Targeting Oxidative Stress for Disease Prevention and Therapy: Where Do We Stand, and Where Do We Go from Here.

Oxidative stress (OxS) is one of the main processes related to aging and a common denominator of many different chronic/degenerative diseases (e.g., cardiovascular and neurodegenerative conditions and cancer). Thus, its potential modulation by supplementation/pharmacological therapy caused a lot of interest. However, these expectations have been mitigated by the obtainment of controversial results (beneficial, null, or adverse effects) following antioxidant interventions. Here, we discuss the current understanding of OxS assessment in health and disease, challenges and the potential of its evaluation in clinical practice, and available and future development for supplementation and pharmacologic strategies targeting OxS.

Effect of white wheat bread and white wheat bread added with bioactive compounds on hypercholesterolemic and steatotic mice fed a high-fat diet.

BACKGROUND: The effects of white wheat bread and white wheat bread added with a bioactive compound mixture (Cyclanthera pedata, Glycine max, Monascus-fermented red mold rice, Cynara scolymus and Medicago sativa) were examined on hypercholesterolemic and steatotic mice, divided into four groups: control diet (CTR), high-fat diet (HFD), high-fat diet with white wheat bread added with 1.5 g kg(-1) of mixture (HFD+AB) and high-fat diet with white wheat bread (HFD+B). RESULTS: Total serum cholesterol in the HFD+AB and HFD+B groups and hepatic triglycerides in the HFD+AB group decreased compared with the HFD group. Liver histology confirmed lower lipid drop accumulation in the HFD+AB group than in the HFD and HFD+B groups. HFD+AB caused a 7.0-fold increase and a 3.5-fold reduction in CYP7A1 and SREBP-1c gene expression respectively compared with the HFD group. Moreover, the HFD+B group showed a 2.2-, 8.4- and 1.5-fold increase in HMG CoA reductase, CYP7A1 and LDLr gene expression respectively compared with the HFD group. CONCLUSION: Both the white wheat bread and the added white wheat bread induced cholesterol reduction by increasing CYP7A1. Moreover, the added white wheat bread improved steatosis by decreasing SREBP-1c gene expression.

[Biomarkers for the diagnosis and management of heart failure: new frontiers]. / Biomarcatori per la diagnosi e la gestione dello scompenso cardiaco: nuove frontiere.

Heart failure (HF) has a complex pathophysiology including neurohormonal activation, inflammation and oxidative stress that, together with comorbidities, promote progressive myocardial damage and cardiac remodeling. Over the years the study of these pathogenic mechanisms has led to the identification of several analytes potentially useful as biomarkers in HF. High-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification of HF, with independent value to natriuretic peptides. Other biomarkers currently being evaluated as predictors of adverse outcome in HF are galectin-3, growth differentiation factor 15, mid-regional pro-adrenomedullin as well as makers of renal dysfunction. The use of multi-marker scores as well as the application of genomics, transcriptomics, proteomics and metabolomics could further refine the management of HF.

Increased plasma levels of osteopontin are associated with activation of the renin-aldosterone system and with myocardial and coronary microvascular damage in dilated cardiomyopathy.

In patients with dilated cardiomyopathy (DCM) abnormal myocardial blood flow (MBF) has been associated with coronary microvascular dysfunction. The aim of this study was to test the hypothesis that osteopontin (OPN) plasma levels could be associated with the activation of the renin-aldosterone system (RAS) in these patients and be involved in mediating myocardial and coronary damage. In 66 patients with idiopathic left ventricular dysfunction of variable severity the plasma levels of OPN were correlated with biomarkers of systemic metabolism, RAS activation, myocardial dysfunction and with clinical indexes of left ventricle (LV) function and perfusion obtained by 2D-echocardiography and PET. As compared to controls, patients showed a significant increase of inflammatory markers (OPN: 508+/-30.8ng/ml vs. 426.9+/-16.4, p<0.05 and interleukin (IL)-6: 1.71+/-0.29pg/ml vs. 0.38+/-0.03pg/ml, p<0.001) and of indexes of cardiac damage. OPN levels were significantly correlated with the extent of microvascular dysfunction (MBF at rest: p=0.01; during dipyridamole: p=0.0003) and with plasma renin activity (PRA) (r=0.26, p=0.04). Both in patients with milder or more severe LV dysfunction lower MBF values were associated with higher OPN levels and PRA. These results suggest a interdependent role of RAS and vascular inflammation in cardiomyopathy.

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.

Cardiovascular risk factors and gamma-glutamyltransferase fractions in healthy individuals.

BACKGROUND: Serum gamma-glutamyltransferase activity (GGT), even when within its normal reference range, catalyzes low density lipoprotein oxidation in vitro and predicts cardiovascular events. Of the four GGT fractions (b-GGT, m-GGT, s-GGT, and f-GGT) recently identified in blood, only b-GGT is found within atherosclerotic plaques. Our goal was to identify the determinants of the GGT fractions (b-, m-, s-, and f-GGT) and their association with established cardiovascular risk factors in healthy subjects. METHODS: Multiple linear regression analysis was applied to estimate the association of fractional GGT with gender, age, body mass index, arterial pressure (AP), plasma glucose, alanine aminotransferase (ALT), high and low density lipoproteins (LDL-C) cholesterol (HDL-C), triglycerides (TG) and C-reactive protein (CRP) in 200 healthy subjects. RESULTS: All GGT fractions were associated with ALT; b-GGT with AP, TG, and CRP; m-GGT with LDL-C, TG and CRP; s-GGT with TG and CRP, and f-GGT only with LDL-C, whereas gender was associated with s-GGT and f-GGT only. CONCLUSIONS: In healthy individuals, cardiovascular risk factors are associated with high molecular weight GGT fractions, namely with b-GGT, the only form present within the plaque. This finding adds to the present knowledge concerning the relevance of GGT, within its reference range, for atherosclerosis-related events.

Adrenomedullin plasma levels predict left ventricular reverse remodeling after cardiac resynchronization therapy.

BACKGROUND: Increase in adrenomedullin (ADM) plasma levels in congestive heart failure (HF) patients is due to many cardiac and systemic factors, particularly to greater fluid retention and to activation of sympathetic nervous system. Aim of this study was to assess the role of plasma ADM levels in HF patients treated by cardiac resynchronization therapy (CRT). METHODS: 50 patients, mean age 70 years, 34 male, New York Heart Association (NYHA) Class III-IV HF, left ventricular ejection fraction (LVEF) < 35%, underwent CRT. All patients were in sinus rhythm and with complete left bundle branch block (QRS duration 138 +/- 6 msec). A complete echoDoppler exam, blood samples for brain natriuretic peptide (BNP), and ADM were obtained from 2 to 7 days before implantation. RESULTS: At 16 +/- 6 months follow-up, >or=1 NYHA Class improvement was observed in 38 patients. However, a >10% reduction in end-systolic dimensions (ESD) was reported in 21 patients (Group I): -16.6 +/- 1.8%; in the remaining 29 patients ESD change was almost negligible: -2.0 +/- 1.03% (Group II), P < 0.0001. The two groups were comparable for age, sex, cause of LV dysfunction, therapy, QRS duration at baseline, preimplantation ESD, LVEF%, and BNP. Significantly higher pre implantation ADM levels were present in Group I than in Group II (27.2 +/- 1.8 pmol/l vs 17.9 +/- 1.4, P = 0.0003). CONCLUSIONS: Significantly higher ADM levels indicate a subgroup of patients in whom reverse remodeling can be observed after CRT. Patients with lower ADM basal values before CRT could represent a group in whom the dysfunction is so advanced that no improvement can be expected.

[Role of biomarkers in the detection of sub-clinical myocardial injury: H-FABP and radiofrequency ablation of ventricular arrhythmias]. / Utilità dei biomarcatori nella valutazione del danno cardiaco subclinico: H-FABP e ablazione in radiofrequenza delle aritmie ventricolari.

The importance of biomarker assay such as cardiac troponins and H-FABP is assuming a pivotal role not only in the diagnosis and follow-up of patients with acute coronary syndromes. Radiofrequency (RF) ablation represents a widely used method for the non pharmacologic treatment of arrhythmias.We report a case of a patient complaining of life-threatening arrhythmias treated by RF in whom temporal changes of cardiac biomarkers was determined after the procedure.

α-1 Antitrypsin as a potential biomarker in chronic heart failure.

BACKGROUND: Heart failure is characterized by a tissue damage that progressively leads to mechanical cardiac dysfunction and remodeling. A recent investigation showed that α-1 antitripsin, an antiprotease, able to inhibit metalloproteinases, provides prognostic information about heart failure and mortality postacute myocardial infarction. Therefore, we conducted a study to establish if α-1 antitrypsin (AAT) could be considered a marker of severity of heart failure. METHODS: A total of 182 heart failure patients (Group 1) were enrolled and AAT values were compared with controls (Group 2). RESULTS: In Group 1 a significant increment of AAT levels respect to Group 2 was observed (P < 0.0001). Moreover, in patients enrolled a progressive elevation of AAT levels across New York Heart Association classes (P < 0.0001) was found. Patients with α-1 antitripsin levels above median value showed lower hemoglobin concentration, higher circulating levels of C-reactive protein, hs-troponin T and B-type natriuretic peptide prohormone. Group 1 AAT levels resulted highly positively associated to B-type natriuretic peptide prohormone, C-reactive protein levels, while negatively associated to left ventricular ejection fraction%. However, at multivariate logistic analysis, only C-reactive protein was confirmed in a subgroup of postischemic heart failure patients. CONCLUSION: Adding AAT levels to the panel of heart failure biomarkers allow a better stratification of patients with heart failure.

New inflammatory and oxidative stress-based biomarker changes in response to a half-marathon in recreational athletes.

BACKGROUND: Modulation of oxidative stress/inflammation during exercise may have both positive and negative health effects, depending by a number of factors (e.g. training status, and exercise type, intensity and duration) and the oxidative stress or inflammation-related biomarkers considered, which may reflect different levels of the oxidative stress/inflammatory multi entities. The aim of this study was to evaluate oxidative stress and inflammatory multi-biomarker panel in response to a half-marathon during early and delayed recovery. METHODS: Blood samples (baseline, postrace within 20 min after the race end, and 24 h and 48 h after the run) from runners (N.=31, 20 males, mean age 47±6 years) were assessed for reactive oxygen species (ROM assay) and total antioxidant capacity (OXY test), leukocyte telomere length (LTL), procoagulant activity of circulating microparticles (MP-PCA), inflammatory parameters obtained by hemocrome, and irisin. RESULTS: A significant decrease for OXY (from 375±71 to 280±66, 239±54, 239±45 µmolHClO/mL) after the half-marathon and during recovery was observed. A reduction for ROMs was also evidenced respect to baseline (from 328±46 to 301±39, 290±56, 320±55 AU). Instead, MP-PCA increased after the race (from 6.2±6 to 10.5±6, 7±4.3 and 5.8±2.1 nmol/L), whereas the other biomarkers did not significantly change. CONCLUSIONS: The oxidant counterpart did not increase in response to the half-marathon, likely counteracted by antioxidants, which appeared greatly worn out. MP-PCA and WBC increase, always within the normality range, may represent an adaptation to regular chronic endurance training. In any case, antioxidant supply could be considered and tailored for each athlete in this exercise setting.

Nitric oxide treatment reduces neo-intimal formation and modulates osteopontin expression in an ex-vivo human model of intimal hyperplasia.

In this study the effects of nitric oxide (NO) on intimal hyperplasia (IH) were evaluated in an ex-vivo model of human saphenous vein (SV). SV segments were cultured in conditions able to reproduce IH (FCS), or in medium alone (RPMI), or in presence of a NO donor (NO). Osteopontin (OPN) and Interleukin (IL)-6 were determined in the medium at different culture times and in the tissue, at the end of experiment. OPN and IL-6 release in medium was increased in FCS with respect to RPMI (OPN: 13.9+/-2.9 vs. 2.3+/-0.8 microg/ml, p=0.0011; IL-6: 304.2+/-64.7 vs. 42.0+/-10.1 ng/ml, p<0.0006) as well as intima thickness, that positively correlated with OPN production (r=0.81). In tissue OPN was higher in FCS (82.0+/-30.3 ng/mg protein) than in RPMI (13.8+/-4.2, p=0.0051) and at baseline (3.7+/-0.7, p=0.018). NO reduces IH progression (25%) and both OPN and IL-6 expression (OPN/GAPDH: undetectable baseline; 0.27+/-0.06 RPMI; 0.89+/-0.28 FCS; 0.09+/-0.05 NO; p=0.026 FCS vs. baseline, p=0.018 vs. RPMI, p=0.005 vs. NO). The beneficial NO effect on IH reduction appears to be mediated by the indirect inhibition of OPN production. NO could modulates the initial inflammatory signals that induces the OPN over-production with the related cascade of events leading to IH.

Age-related changes in endothelin-1 receptor subtypes in rat heart.

Density, affinity, and subtype distribution of endothelin-1 (ET-1) binding sites were determined in rat cardiac tissue as a function of age in order to evaluate the association of alterations in the endothelin receptor system and aging in the heart. A significant decrease in the receptor subtype ET-A, which represents 70% to 80% of the total receptor population in cardiac tissue of 3- and 12-month-old rats, was observed in 24-month-old rats with respect to the younger groups. These findings indicate an alteration in ET-1 cardiac receptors associated with aging, mainly due to a variation in the receptor subtype distribution.

Circulating heat shock proteins and inflammatory markers in patients with idiopathic left ventricular dysfunction: their relationships with myocardial and microvascular impairment.

Little information is available on peripheral levels of Hsp72, Hsp60, and anti-Hsp60 antibodies in patients with left ventricular (LV) dysfunction due to non-atherosclerotic cardiac disease. In this study, serum Hsp72, Hsp60 and anti-Hsp60 antibodies, IL-6, and C-reactive protein (CRP) were measured in 44 healthy controls and in 82 patients with angiographically normal coronary arteries (LV ejection fraction [EF] > or = 50%, n=22; -35% to <50%, n=32; <35%, n=28). Patients with more severe disease (more depressed myocardial blood flow at rest and during dipyridamole, indicative of coronary microvascular impairment) showed more elevated circulating Hsp60 and auto-antibodies, Hsp72, and CRP levels. IL-6 was increased progressively as a function of severity of LV dysfunction. Anti-Hsp60 antibodies, Hsp72, and IL-6 were significantly correlated with brain natriuretic peptide (BNP) levels and LV end-diastolic dimensions (LVEDD) values. IL-6 tended to be related with Hsp72 in particular in patients with more severe disease (r = 0.45, P = 0.021). Hsp60 and Hsp72 activation and inflammatory markers were correlated with the extent of cardiac and microvascular dysfunction in patients with angiographycally normal coronary arteries. These results suggest a pathogenic role of infective-metabolic insult and inflammatory reaction in the development of vascular and myocardial damage in patients with heart failure even in the absence of overt coronary artery disease.

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.

Increased levels of C-type natriuretic peptide in patients with idiopathic left ventricular dysfunction.

C-type natriuretic peptide (CNP) is expressed in the vascular endothelium. It is not known whether CNP is specifically increased in patients with idiopathic left ventricular systolic dysfunction (ILVDys) with or without overt heart failure, and whether in these patients it is related with indicators of myocardial and/or endothelial/microvascular impairment. We determined plasma CNP levels in 51 ILVDys and in 60 controls. We observed a significant increase in patients with (7.0+/-0.9 pg/ml) or without (6.1+/-0.53 pg/ml) overt heart failure (p<0.001) in respect to controls (2.5+/-0.12 pg/ml). CNP was significantly correlated with LVEF (p<0.001), end-diastolic dimension (p<0.05), ANP (p<0.001) and BNP (p<0.001), interleukin-6 (p<0.001), total cholesterol (p<0.05), low-density lipoprotein (p=0.05), ratio total cholesterol/ high-density lipoprotein (p=0.05) and, in a subgroup of patients, with abnormal vasodilating capacity of the coronary microcirculation. In conclusion, CNP is activated in patients with LV dysfunction but without coronary artery disease, independently of the presence of overt heart failure and in tune with the extent of myocardial functional involvement. In these patients CNP is also related with both systemic and coronary indicators of endothelial/microvascular damage.

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 < 0.001) and glycemia (p < 0.05) emerged as independent 25(OH)D predictors. Aging (p < 0.001), male sex (p < 0.05), and obesity (p < 0.05) represented independent OC determinants. Aging (p < 0.05) was the only independent BALP determinant. After multivariate adjustment, low 25(OH)D (<20 ng/mL) (Odds ratio OR (95% confidence intervals CI)) (5 (1.4-18) p < 0.05) and elevated OC (>75th percentile-16.6 ng/mL) (6.7 (1.9-23.8) p < 0.01) were found to be significant FRS predictors, while subjects with elevated OC and/or BALP (>75th percentile-9.8 µg/L) showed a higher CV risk as estimated by PROCAM (3.6 (1.2-10.7) p < 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.

Plasma adrenomedullin relation with Doppler-derived dP/dt in patients with congestive heart failure.

BACKGROUND: Increased circulating adrenomedullin (AM) concentration has been reported in congestive heart failure (HF) and considered as a possible marker of cardiac dysfunction. HYPOTHESIS: The study was undertaken to assess the relationship between circulating AM concentration and left ventricular (LV) functional state, estimated by echo-Doppler techniques in patients with mild to moderate HF and different degrees of LV dysfunction. METHODS: Plasma AM, B-type natriuretic peptide (BNP), and N-terminal (NT) proBNP levels were measured in 55 patients with HF (New York Heart Association [NYHA] I n = 8, II n = 26, III n = 21) and in 20 controls; dP/dt was calculated by the Doppler tracing of the mitral regurgitation jet. RESULTS: The study was completed in 51 patients. Adrenomedullin levels were higher than in controls (19.2 +/- 1.4 vs. 13.3 +/- 0.7, p < 0.005) and elevated in proportion to NYHA functional class. B-type natriuretic peptide and NT-proBNP were 344 +/- 67 vs. 12 +/- 2 pg/ml and 2196 +/- 623 vs. 52 +/- 4 pg/ml, respectively (p < 0.0001); dP/dt was better related to AM (r = 0.582, p < 0.001) than to the other peptides. Adrenomedullin was significantly (p < 0.001) different between patients grouped according to the dP/dt cut-off predictive of event-free survival. CONCLUSIONS: The combination of depressed contractility and increased AM may provide a clue for further characterization of the severity of LV dysfunction in HF, independent of baseline LV ejection fraction.

C-type natriuretic peptide is closely associated to obesity in Caucasian adolescents.

CNP is a natural regulator of adipogenesis playing a role in the development of obesity in childhood. Aim of the study was to evaluate CNP plasma levels in normal-weight (N), overweight (OW) and obese adolescents (O). Eighty two subjects (age:12.8±2.4, years) without cardiac dysfunction were enrolled and CNP plasma levels were measured by RIA. NT-proBNP, MR-proANP, AGEs, reactive hyperemia index (RHI) and standard clinical chemistry parameters were also measured. O and OW adolescents had higher values of BMI and fat mass than N. CNP levels were significantly lower in OW:4.79[3.29-21.15] and O:3.81[1.55-13.4] than in N:13.21[7.6-37.8]; p<0.0001N vs O, p=0.0003N vs OW). LogCNP values correlated significantly and inversely with BMI z-score, FM%, TF% and circulating levels of CRP, insulin, total cholesterol, LDL, and triglycerides, in addition to an inverse relationship with skin AGEs and a direct correlation with RHI. LogCNP was also inversely associated with LogNT-proBNP and LogMR-proANP values. Using ROC analysis the risk of obesity resulted significantly (p≪0.0001) associated with CNP values (AUC=0.9724). These results suggest that CNP may play a more important role than BNP and ANP related peptides, as risk marker of obesity, in addition to its involvement in adipogenesis and endothelial dysfunction.

C-type natriuretic peptide plasma levels increase in patients with chronic heart failure as a function of clinical severity.

BACKGROUND: [corrected] C-type natriuretic peptide (CNP), secreted by the endothelium and the heart, is structurally related to atrial and brain natriuretic peptides, but its clinical significance in chronic heart failure (CHF) is controversial. AIM: To investigate the role of CNP in CHF, plasma CNP levels were determined in a prospective series of 133 patients with CHF (age 64 +/- 1 years, left ventricular ejection fraction (EF), 31.5 +/- 0.7%, mean +/-S.E.M.) and in 21 age-matched healthy subjects. METHODS AND RESULTS: CNP was measured by a radioimmunoassay (sensitivity: 0.41+/-0.009 pg/tube) after a preliminary solid-phase extraction. Plasma level of CNP in healthy subjects was 2.7 +/- 0.2 pg/ml and significantly increased in CHF, as a function of clinical severity: 4.9 +/- 0.7 pg/ml in NYHA class I; 7.0 +/- 0.4 pg/ml in class II (p < 0.001 vs. controls); 9.6 +/- 0.7 pg/ml in class III (p < 0.001 vs. controls and class I and II), and 11.8 +/- 2.0 pg/ml in class IV (p < 0.001 vs. controls, class I and II; Fisher's test after ANOVA). A significant relation was also found between CNP plasma levels and EF (R = 0.40, p < 0.001). CONCLUSION: Plasma CNP elevation is related to clinical and functional disease severity. These findings suggest a pathophysiological role for this peptide that, for its vasorelaxing activity, could influence the endothelial vasomotor response in CHF.

Adiponectin is associated with abnormal lipid profile and coronary microvascular dysfunction in patients with dilated cardiomyopathy without overt heart failure.

Reduced plasma adiponectin has been associated with abnormal lipid profile, reduced left ventricle (LV) function, and the extent of coronary atherosclerosis in coronary artery disease. The aim of this study was to assess these relationships in patients with dilated cardiomyopathy (DCM) without overt heart failure. Plasma adiponectin was measured in 55 DCM patients (age, 59 ± 12 years; male, 36; body mass index [BMI], 26.9 ± 0.49 kg/m²; LV ejection fraction, 39.8% ± 1.3%; New York Heart Association class I-II) and in 40 age- and BMI-matched healthy controls. In a subset of 25 patients, myocardial blood flow (MBF) was measured at rest and during intravenous dipyridamole (0.56 mg/kg in 4 minutes) by positron emission tomography and ¹³N-ammonia as a flow tracer. Adiponectin was 6.6 ± 0.34 µg/mL in controls and 10.9 ± 0.85 µg/mL in DCM patients (P < .001), where it was related inversely with BMI (P = .009) and directly with brain natriuretic peptide (P = .017), high-density lipoprotein (HDL) cholesterol (P = .002), and MBF dipyridamole (P = .020). Adiponectin lesser than median value in patients was associated with higher total to HDL cholesterol ratio (4.8 ± 0.24 vs 3.9 ± 0.18, P = .009) and lower MBF reserve (1.76 ± 0.16 vs 2.43 ± 0.19, P = .01). These results could suggest that down-regulation of the adiponectin levels and reduced HDL cholesterol have a key role in causing impaired coronary function and myocardial perfusion in DCM.