Adrenomedullin plasma levels as predictors of left ventricular reverse remodelling in patients treated with cardiac resynchronization therapy

Purpose: Adrenomedullin (ADM), a potent natriuretic and vasorelaxing peptide, has been isolated from human pheochromocytoma cells and from cardiovascular tissue. Increase in ADM plasma levels in congestive heart failure (CHF) patients (pts) is due to many cardiac and systemic factors and in particular to the greater plasma volume and to the activation of sympathetic nervous system. Aim of this study was to assess the role of plasma ADM levels in CHF pts treated by cardiac resynchronization therapy (CRT). Methods: 42 pts, mean age 70 years, 27 males, NYHA Class III-IV CHF underwent CRT. Cause of CHF were idiopathic dilated cardiomyopathy in 27 pts, post ischemic in 15; all pts were in sinus rhythm and with complete left bundle branch block (QRS duration 138?8 msec). A complete echoDoppler exam, blood samples for brain natriuretic peptide (BNP) and ADM were obtained within 2 days before implantation. Results: At 18?6 months follow-up, >1 NYHA Class improvement was observed in 31/42 pts. However, a >10% reduction in end-systolic dimensions (ESD): -18.2?2.3% was reported in 16 pts (Group I); in the remaining 26 pts ESD change was almost negligible: -1.5?3.2% (Group II). The two groups were comparable for age, sex, cause of LV dysfunction, ongoing therapy, QRS duration at baseline, pre implantation ESD (60.6?1.8 vs 59.9?1.9 mm - Group I vs II), LVEF% (24.3?1.2 vs 25.4?1.3%) and BNP (545?80 vs 494?89 pg/ml). Significantly higher pre implantation ADM levels were present in Group I than in Group II (25.8?2.4 pmol/l vs. 17.1?1.6, p = 0.005). Conclusions: Significantly higher ADM levels indicate a subgroup of pts in whom significant reverse remodelling can be observed after CRT. Since AM is also produced in cardiac myocytes, lower ADM values before CRT could suggest the presence of more severe myocardial damage which may impair LV reverse remodelling even in the setting of clinically successful resynchronization

Plasma adiponectin is a marker of severity in heart failure

Purpose. Adiponectin, a 247 aminoacid protein produced mainly by adipose tissue, beside its effects on glucose metabolism, plays important protective function against cardiovascular disease. Adiponectin is inversely correlated with an increased cardiovascular risk and hypo-adiponectinemia is considered an independent cardiovascular risk factor. On the contrary, the role of adiponectin in heart failure (HF) is not fully known. In order to evaluate the prognostic value of circulating adiponectin, we measured total adiponectin plasma levels in patients with HF of different severity. Methods. Total adiponectin, leptin and interleukin(IL)-6 levels were measured in plasma samples of 159 no diabetic patients with different etiology HF (17 in NYHA class I, 82 in NYHA class II, 46 in NYHA class III and 14 in NYHA class IV, age 62?14 yrs, LEVF% 32.5?0.79, mean?sem) and in 31 healthy subjects as control, by dedicated ELISA (Linco Res-US, DRG Diagnostics-Germany, Diaclone Research-France, respectively). In the same group brain natriuretic peptide (BNP) levels were determined by IRMA (Shionogi, Osaka, Japan). Results. Our findings indicated that total adiponectin levels increased significantly as a function of disease severity (7.1?0.61 mg/ml vs 10.9?1.4 in NYHA class I vs 12.8?0.95 in NYHA class II vs 15.7?1.3 in NYHA III vs 16.7?1.8 in NYHA class IV; p<0.001 NYHA II, III and IV vs controls) and they correlated negatively with LVEF% (p=0.0009), positively with cardiac function (BNP levels) (p<0.0001) and inflammation (IL-6 levels) (p<0.0001). We did not observe any correlation with metabolism (BMI) in patients with HF, while a significant correlation was found between leptin and BMI (p<0.0001). Conclusion. Circulating adiponectin is associated with cardiovascular function and inflammation in HF patients. The increased adiponectin plasma levels in HF is a marker of disease severity, indipendent of metabolism

High molecular weight adiponectin is increased in plasma of patients with idiopathic dilated cardiomyopathy with and without overt heart failure

Purpose: Adiponectin, a biologically active substance with multimeric structure released by adipocytes, is considered as a new diagnostic/prognostic marker in the cardiovascular disease. The trimeric low-(LMW), the hexameric middle-(MMW) and the high-molecular weight (HMW) isoforms have been found in human peripheral circulation. It has been hypothesized that the HMW, that is an active form, has cardioprotective effects and its determination could give additional information on the role of this protein in cardiovascular diseases. Aim of the study was to determine the levels of adiponectin multimers in patients with dilated cardiomyopathy (DCM) and to evaluate its relationship with inflammatory profile and left ventricular (LV) function. Methods: The plasma levels of total (T) and adiponectin multimers were evaluated in 50 no diabetic patients with DCM (30 males, 38 in NYHA class I-II, 12 in NYHA class III, LVEF% 40.6?1.4, age 57?1 yrs, BMI 26.6?0.41 kg/m2, mean?sem) and in 25 age- and BMI-matched healthy subjects as controls. An Elisa system (Alpco Diagnostics, US) was used to directly measure T and, after treatment with two different specific proteases, the HMW and the sum of MMW and HMW forms while the levels of the MMW and LMW were obtained by difference. Results: T adiponectin in DCM increased with respect to controls as a function of disease severity (3.8?0.38 mg/ml vs 5.4?0.48 in NYHA class I-II vs 8.0?1.9 in NYHA class III; p<0.05 NYHA III vs controls and NYHA I-II) and correlated with functional and inflammatory indices. HMW was the predominant isoform in plasma, accounting for 50% of T adiponectin to which was positively correlated (p<0.001); MMW and LMW represented each the 25% of total protein. HMW significantly increased in DCM with respect to controls (1.8?0.15 mg/ml vs 2.5?0.21 in NYHA class I-II vs 4.8?1.2 in NYHA class III; p<0.001 NYHA III vs controls and NYHA I-II) while MMW and LMW did not vary with respect to controls or as a function of NYHA class. HMW correlated negatively with LVEF% (p=0.0041), positively with Interleukin-6 (p<0.001) and BNP (p=0.003). No significant correlation with BMI was observed both for total and HMW adiponectin. Conclusions: This study demonstrates that HMW adiponectin is elevated in DCM patients and increases significantly as a function of severity. Although many studies need to identify if the HMW isoform is associated to cardioprotection, the significant relation with markers of inflammation and cardiac dysfunction, lacking for MMW and LMW forms, underlines the importance to investigate the role of HMW in this disease

Adiponectin Mediates the Effects of Atherogenic Risk Profile on the Coronary Microcirculation in Patients with Idiopathic Lv Systolic Dysfunction

Purpose. Adiponectin (ADN), a biologically active protein produced by the adipose tissue, has protective vascular effects. Accordingly, ADN plasma levels are reduced in patients with coronary artery disease (CAD) while in heart failure ADN tends to increase. We hypothesized that ADN plasma levels could mediate the effects of atherogenic risk profile on the coronary microcirculation of patients with early LV systolic dysfunction (ILVDys) not secondary to established CAD. Methods. Plasma ADN was measured in 55 patients (age 59?1 yrs, 36 males, BMI 26.9?0.49 Kg/m2, mean?sem) with angiographically normal coronary arteries, LV systolic dysfunction (LVEF 39.8?1.3 % range 22-54 %) but without overt heart failure (NYHA class I-II) and in 40 age- and BMI-matched healthy controls by using a specific Elisa (Linco Res). BMI, cholesterol and glucose profiles were assessed in all. In a subset of 25 patients coronary microvascular function was studied by PET and 13N-Ammonia as a flow tracer. Myocardial blood flow (MBF) was measured at rest and during i.v. dipyridamole (Dip) (0.56 mg/Kg in 4 min). Results. ADN was 6.6?0.34 &#956;g/ml in controls and 10.9?0.85 in ILVDys patients (p<0.001). In patients ADN levels were inversely related with BMI (p=0.009) and directly related with age (p=0.007), HDL Cholesterol (p=0.003) and MBF Dip (0.020). Patients showing more severe coronary microvascular dysfunction (MBF Dip<1.42 ml/min/g, median value in patients) had significantly depressed ADN (9.7?2.3 vs 13.7?1.6, p=0.021) as compared with the remaining patients. Conclusions. This is the first study which associates adiponectin plasma levels with atherogenic risk profile and coronary microvascular function in patients with idiopathic LV dysfunction. These results suggest that adiponectin signal is strongly involved in mediating coronary vascular function independently of the presence of overt CAD or heart failure

Relationship between Bone Health Biomarkers and Cardiovascular Risk in a General Adult Population

Purpose/Introduction: Osteoporosis (OP) and cardiovascular (CV) disease emerge as closely related conditions, showing common risk factors and/or pathophysiological mechanisms. The aim of this study was to evaluate the association between bone health markers (BHM) and individual CV risk factors and overall CV risk (FRAMINGHAM-FRS, and PROCAM scores) in a general adult population. Methods: In 103 subjects (21 males; age: 56 ± 12 years), vitamin D (25(OH)D), osteocalcin (OC), bone alkaline phospatase (BALP), procollagen I aminoterminal propeptide (P1NP), CTx-telopeptide, as well clinical history and life style were evaluated. Results: Aging (p &lt; 0.001) and glycemia (p &lt; 0.05) emerged as independent 25(OH)D predictors. Aging (p &lt; 0.001), male sex (p &lt; 0.05), and obesity (p &lt; 0.05) represented independent OC determinants. Aging (p &lt; 0.05) was the only independent BALP determinant. After multivariate adjustment, low 25(OH)D (&lt;20 ng/mL) (Odds ratio OR (95% confidence intervals CI)) (5 (1.4–18) p &lt; 0.05) and elevated OC (&gt;75th percentile-16.6 ng/mL) (6.7 (1.9–23.8) p &lt; 0.01) were found to be significant FRS predictors, while subjects with elevated OC and/or BALP (&gt;75th percentile-9.8 μg/L) showed a higher CV risk as estimated by PROCAM (3.6 (1.2–10.7) p &lt; 0.05). CTx and P1NP did not significantly correlate with CV risk factors or scores. Conclusion: As we go further into bone and CV physiology, it is evident that a close relationship exists between these diseases. Further studies are needed to investigate mechanisms by which bone turnover markers are related to metabolic risk and could modulate CV risk. This knowledge may help to develop possible multiple-purpose strategies for both CV disease and OP prevention and treatment

A methodological reappraisal of total and high molecular weight adiponectin determination in human peripheral circulation: Comparison of four immunometric assays

Background: Adiponectin, present in different multimeric forms in circulation, is increasingly used in clinical settings as a cardiometabolic marker. The development of several commercially available enzyme-linked immunosorbent assays (ELISA) has allowed for the widespread measurement of adiponectin in research as well as in clinical practice. The comparative performance of these assays is thus an issue of major relevance. Methods: The analytical performance of four different ELISAs (LINCO, B-Bridge, SPIbio and ALPCO) was evaluated. Samples from 102 cardiac patients and 40 healthy subjects were tested using LINCO and ALPCO. The latter is able to measure the concentrations of multimers. For the multimer assay, an error propagation study was performed. A subset of subjects was tested by all four ELISAs for comparison purposes. Results: Bland-Altman plots revealed differences between the results of the four ELISAs, mainly for ALPCO. However, a strong correlation between the different ELISAs (ALPCO, r=0.83; B-Bridge, r=0.98; SPIbio, r=0.91 vs. LINCO) was observed. Total adiponectin measured by LINCO showed a better association with cardiac disease [receiver-operating characteristic (ROC) curves] than total and high molecular weight adiponectin measured by ALPCO. Conclusions: The results of this study contribute to a better understanding of the methodological features of the several ELISAs, and help in the evaluation and comparison of the relative results. © 2010 by Walter de Gruyter Berlin New York

Sequencing and cardiac expression of natriuretic peptide receptor 2 (NPR-B) in Sus Scrofa.

The cardiovascular actions of the C-type natriuretic peptide (CNP) are mainly mediated by the interaction with natriuretic peptide receptor-B (NPR-B). The aim of this study was to identify the sequence of NPR-B in Sus Scrofa, which is not present in GenBank, to verify the expression of NPR-B in the different cardiac chambers of normal pigs and evaluate its homology with murine and human species. Using the guanidinium thyocyanate-phenol-chloroform method, we extracted total RNA from samples obtained from heart of mouse and from the atrium, ventricle, and septum of normal pigs. Pig NPR-B mRNA was sequenced using polymerase chain reaction primers designed from mouse consensus sequences. Sus Scrofa natriuretic peptide receptor 2 mRNA, 1-396 bp, was submitted to GenBank (accession number DQ487044). The presence of NPR-B at mRNA level was detected in all the cardiac chambers; moreover, the bands obtained from pig cardiac tissue shared a 93% sequence homology with a region of the mouse NPR-B and a 95% sequence homology with Homo sapiens. Therefore, NPR-B sequencing provides a new tool to investigate the role of CNP under physiological and pathological conditions in the experimental and clinical setting