Pro Natriuretic Peptide Research Articles

Characterizing heart failure with preserved and reduced ejection fraction: An imaging and plasma biomarker approach.

IntroductionThe pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. We aimed to characterize HFpEF compared to heart failure with reduced ejection fraction (HFrEF) and asymptomatic hypertensive or non-hypertensive controls.Materials and methodsProspective, observational study of 234 subjects (HFpEF n = 140; HFrEF n = 46, controls n = 48, age 73±8, males 49%) who underwent echocardiography, cardiovascular magnetic resonance imaging (CMR), plasma biomarker analysis (panel of 22) and 6-minute walk testing (6MWT). The primary end-point was the composite of all-cause mortality and/or HF hospitalization.ResultsCompared to controls both HF groups had lower exercise capacity, lower left ventricular (LV) EF, higher LV filling pressures (E/E’, B-type natriuretic peptide [BNP], left atrial [LA] volumes), more right ventricular (RV) systolic dysfunction, more focal and diffuse fibrosis and higher levels of all plasma markers. LV remodeling (mass/volume) was different between HFpEF (concentric, 0.68±0.16) and HFrEF (eccentric, 0.47±0.15); p<0.0001. Compared to controls, HFpEF was characterized by (mild) reductions in LVEF, more myocardial fibrosis, LA remodeling/dysfunction and RV dysfunction. HFrEF patients had lower LVEF, increased LV volumes, greater burden of focal and diffuse fibrosis, more RV remodeling, lower LAEF and higher LA volumes compared to HFpEF. Inflammatory/fibrotic/renal dysfunction plasma markers were similarly elevated in both HF groups but markers of cardiomyocyte stretch/damage (BNP, pro-BNP, N-terminal pro-atrial natriuretic peptide and troponin-I) were higher in HFrEF compared to HFpEF; p<0.0001. Focal fibrosis was associated with galectin3, GDF-15, MMP-3, MMP-7, MMP-8, BNP, pro-BNP and NTproANP; p<0.05. Diffuse fibrosis was associated with GDF-15, Tenascin-C, MMP-2, MMP-3, MMP-7, BNP, proBNP and NTproANP; p<0.05. Composite event rates (median 1446 days follow-up) did not differ between HFpEF and HFrEF (Log-Rank p = 0.784).ConclusionsHFpEF is a distinct pathophysiological entity compared to age- and sex-matched HFrEF and controls. HFpEF and HFrEF are associated with similar adverse outcomes. Inflammation is common in both HF phenotypes but cardiomyocyte stretch/stress is greater in HFrEF.

Midregional pro atrial natriuretic peptide: a novel important biomarker for noise annoyance-induced cardiovascular morbidity and mortality?

BackgroundEnvironmental noise exposure has been associated with increased cardiovascular morbidity and mortality. Recently, noise annoyance was shown to induce atrial fibrillation, which was accompanied by significantly increased levels of midregional pro atrial natriuretic peptide (MR-proANP). Therefore, the aim of the present study was to analyze the association between noise annoyance, MR-proANP, incident cardiovascular events, and all-cause mortality.MethodsLevels of MR-proANP were measured in the first 5000 participants of the population-based Gutenberg Health Study. Annoyance was assessed separately for aircraft, road traffic, railway, neighborhood, and industrial/construction noise during the day and sleep.ResultsIn cross-sectional analyses, aircraft noise annoyance during day and sleep, industrial/construction noise annoyance during day, and railway noise annoyance during sleep were independently associated with increased levels of MR-proANP after multivariable adjustment. After a 5-year follow-up period, there were 43 cases of incident atrial fibrillation and 103 of incident cardiovascular disease (comprising atrial fibrillation, coronary artery disease, myocardial infarction, heart failure, or stroke). Moreover, there were 301 deaths after a mean follow-up of 7.42 ± 1.66 years. An odds ratio (OR) of 2.82 ([95% confidence interval (CI) 1.86; 4.35], p < 0.0001) for incident atrial fibrillation and an OR of 1.49 ([95% CI 1.13; 1.96], p = 0.0046) for incident cardiovascular disease per 1-standard deviation (SD) increase in MR-proANP levels were found. A 36% (hazard ratio: 1.36 [95% CI 1.19; 1.55], p < 0.0001) higher risk of death was found per 1-SD increase in MR-proANP levels.ConclusionsNoise annoyance may contribute to cardiovascular morbidity and mortality and is characterized by increased levels of MR-proANP.Graphic abstract

Body Composition Indices and Cardiovascular Risk in Type 2 Diabetes. CV Biomarkers are not Related to Body Composition.

BackgroundThis study aims to explore the correlations of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and body composition with levels of asymmetric dimethylarginine (ADMA), endothelin 1(ET-1), N-terminal brain natriuretic pro-peptide (NT-proBNP) and calculated cardiovascular risks.Methods102 women and 67 men with type 2 diabetes participated. Serum levels of NT-proBNP were measured by electro-hemi-luminescence while ELISA were used for ADMA and ET-1. Cardiovascular risks were calculated using the Framingham Risk Score (FRS), the UKPDS 2.0 and the ADVANCE risk engines. Statistical analysis was performed on an IBM SPSS 19.0.ResultsThe BMI outperformed all other indices of obesity (WC, WHtR, WHR), as well as body composition parameters (body fat%, fat mass, fat free mass and total body water) in relation to the estimated risks for coronary heart disease and stroke, based on different calculators. The correlations of the obesity indices with the serum cardiovascular biomarkers were not significant except for BMI and fat mass versus ET-1, and for fat free mass and total body water versus ADMA.ConclusionsThe WC, WHR, WHtR, BF%, FM and FFM apparently do not add significant information related to the levels of cardiovascular biomarkers or the calculated CV-risks.

Abstract 51: Effects of Dietary Patterns on Subclinical Cardiac Damage: Results From the DASH Trial

Background: The Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruit (F), vegetables (V), low-fat dairy, and fiber, and reduced in saturated fat and cholesterol) lowered blood pressure (BP) and low-density lipoprotein cholesterol after 8 weeks compared with a typical American diet. However, direct effects on cardiovascular damage are unknown. Hypothesis: The DASH diet reduces cardiac injury, strain, and inflammation compared to a typical American diet. Methods: The DASH feeding study was a 3-arm, parallel-design, randomized controlled trial of adults with systolic BP (SBP) &lt;160 mm Hg and diastolic BP (DBP) of 80-95 mm Hg, without cardiovascular disease (CVD) and not taking BP medications. Participants were randomized to 8 weeks of monitored feeding with: a typical American diet with 3.6 servings of F/V per day (ref), a F/V-enriched diet (8.5 servings of F/V per day), or the DASH diet (9.6 servings of F/V per day). Calories were adjusted to keep weight constant throughout feeding. We compared the effects of these diets on 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI), N-terminal b-type pro natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP), measured in stored serum collected at baseline and after feeding. Results: Of the 257 participants with available specimens, 33% were aged &gt;50 yrs, 48% were women, and 56% were non-white. Mean baseline SBP/DBP was 131/85 mmHg. Compared to control, the F/V-enriched diet reduced hs-cTnI by 53% (95% CI: 18, 73; P = 0.008) and NT-proBNP by 24% (95% CI: 7, 38; P = 0.01) ( Figure ). Similarly, compared to control, DASH reduced hs-cTnI by 49% (95% CI: 11, 71; P = 0.02) and NT-proBNP by 20% (95% CI: 2, 35; P = 0.04). Hs-CRP did not differ between diets, and none of the markers differed between DASH and F/V-enriched diets. Conclusions: In adults with high BP but not CVD, both F/V-enriched and DASH diets lowered sensitive markers of cardiac injury and strain over 8 weeks. Our study demonstrates early, direct cardiovascular benefits from diets rich in F/V.

MR PROANP MEASURED AT ADMISSION IS ASSOCIATED WITH INCIDENT AF AFTER STEMI

Atrial fibrillation (AF) is common following ST-segment elevation myocardial infarction (STEMI) and is associated with increased morbidity and mortality. Increased blood levels of the prohormone mid-regional pro atrial natriuretic peptide (MR-proANP) have been associated with a higher incidence of

Low-density lipoprotein receptor-related protein 1 deficiency in cardiomyocytes reduces susceptibility to insulin resistance and obesity

BackgroundLow-density lipoprotein receptor-related protein 1 (LRP1) plays a key role in fatty acid metabolism and glucose homeostasis. In the context of dyslipemia, LRP1 is upregulated in the heart. Our aim was to evaluate the impact of cardiomyocyte LRP1 deficiency on high fat diet (HFD)-induced cardiac and metabolic alterations, and to explore the potential mechanisms involved. MethodsWe used TnT-iCre transgenic mice with thoroughly tested suitability to delete genes exclusively in cardiomyocytes to generate an experimental mouse model with conditional Lrp1 deficiency in cardiomyocytes (TNT-iCre+-LRP1flox/flox). FindingsMice with Lrp1-deficient cardiomyocytes (cm-Lrp1−/−) have a normal cardiac function combined with a favorable metabolic phenotype against HFD-induced glucose intolerance and obesity. Glucose intolerance protection was linked to higher hepatic fatty acid oxidation (FAO), lower liver steatosis and increased whole-body energy expenditure. Proteomic studies of the heart revealed decreased levels of cardiac pro-atrial natriuretic peptide (pro-ANP), which was parallel to higher ANP circulating levels. cm-Lrp1−/− mice showed ANP signaling activation that was linked to increased fatty acid (FA) uptake and increased AMPK/ ACC phosphorylation in the liver. Natriuretic peptide receptor A (NPR-A) antagonist completely abolished ANP signaling and metabolic protection in cm-Lrp1−/− mice. ConclusionsThese results indicate that an ANP-dependent axis controlled by cardiac LRP1 levels modulates AMPK activity in the liver, energy homeostasis and whole-body metabolism.

Placental Overexpression of Soluble CORIN in Preeclampsia

Preeclampsia (PE) is a hypertensive disease of pregnancy associated with substantial maternal and fetal morbidity and mortality. CORIN is a transmembrane type II serine protease expressed in cardiomyocytes that converts pro-atrial natriuretic peptide into atrial natriuretic peptide, a cardiac hormone that regulates blood pressure. High levels of soluble CORIN have been reported in PE and are supposed to be cardiac in origin. We hypothesized that during pregnancy soluble CORIN is released by the syncytiotrophoblast and that increased levels of soluble CORIN in preeclampsia originate from placenta. A total of 375 patients (181 PE patients and 194 controls) were analyzed. High levels of soluble CORIN were confirmed in maternal blood from preeclamptic pregnancies compared with controls. Differentiated primary villous cytotrophoblasts showed that CORIN was expressed (mRNA and protein levels) and secreted by trophoblastic cells, mostly by the syncytiotrophoblast. Finally, placental explants showed a significant increase in CORIN production and secretion in PE cases compared with controls. This study showed that CORIN is secreted by trophoblastic cells and that high levels of soluble CORIN in preeclampsia have a placental origin.

Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry.

Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking. We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001). The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.

Heart of the World's Top Ultramarathon Runner-Not Necessarily Much Different from Normal.

The impact of ultramarathon (UM) runs on the organs of competitors, especially elite individuals, is poorly understood. We tested a 36-year-old UM runner before, 1–2 days after, and 10–11 days after winning a 24-h UM as a part of the Polish Championships (258.228 km). During each testing session, we performed an electrocardiogram (ECG), transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (MRI), cardiac 31P magnetic resonance spectroscopy (31P MRS), and blood tests. Initially, increased cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were identified. The day after the UM, increased levels of white blood cells, neutrophils, fibrinogen, alanine aminotransferase, aspartate aminotransferase, creatine kinase, C-reactive protein, and N-terminal type B natriuretic propeptide were observed. Additionally, decreases in hemoglobin, hematocrit, cholesterol, LDL-C, and hyponatremia were observed. On day 10, all measurements returned to normal levels, and cholesterol and LDL-C returned to their baseline abnormal values. ECG, TTE, MRI, and 31P MRS remained within the normal ranges, demonstrating physiological adaptation to exercise. The transient changes in laboratory test results were typical for the extreme efforts of the athlete and most likely reflected transient but massive striated muscle damage, liver cell damage, activation of inflammatory processes, effects on the coagulation system, exercise-associated hyponatremia, and cytoprotective or growth-regulatory effects. These results indicated that many years of intensive endurance training and numerous UMs (including the last 24-h UM) did not have a permanent adverse effect on this world-class UM runner’s body and heart. Transient post-competition anomalies in laboratory test results were typical of those commonly observed after UM efforts.

The use of low-dose intermittent levosimendan infusion therapy as bridge-to-left ventricular assist device in advanced chronic heart failure secondary to isolated cardiac sarcoidosis

Heart failure (HF) is a progressive condition that usually involves a debilitating late course with poor health-related quality of life and increasing mortality rate. In this report, we demonstrate the efficacy and safety of intermittent levosimendan infusion as a bridging therapy to left ventricular assist device use in a patient suffering from cardiac sarcoidosis who failed to respond to optimized medical therapy. Levosimendan was administered in an outpatient infusion-therapy facility every 2 weeks as a single intravenous infusion over 6 h at dose and rate of 0.2 μg/kg/min not proceeded by a bolus. The primary observation we are reporting is the efficacy of this approach reflected on serum concentrations of N-terminal brain natriuretic propeptide and creatinine levels. Secondary observation comprised patient-reported outcomes and clinical events including hospitalization (s).

Elevated MR-proANP plasma concentrations are associated with sepsis and predict mortality in critically ill patients

Background and aimsMid-regional pro atrial natriuretic peptide (MR-proANP) is an established biomarker for heart failure, based on its key role in regulating homeostasis of water balance and blood pressure. The aim of the study was to determine the value of MR-proANP as a clinical biomarker in critical illness and/or sepsis. Upon admission to the medical intensive care unit (ICU), we investigated MR-proANP plasma concentrations in 217 critically ill patients (144 with sepsis, 73 without sepsis). Results were compared with 65 healthy controls.ResultsMR-proANP plasma levels were significantly elevated in critically ill patients, when compared to healthy controls. Notably, MR-proANP levels were significantly higher in ICU patients with sepsis. MR-proANP levels were not associated with metabolic comorbidities like diabetes or obesity. In critically ill patients, MR-proANP plasma concentrations correlated with inflammatory cytokines, markers of organ dysfunction and several adipocytokines, such as resistin, retinol-binding protein 4 (RBP4) and adiponectin. Importantly, high MR-proANP plasma levels were associated with mortality, as MR-proANP levels above 227.0 pmol/l indicated a particularly increased mortality risk in ICU patients. The association between MR-proANP and mortality was independent of single organ failure and inflammation markers.ConclusionOur study emphasizes the role of circulating MR-proANP as a biomarker in critically ill patients, in which high MR-proANP indicates organ dysfunction, sepsis and mortality risk. The association between high MR-proANP and inflammatory as well as adipose tissue-derived endocrine mediators warrants further pathophysiological investigations.

Multidisciplinary team management of carcinoid heart disease.

Carcinoid heart disease (CHD) is a consequence of valvular fibrosis triggered by vasoactive substances released from neuroendocrine tumours, classically in those with metastatic disease and resulting in tricuspid and pulmonary valve failure. CHD affects one in five patients who have carcinoid syndrome (CS). Valve leaflets become thickened, retracted and immobile, resulting most often in regurgitation that causes right ventricular dilatation and ultimately, right heart failure. The development of CHD heralds a significantly worse prognosis than those patients with CS who do not develop valvular disease. Diagnosis requires a low threshold of suspicion in all patients with CS, since symptoms occur late in the disease process and clinical signs are difficult to elicit. As a result, routine screening is recommended using the biomarker, N-terminal pro-natriuretic peptide, and regular echocardiography is then required for diagnosis and follow-up. There is no direct medical therapy for CHD, but the focus of non-surgical care is to control CS symptoms, reduce tumour load and decrease hormone levels. Valve surgery improves long-term outcome for those with severe disease compared to medical management, although peri-operative mortality remains at between 10 and 20% in experienced centres. Therefore, care needs to be multidisciplinary at all stages, with clear discussion with the patient and between teams to ensure optimum outcome for these often-complex patients.

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

The 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. 82 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. The 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. This 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.

Impact of parturition on maternal cardiovascular and neuronal integrity in a high risk cohort \u2013 a prospective cohort study

BackgroundTo better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke.MethodsThe study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data.ResultsPlacental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median [interquartile range]) increased significantly post-partum: 49.4 (34.7–77.8) vs 27.7 (16.7–31.4) pg/ml (p < 0.0001). Antepartum NfL was the sole independent predictor of NfL peri-partum change; mode of delivery, duration of labor, clinical characteristics and other biomarkers were all unrelated. Antepartum NfL levels were themselves independently predicted only by maternal age.ConclusionsParturition per se increases maternal serum NfL levels, suggesting a possible impact of parturition on maternal neuronal integrity.

Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction.

A fundamental tenet of heart failure (HF) pathophysiology hinges on a propensity for fluid retention leading to blood volume (BV) expansion and hemodilution. Whether this can be applied to heart failure patients with preserved ejection fraction (HFpEF) remains uncertain. The present study sought to determine BV status and key hormones regulating fluid homeostasis and erythropoiesis in HFpEF patients. BV and hemoglobin mass (Hbmass) were determined with high‐precision, automated carbon monoxide (CO) rebreathing in 20 stable HFpEF patients (71.5 ± 7.3 years, left ventricular ejection fraction = 55.7 ± 4.0%) and 15 healthy age‐ and sex‐matched control individuals. Additional measurements comprised key circulating BV‐regulating hormones such as pro‐atrial natriuretic peptide (proANP), copeptin, aldosterone and erythropoietin (EPO), as well as central hemodynamics and arterial stiffness via carotid–femoral pulse wave velocity (PWV). Carotid–femoral PWV was increased (+20%) in HFpEF patients versus control individuals. With respect to hematological variables, plasma volume (PV) did not differ between groups, whereas BV was decreased (−14%) in HFpEF patients. In consonance with the hypovolemic status, Hbmass was reduced (−27%) in HFpEF patients, despite they presented more than a twofold elevation of circulating EPO (+119%). Plasma concentrations of BV‐regulating hormones, including proANP (+106%), copeptin (+99%), and aldosterone (+62%), were substantially augmented in HFpEF patients. HFpEF patients may present with hypovolemia and markedly reduced Hbmass, underpinned by a generalized overactivation of endocrine systems regulating fluid homeostasis and erythropoiesis. These findings provide a novel perspective on the pathophysiological basis of the HFpEF condition.

Atrial natriuretic peptide predicts disease progression and digital ulcers development in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients. Seventy patients were enrolled (64 women and six men; mean age 56.7 ± 14 years) with a disease duration of 11.1 ± 8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan-Meier and Cox regression analyses. Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development. Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.

Dyspnoea symptom intensity and impact on health-related quality of life in patients with cardiovascular or pulmonary diseases: a longitudinal observational study

Introduction: Dyspnoea is a prevalent symptom associated with significantly reduced health-related quality of life (HRQoL). Accurate estimates of the severity and intensity of dyspnoea using standard tools in the clinic are important for the assessment of the severity of symptoms at later follow ups. Objectives: The current study had two aims. First, we sought to determine one-year changes in dyspnoea and health-related quality of life in patients with cardiac or respiratory diseases. Second, we sought to analyse the long-term associations between one-dimensional measurement methods and a generic instrument reflecting the multi-dimensionality of dyspnoea using the Short-Form Health Survey (SF-36). Methods: We prospectively recruited adult dyspnoeic patients in a rural primary health care centre. Participants were assessed for demographics, symptoms, medications, and N-terminal B-Type natriuretic pro-peptide (Nt-proBNP) level, and underwent spirometry and echocardiography. Results were analysed at baseline and one-year after enrolment. Based on the assessment results, we categorized the patients into one of three groups as the underlying disorder for dyspnoea: cardiovascular, pulmonary or psychiatric disease. Results: The ordinal scales [New York Heart Association (NYHA), modified Medical Research Council (mMRC) and Verbal Rating Scale (VRS)] indicated a slight but not significant decrease in dyspnoea severity, whereas the VAS showed a significant reduction in dyspnoea severity (p = 0.001) overall as well as in the cardiovascular group. By contrast, patients with pulmonary disease showed no improvement. HRQoL, as determined by the eight domains of SF-36, was unchanged, and dyspnoea severity had no impact on the worsening of health status. The correlation coefficient by test-re-test (reliability) of values at baseline and at the end of the study was highly significant. Conclusion: As appropriate measurements for the assessment of dyspnoea using one-dimensional scales, both mMRC and VAS should be considered for measuring changes in dyspnoea severity. VAS should be considered particularly for long-term changes in dyspnoeic patients with cardiovascular disorders. Changes in the different domains of the SF-36 were not seen after one year.

P4628A multiple biomarker approach for risk assessment after ST-segment elevation myocardial infarction

Abstract Background Several biomarkers independently predict outcome following ST-segment elevation myocardial infarction (STEMI). We hypothesized that combining information from multiple circulating biomarkers with numerous pathophysiological pathways may improve biomarker risk stratification following a STEMI. Method This was a prospective study of 735 patients with STEMI treated with primary percutaneous coronary intervention. Seventeen biomarkers were drawn before revascularization, including adrenalin, noradrenalin, C-reactive protein (CRP), neutrophil gelatinase-associated lipocalin (NGAL), pro-atrial natriuretic peptide (pro-ANP), alfa-defensin, adiponectin, troponin I, hemoglobin, thrombocyte, and total leukocyte count. The primary outcome was a composite of cardiovascular death or heart failure (CVD/HF) identified by national registries. In the effort to identify the best model, the population was randomly split into two equally sized groups, a derivation cohort and a validation cohort. We used classification and regression tree (CART) analysis to develop a risk model. The identified risk model was hereafter applied to the whole cohort. Results Mean age was 63 years, 74% were male and 33% had hypertension. During a median follow-up time of 5.0 years (3.2; 5.0), we observed 185 primary events. After including all biomarkers in the initial model, the CART analysis created a risk model including pro-ANP, NGAL, and CRP (Figure 1a). The risk of CVD/HF increased incrementally with increasing risk group (Figure 1b). The risk remained significantly higher in groups 3 and 4 after multivariable adjustments (hazard ratio (HR)=3.38 [95% confidence interval (CI): 1.60; 7.16] p=0.001 and HR=6.55 [95% CI: 2.73; 15.76] p&lt;0.001, respectively) when compared with group 1. Figure 1 Conclusion We developed a risk model based on multiple biomarkers (NGAL, CRP, and pro-ANP) determined from a CART analysis which may ease risk stratification after STEMI. Acknowledgement/Funding Sif Rasmussen received a scholarship grant from Herlev &amp; Gentofte Hospital and the P. Carl Petersens Fond during preparation of this manuscript.

P4449Incident cardiovascular disease in patients with type 2 diabetes: Established cardiovascular disease versus traditional risk markers

Abstract Background/Introduction It is well established that patients with both T2D and established cardiovascular disease (CVD) are at high-risk of a re-event and should be treated with either a glucagon-like peptide-1 (GLP-1) analogue or a sodium-glucose transporter-2 (SGLT-2) inhibitor. Other high-risk patients with T2D may also benefit from these treatments. Whether traditional risk markers can identify patients with T2D without CVD with a similar incidence of CVD events as patients with T2D with established CVD is unknown. Purpose To compare the CVD incidence in patients with T2D with and without established CVD, stratified according to mid-regional pro-atrial natriuretic peptide (MR-proANP), albuminuria, electrogardiogram (ECG), echocardiography and age, to identify patients without established CVD who are at high risk of a CVD event. Methods In this prospective cohort study, patients with T2D (n=921) from a specialized diabetes clinic were examined at baseline regarding the different risk markers. Increasing cut-offs for MR-proANP were analysed to identify high-risk patients. Albuminuria included both micro- and macroalbuminuria. An abnormal ECG was defined as the presence of ST-/T-changes, bundle branch block or atrial fibrillation, and an abnormal echocardiography was defined as either heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Established CVD was reported at baseline as prior myocardial infarction, coronary revascularization, cerebrovascular disease or peripheral artery disease. Information regarding CVD events was retrieved through national registers and a CVD event was similarly defined as established CVD, but in addition also included hospitalisation for heart failure and CVD death. Results In total, 224 (24%) patients had established CVD at baseline. Median [interquartile range] of follow-up was 4.7 [4.0–5.3] years. The incidence of CVD events among patients with established CVD was 95.7 per 1000-person years. Using a cut-off for MR-proANP of 190 pmol/l revealed that patients with a value above had similar incidence (93.9 per 1000-person years) and was found in 47 of 697 (6.7%) patients without CVD. In contrast, patients without CVD and with albuminuria (146 of 685 (21.3%) patients) or abnormal ECG (147 of 679 (21.6%)) or abnormal echocardiography (221 of 618 (35.7%)) or an age&gt;65 years (335 of 697 (35.7%)) had substantial lower incidence (47.1, 35.1, 32.7 and 33.7 per 1000-person years, respectively). Kaplan-Meier curves Conclusion(s) In patients with T2D without established CVD, using a range of traditional risk markers, we were only able to identify a subgroup of patients with MR-proANP values above 190 pmol/l who had a similar high incidence of CVD as T2D patients with established CVD. This subgroup may benefit from treatment with a GLP-1 analog or a SGLT-2 inhibitor. In contrast, the presence of other traditional risk markers in T2D was not associated with risk of incident CVD similar to patients with established CVD. Acknowledgement/Funding Thermo Fisher Scientific (Germany) funded the MR-proANP kits

Effect of Early vs Delayed Activation of Thoracic Epidural Anesthesia on Plasma Pro-Atrial Natriuretic Peptide to Indicate Deviations in Central Blood Volume during Esophagectomy

Effect of Early vs Delayed Activation of Thoracic Epidural Anesthesia on Plasma Pro-Atrial Natriuretic Peptide to Indicate Deviations in Central Blood Volume during Esophagectomy