicenter study was carried out in the most important children’s hospitals (n = 11) in Italy and 433 otherwise healthy children hospitalized for radiologically confirmed CAP were enrolled. Among cases for whom etiology could be determined, CAP was ascribed to bacteria in 235 (54.3%) children and to one or more viruses in 111 (25.6%) children. A total of 312 (72.2%) children had severe disease.ResultsCRP and PCT had the best performances for both bacterial and viral CAP identification. The cut-off values with the highest combined sensitivity and specificity for the identification of bacterial and viral infections using CRP were ≥7.98 mg/L and ≤7.5 mg/L, respectively. When PCT was considered, the cut-off values with the highest combined sensitivity and specificity were ≥0.188 ng/mL for bacterial CAP and ≤0.07 ng/mL for viral CAP. For the identification of severe cases, the best results were obtained with evaluations of PCT and MR-proANP. However, in both cases, the biomarker cut-off with the highest combined sensitivity and specificity (≥0.093 ng/mL for PCT and ≥33.8 pmol/L for proANP) had a relatively good sensitivity (higher than 70%) but a limited specificity (of approximately 55%).ConclusionsThis study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard.

Cardiac Biomarkers of Low Cardiac Output Syndrome in the Postoperative Period After Congenital Heart Disease Surgery in Children

Introduction and objectivesTo assess the predictive value of atrial natriuretic peptide, β-type natriuretic peptide, copeptin, mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I) as indicators of low cardiac output syndrome in children with congenital heart disease undergoing cardiopulmonary bypass (CPB). MethodsAfter corrective surgery for congenital heart disease under CPB, 117 children (aged 10 days to 180 months) were enrolled in a prospective observational pilot study during a 2-year period. The patients were classified according to whether they developed low cardiac output syndrome. Biomarker levels were measured at 2, 12, 24, and 48 hours post-CPB. The clinical data and outcome variables were analyzed by a multiple logistic regression model. ResultsThirty-three (29%) patients developed low cardiac output syndrome (group 1) and the remaining 84 (71%) patients were included in group 2. cTn-I levels >14 ng/mL at 2hours after CPB (OR, 4.05; 95%CI, 1.29-12.64; P=.016) and MR-proADM levels>1.5 nmol/L at 24hours following CPB (OR, 15.54; 95%CI, 4.41-54.71; P<.001) were independent predictors of low cardiac output syndrome. ConclusionsOur results suggest that cTn-I at 2hours post-CPB is, by itself, an evident independent early predictor of low cardiac output syndrome. This predictive capacity is, moreover, reinforced when cTn-I is combined with MR-proADM levels at 24hours following CPB. These 2 cardiac biomarkers would aid in therapeutic decision-making in clinical practice and would also enable clinicians to modify the type of support to be used in the pediatric intensive care unit.

Inflammation versus mechanical stretch biomarkers over time in acutely decompensated heart failure with reduced ejection fraction

Heart failure can be associated with inflammation but it is unclear if inflammation is directly related to hemodynamic worsening or is an independent pathway. Our aim was to investigate inflammation and mechanical stress using serial measurements of biomarkers in acute and chronic heart failure with reduced ejection fraction (AHF and CHF). MethodThe following biomarkers were measured on admission, at discharge and one month after discharge: B-type natriuretic peptide (BNP), high-sensitivity C-Reactive protein (hsCRP), Tumour Necrosis Factor alpha (TNFα), interleukin 6 (IL6), myeloperoxidase (MPO), suppression of tumorigenicity 2 (ST2), mid-regional pro-adrenomedullin (MR-proADM), galectin 3 (Gal3), Growth differentiating factor 15 (GDF15) and procalcitonin (PCT). ResultsIn control CHF group (n=20, 69±11y, NYHA 1–2), most biomarker levels were low and stable over time. In AHF (n=55, 71±14y), BNP, ST2 and GDF15 levels were highly increased on admission and then decreased rapidly with clinical improvement; BNP, ST2 and GDF15 levels were statistically correlated (r=0.64, 0.46 and 0.39; p<0.001 for both). Both hsCRP, MPO, TNFα and Gal3 levels were increased in most AHF patients (70, 56, 83 and 98% respectively) with poor change over time. HsCRP, MPO and TNFα levels were correlated. IL6, MR-proADM and PCT levels were slightly increased, without change over time. Highest quartiles of BNP and ST2 were associated with death or readmission at one year (HR 2.33 [95CI 1.13–4.80] and 2.42 [1.27–4.60]). ConclusionAHF is associated with systemic inflammation. This inflammatory response continued up to one month after discharge despite normalisation of mechanical stress-related markers.

Prognostic value of different biomarkers for cardiovascular death in unselected older patients in the emergency department.

Risk stratification of elderly patients presenting with heart failure (HF) to an emergency department (ED) is an unmet challenge. We prospectively investigated the prognostic performance of different biomarkers in unselected older patients in the ED. We consecutively enrolled 302 non-surgical patients ⩾70 years presenting to the ED with a wide range of cardiovascular and non-cardiovascular comorbid conditions. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), ultrasensitive C-terminal pro-arginine-vasopressin (Copeptin-us) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of HF after reviewing all available baseline data using circulating NT-proBNP levels. A final diagnosis of HF was found in 120 (40%) of the 302 patients. All patients were followed up for cardiovascular death within the following 12 months. In order to test the prognostic performance of the investigated biomarkers we used boosting models with age and sex as mandatory covariates. Boosting is a statistical learning technique with built-in variable selection developed to obtain sparse and interpretable prediction models. Follow-up was 100% complete. During a median follow-up time of 225 days (interquartile range (IQR) 156-319 days), 30 (9.9%) of 302 patients (aged 81±6 years) had cardiovascular deaths. Of these 30 patients, 21 had HF and nine had no HF diagnosed prior to admission. The boosting model selected MR-proADM and hs-cTNT as predictors of cardiovascular deaths. The median values of MR-proADM and hs-cTnT at presentation were significantly higher in patients with cardiovascular deaths compared to surviving patients during follow-up (2.56 nmol/L (IQR 1.62-4.48) vs. 1.11 nmol/L (IQR 0.83-1.80), P<0.001 and 81 ng/L (IQR 38-340) vs. 17 ng/L (IQR 0.9-38), P=0.004). One unit increase in the log-transformed MR-proADM levels was associated with a 1.99-fold risk of death (95% confidence interval (CI) 1.61-2.45, P<0.001). The second marker, hs-cTnT, showed an increased predicted risk but was not significantly correlated to event-free survival (hazard ratio 3.22, 95% CI 0.97-10.68, P=0.056). Within different biomarkers, MR-proADM was the only predictor of cardiovascular deaths in unselected older patients presenting to the ED.

New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure

Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator. It has been described high levels in septic patients, interacting directly with the relaxation of vascular tone, triggering hypotension of these patients. It is also found high levels in other diseases such as hypertension, heart failure, respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels and clearance marker to the 2nd-5th days of admission help to determine the poor performance and the risk of mortality in patients with severe sepsis admitted to the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C-reactive protein (CRP) levels to determine an unfavorable outcome and the risk of mortality in patients with sepsis admitted to the ICU. It has also proved useful in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM levels are independent of the germ conversely it is related to the magnitude of organ failure and therefore severity. We consider advisable incorporating the MR-proADM the panel of biomarkers necessary for the diagnosis and treatment of critically ill patients admitted to the ICU with severe sepsis. The combined PCT and MR-proADM levels could represent a valid tool in the clinical practice to timely identify patients with bacterial infections and guide the diagnosis and treatment of sepsis and septic shock.

Prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with community-acquired pneumonia: a systematic review and meta-analysis.

BackgroundThe early identification of patients at risk of dying from community-acquired pneumonia (CAP) is critical for their treatment and for defining hospital resource consumption. Mid-regional pro-adrenomedullin (MR-proADM) has been extensively investigated for its prognostic value in CAP. However, the results are conflicting. The purpose of the present meta-analysis was to explore the diagnostic accuracy of MR-proADM for predicting mortality in patients suffering from CAP, particularly emergency department (ED) patients.MethodWe systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if a 2 × 2 contingency table could be constructed based on both the MR-proADM level and the complications or mortality of patients diagnosed with CAP. The prognostic accuracy of MR-proADM in CAP was assessed using the bivariate meta-analysis model. We used the Q-test and I2 index to evaluate heterogeneity.ResultsMR-proADM displayed moderate diagnostic accuracy for predicting complications in CAP, with an overall area under the SROC curve (AUC) of 0.74 (95 % CI: 0.70–0.78). Eight studies with a total of 4119 patients in the emergency department (ED) were included. An elevated MR-proADM level was associated with increased risk of death from CAP (RR 6.16, 95 % CI 4.71–8.06); the I2 value was 0.0 %, and a fixed-effects model was used to pool RR. The pooled sensitivity and specificity were 0.74 (95 % CI: 0.67–0.79) and 0.73 (95 % CI: 0.70–0.77), respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.8 (95 % CI, 2.3–3.3) and 0.36 (95 % CI, 0.29–0.45), respectively. In addition, the diagnostic odds ratio (DOR) was 8 (95 % CI, 5–11), and the overall area under the SROC curve was 0.76 (95 % CI, 0.72–0.80).ConclusionsOur study has demonstrated that MR-proADM is predictive of increased complications and higher mortality rates in patients suffering from CAP. Future studies are warranted to determine the prognostic accuracy of MR-proADM in conjunction with severity scores or other biomarkers and to determine an optimal cut-off level.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1566-3) contains supplementary material, which is available to authorized users.

Association of metabolic complications with plasma mid-regional pro-adrenomedullin level in stable kidney transplant recipients

BackgroundRecently, increased plasma mid-regional pro-adrenomedullin (MR-proADM) concentrations have been demonstrated in patients with chronic renal failure. In this study, we attempted to identify significant clinical factors associated with MR-proADM concentration in stable kidney transplant recipients. MethodsForty-seven Japanese kidney transplant recipients who underwent transplantation >180days prior to the study were analyzed. To facilitate comparability of anti-hypertensive regimens across recipients taking different drugs, we calculated the treatment intensity score of anti-hypertensive drugs in each recipient. Morning blood samples were collected and plasma MR-proADM concentrations were measured using an enzyme immunoassay. ResultsMultiple regression analysis identified treatment intensity score for anti-hypertensive drugs, serum albumin, creatinine clearance and use of lipid-lowering agents as significant independent factors associated with plasma MR-proADM concentration. Adjusted coefficient of determination for this model was 0.46. ConclusionApart from indicating lowered renal function, plasma MR-proADM concentration may be a useful biomarker for metabolic disorders, especially hypertension and hyperlipidemia, in stable kidney transplant patients.

Diagnostic and prognostic usefulness of mid-regional pro-adrenomedullin levels in patients with severe sepsis

Mid-regional pro-adrenomedullin (MR-proADM) is a fragment of 48 amino acids which splits from the final proADM molecule in a ratio of 1:1 with ADM. It is essentially irrelevant, but proportionally represents the levels and activity of ADM. Its half-life is several hours longer, and its plasma concentrations can be determined in clinical practice. It has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis.

Plasma mid-regional pro-adrenomedullin levels are inversely associated with anxiety but unrelated to depression: Results from the observational DIAST-CHF study in patients with cardiovascular risk factors

ObjectivesIt has been postulated that patients with heart failure have a high risk of ventricular arrhythmias and sudden cardiac death resulting from anxiety-induced autonomic arousal. In the prospective and multicenter DIAST-CHF (Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure) study, we therefore, tested the hypothesis that adrenomedullin (ADM), a well-established predictor for cardiovascular outcome, is associated with self-rated anxiety symptoms in patients at risk of suffering from or actually with overt heart failure. Participants and measuresStudy participants with risk factors for diastolic dysfunction were requested to complete the Hospital Anxiety and Depression Scale (HADS), and plasma mid-regional pro-adrenomedullin (MR-proADM) concentrations were measured. ResultsIn bivariate analysis, we found significantly lower plasma MR-proADM levels in patients with elevated HADS-anxiety scores above the clinically relevant cut-off level of ≥11 (n=118, 536pmol/l, interquartile range [IQR] 449–626) as compared to non-anxious study participants (n=1,292, 573pmol/l, IQR 486–702, p=0.001). A set of multivariate models adjusted for potential confounders confirmed the negative association between self-rated anxiety symptoms and plasma MR-proADM. In similar models, no significant association was detected between HADS-depression scores and MR-proADM. ConclusionsThe inverse relationship between plasma MR-proADM and anxiety observed in patients with cardiovascular risk factors supports a previous experimental study using a mutant mouse line with a brain-specific loss of ADM expression which displayed hyperactive and over-anxious behavior. Further experimental and clinical studies are warranted to test the hypothesis that also in humans ADM acts as a neuromodulator with anxiolytic properties.

Biomarkers of hemodynamic stress and aortic stiffness after STEMI: a cross-sectional analysis.

Aim. Increased aortic stiffness might adversely affect cardiac structure, function, and perfusion. Release of biomarkers of hemodynamic stress is thought to be enhanced by these alterations. We aimed to evaluate the association between biomarkers of hemodynamic stress and aortic stiffness assessed at a chronic stage after ST-segment elevation myocardial infarction (STEMI). Methods. Fifty-four patients four months after STEMI were enrolled in this cross-sectional, single-center study. N-terminal pro–B-type natriuretic peptide (NT-proBNP), mid-regional pro–A-type natriuretic peptide (MR-proANP), and mid-regional proadrenomedullin (MR-proADM) levels were measured by established assays. Aortic stiffness was assessed by the measurement of pulse wave velocity using phase-contrast cardiovascular magnetic resonance. Results. NT-proBNP, MR-proANP, and MR-proADM concentrations were all correlated with aortic stiffness in univariate analysis (r = 0.378, r = 0.425, and r = 0.532; all P < 0.005, resp.). In multiple linear regression analysis, NT-proBNP (β = 0.316, P = 0.005) and MR-proADM (β = 0.284, P < 0.020) levels were associated with increased aortic stiffness independently of age, blood pressure, and renal function. NT-proBNP was the strongest predictor for high aortic stiffness (area under the curve: 0.82, 95% CI 0.67–0.96). Conclusion. At a chronic stage after STEMI, concentrations of biomarkers for hemodynamic stress, especially NT-proBNP, are positively correlated with aortic stiffness. These biomarkers might also be useful as predictors of high aortic stiffness after STEMI.

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Objectives Plasma levels of adrenomedullin (AM), an anti-inflammatory, vasodilatory peptide hormone, are physiologically elevated during a healthy pregnancy, but it is uncertain whether these levels are altered during complications of pregnancy like preeclampsia. A byproduct of the preprohormone of AM, midregional pro-adrenomedullin (MR-proADM), is produced in a one-to-one ratio with mature AM and can be measured as a surrogate analyte for AM. Therefore, we tested the hypothesis that MR-proADM can serve as a biomarker for preeclampsia. Methods We selected 30 women with preeclampsia and 30 normotensive controls from a prospective study that collected blood and tissue samples as patients presented to Duke University Hospital for delivery. Exclusion criteria were: mild preeclampsia ( n = 5), postpartum plasma collection ( n = 12), twin pregnancies ( n = 3), and smokers ( n = 7). Endoglin, placental growth factor (PlGF), and MR-proADM concentrations were quantified in plasma using a commercial ELISA kit or immunofluorescent assay. Endoglin, PlGF, and MR-proADM were then analyzed as biomarkers of severe preeclampsia by comparing the areas under the curve (AUC) of receiver operating characteristic (ROC) curves generated by logistic regression models of these analytes. Results MR-proADM concentrations were blunted in plasma from women with severe preeclampsia (Matson et al., 2014). In our dataset, endoglin (AUC = 0.73) and MR-proADM (AUC = 0.69) were similarly effective at classifying women with severe preeclampsia and controls, while PlGF was more informative (AUC = 0.85). Endoglin and MR-proADM together (AUC = 0.80) discriminate patients from controls better than they do individually, as do PlGF and MR-proADM together (AUC = 0.87). Conclusions MR-proADM can classify women with severe preeclampsia and controls and may provide a biomarker for severe preeclampsia. However, analysis of MR-proADM levels at earlier gestational ages is needed to determine whether MR-proADM can predict the development of preeclampsia later in pregnancy. Disclosures B. Matson: Research Support Recipient: Ferring Innovation Fellowship. N. Karpinich: None. A. Murtha: None. W. Valdar: None. C.A. Grotegut: None. K.M. Caron: Research Support Recipient; Commercial Interest: Ferring Pharmaceuticals, Inc.

Mid-regional proadrenomedullin levels predict recurrence of atrial fibrillation after catheter ablation

BackgroundWe evaluated the prognostic value of mid-regional proadrenomedullin (MR-proADM) in atrial fibrillation (AF) patients undergoing radiofrequency ablation. MethodsPlasma concentrations of MR-proADM were measured at baseline and after 12months in 87 AF patients in whom radiofrequency ablation was performed. The association between MR-proADM and AF recurrence was tested by univariable and multivariable Cox models. ResultsIn all 87 patients radiofrequency ablation was successfully performed. Of the total population 54% had paroxysmal AF. The mean left ventricular ejection fraction was 54% (minimum 25%). After 12months of follow-up, 71% of the patients were free of AF recurrence. At baseline, mean MR-proADM in the total population was 0.72nmol/l±0.22. Patients with AF recurrence had significantly higher baseline MR-proADM (0.89nmol/l±0.29) as compared with patients without AF recurrence (0.65nmol/l±0.14; p<0.001). After 12months, mean MR-proADM plasma concentration remained higher in patients with AF recurrence (0.81nmol/l±0.22 as compared with patients free of AF 0.54nmol/l±0.20; p<0.001). Receiver operating characteristic (ROC) curve analysis for MR-proADM yields a specificity of 98% and a sensitivity of 64% with an optimal cut-off value of 0.82nmol/l to predict recurrence of AF after catheter ablation. In the logistic regression analysis only MR-proADM remained independently predictive for AF recurrence. ConclusionThis is the first study revealing the association between MR-proADM elevation before ablation and poor outcomes after ablation of AF. Larger studies are needed to validate these results.

Prognostic value of pro-adrenomedullin, procalcitonin and C-reactive protein in predicting outcome of febrile urinary tract infection

Bacterial infections such as febrile urinary tract infection (fUTI) may run a complicated course that is difficult to foretell on clinical evaluation only. Because the conventional biomarkers erythrocyte sedimentation rate (ESR), leucocyte count, C-reactive protein (CRP) and procalcitonin (PCT) have a limited role in the prediction of a complicated course of disease, a new biomarker—plasma midregional pro-adrenomedullin (MR-proADM)—was evaluated in patients with f UTI. We conducted a prospective multicentre cohort study including consecutive patients with f UTI at 35 primary-care centres and eight emergency departments. Clinical and microbiological data were collected and plasma biomarker levels were measured at presentation to the physician. Survival was assessed after 30 days. Of 494 fUTI patients, median age was 67 (interquartile range 49-78) years, 40% were male; two-thirds of them had significant co-existing medical conditions. Median MR-proADM level was 1.42 (interquartile range 0.67-1.57) nM; significantly elevated MR-proADM levels were measured in patients with bacteraemia, those admitted to the intensive care unit, and in 30-day and 90-day non-survivors, compared with patients without these characteristics. The diagnostic accuracy for predicting 30-day mortality in fUTI, reflected by the area-under-the-curve of receiver operating characteristics were: MR-proADM 0.83 (95% CI 0.71-0.94), PCT 0.71 (95% CI 0.56-0.85); whereas CRP, ESR and leucocyte count lacked diagnostic value in this respect. This study shows that MR-proADM assessed on first contact predicts a complicated course of disease and 30-day mortality in patients with fUTI and in this respect has a higher discriminating accuracy than the currently available biomarkers ESR, CRP, PCT and leucocyte count.