adrenomedullin and Coronary-Artery-Disease

In patients with stable coronary heart disease (CHD), we aimed to assess 1. the prognostic power of biomarkers reflecting haemodynamics, micronecrosis, inflammation, coagulation, lipids, neurohumoral activity, and renal function; 2. whether changes in concentrations of these biomarkers over 12 months affected subsequent CHD risk; and 3. whether pravastatin modified the change in biomarker concentrations and this influenced the risk of future events.. In the LIPID study, 9014 patients were randomised to pravastatin 40 mg or placebo 3-36 months after an acute coronary syndrome. Eight biomarkers were measured at baseline (n=7863) and 12 months later (n=6434).. During a median of 6.0 (IQR 5.5-6.5) years follow-up, 1100 CHD-related deaths and nonfatal myocardial infarctions occurred, 694 after biomarker measurement at 12 months. Baseline BNP, CRP, cystatin C, D-dimer, midregional pro-adrenomedullin, and sensitive troponin I predicted recurrent CHD events. In a multivariable model, sensitive troponin I, BNP, and cystatin C had the strongest associations with outcome (P<0.001 for trend). The strongest improvement in risk prediction was achieved by including sensitive troponin I (net reclassification improvement (NRI) 5.5%; P=0.003), BNP (4.3%; P=0.02), history of MI (NRI 7.0%; P<0.001). In landmark analyses, among biomarkers, changes to 12 months in sensitive troponin I (HR 1.32 (1.03-1.70) for T3/T1), BNP (HR 1.37 (1.10-1.69) for Q4/Q1) and Lp-PLA2 (HR 1.52 (1.16-1.97)) improved CHD risk prediction.. Baseline levels and changes in sensitive troponin I, and BNP may have the potential to guide the intensity of secondary prevention therapy.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adrenomedullin; Adult; Aged; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Cystatin C; Female; Fibrin Fibrinogen Degradation Products; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pravastatin; Predictive Value of Tests; Prognosis; Risk Factors; Troponin I; Troponin T

Endothelin-1 (ET-1) is a vasoconstrictor associated with cardiovascular disease, whereas adrenomedullin (ADM) is a vasorelaxant with cardioprotective properties. We sought to determine the relationship between plasma ET-1 and ADM with coronary circulatory function and long-term major adverse cardiovascular events (MACE).. Thirty-two patients undergoing coronary angiography for chest pain were recruited. Baseline plasma ET-1 and ADM levels were measured. The index of microcirculatory resistance (IMR), coronary flow mediated dilatation (cFMD) and coronary flow reserve (CFR) were measured in a non-obstructed coronary artery. Patients were assessed for MACE over a median period of 8.8 years.. Plasma ET-1 levels correlated with IMR (r = 0.57; p < 0.01) and ADM levels correlated with CFR (r = 0.50; p = 0.04) and cFMD (r = 0.62; p = 0.01). After adjustment for age, gender and cardiovascular risk factors, the association between ADM and cFMD (β = 0.79; p < 0.01) and between ET-1 and IMR (β = 5.7; p = 0.01) remained significant. IMR was higher, although not statistically significant, in patients with long-term MACE (17.9 ± 5.3 vs. 13.1 ± 6.0 units; p = 0.14). In patients free of MACE, cFMD (9.3 ± 7.6 vs. 2.8 ± 5.0%; p = 0.01) and plasma ADM levels (7.6 ± 5.3 vs. 4.0 ± 1.9 pmol/L; p = 0.07) were higher.. Plasma ET-1 and ADM were associated with measures of coronary microvascular and coronary conduit vessel function, respectively. Increased cFMD and elevated plasma ADM were associated with a cardioprotective effect.

Topics: Adrenomedullin; Aged; Biomarkers; Chest Pain; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Endothelin-1; Female; Follow-Up Studies; Fractional Flow Reserve, Myocardial; Humans; Male; Middle Aged

Midregional proadrenomedullin (MR-proADM) is elevated in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the association of MR-proADM with the grade of coronary artery stenosis, presence of coronary artery soft plaques and coronary artery calcification score (CACS), determined by 64-multislice computed tomography (MSCT) in patients without known prior cardiovascular disease. This retrospective study included 107 patients undergoing MSCT for confirmation (or exclusion) of coronary artery disease. MR-proADM levels were measured in all patients. The assessment of coronary artery stenoses, CACS and soft coronary plaques was made by MSCT using known criteria. The MR-proADM [median (25th-75th percentiles)] level was 0.33 (0.21-0.43) nmol/l. The MR-proADM level was 0.28 (0.22-0.40) nmol/l in patients with coronary stenoses ≥50% (n = 23) versus 0.33 (0.27-0.40) nmol/l in patients with coronary stenoses <50% (n = 83, P = 0.59), 0.33 (0.26-0.40) nmol/l in patients with soft plaques (n = 56) versus 0.33 (0.25-0.41) nmol/l in patients without soft plaques (n = 50, P = 0.73) and 0.33 (0.25-0.39) nmol/l in patients with CACS <200 (n = 81) versus 0.32 (0.26-0.44) nmol/l in patients with CACS ≥200 (n = 26, P = 0.77). In multivariate analysis, the MR-proADM level was a significant correlate of coronary artery stenoses [odds ratio (OR) = 0.93; 95% confidence interval (CI) 0.86-0.99; P = 0.026] and soft plaques (OR = 0.94; 95% CI 0.90-0.99; P = 0.015) but not of CACS (OR = 0.98; 95% CI 0.93-1.03; P = 0.36). A decreased MR-proADM level is an independent correlate of the presence of coronary artery disease and of soft atherosclerotic plaques. Patients with decreased MR-proADM levels may need invasive examinations to diagnose more severe forms of coronary artery disease.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Biomarkers; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Coronary Vessels; Down-Regulation; Female; Germany; Humans; Logistic Models; Male; Middle Aged; Multidetector Computed Tomography; Multivariate Analysis; Odds Ratio; Peptide Fragments; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; Risk Assessment; Risk Factors; ROC Curve; Severity of Illness Index; Vascular Calcification

Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR-proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation.. We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years.. The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individuals presenting with SAP had only slightly lower plasma MR-proADM concentrations than those with ACS (0.53 vs 0.55 nmol/L, P=0.006). MR-proADM showed a moderate association with age, serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, serum C-reactive protein, hypertension, diabetes, and prevalent multivessel disease (all P<0.0005). Individuals suffering from a cardiovascular event had higher MR-proADM concentrations at baseline in both groups (SAP 0.63 vs 0.53 nmol/L and ACS 0.65 nmol/L vs 0.55 nmol/L, both P<0.0005). Cox regression analysis incorporating various variables of cardiovascular risk and NT-proBNP revealed a hazard ratio of 1.4 (95% CI 1.2-1.6; P<0.0005) per increment of MR-proADM by 1SD. In risk models for secondary prevention, MR-proADM provided information comparable to that of NT-proBNP.. MR-proADM is an independent predictor for future cardiovascular events in patients with symptomatic coronary artery disease, providing information comparable to NT-proBNP for secondary risk stratification.

Topics: Acute Coronary Syndrome; Adrenomedullin; Aged; Angina Pectoris; Biomarkers; Coronary Artery Disease; Female; Humans; Immunoassay; Kaplan-Meier Estimate; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment

Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis. The aim of our study was to investigate whether circulating AM might be related to cardiac function, volume overload, oxidative stress and inflammation in hemodialysis patients. Plasma adrenomedullin, C-reactive protein (CRP), oxidized LDL (ox-LDL), lipoprotein (a), systolic and diastolic cardiac functions were assessed before hemodialysis in 80 patients as well as in 40 healthy control subjects. Plasma adrenomedullin levels were significantly higher in the hemodialysis group compared to the control group. Plasma adrenomedullin levels were negatively correlated with systolic and diastolic blood pressure, S/D ratio, deceleration time, left ventricular ejection fraction, ox-LDL and lipoprotein (a). However, it was positively correlated with CRP, delta body weight, mitral E/A wave, and inferior vena cava diameter. Higher plasma adrenomedullin levels may provide a possible index of cardiac dysfunction, systemic inflammation, and volume overload conditions in haemodialysis patients with concomitant cardiovascular disease. In addition, the negative correlation between ox-LDL, lipoprotein (a) and adrenomedullin may suggest that endogenous AM is an important protective factor in anti-atherosclerosis and might be useful as a new target for prevention and therapy for the disease.

Topics: Adrenomedullin; Adult; Blood Pressure; Blood Volume; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Echocardiography, Doppler; Female; Humans; Inflammation; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Renal Dialysis

Growing evidence suggests that the epicardial adipose tissue may have local interactions with coronary arteries. In addition, vasoactive peptides such as adrenomedullin and natriuretic peptide has an interaction with adipose tissue. In this study, we investigated the relationship between adipokines, adipocytokines, and vasoactive peptides expressed in epicardial adipose tissue and subcutaneous adipose tissue in patients with and without coronary artery disease (CAD).. We studied 20 patients with CAD and 14 patients without CAD. We obtained blood samples and epicardial and subcutaneous adipose tissue at open-heart surgery. We measured serum cytokine levels and used real-time polymerase chain reaction (PCR) to measure mRNA levels of various molecules in epicardial and subcutaneous tissue and investigated the relation between mRNA levels and clinical parameters.. The mRNA levels of IL-6, IL-1beta, MCP-1, and TNF-alpha were significantly higher in epicardial adipose tissue than in subcutaneous adipose tissue. Interestingly, the mRNA levels of IL-6, IL-1beta, MCP-1, natriuretic peptide receptor-C (NPR-C), adrenomedullin, and leptin in epicardial adipose tissue were higher in patients with CAD than those without CAD. In contrast, mRNA levels of adiponectin, PPAR-gamma, and NPR-A were similar in the two groups. In subcutaneous tissue, mRNA expressions of IL-6, IL-1beta, MCP-1, NPR-C, adrenomedullin, and leptin were modestly higher in patients with CAD than in those without CAD. There were no differences in plasma cytokine levels between the two groups.. The mRNA levels of inflammatory cytokines, adipokines, neurohumoral factors and their receptors appear to be increased in epicardial adipose tissue independent of plasma levels of these molecules. Further studies are necessary to elucidate the pathophysiological role of these molecules in CAD.

Topics: Adipose Tissue; Adrenomedullin; Aged; Chemokine CCL2; Coronary Artery Disease; Cytokines; Female; Humans; Interleukin-1beta; Interleukin-6; Male; Middle Aged; Pericardium; Receptors, Atrial Natriuretic Factor; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

The aim of the study was to test 1) whether chronic and stable coronary artery disease (CAD) could downregulate epicardial fat adrenomedullin synthesis and secretion, and decrease intracoronary plasma adrenomedullin levels, and 2) whether intracoronary plasma adrenomedullin levels could be related to epicardial adipose tissue adrenomedullin gene and protein expression in subjects with CAD. We examined 12 patients with CAD who required coronary artery bypass graft (CABG) and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adrenomedullin were measured in peripheral vein circulation, in left coronary artery (LCA) and coronary sinus (CS) during coronary angiography. Epicardial adipose tissue biopsy for Reverse Transcription and Real-Time PCR (RT-PCR) adrenomedullin mRNA analysis and Western Blotting (WB) protein expression was performed during cardiac surgery in all subjects. Peripheral, LCA, and CS plasma adrenomedullin levels were significantly lower in CAD patients than in those with non-CAD (3.0+/-0.9 vs. 4.4+/-0.9 pg/ml p<0.01; 2.9+/-1 vs. 4.05+/-0.8 pg/ml, p<0.01, 3.1+/-0.9 vs. 3.98+/-0.9 pg/ml p=0.04, respectively). However, CS adrenomedullin levels were not statistically different than those in LCA suggesting that adrenomedullin was not secreted from epicardial fat into the coronary artery lumen. Epicardial fat adrenomedullin mRNA levels and protein expression were lower in patients with CAD than in those with non-CAD (p<0.01 for both). We conclude that 1) epicardial fat adrenomedullin gene and protein expression can be downregulated in CAD subjects, and 2) intracoronary adrenomedullin levels are lower in CAD. No evidence that epicardial adipose tissue really contributes intracoronary adrenomedullin can be provided at this time.

Topics: Adipose Tissue; Adrenomedullin; Aged; Coronary Artery Disease; Coronary Circulation; Female; Gene Expression Regulation; Humans; Male; Pericardium; RNA, Messenger

Our previous study showed that static handgrip caused increases in the plasma adrenomedullin (ADM) both in patients with heart failure (HF) and healthy subjects. The present study was designed to determine the role of the sympathetic nervous system in mediating plasma ADM changes during handgrip in patients with HF. Twelve male HF patients (II class NYHA) treated with carvedilol, a non-selective adrenergic blocker (TC) and 12 patients untreated with carvedilol (UC) performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand. At the end of both exercise bouts and in 5 min of the recovery period, plasma ADM and catecholamines were determined. In addition, heart rate, blood pressure and stroke volume (SV) were measured. The baseline plasma ADM, noradrenaline (NA) and adrenaline (A) levels were similar in the two groups of patients, while SV was higher (P<0.05) in TC than in UC. During exercise plasma ADM concentrations were lower (P<0.05) in TC than in UC, but the handgrip-induced increases in plasma ADM did not differ between the groups. Plasma ADM correlated with NA concentrations (r = 0.764) and with SV (r = -0.435) and increases in plasma ADM expressed as percentage of baseline values correlated with those of plasma NA (r = 0.499), diastolic BP (r = 0.550) and total peripheral resistance (r = 0.435). The study suggests that the sympathetic nervous system may be involved in the stimulation of ADM secretion during static exercise either directly or by changes in the haemodynamic response.

Topics: Adrenergic beta-Antagonists; Adrenomedullin; Aged; Analysis of Variance; Biomarkers; Blood Pressure; Carbazoles; Cardiac Output; Carvedilol; Chronic Disease; Coronary Artery Disease; Epinephrine; Exercise Test; Heart Failure; Heart Rate; Humans; Linear Models; Male; Middle Aged; Norepinephrine; Propanolamines; Sympathetic Nervous System; Treatment Outcome; Vascular Resistance

It has been suggested that, like ANP and BNP, high plasma levels of mature adrenomedullin (mAM) indirectly reflect the severity of heart failure or renal failure. However, the relationship between mAM levels and hemodynamics and cardiac function has not been examined in hemodialysis (HD) patients with coronary artery disease (CAD). The best marker, among mAM, ANP and BNP, for left-ventricular function in those patients is also unclear.. Plasma levels of mAM, total AM (tAM), ANP and BNP were determined before HD in chronic HD patients with CAD (group 1; n = 17) and were compared with those of HD patients without cardiac disease (group 2; n = 22). We examined their relationship to hemodynamics and cardiac function in group 1 using data obtained by cardiac catheterization.. Plasma levels of ANP and BNP were significantly higher in group 1 than in group 2, but there was no significant difference in plasma levels of mAM and tAM between the two patient groups. Plasma levels of both mAM and tAM significantly correlated with right atrial pressure (RAP), and only plasma tAM levels correlated with pulmonary artery pressure (PAP) and pulmonary artery wedge pressure (PAWP). However, no correlations were found between levels of the two forms of AM and ejection fraction (EF). In contrast, plasma ANP and BNP levels significantly correlated with both PAP and PAWP, and also with EF, although they did not correlate with RAP. The correlation of PAP and PAWP with ANP and BNP levels was closer than that with tAM levels. The most significant correlation was between BNP levels and EF (r = -0.756, p < 0.0001).. Our results suggest that the mAM level may be less useful than natriuretic peptide levels as a marker of cardiac function in HD patients with CAD, and that the BNP level might be the best indicator of left-ventricular function. In addition, cardiac disease such as CAD may have a minor impact on mAM levels compared to renal failure.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiac Catheterization; Coronary Artery Disease; Female; Heart; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides; Regression Analysis; Renal Dialysis