Dataset Information

The association of mid-regional pro-adrenomedullin and mid-regional pro-atrial natriuretic peptide with mortality in an incident dialysis cohort.

ABSTRACT: High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are associated with clinical outcomes in the general population. Data in patients with chronic kidney disease are sparse. We therefore investigated the association of MR-proANP and MR-proADM levels with all-cause and cardiovascular (CV) mortality, CV events and peripheral arterial disease in 201 incident dialysis patients of the INVOR-Study prospectively followed for a period of up to more than 7 years. The overall mortality rate was 43%, thereof 43% due to CV events. Both baseline MR-proANP and MR-proADM were associated with higher risk of all-cause (HR?=?1.44, p?=?0.001 and HR?=?1.32, p?=?0.002, respectively) and CV mortality (HR?=?1.75, p<0.001 and HR?=?1.41, p?=?0.007, respectively) after adjustment for age, sex, previous CV events, diabetes mellitus and time-dependent type of renal replacement therapy. We then stratified patients in high risk (both peptides in the upper tertile), intermediate risk (only one of the two peptides in the upper tertile) and low risk (none in the upper tertile). Although demographic, clinical and laboratory variables were similar among the intermediate and high risk group, to be with both parameters in the upper tertile was associated with a 3-fold higher risk for all-cause (HR?=?2.87, p<0.001) and CV mortality (HR?=?3.58, p?=?0.001). In summary, among incident dialysis patients MR-proANP and MR-proADM were shown to be associated with all-cause and CV mortality, with the highest risk when both parameters were in the upper tertiles.

SUBMITTER: Gouya G

PROVIDER: S-EPMC3049793 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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The association of mid-regional pro-adrenomedullin and mid-regional pro-atrial natriuretic peptide with mortality in an incident dialysis cohort.

Gouya Ghazaleh G Sturm Gisela G Lamina Claudia C Zitt Emanuel E Freistätter Otto O Struck Joachim J Wolzt Michael M Knoll Florian F Lins Friederike F Lhotta Karl K Neyer Ulrich U Kronenberg Florian F

PloS one 20110307 3

High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are associated with clinical outcomes in the general population. Data in patients with chronic kidney disease are sparse. We therefore investigated the association of MR-proANP and MR-proADM levels with all-cause and cardiovascular (CV) mortality, CV events and peripheral arterial disease in 201 incident dialysis patients of the INVOR-Study prospectively foll ...[more]

PMID: 21408188

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Project description:New findingsWhat is the central question in this study? Atrial natriuretic peptide (ANP) is secreted in response to atrial wall distension and thus allows for evaluation, albeit indirect, of the central blood volume. Adrenaline has chronotropic and inotropic effects. We evaluated whether the chronotropic and inotropic effects of adrenaline were reflected in mid-regional proANP. What is the main finding and its importance? Central blood volume remained stable with infusion of adrenaline and yet mid-regional proANP increased. Thus, the chronotropic and inotropic state of the heart or adrenaline directly induces release of ANP variants from the myocytes.AbstractAtrial natriuretic peptide (ANP) has vasodilatory, natriuretic and diuretic properties. It is secreted in response to atrial wall distension and thereby provides an indirect evaluation of central blood volume (CBV). Adrenaline has chronotropic and inotropic effects that increase cardiac output. In the present study, we evaluated whether these effects were influenced by an increase in CBV and reflected in mid-regional proANP (MR-proANP) concentrations in the circulation, a stable proxy marker of bioactive ANP. Changes in CBV were evaluated by thoracic electrical admittance and haemodynamic variables monitored by pulse-contour analysis during two intervals with graded infusion of adrenaline. Adrenaline infusion increased heart rate (by 33 ± 18%) and stroke volume (by 6 ± 13%), hence cardiac output (by 42 ± 23%; all P < 0.05). The increase in cardiac output did not result from an increase in CBV, because thoracic electrical admittance remained stable (-3 ± 17%; P = 0.230). Serum MR-proANP concentrations were increased (by 26 ± 25%; P < 0.001) by adrenaline infusion and remained elevated 60 min postinfusion. We conclude that MR-proANP in the circulation is affected not only by CBV, but also by increased chronotropy/inotropy of the heart, or that adrenaline directly induces release of ANP variants from the myocytes.

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

Dataset Information

The association of mid-regional pro-adrenomedullin and mid-regional pro-atrial natriuretic peptide with mortality in an incident dialysis cohort.

Publications

The association of mid-regional pro-adrenomedullin and mid-regional pro-atrial natriuretic peptide with mortality in an incident dialysis cohort.

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