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

Abstract

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.     

Biomarker dynamics in cardiac surgery: a prospective observational study on MR-proADM,MR-proANP,hs-CRP and sP-selectin plasma levels in the perioperative period

Abstract

Background: For many biomarkers in cardiac surgery, there is a lack of knowledge regarding the normal dynamics of plasma levels during the perioperative course. The aim of this study was to investigate the perioperative dynamics of MR-proADM, MR-proANP, hs-CRP and sP-selectin in cardiac surgery.

Method: A prospective observational pilot study with 20 patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB). Plasma samples were taken for each patient and biomarker during the pre-, per- and postoperative period until Day 6 postoperatively.

Results: MR-proADM increased significantly from 0.62 [IQR; 0.54–0.93]?nmol/L preoperatively to 1.20 [1.04–1.80]?nmol/L postoperative Day 1. MR-proANP increased significantly from 125 [77–152]?pmol/L preoperatively to 198 [168–307]?pmol/L on weaning from CPB. hs-CRP increased significantly from 2.5?mg/L [0.4–12] preoperatively to peak at 208?mg/L [186–239] postoperative Day 3. The preoperative level of sP-selectin at 23.0 [21.3–26.3]?ng/mL initially fell at weaning from CPB, followed by a significant peak of 25.5 [22.7–27.7]?ng/mL 8?h postoperatively.

Conclusions: The findings in this study may help to understand the physiology of the biomarkers analysed and their response to cardiac surgical trauma including CPB. Furthermore, these findings will guide us in further research on the clinical usefulness of these biomarkers.     

Diagnostic utility of MR-proANP and NT-proBNP in elderly outpatients with a high risk of heart failure: the Copenhagen heart failure risk study

Abstract

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.

Methods: This prospective study included 399 outpatients. Inclusion criteria were: age?≥?60?years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.

Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N?=?12 LVEF?≤?40%, N?=?7 LVEF?>?40% to ≤50%, N?=?46 LVEF?>?50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p?=?0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p?<?0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC?=?0.886; p?<?0.001) and NT-proBNP (AUC?=?0.910; p?<?0.001) compared to patient-reported symptoms of HF (AUC?=?0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p?=?0.022).

Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.     

Midregional-proAtrial Natriuretic Peptide and High Sensitive Troponin T Strongly Predict Adverse Outcome in Patients Undergoing Percutaneous Repair of Mitral Valve Regurgitation

Background

It is not known whether biomarkers of hemodynamic stress, myocardial necrosis, and renal function might predict adverse outcome in patients undergoing percutaneous repair of severe mitral valve insufficiency. Thus, we aimed to assess the predictive value of various established and emerging biomarkers for major adverse cardiovascular events (MACE) in these patients.

Methods

Thirty-four patients with symptomatic severe mitral valve insufficiency with a mean STS-Score for mortality of 12.6% and a mean logistic EuroSCORE of 19.7% undergoing MitraClip therapy were prospectively included in this study. Plasma concentrations of mid regional-proatrial natriuretic peptide (MR-proANP), Cystatin C, high-sensitive C-reactive protein (hsCRP), high-sensitive troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), galectin-3, and soluble ST-2 (interleukin 1 receptor-like 1) were measured directly before procedure. MACE was defined as cardiovascular death and hospitalization for heart failure (HF).

Results

During a median follow-up of 211 days (interquartile range 133 to 333 days), 9 patients (26.5%) experienced MACE (death: 7 patients, rehospitalization for HF: 2 patients). Thirty day MACE-rate was 5.9% (death: 2 patients, no rehospitalization for HF). Baseline concentrations of hsTnT (Median 92.6 vs 25.2 ng/L), NT-proBNP (Median 11251 vs 1974 pg/mL) and MR-proANP (Median 755.6 vs 318.3 pmol/L, all p<0.001) were clearly higher in those experiencing an event vs event-free patients, while other clinical variables including STS-Score and logistic EuroSCORE did not differ significantly. In Kaplan-Meier analyses, NT-proBNP and in particular hsTnT and MR-proANP above the median discriminated between those experiencing an event vs event-free patients. This was further corroborated by C-statistics where areas under the ROC curve for prediction of MACE using the respective median values were 0.960 for MR-proANP, 0.907 for NT-proBNP, and 0.822 for hsTnT.

Conclusions

MR-proANP and hsTnT strongly predict cardiovascular death and rehospitalization for HF in patients undergoing percutaneous repair of mitral valve insufficiency. Both markers might be useful components in new scoring systems to better predict short- and potentially long-term mortality and morbidity after MitraClip procedure.     

Biomarker response and therapy prediction in renal denervation therapy – the role of MR-proadrenomedullin in a multicenter approach

Background: Renal denervation has been proposed as a therapeutic option in patients with resistant hypertension. Circulating blood borne biomarkers might be helpful to identify individuals responding to RDN therapy. MR-proADM is a strong prognostic marker in patients with cardiovascular disease. The aim of this multicenter study was to evaluate the effect of RDN on MR-proADM concentrations.

Methods and results: We measured MR-proADM, BNP, and MR-proANP in 110 patients before and after RDN in a multicenter setting. All patients were followed up after 1 and 6 months by office and ambulatory blood pressure (BP) measurements. The mean office BP decreased from 165/89 to 152/87?mmHg 6 months after RDN (systolic: p?<?0.001; diastolic: ns), the responder-rate was 74%. Intriguingly MR-proADM concentrations increased from 0.66 to 0.69?nmol/L (p?<?0.001) and were significantly associated with reduction of systolic office BP after 6 months in multivariate analyses (coefficient ?0.0018, p?<?0.001). In therapy-responders MR-proADM concentrations showed a significantly higher increase over time (coefficient 0.0105, p?<?0.05), as compared to non-responders. There were no significant differences in BP change for individuals with low and high baseline MR-proADM (BP-Delta low MR-proADM ?23/?4?mmHg vs. high MR-proADM ?24/?5?mmHg). The natriuretic biomarkers BNP and MR-proANP did not change significantly after 6 months. Biomarkers at baseline were not able to predict for therapy-responder.

Conclusion: In patients undergoing RDN, baseline measurements of various biomarkers had no prognostic use for therapy success in this short time follow-up period in a multicenter approach. Intriguingly, MR-proADM showed a significant association with BP reduction after 6 months.     

How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

Background

High N-terminal pro-brain-type natriuretic peptide levels have been associated with a lower risk of type 2 diabetes mellitus (T2D). However, less is known about other cardiac stress biomarkers in this context. Here we evaluated the association of mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine vasopressin (copeptin), C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM) with incident T2D and changes in glucose metabolism.

Methods

We performed a prospective cohort study using data from the population-based KORA F4/FF4 study. 1773 participants (52.3% women) with MR-proANP measurements and 960 (52.7% women) with copeptin, CT-proET-1 and MR-proADM measurements were included. We examined associations of circulating plasma levels of MR-proANP, copeptin, CT-proET-1 and MR-proADM with incident T2D, the combined endpoint of incident prediabetes/T2D and with fasting and 2 h-glucose, fasting insulin, HOMA-IR, HOMA-B and HbA1c at follow-up. Logistic and linear regression models adjusted for age, sex, waist circumference, height, hypertension, total/HDL cholesterol ratio, triglycerides, smoking, physical activity and parental history of diabetes were used to compute effect estimates.

Results

During a median follow-up time of 6.4 years (25th and 75th percentiles: 6.0 and 6.6, respectively), 119 out of the 1773 participants and 72 out of the 960 participants developed T2D. MR-proANP was inversely associated with incident T2D (odds ratio [95% confidence interval]: 0.75 [0.58; 0.96] per 1-SD increase of log MR-proANP). Copeptin was positively associated with incident prediabetes/T2D (1.29 [1.02; 1.63] per 1-SD increase of log copeptin). Elevated levels of CT-proET-1 were associated with increased HOMA-B at follow-up, while elevated MR-proADM levels were associated with increased fasting insulin, HOMA-IR and HOMA-B at follow-up. These associations were independent of previously described diabetes risk factors.

Conclusions

High plasma concentrations of MR-proANP contributed to a lower risk of incident T2D, whereas high plasma concentrations of copeptin were associated with an increased risk of incident prediabetes/T2D. Furthermore, high plasma concentrations of CT-proET-1 and MR-proADM were associated with increased insulin resistance. Our study provides evidence that biomarkers implicated in cardiac stress are associated with incident T2D and changes in glucose metabolism.

     

Kinetics of c-reactive protein (CRP) and serum amyloid A protein (SAA) in patients with community-acquired pneumonia (CAP), as presented with biologic half-life times

Context: In management of community-acquired pneumonia (CAP), excellent biomarkers for inflammation would be helpful in our practice.

Objectives: Kinetics of c-reactive protein (CRP) and serum amyloid A (SAA) was characterized, using their biologic half-life times.

Materials and methods: Time course of CRP and SAA levels in the successfully treated 36 CAP patients were investigated and their half-life times were determined and compared.

Results & Discussions: SAA and CRP declined in an exponential mean and the biologic half-life times of SAA levels was 34.9?±?28.7?h, significantly shorter than that of CRP, 46.4?±?21.7?h (p?=?0.0014). Conclusion: The kinetic evidence, presented as biologic half-life times of CRP and SAA, helps us make a clinical assessment of CAP patients.     

Relationship between plasma copeptin levels and complications of community-acquired pneumonia in preschool children

High plasma copeptin level has been associated with clinical outcomes after acute illness. The present study was undertaken to investigate the plasma copeptin concentrations in preschool children with community-acquired pneumonia (CAP) and to analyze the correlations of copeptin with CAP-related complications and pleural effusion. Plasma copeptin concentrations of 100 healthy children and 165 preschool children with CAP were measured. 35 children (21.2%) presented with complicated CAP and 28 children (17.0%) presented with pleural effusion. The admission copeptin levels were significantly increased in all patients (49.7 ± 21.4 pmol/L), children with complicated CAP (73.0 ± 16.9 pmol/L), those with uncomplicated CAP (43.4 ± 17.8 pmol/L), those with pleural effusion (70.9 ± 17.4 pmol/L) and those without pleural effusion (45.3 ± 19.5 pmol/L) compared with healthy control individuals (9.0 ± 2.7 pmol/L, all P < 0.001). Multivariate logistic regression analysis showed that plasma copeptin levels were independently related to CAP-related complications (odds ratio 1.214, 95% confidence interval 1.104–1.872, P < 0.001) and pleural effusion (odds ratio 1.226, 95% confidence interval 1.109–1.917, P < 0.001). A receiver operating characteristic curve analysis showed plasma copeptin level better predicted CAP-related complications (area under curve 0.876, 95% confidence interval 0.815–0.922) and pleural effusion (area under curve 0.831, 95% confidence interval 0.765–0.885). Thus, plasma copeptin level may represent a novel biomarker for predicting CAP-related complications in preschool children.     

Copeptin levels are independent of ingested nutrient type after standardised meal administration – the CoMEAL study

Abstract

Context/objective: To clarify ambiguous published data, we determined whether standardized nutrient intake influences serum copeptin concentrations.

Materials/methods: Thirty healthy volunteers underwent oral glucose tolerance testing (OGTT) and mixed-meal tolerance testing (MMTT), respectively drinking 300?ml/237?ml of glucose-containing or fat/protein/carbohydrate-containing fluid. Copeptin was measured 30?min pre-(“baseline”)–180?min post-fluid intake.

Results: Median [25th–75th percentile] copeptin fell from 4.9 [3.6–8.3]/4.9 [3.6–7.1] pmol/l at OGTT/MMTT baselines to 3.2 (2.8–5.9)/4.1 (2.7–6.1) pmol/l at post-OGTT/post-MMTT nadirs (150?min/120?min; p?<?0.001, linear mixed-effect modeling).

Discussion/conclusions: Regardless of nutrient type ingested, copeptin did not increase, suggesting values can be interpreted independently of prandial status.     

An observational study on disturbed peripheral circadian rhythms in hemodialysis patients

The quality of life of hemodialysis (HD) patients is hampered by reduced nocturnal sleep quality and excessive daytime sleepiness. In addition to the sleep/wake cycle, levels of circadian biomarkers (e.g. melatonin) are disturbed in end-stage renal disease (ESRD). This suggests impaired circadian clock performance in HD patients, but the underlying mechanism is unknown. In this observational study, diurnal rhythms of sleep, serum melatonin and cortisol concentrations and clock gene mRNA expression are compared between HD patients (n?=?9) and healthy control subjects (n?=?9). In addition, the presence of circulating factors that might affect circadian rhythmicity is tested in vitro with cell culture experiments. Reduced sleep quality (median sleep onset latency [interquartile range] of 23.9 [17.3]?min for patients versus 5.0 [10] minutes for controls, p?<?0.01; mean (± SD) sleep efficiency 70.2?±?8.1% versus 82.9?±?10.9%, p?=?0.02 and mean awake minutes after sleep onset 104.8?±?27.9 versus 54.6?±?41.6 minutes, p?= 0.01) and increased daytime sleepiness (mean Epworth Sleepiness Score of 10.0?±?4.8 versus 3.9?±?2.0, p?<?0.01) were confirmed in HD patients. Reduced nocturnal melatonin concentrations (1 AM: 98.1 [122.9] pmol/L versus 12.5 [44.2] pmol/L, p?= 0.019; 5 AM: 114.0 [131.6] pmol/L versus 11.8 [86.8] pmol/L, p?= 0.031) and affected circadian control of cortisol rhythm and circadian expression of the clock gene REV-ERBα were found. HD patient serum had a higher capacity to synchronize cells in vitro, suggesting an accumulated level of clock resetting compounds in HD patients. These compounds were not cleared by hemodialysis treatment or related to frequently used medications. In conclusion, the abovementioned results strongly suggest a disturbance in circadian timekeeping in peripheral tissues of HD patients. Accumulation of clock resetting compounds possibly contributes to this. Future studies are needed for a better mechanistic understanding of the interaction between renal failure and perturbation of the circadian clock.     

Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study

BackgroundElevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl.MethodsWe conducted a population-based cohort study using data from Danish medical registries during 1998–2014. The study included 25,017 patients with a cancer diagnosis and Cbl levels of 200–600 pmol/L (reference/normal range), 601–800 pmol/L and >800 pmol/L measured up to one year prior to diagnosis, and a comparison cohort of 61,988 cancer patients without a plasma Cbl measurement. Patients treated with Cbl were excluded. Survival probability was assessed using Kaplan–Meier curves. Mortality risk ratios (MRR) were computed using Cox proportional hazard regression, adjusted for age, sex, calendar year, cancer stage and comorbidity, scored using the Charlson comorbidity index.ResultsSurvival probabilities were lower among patients with elevated Cbl levels than among patients with normal levels and among members of the comparison cohort [(1-year survival,%) Cbl: 200–600 pmol/L: 69.3%; 601–800 pmol/L: 49.6%; >800 pmol/L: 35.8%; comparison cohort: 72.6%]. Thirty-day mortality was elevated for patients with Cbl levels of 601–800 pmol/L or >800 pmol/L, compared to patients with levels of 200–600 pmol/L [(MRR (95% confidence interval): 601–800 pmol/L vs. 200–600 pmol/L: 1.9 (1.6–2.2); >800 pmol/L vs. 200–600 pmol/L: 2.7 (2.4–3.1)]. This association remained robust for 31–90-day and 91–365-day mortality, showing similar dose-response patterns.ConclusionCancer patients with elevated Cbl levels had higher mortality than those with normal Cbl levels. These findings may have clinical significance for assessing the prognosis of cancer patients.     

Growth hormone for risk stratification and effects of therapy in acute myocardial infarction

Abstract

Context: Excess growth hormone (GH) is associated with early mortality.

Objectives: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies.

Methods: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1?±?12.8 years).

Results: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04–26.28] μg/L) compared to event-free survivors (0.59 [0.02–21.6], p?<?0.0005). In multivariate Cox survival analysis, GH was a significant predictor of MACE (hazard ratios 1.43, p?=?0.026 and 1.49, p?=?0.01, respectively) with significant interactions with beta blocker therapy (p?=?0.047) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) therapy (p?=?0.016).

Conclusions: GH levels post-AMI are prognostic for MACE and may indicate those patients who benefit from beta blocker and ACE/ARB therapy.     

Leptin to high-molecular-weight adiponectin ratio is independently correlated with carotid intima-media thickness in men,but not in women

Background: The leptin:adiponectin ratio (L:A ratio) is an independent predictor of carotid intima-media thickness (CIMT).

Objective: To evaluate whether the leptin:high-molecular-weight adiponectin ratio (L:HA ratio) is associated with CIMT in the general population.

Methods: We investigated the relationship between the L:HA ratio and CIMT in 233 Japanese study participants (106 men and 127 women).

Results: After adjustment for confounding factors, CIMT was significantly correlated with the log L:HA ratio (β?=?0.11, p?=?0.014) in men, whereas no correlation was observed in women (β?=?0.01, p?=?0.50).

Conclusion: The L:HA ratio is closely correlated with CIMT in men, but not in women.     

CAP Binding Sites Reveal Pyrimidine-Purine Pattern Characteristic of DNA Bending

Abstract

To investigate the intrinsic bending of DNA at sites where proteins bind, we analyzed catabolite gene activator protein (CAP) binding sites and various operators from the viewpoint of DNA bending flexibility. Theoretical conformational analysis, DNase I digestion and x-ray crystallography data indicate that bending of B-DNA is highly anisotropic and sequence-dependent. Certain dimers prefer to bend into the major groove (“major-philic”) and others prefer to bend into the minor groove (“minor-philic” dimers). From these data we considered TA CG, CA:TG and GG:CC as major-philic dimers and AT, AA:TT and GT:AC as minor-philic ones.

Analysis of 31 CAP binding sites has identified strong major-philic tendencies 5–7 base pairs (bp) away from the center. In addition, we found minor-philic poly-A tracts extending 4–5 bp away from the proposed major-philic bends. Finally, to analyze the central regions we followed the lead of Shumilov and classified the DNA sites by their spacer lengths [V.Y. Shumilov, Mol. Biol. (Mosk) 21, 168–187 (1987)]. In this way, we identified two subsets of CAP binding sites: one with 6 bp between the TGTGA:TCACA consensus boxes (N6-set) and one with 8 central bp (N8-set). We discovered that the dimer at the center of an N6-set site was usually major-philic, whereas at the center of an N8-set site more often minor-philic. Analysis of phages 434, P22, λ and trp operators revealed similar results.

In conclusion, our data show that CAP binding sites have major-philic and minor-philic dimers at specific positions; the location of these dimers may facilitate wrapping of DNA around CAP. A similar pattern is seen in nucleosomes.     

Prognostic value of PCT,copeptin, MR-proADM,MR-proANP and CT-proET-1 for severe acute dyspnea in the emergency department: the BIODINER study

Context: Acute dyspnea is a frequent complaint in patients attending the emergency department (ED).

Objective: To evaluate the accuracy of PCT, MR-proANP, MR-proADM, copeptin and CT-proET1 for the risk-stratification of severe acute dyspnea patients presenting to the ED.

Methods: Multicenter prospective study in adult patients with a chief complaint of acute dyspnea. Pro-hormone type biomarkers concentrations were measured on arrival. Combined primary endpoint was a poor outcome.

Results: Three hundred and ninety-four patients were included, 137 (35%) met the primary endpoint. MR-proADM was the only biomarker associated with the primary endpoint (odds ratio 1.43 [95%CI: 1.13–1.82], p?=?0.003) as were the presence of paradoxical abdominal breathing (odds ratio 2.48 [95%CI: 1.31–4.68]) or cyanosis (odds ratio 3.18 [1.46–6.89])

Conclusions: In patients with severe acute dyspnea in the ED, pro-hormone type biomarkers measurements have a low added value to clinical signs for the prediction of poor outcome.     

Circulating chromogranin B levels in patients with acute respiratory failure: data from the FINNALI Study

Purpose: Circulating chromogranin B (CgB) levels are increased in situations characterized by systemic and myocardial stress, but whether CgB provides prognostic information in patients with acute respiratory failure (ARF) is unknown.

Methods: We included 584 patients with ARF, defined as ventilatory support?>6?h, and with blood samples available on Intensive Care Unit (ICU) admission and day 3 (n?=?479). CgB levels were measured by radioimmunoassay and follow-up was 90 days.

Results: One-hundred-sixty-nine patients (29%) died during follow-up. Admission CgB levels separated non-survivors from survivors: median 1234 (Q1-3 989–1742) vs. 917 (753–1224) pmol/L, respectively, p?<?0.001. CgB levels on ICU admission (logarithmically transformed) were associated with time to death after adjustment for established risk indices available on ICU admission, including N-terminal pro-B-type natriuretic levels: HR 2.62 (95%C.I. 1.82–3.77), p?<?0.001. Admission CgB levels also improved prognostication on top of SOFA and SAPS II scores as assessed by Cox regression analyses and the category-free net reclassification index. The area under the curve (AUC) for admission CgB levels to separate survivors and non-survivors was 0.72 (95%CI 0.67–0.76), while the AUC on day 3 was 0.60 (0.54–0.66).

Conclusions: CgB levels measured on ICU admission provided additional prognostic information to established risk indices in ARF patients.     

Copeptin,resistant hypertension and renal sympathetic denervation

Background: Renal denervation is used as a treatment option for patients with resistant hypertension. But only a subgroup of patients benefits from renal sympathetic denervation (RDN). Biomarkers might be helpful to identify patients who respond to RDN. Copeptin as a surrogate for vasopressin levels is increased in hypertension and other cardiovascular diseases. This study aims to evaluate the effect of RDN on Copeptin and its prognostic value for response to RDN.

Method and results: A total of 40 patients have been included in the study. The responder rate was 47.5% on 24?h ambulatory blood pressure measurements. The mean systolic 24?h blood pressure dropped from 152?±?10?mmHg to 147?±?17?mmHg (p?=?.044) in the six month follow up. The mean baseline level of Copeptin was 7.4?pmol/l (interquartile range 3.7–11.6) for responders and 8.4?pmol/l (interquartile range 5.7–11–8) for non-responders (p?=?.53). The Copeptin levels did not change over time after renal denervation.

Conclusion: Baseline measurements of Copeptin in patients undergoing RDN for resistant hypertension have no predictive value for response to RDN. Despite lowering the blood pressure RDN has no influence on Copeptin levels in this short time follow up period.     

Comparison of temporal changes in established cardiovascular biomarkers after acute coronary syndrome between Caucasian and Chinese patients with diabetes mellitus

Abstract

Background: Population means of conventional cardiovascular biomarkers are known to differ between ethnic groups. In this study we performed detailed comparisons in the temporal pattern of these biomarkers between Caucasian and Chinese diabetic patients with acute coronary syndrome (ACS).

Methods: We studied differences in temporal changes of established cardiovascular biomarkers, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, cardiac Troponin T (TnT), NT-proBNP and C-reactive protein (CRP), in 48 Chinese and 48 clinically matched Caucasian patients with type 2 diabetes mellitus who were admitted for ACS. Blood samples were collected at regular time intervals during 30?days to 1?year after the index ACS.

Results: In the >30?day post ACS period, mean serum levels of LDL (2.16 vs. 1.47?mmol/L; p-value <0.001), total cholesterol (4.08 vs. 3.11?mmol/L; p-value <0.001), TnT (11.0 vs. 7.76?ng/L; p-value 0.010) and CRP (2.0 vs. 0.78?mg/L; p-value <0.001) were systematically higher in Caucasian than in Chinese patients. HDL and NT-proBNP levels were similar.

Conclusions: Our study showed clinically relevant differences in levels of established cardiovascular biomarkers between Caucasian and Chinese post ACS patients. Further cross-ethnic studies are warranted to determine secondary prevention treatment biomarker targets in specific populations.     

MR-proADM and MR-proANP levels in patients with acute pulmonary embolism

BackgroundThe aim of this study was to determine levels of Mid-regional Pro-adrenomedullin (MR-proADM) and Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) in patients with acute pulmonary embolism (PE), the relationship between these parameters and the risk classification in addition to determining the relationship between 1and 3month mortality.Methods82 PE patients and 50 healthy control subjects were included in the study. Blood samples for Mr-proANP and Mr-proADM were obtained from the subjects prior to the treatment. Risk stratification was determined according to sPESI (Simplified Pulmonary Embolism Severity Index). Following these initial measurements, cases with PE were assessed in terms of all causative and PE related mortalities.ResultsThe mean serum Mr-proANP and Mr-proADM levels in acute PE patients were found to be statistically higher compared to the control group (p < 0.001, p < 0.01; respectively) and statistically significantly higher in high-risk patients than low-risk patients (p < 0.01, p < 0.05; respectively). No statistical difference was determined in high-risk patients in case of sPESI compared to low-risk patients while hospital mortality rates were higher. It was determined that the hospital mortality rate in cases with Mr-proANP ≥ 123.30 pmol/L and the total 3-month mortality rate in cases with Mr-proADM ≥ 152.2 pg/mL showed a statistically significant increase.ConclusionsThis study showed that Mr-proANP and MRproADM may be an important biochemical marker for determining high-risk cases and predicting the mortality in PE patients and we believe that these results should be supported by further and extensive studies.     

Copeptin,B-type natriuretic peptide and cystatin C are associated with incident symptomatic PAD

Purpose: The aim of this study is to evaluate plasma biomarkers as predictors for peripheral arterial disease (PAD).

Materials and methods: Prospective longitudinal cohort study of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (MDCS) (n?=?5550; 1991–94). Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriuretic peptide (MR-proANP), mid-regional proadrenomedullin (MR-proADM), and conventional risk factors were measured at baseline. The diagnosis of symptomatic PAD was validated in 97% of the cases.

Results: Cumulative incidence of PAD during median follow up of 23.4?years was 4.4% (men 5.9%, women 3.3%). Adjusted for age, sex, smoking, body mass index, hypertension, diabetes mellitus and total cholesterol, copeptin (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.19–1.80), N-BNP (HR 1.28; 95% CI 1.11–1.48), and cystatin C (HR 1.19; 95% CI 1.10–1.29) were independently associated with incident PAD. Subjects with the three biomarkers copeptin, N-BNP, and cystatin C in the highest quartiles, ran a high risk of incident PAD (HR 3.29; 95% CI 1.76–6.17) compared to those with no biomarker in the highest quartile.

Conclusion: Copeptin, N-BNP, and cystatin C were associated with incident symptomatic PAD, implying that these biomarkers are sensitive indicators of early subclinical PAD.

• Clinical significance

• First prospective longitudinal cohort study evaluating Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriuretic peptide (MR-proANP), and mid-regional proadrenomedullin (MR-proADM) as predictors for peripheral arterial disease (PAD).

• Copeptin, N-BNP, and Cystatin C where independently associated with incident symptomatic PAD after adjustment for conventional risk factors.

• Copeptin, N-BNP, and Cystatin C seem to be sensitive indicators of early subclinical PAD.