Mid-regional Pro-atrial Natriuretic Peptide Concentrations Research Articles

150. Uteroplacental acute atherosis, cardiovascular biomarkers and vasoactive hormones in pregnancy

Introduction Cardiovascular disease (CVD) is the leading cause of death for women. A history of hypertensive disorders of pregnancy increases the risk. Uteroplacental spiral arterial.acute atherosis is a pregnancy-specific lesion resembling early atherosclerosis, frequently found in preeclampsia. The renin-angiotensin-system (RAS) plays a role in atherosclerosis and is dysregulated in preeclampsia. RAS and natriuretic peptides are physiological opponents in the regulation of arterial blood pressure and intravascular volume control. We previously reported increased concentrations of the natriuretic hormone precursor midregional proatrial natriuretic peptide (MR-proANP) in preeclampsia and suggested a cardiac origin. Objective To assess whether uteroplacental acute atherosis correlates with cardiovascular biomarkers and vasoactive hormones in maternal circulation at delivery in preeclamptic and normotensive pregnancies. Methods Third trimester maternal blood samples were analyzed for renin, prorenin and MR-proANP [normotensive pregnancies n = 50, preeclampsia (PE) n = 71]. Decidua basalis tissue for acute atherosis diagnosis (immunohistochemistry) was available for 53 of these pregnancies (normotensives n = 25 and PE n = 28). Statistical analyses: Skewed data were log-transformed. Linear regression and Fisher’s Exact test were applied as appropriate. A p-value Results A negative correlation between renin and MR-proANP concentrations was confirmed for both study groups. The presence of acute atherosis was not associated with maternal levels of circulating renin, prorenin or MR-proANP. Presence of acute atherosis was neither associated with MR-proANP/renin ratio nor maternal renin in the lower 2 quartiles in combination with MR-proANP in the upper 2 quartiles (normotensives p = 1.0 and PE p = 0.7). Discussion This is the first report on RAS and vasoactive hormones in pregnancy in relation to uteroplacental acute atherosis. We find that maternal circulating biomarkers previously shown to indicate hemodynamic stress in preeclampsia are not increased in pregnancies with acute atherosis. Further studies exploring the longitudinal association between maternal circulating cardiovascular biomarkers and postpartum CVD surrogate markers are underway.

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

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

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

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

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

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

Increased plasma concentrations of midregional proatrial natriuretic Peptide is associated with risk of cardiorenal dysfunction in type 1 diabetes.

To examine possible associations between midregional proatrial natriuretic peptide (MR-proANP) and diabetic complications at baseline and risk of mortality and end-stage renal disease (ESRD) during follow-up in type 1 diabetes. Observational study including 667 patients, with plasma MR-proANP measured at baseline. Complications were defined as micro- (n = 168) or macroalbuminuria (n = 190) (urinary albumin excretion rate (UAER) 30-299 or ≥ 300 mg/24h), previous cardiovascular disease (CVD) (n = 143), cardiac autonomic dysfunction (heart rate variability < 11 beats/min) (n = 369), and retinopathy (n = 523). Adjustments included gender, age, systolic blood pressure, estimated glomerular filtration rate (eGFR), UAER, HbA1c, total cholesterol, 24-hour urinary sodium excretion (24h-U(Na)), body mass index, daily insulin dose, antihypertensive treatment, and smoking in linear regression analyses and analysis of covariance models. Development of ESRD (dialysis, renal transplantation, or GFR/eGFR < 15 ml/min/1.73 m(2)) and mortality was recorded through national registers. The cohort included 293 (44%) females, aged 55 ± 13 years. Plasma MR-proANP (median (interquartile)) was 74.7 (49.2-116.8) pmol/L. Adjusted, MR-proANP correlated positively with age and UAER and negatively with eGFR, 24h-U(Na), total cholesterol, and HbA1c (P < 0.05). Moreover, MR-proANP levels increased with albuminuria degree and were higher in patients with previous CVD (P ≤ 0.001), but similar in patients with or without autonomic dysfunction or retinopathy (P ≥ 0.076). During follow-up (3.5 (3.1-4.0) years), higher MR-proANP concentrations predicted ESRD and mortality combined (n = 35) adjusted for gender, age, systolic blood pressure, eGFR, and previous CVD (hazard ratio per 1SD increase in logANP: 2.8 (1.6-4.7; P < 0.001)). Increased plasma MR-proANP was associated with impaired renal function, increased albuminuria, and previous CVD. Moreover, MR-proANP concentrations were associated with increased risk of development of ESRD and mortality combined during follow-up.

Prognostic Performance of Multiple Biomarkers in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome: Analysis From the MERLIN–TIMI 36 Trial (Metabolic Efficiency With Ranolazine for Less Ischemia in Non−ST-Elevation Acute Coronary Syndromes–Thrombolysis In Myocardial Infarction 36)

The aim of this study was to assess the prognostic performance of C-terminal provasopressin (copeptin), midregional pro-adrenomedullin (MR-proADM), and midregional pro-atrial natriuretic peptide (MR-proANP) in a large prospective cohort of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Copeptin, MR-proADM, and MR-proANP are emerging biomarkers of hemodynamic stress that have been associated with adverse cardiovascular (CV) outcomes in heart failure (HF) and stable ischemic disease. We measured copeptin, MR-proADM, and MR-proANP concentrations in 4,432 patients with NSTE-ACS who were randomized to treatment with ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36) trial and followed up for 1 year. A high concentration (quartile 4 vs. quartiles 1 to 3) of each biomarker identified an increased risk of CV death or HF(copeptin: 13.2% vs. 5.0%, p < 0.001; MR-proADM: 15.8% vs. 4.1%, p < 0.001; MR-proANP: 17.7% vs. 3.5%, p < 0.001)as well as CV death, HF, and myocardial infarction individually (all p ≤ 0.001). After adjustment for important covariates, each biomarker remained associated with CV death or HF at 1 year (adjusted hazard ratio: copeptin, 1.71; MR-proADM, 1.96; MR-proANP, 2.20; all p ≤ 0.001).These biomarkers improved prognostic discrimination and patient re-classification for CV death or HF at 1 year(all categorical NRI >10%, p < 0.001), and maintained independent association with composite CV death or HF when concurrently assessed in a model with clinical indicators plus BNP, cTnI, ST2, PAPP-A, and MPO (each p≤0.01) [corrected]. Copeptin, MR-proADM, and MR-proANP are complementary prognostic markers for CV death and HF in patients with NSTE-ACS that perform as well as or better than established and other emerging biomarkers and warrant further investigation of application for therapeutic decision making. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788).

Metabolic Rather Than Body Composition Measurements Are Associated With Lower Serum Natriuretic Peptide Concentrations in Normal Weight and Obese Men

Several studies have shown that obese persons have lower circulating natriuretic peptide (NP) concentrations. The cause of the relative NP deficiency seen in obese persons is poorly understood, although variation in body composition and metabolic abnormalities has been suggested to play a role. Thus, the aim of this study was to assess whether variation in circulating NP concentrations would be associated with differences in metabolic disturbances rather than with differences in body composition. In 27 normal weight men (body mass index (BMI) = 20.0-24.9kg/m(2)) and 103 obese men (BMI ≥ 30kg/m(2)), we determined body composition (total, android, and gynoid fat mass) by dual energy x-ray absorptiometry scanning, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP) and insulin, as well as fasting plasma glucose concentrations. Mean weight ± SD was 74.9±6.7kg in the normal weight men and 106.1±10.8kg in obese men. Applying multiple regressions, adjusting for age and weight status (normal weight vs. obese), serum MR-proANP concentrations were significantly inversely associated with serum insulin concentrations (β = -0.39; P < 0.0001) and plasma glucose concentrations (β = -0.21; P = 0.02) but not with total (β = 0.00), android (β = -0.01), or gynoid (β = 0.03) fat mass percentage (P > 0.76). No significant interaction effects between metabolic measurements or body composition measurements and weight status on MR-proANP concentrations were found (P > 0.08). In normal weight and obese men, lower circulating NP concentrations are associated with higher insulin and glucose concentrations and not with the proportion of total fat mass or the distribution of fat mass.

MR-proANP and MR-proADM for risk stratification of patients with acute chest pain

ObjectiveTo evaluate mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) as prognostic biomarkers in a representative ‘real world’ cohort of patients with suspected acute coronary syndrome (ACS).DesignProspective observational multicentre...

Midregional pro-atrial natriuretic peptide in the general population/Insights from the Gutenberg Health Study

The use of biomarkers is firmly established for the assessment of cardiovascular disease. Emerging biomarkers such as midregional pro-atrial natriuretic peptide (MR-proANP) challenge established markers regarding risk prediction and stratification ability. The aim of the present study was to describe the distribution of a contemporary MR-proANP assay in a large population-representative sample and to evaluate the association with prevalent cardiac diseases and cardiovascular risk factors. MR-proANP was determined by the use of a contemporary commercially available assay (BRAHMS GmbH, Hennigsdorf, Germany) in a representative sample of 5000 participants from the large population-based Gutenberg Health Study. N-terminal pro B-type natriuretic peptide (NT-proBNP) was used as a comparator. Mean age was 55.5 ± 10.9 years. Coronary artery disease (CAD) was documented in 4.6%, heart failure (HF) in 1.5% of the study participants. We observed a moderate to strong correlation of the biomarkers with age, diabetes, hypertension, smoking, renal function, prevalence of CAD and HF. Males showed lower MR-proANP concentrations than females. MR-proANP showed no relevant correlation with BMI (ρ=-0.030) and CRP (ρ=0.039). Reference limits for MR-proANP representing the 95th/97.5th/99th percentile were determined for healthy individuals with 116/132/169 pmol/mL. The current analysis in a large population-based sample elucidates the correlations and distribution of MR-proANP. Its concentration in healthy individuals depends on prevalent cardiovascular diseases and classical risk factors. The reported population-based reference values might be useful for distinguishing between healthy and diseased individuals, thus improving risk stratification and triaging in various clinical settings.

Acarbose treatment enhances mid-regional pro-atrial natriuretic peptide concentrations in non-diabetic individuals: further evidence for a common cardiometabolic pathway?

To the Editor: Heinisch et al reported that acute infusion of B-type natriuretic peptide (NP) enhances the initial glucose distribution, resulting in a decrease of postload glucose concentrations by beta cell-independent mechanisms in healthy individuals [1]. This study added to growing evidence regarding a close pathophysiological link between NPs and metabolic traits in obesity, type 2 diabetes and associated diseases [2]. The mechanisms by which NP regulates glucose metabolism are not fully understood, but a reciprocal relationship between glucose regulation and NP has been suggested in type 2 diabetes and cardiovascular diseases (CVDs) [1, 2]. In addition, we and others observed the same type of relations between insulin and NP in obesity [3, 4]. Previous large-cohort observations such as the Study to Prevent NIDDM (STOP-NIDDM) [5, 6] indicate that reduction of postprandial glucose load may be involved in the prevention of both type 2 diabetes and incident hypertension, pointing to a potential ‘bi-directional relationship’

Cardiovascular risk markers in pregnancies complicated by diabetes mellitus or preeclampsia

ObjectiveTo explore biomarkers indicating cardiovascular disease in pregnant women with diabetes or preeclampsia, since these women are at increased risk for future cardiovascular disease. Study designEDTA-plasma from 262 women in gestational week 24–42 (healthy pregnancies n=71, preeclampsia n=105, type 2 diabetes n=17, gestational diabetes n=61, diabetes with preeclampsia n=8) was analyzed by immunoassay for neopterin, midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-arginine vasopressin (CT-proAVP). The diabetes groups were also analyzed for midregional pro-atrial natriuretic peptide (MR-proANP), and compared to previously reported MR-proANP concentrations for healthy, normotensive and preeclamptic patients. ResultsIn contrast to preeclampsia, median plasma MR-proANP was not increased in pregnancies complicated by diabetes, but in fact lower, compared to healthy pregnancies. Neopterin was increased in diabetic pregnancies and in late onset preeclampsia, compared to healthy pregnancies. Median plasma MR-proADM was increased in pregnancies complicated by gestational diabetes or preeclampsia, compared to healthy pregnancies. Median plasma MR-proANP was increased in diabetic pregnancies complicated by preeclampsia compared to pregnant women with diabetes only. ConclusionWomen with pregnancies complicated by diabetes mellitus or preeclampsia are at risk for future cardiovascular disease, but differ in circulating cardiovascular biomarker profile. A cardiovascular biomarker profiling during pregnancy might prove helpful in identifying women at risk for future cardiovascular disease, thus enabling targeted prophylactic interventions and follow-up.

Midregional Pro–Atrial Natriuretic Peptide for the Diagnosis of Cardiac-Related Dyspnea according to Renal Function in the Emergency Department: A Comparison with B-Type Natriuretic Peptide (BNP) and N-Terminal ProBNP

Although renal dysfunction influences the threshold values of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in diagnosis of cardiac-related dyspnea (CRD), its effects on midregional pro-atrial natriuretic peptide (MR-proANP) threshold values are unknown. We evaluated the impact of renal function on MR-proANP concentrations and compared our results to those of BNP and NT-proBNP. MR-proANP, BNP, and NT-proBNP concentrations were measured in blood samples collected routinely from dyspneic patients admitted to the emergency department. Patients were subdivided into tertiles based on their estimated glomerular filtration rate [eGFR, in mL · min(-1) · (1.73 m(2))(-1)]: tertiles 1 (<44.3), 2 (44.3-58.5), and 3 (≥58.6). Of 378 patients studied, 69% (n = 260) had impaired renal function [<60 mL · min(-1) · (1.73 m(2))(-1)] and 30% (n = 114) had CRD. MR-proANP, BNP, and NT-proBNP concentrations were significantly increased in patients with impaired renal function. In each tertile, all peptides remained significantly increased in CRD patients by comparison with non-CRD patients. By ROC analysis, MR-proANP, BNP, and NT-proBNP threshold values for the diagnosis of CRD increased as eGFR decreased from tertile 3 to tertile 1. Areas under the ROC curve for all peptides were significantly lower in tertile 1. Using adapted thresholds, MR-proANP, BNP, and NT-proBNP remained independently predictive of CRD, even in tertile 1 patients. Renal function influences optimum cutoff points of MR-proANP for the diagnosis of CRD. With use of an optimum threshold value adapted to the eGFR category, MR-proANP remains as effective as BNP and NT-proBNP in independently predicting a diagnosis of CRD in the emergency department.

Midregional Pro-Atrial Natriuretic Peptide and Outcome in Patients With Acute Ischemic Stroke

The purpose of this study was to examine the prognostic value of midregional pro-atrial natriuretic peptide (MR-proANP) in patients with acute ischemic stroke. The rapid and reliable estimation of prognosis in acute ischemic stroke is pivotal to optimize clinical care. MR-proANP, a recently described, stable fragment of the ANP precursor hormone, may be useful in this setting. In a prospective observational study, we measured MR-proANP on admission in plasma of 362 consecutive patients presenting with acute ischemic stroke. The prognostic value of MR-proANP to predict mortality within 90 days and functional outcome (defined as a modified Rankin Scale of ≤2 or ≥3) was evaluated and compared with the National Institutes of Health Stroke Scale (NIHSS) score. The discriminatory accuracy, calculated with the area under the curve (AUC) of the receiver operating characteristics curve, of MR-proANP to predict death was comparable to the NIHSS (AUC: 0.86 [95% confidence interval (CI): 0.82 to 0.90] and 0.85 [95% CI: 0.81 to 0.89; p = 0.7]). Combined, the accuracy significantly improved (0.92 [95% CI: 0.88 to 0.96; p < 0.01]). The AUC of MR-proANP to predict functional outcome was 0.70 (95% CI: 0.65 to 0.75), similar to the NIHSS (0.75 [95% CI: 0.70 to 0.80]; p = 0.16). The prognostic value of MR-proANP for both outcomes was independent of the NIHSS. Higher MR-proANP concentrations were found in stroke of cardioembolic etiology. MR-proANP is a prognostic marker in the acute phase of stroke, improving the discriminatory value of the NIHSS, independently predicting post-stroke mortality and functional outcome. (The "COSMOS"-Study [Copeptin in Osmoregulation and Stress Assessment]; NCT00390962).

The predictive value of stable precursor fragments of vasoactive peptides in patients with chronic heart failure: data from the GISSI‐heart failure (GISSI‐HF) trial

Though various neurohormonal systems are concurrently activated during heart failure (HF), their biological effectors are not always easy to measure due to their short life in vivo, instability in biological samples, or very low concentrations. We measured the plasma concentrations of four stable precursor fragments of neurohormonal systems in patients with chronic HF and evaluated their relationship with outcome. This study was performed in 1237 patients with chronic and stable HF enrolled in the GISSI-heart failure trial (GISSI-HF). The following four precursor fragments, mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1) and C-terminal pro-vasopressin (CT-proAVP or copeptin), were measured at randomization and after 3 months. Baseline concentrations were independent predictors of clinical outcome (median follow-up 3.9 years). The addition of MR-proANP improved net reclassification for mortality when added to multivariable models based on clinical risk factors alone [net reclassification improvement (NRI) = 0.12, P = 0.0007] or together with NT-proBNP (NRI = 0.06, P = 0.01). Changes in MR-proANP concentrations were related to mortality [HR (95% CI) 1.38 (0.99-1.93), P = 0.0614 and 1.58 (1.13-2.21), P = 0.0078 in the middle and highest vs. lowest tertiles], while changes in the other markers were not. In patients with chronic and stable HF enrolled in a multicentre, randomized, clinical trial, measurement of stable precursor fragments of vasoactive peptides provided prognostic information independent of natriuretic peptides which are currently the best biomarkers for risk stratification.

Midregional Pro-A-Type Natriuretic Peptide and Carboxy-Terminal Provasopressin May Predict Prognosis in Community-Acquired Pneumonia

Markers to better assess severity of disease in patients with community-acquired pneumonia (CAP) would help improve medical care of this condition. The hemodynamic biomarkers carboxy-terminal provasopressin (CT-proAVP; copeptin) and midregional proatrial natriuretic peptide (MR-proANP) are increased under septic conditions, in which MR-proANP has been described as a prognostic predictor. We aimed to explore the diagnostic accuracy of MR-proANP and CT-proAVP to predict mortality in patients with CAP. We conducted a prospective observational study of patients with CAP. We measured biomarkers in serum samples obtained at diagnosis and performed univariate and multivariate analyses to identify potential predictors of mortality. CT-proAVP and MR-proANP concentrations were measured in 173 patients. We found a positive correlation between pneumonia severity index (PSI) and MR-proANP (r(s) = 0.68, P <0.0001) and between PSI and CT-proAVP (r(s) = 0.44, P <0.0001). Median (interquartile range) CT-proAVP and MR-proANP values were 8.2 (5.3-16.8) and 73.6 (44.6-144.0) pmol/L, respectively. Nonsurvivors had significantly higher MR-proANP and CT-proAVP than survivors (median 259.0 vs 71.8 pmol/L, P = 0.01, and 24.9 vs 8.1 pmol/L, P = 0.03, respectively). In multivariate analysis including PSI, procalcitonin, C-reactive protein, lipopolysaccharide-binding protein, CT-proAVP, and MR-proANP concentrations, only CT-proAVP remained an independent predictor of death (odds ratio 1.05, P = 0.007). Cutoff values of >18.9 pmol/L for CT-proAVP and >227 pmol/L for MR-proANP showed the highest diagnostic accuracy to predict mortality. CT-proAVP and MR-proANP may be used to predict prognosis in patients with CAP.

3531 POSTER Toxicity and outcomes of chemoradiation without elective nodal irradiation after chemotherapy for unresectable pancreatic cancer

To explore biomarkers indicating cardiovascular disease in pregnant women with diabetes or preeclampsia, since these women are at increased risk for future cardiovascular disease.EDTA-plasma from 262 women in gestational week 24–42 (healthy pregnancies n = 71, preeclampsia n = 105, type 2 diabetes n = 17, gestational diabetes n = 61, diabetes with preeclampsia n = 8) was analyzed by immunoassay for neopterin, midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-arginine vasopressin (CT-proAVP). The diabetes groups were also analyzed for midregional pro-atrial natriuretic peptide (MR-proANP), and compared to previously reported MR-proANP concentrations for healthy, normotensive and preeclamptic patients.In contrast to preeclampsia, median plasma MR-proANP was not increased in pregnancies complicated by diabetes, but in fact lower, compared to healthy pregnancies. Neopterin was increased in diabetic pregnancies and in late onset preeclampsia, compared to healthy pregnancies. Median plasma MR-proADM was increased in pregnancies complicated by gestational diabetes or preeclampsia, compared to healthy pregnancies. Median plasma MR-proANP was increased in diabetic pregnancies complicated by preeclampsia compared to pregnant women with diabetes only.Women with pregnancies complicated by diabetes mellitus or preeclampsia are at risk for future cardiovascular disease, but differ in circulating cardiovascular biomarker profile. A cardiovascular biomarker profiling during pregnancy might prove helpful in identifying women at risk for future cardiovascular disease, thus enabling targeted prophylactic interventions and follow-up.