Plasma BNP Levels Research Articles

Elevated plasma levels of TNF-alpha and Interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders

BackgroundDiabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6) and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease.MethodsWe enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes.ResultsPatients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 (P = 0,001), TNF-alpha (P < 0,001) and NT-pro- BNP (P = 0,001) plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6 (P = 0,006) and TNF-alpha (P = 0,002) remained significantly elevated in subjects with E/Em ratio ≥ 15.ConclusionThis study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

Study on the changes of plasma levels of brain natriureticpeptide and homocysteine in patients with acute cerebral infarction

Objective To explore the changes of plasma levels of BNP and Hcy in patients with acute cerebral infarction and the possible pathophysiologic implications.Methods Plasma BNP and Hcy levels in 80 patients with acute cerebral infarction and 30 healthy controls were determined by chemiluminescence method.Results The levels of BNP and Hcy[(153.24±69.76 )ng/L,(30.34±9.46 ) μmol/L]in patients with acute cerebral infarction were significantly higher than those in control groups[( 85.16 ±28.15 ) ng/L,(11.54±3.29) μmol/L](P＜0.01),and plasma BNP and Hcy levels in patients with large infarction area were significandy higher than those in patients with small infarction area (P＜0.01).Conclusion Plasma BNP and Hcy are increased significantly in patients with cerebral infarction,and are highly associated with the occurence of cerebral infarction.They possibly play a key role in the pathogenesis of cerebral infarction. Key words: Acute cerebral infarction; Brain natriuretiepeptide; Homocysteine

Dramatic Reverse Left Ventricular Remodeling by Carvedilol in Hypertensive Cardiomyopathy: A Case Report

A 51-year-old man had a 17-year history of untreated hypertension. He was first referred to our hospital because of orthopnea in July 2003. On admission, blood pressure level was 202/110 mmHg. Chest radiography and echocardiography showed cardiomegaly with lung congestion and diffuse severe hypokinesis (LVEF; 23%) with LVDd of 76 mm, respectively. A month after the treatment of congestive heart failure with conventional medication, patient's symptoms were decreased concomitant with improved cardiomegaly with lung congestion and the decreased in plasma BNP level (CTR; 61 to 51%, BNP level; 1,540 to 127 pg/mL, respectively). However, echocardiography showed still diffuse severe hypokinesis. To exclude ischemic cardiomyopathy, we performed coronary angiography and left ventriculography that revealed normal coronary arteries and diffuse hypokinesis (LVEF; 35%). Therefore, we finally made a diagnosis hypertensive cardiomyopathy. One year after the treatment including carvedilol, angiotensin II receptor blocker and diuretics, clinical status was gradually improved. In addition, echocardiography revealed that LVDd reduced 76 mm to 53 mm and LVEF increased 23% to 63%. So, we could stop prescription of diuretics. After a 6-year follow-up period, he remains asymptomatic and echocardiography continue to show normal LVDd and LVEF with normal BNP level. Here, we reported a case of hypertensive cardiomyopathy who had a dramatic reverse left ventricular remodeling by the treatment of carvedilol.

Diagnostic role of plasma BNP levels in neonates with signs of congenital heart disease

Only a few studies have examined the relationship of plasma BNP levels and congenital heart disease (CHD) in neonates and these mainly concern preterm neonates with patent ductus arteriosus. We aimed to investigate the diagnostic role of plasma BNP in neonates admitted in the neonatal intensive care unit, (NICU), with signs of congenital heart disease (CHD). Prospective assessment of plasma BNP levels in 75 consecutive neonates with suspected CHD (heart murmur, respiratory distress, or cyanosis), admitted in the NICU of our university hospital. The final diagnosis was done with echocardiography. Haemodynamically significant Left to Right shunts, (hsLtR), were found in 29 neonates, insignificant LtR shunts in 22, no heart disease in 15 and cyanotic heart disease in 9. BNP levels were significantly higher in neonates with hsLtR shunts vs. all other groups (logBNP 2.9 ± 0.5 pg/ml vs. 1.5 ± 0.4 pg/ml vs. 1.5 ± 0.3 pg/ml vs. 1.6 ± 0.2 pg/ml, p < 0.0001). Plasma BNP levels > 132.5 pg/ml had 93.1% sensitivity and 100% specificity for diagnosing hsLtR shunts (accuracy 99.6%). Plasma BNP is a reliable test for diagnosing hsLtR shunts in the NICU. This will alert the neonatologist for ordering an echocardiographic examination, or if the latter is not available, for transferring the neonate to an appropriate tertiary centre with neonatal-paediatric cardiology facilities. Normal BNP levels imply the absence of a significant LtR shunt, but may not exclude cyanotic heart disease.

Effect of simvastatin on plasma interleukin-6 in patients with unstable angina

The primary aim of the study was to investigate the effect of sinvastatin on plasma interleukin-6 (IL-6) in patients with unstable angina pectoris (UAP). Eighty-six patients with UAP were randomized into simvastatin (40 mg/d for 4 weeks) and the placebo group. Plasma IL-6 was measured by ELISA. There was a reduction in the plasma total cholesterol and LDL in the simvastatin group (P < 0.01). The simvastatin group also had better angina control than the placebo group (post-treatment angina score, 0.72+/-0.59 vs 1.07+/-0.76, P < 0.05). Following treatment, the average left ventricular ejection fraction in the simvastatin group was higher than in the placebo group (0.54+/-0.06 vs 0.51+/-0.05, P < 0.05), whereas the plasma BNP levels were lower (16.8+/-6.6 vs 26.4+/-1.4, P < 0.01). Before treatment, there was no difference in the plasma levels of IL-6 between the simvastatin and the placebo groups (P > 0.05). Following treatment, the IL-6 levels in the simvastatin group were lower than in the placebo group (0.7+/-0.4 vs 1.2+/-0.4 pg/ml, P < 0.05). Short-term treatment with simvastatin reduces plasma IL-6. The anti-inflammatory effect of simvastatin may contribute to its beneficial effects on the ventricular function and angina control.

Cardio-Humoral Actions of the Phosphodiesterase-V Inhibitor Vardenafil in Experimental Diabetic Cardiomyopathy

Background: Diabetic cardiomyopathy (DMC) is defined as the presence of left ventricular (LV) dysfunction (systolic and/or diastolic) in diabetes mellitus without a prior history of coronary artery disease, hypertension or valvular disease. Cyclic guanosine 3’,5’-monophosphate (cGMP) the second messenger of the natriuretic peptide system and the nitric oxide system plays an important role in the preservation of myocardial function. We determined the cardio-humoral effects of chronic treatment with the phosphodiesterase-V inhibitor (PDEVI) vardenafil in rat model of DMC. Methods: Diabetes mellitus was induced in male Wistar rats by a single dose of intra peritoneal injection of Streptozotocin (65 mg/Kg). Four weeks after establishing diabetes, the treatment group (n=6) received a suspension of vardenafil daily by gavage for two months at the dose of 5mg/kg/day and the diabetic control group (n=12) received no treatment. A non-diabetic control group (n=13) was maintained as positive control. Echocardiography was used to assess LV structure and function. Plasma humoral profile was assessed and at 3 months, the hearts were harvested for analysis. Results: As compared with non-diabetic controls, the diabetic controls had LV hypertrophy (LVH) (0.25 ± 0.01 vs 0.18 ± 0.01 LV/body weight %) and systolic and diastolic myocardial dysfunction as measured by peak circumferential contraction strains (Cs-C) (10.8 ± 0.7 vs 14.3 ± 0.6 %), strain rates (Csr-C) (2.3 ± 0.1 vs 3.9 ± 0.3 s -1) and early diastolic strain rates (Csr-E) (2.6 ±0.2 vs 3.9 ± 0.3 s -1) (p<0.05). These changes were associated with increased plasma BNP, renin and aldosterone levels. The LVH decreased and LV dysfunction improved significantly with vardenafil treatment as compared to the diabetic controls (p<0.05) and was associated with decreases in plasma BNP, renin and aldosterone levels. Conclusion: PDEV inhibition with Vardenafil attenuated LVH and improved LV systolic and diastolic myocardial function, associated with suppression of aldosterone and renin in a rat model of experimental DM cardiomyopathy. These findings suggest that both the PDEV and renin-aldosterone systems are involved in the pathophysiology of DMC.

Relationship between B-type natriuretic peptide and Tei index in elderly patients with heart failure

Objective To study the relationship between B-type natriuretic peptide and Tei index in elderly patients with heart failure(HF). Methods The plasma BNP levels in elderly patients with HF( n = 65 ) and normal control group(n=30) were measured;at one time, series of ultrasonic parameters were measured by the color Doppler ultrasound,counting up Tei index. Results The plasma BNP levels and Tei index in elderly patients with HF were significantly higher than those in control group (P＜0. 01 ), with NYHA cardiac function classification aggravating,they were significantly higher by levels(P＜0. 01 ) ; the plasma BNP levels were positively related to Tei index(r=0. 517, P＜0. 05). Conclusion Plasma BNP levels and Tei index can be used as clinical indicators to determine the serious degree of elderly HF, and they have good correlation. Key words: Heart failure; B-type natriuretic peptide

PARP inhibition delays transition of hypertensive cardiopathy to heart failure in spontaneously hypertensive rats

Oxidative stress followed by abnormal signalling can play a critical role in the development of long-term, high blood pressure-induced cardiac remodelling in heart failure (HF). Since oxidative stress-induced poly(ADP-ribose)polymerase (PARP) activation and cell death have been observed in several experimental models, we investigated the possibility that inhibition of nuclear PARP improves cardiac performance and delays transition from hypertensive cardiopathy to HF in a spontaneously hypertensive rat (SHR) model of HF. SHRs were divided into two groups: one received no treatment (SHR-C) and the other (SHR-L) received 5 mg/kg/day L-2286 (PARP-inhibitor) orally for 46 weeks. A third group was a normotensive age-matched control group (CFY) and a fourth was a normotensive age-matched group receiving L-2286 treatment 5 mg/kg/day (CFY+L). At the beginning of the study, systolic function was similar in both CFY and SHR groups. In the SHR-C group at the end of the study, eccentric hypertrophy with poor left ventricular (LV) systolic function was observed, while PARP inhibitor treatment preserved systolic LV function. Due to these favourable changes, the survival rate of SHRs was significantly improved (P < 0.01) by the administration of the PARP inhibitor (L-2286). The PARP inhibitor used did not affect the elevated blood pressure of SHR rats, but moderated the level of plasma-BNP (P < 0.01) and favourably influenced all the measured gravimetric parameters (P < 0.05) and the extent of myocardial fibrosis (P < 0.05). The inhibition of PARP increased the phosporylation of Akt-1/GSK-3beta (P < 0.01), ERK 1/2 (P < 0.01), and PKC epsilon (P < 0.01), and decreased the phosphorylation of JNK (P < 0.05), p-38 MAPK (P < 0.01), PKC pan betaII and PKC zeta/lambda (P < 0.01), and PKC alpha/betaII and delta (P < 0.05). These data demonstrate that chronic inhibition of PARP induces long-term favourable changes in the most important signalling pathways related to oxidative stress. PARP inhibition also prevents remodelling, preserves systolic function, and delays transition of hypertensive cardiopathy to HF in SHRs.

S7-2 Multi-Biomarkers and Left Ventricular Remodeling in Hypertrophic Cardiomyopathy

Limited data are available regarding the significance of biomarker in hypertrophic cardiomyopathy (HCM). We evaluated the relationship between several biomarkers and clinical/echocardiographic parameters. Results: 1. BNP: The plasma BNP levels were increased in patients with left ventricular (LV) outflow obstruction 30mmHg, maximum LV thickness 30mm and atrial fibrillation. Moreover, plasma BNP levels were significantly increased in those with adverse cardiovascular events. 2. Adiponectin: The plasma adiponectin levels were related to age, gender, body mass index, atrial fibrillation, %fractional shortening and maximum LV wall thickness, but were not related to LV outflow gradient. Multivariate analysis showed that %fractional shortening and maximum LV wall thickness were the independent echocardiographic predictors of the plasma adiponectin levels. 3. Matrix metalloproteinase (MMP)-2: The plasma MMP-2 levels in patients with LV systolic dysfunction were significantly higher than those in patients without systolic dysfunction. MMP-2 levels were positively related to LV end-diastolic dimension and left atrial dimension, and inversely related to maximum LV wall thickness and %fractional shortening. Conclusions: Each of these biomarkers is important for assessing the LV remodeling process. Measurement of multibiomarkers is useful to evaluate the disease severity and to predict the prognosis in HCM.

The Efficacy of Different Therapy Protocols for Heart Failure in Patients with Heart Failure and Increased Natriuretic Peptide Level

The Efficacy of Different Therapy Protocols for Heart Failure in Patients with Heart Failure and Increased Natriuretic Peptide Level Natriuretic peptide BNP might be clinically useful for monitoring treatment effects in patients with heart failure (HF). In order to investigate the pharmacological effects of different therapy protocols for patients with HF based on the BNP level before and after therapy, we performed an open randomized comparative trial. Sixty-two HF patients with increased natriuretic peptide level, aged 55.82±9.09, II-III NYHA functional classes, ejection fraction (EF) &lt;45%, received a 12-week treatment with either traditional pharmacotherapy for HF with ACE inhibitors and β-blockers (1st group), or ACE inhibitors and angiotensin II receptor blockers (ARBs) (2nd group), or β-blockers and ARBs (3rd group), and ACE inhibitors, β-blockers and ARBs (4th group). We evaluated the BNP plasma level, hemodynamic state (pulmonary capillary wedge pressure (PCWP), cardiac output (CO), EF and exercise capacity. The BNP plasma level decreased significantly in the 4th group of patients who received ACE inhibitors, β-blockers and ARBs, in comparison to other groups. A beneficial influence on hemodynamic and exercise capacity was significantly pronounced in this group, compared to the other therapy regimes. In conclusion, the therapeutic protocol: ACE inhibitors, β-blockers and ARBs in HF patients with increased natriuretic peptide level significantly improves the quality of life, left ventricular function, hemodynamic parameters and exercise capacity. All these changes were accompanied with a decreasing of the BNP plasma level.

Molecular Mechanism of Heart Failure in Rats Induced by Chronic Systemic Hypoxia: Role of Hypoxia Inducible Factor‐1α in the Regulation of B‐type Natiuretic Peptide‐45 Gene Expression

Plasma BNP levels have been shown to correlate closely with the left ventricle pressure, makes it the first biomarker for heart failure. Although BNP has been applied broadly, its biochemistry is far from complete and its expression remained elusive. At the molecular level the reaction of the organism to hypoxia is mediated by HIF‐1α which activates more than 200 of target genes, but its linked to BNP has not reported yet. The aim of recent study is to develop heart failure model in rats. Rats, male, were randomized into 7 groups (n = 4 per group): control normoxia group exposed to room air, hypoxia group were caged in hypoxic chambers (O2 8%) for 1, 3, 7, 14, 21, and 28 days.Resulthistopathologic examination shows massive hypertrophy of cardiomyocytes, accompanied by damage to the structure of intercalated disk (ID), necrosis, fibrosis and apoptosis as a hallmark of ventricular remodeling. Drastic increase in plasma BNP‐45 levels on 21 day exposure, BNP mRNA expression increased &gt; 7 fold changed and activities of HIF‐1α were significantly increased, compared with control group.ConclusionsChronic systemic hypoxia causes: Ventricular hypertrophy accompanied by damage in the structure of ID and then progress to heart failure. There were changes in the gene expression either in transcription and post‐transcription level.

Improvement of Cardiac Function after Granulocyte-colony Stimulating Factor-mobilized Peripheral Blood Mononuclear Cell Implantation in a Patient with Non-ischemic Dilated Cardiomyopathy Associated with Thromboangiitis Obliterans

Cardiac involvement is a rare complication with thromboangiitis obliterans (TAO). We report a 29-year-old man with TAO accompanied with non-ischemic dilated cardiomyopathy. He had no history of heart disease, but echocardiogram demonstrated diffuse hypokinesis and dilated left ventricle. Coronary angiography revealed no organic stenotic lesion. For limb salvage, he was treated with granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cell (PBMNC) implantation on his right leg. Not only ischemic leg symptoms, but also plasma level of BNP and (123)I-metaiodobenzylguanidine scintigraphic parameters improved after 24 weeks. G-CSF-mobilized PBMNC implantation could be an effective approach to treating non-ischemic cardiomyopathy.

DETERMINACIÓN DEL PEPTIDO NATRIURÉTICO CEREBRAL EN PACIENTES SOMETIDOS A DIFERENTES TÉCNICAS DE HEMODIAFILTRACIÓN.

IB-type natriuretic peptide is a cardíac neurohormone secreted by the cardíac ventricules in response to ventricular dilatation so plasma BNP level correlate with left ventricular mass and dysfunction. Dialysis patients have much greater levels of BNP due to the volume overload and because of reduced renal clearance. The aim of this study was to mesure and compare the BNP levels in three groups of patients who received different hemodiafiltration techniques: Daily online hemodiafiltration (HDFOLd), on-line hemodiafiltration (HDFOL) and low convective volume hemodiafiltration (HDF). Fifteen patients were included, five in each group. Pre and postdialysis BNP leves were measured during 8 weeks. The measure was done at the beginning of the week (long period), and at the end (short period), in order to study if there were significative differences between techniques and periods. We found significative differences between predialysis BNP levels in the short period (BNPpreC) and the long period (BNPpre-L). We also found significative differences with the posdialysis BNP in both periods; BNPpre- L vs. BNPpos-L (1069+/-1031 vs. 612 +/- 540). After comparing the three techniques the study showed significative differences between BNPpreC in HDF and HDFOL compared with HDFOld. And also after dialysis between BNPpos-C in HDFOLd compared with the other techniques. Although previous papers have shown that BNP levels have limited potential for assessment of hydration in hemodialysis patients, in this study our data demonstrate that after dialysis BNP levels decline in a significative way in the long and short period and we have found that patients on daily hemodialysis show lower BNP levels, and maybe this could be explained because daily on-line haemodiafiltration patients had lower weight rise between dialysis sessions and also better haemodynamic tolerance.

Early detection of myocardial dysfunction in children with beta-thalassaemia major

To evaluate left and right ventricular myocardial performance using pulsed-tissue Doppler imaging (TDI) and its relation to BNP levels in patients with beta-thalassaemia major (beta-TM). We enrolled 36 thalassaemic patients (21 male, 15 female; mean age: 14.2 +/- 4.1 years) with normal left ventricular systolic and diastolic functions with conventional echocardiography and 30 healthy control subjects (18 male, 12 female, and 12.5 +/- 4.2 years). Myocardial performance indexes (MPI) of left ventricular (LV) lateral wall, interventricular septum (IVS) and right ventricular (RV) lateral wall were calculated with TDI. Plasma BNP levels were measured in all patients. MPIs and other echocardiographic parameters of patients with beta-TM were compared with control group. All the patients' plasma BNP levels were within normal limits. There were no differences between conventional echocardiographic parameters of patients and control group. MPI of LV, IVS, and RV of patients were significantly higher than control group (P = 0.01, and P < 0.01, and P < 0.001, respectively). Our study confirms that MPI obtained by TDI seems to be an early sensitive parameter of cardiac dysfunction in beta-TM. We concluded that MPI obtained by TDI may be an adjunctive parameter to conventional echocardiography for detecting early myocardial damage.

The BNP concentrations and exercise capacity assessment with cardiopulmonary stress test in cyanotic adult patients with congenital heart diseases

Cyanosis is observed in patients with complex congenital heart disease (CHD) and pulmonary hypertension, heart failure represents an important clinical problem in such patients. The aim of this study was to evaluate the exercise capacity in patients with cyanotic CHDs using cardiopulmonary exercise test, measuring serum BNP levels as well as to seek correlation between BNP levels and cardiopulmonary exercise test parameters and identify the effects of blood oxygen desaturation and pulmonary hypertension on these indices.The study group consisted of 53 patients (21 males) at the mean age of 39.4±14.3 years, of whom 19 were operated on at the mean age of 9.6±8.6 years. Mean blood oxygen saturation (SO2) in patients was 81.2±6.2%. Twenty four patients presented with Eisenmenger syndrome, 16 — univentricular hearts, 4 — transposition of the great arteries, 6 — Fallot's tetralogy, and 3 — Ebstein anomaly. The control group comprised 32 healthy individuals (16 males) at the mean age of 40.7±9.9 years. Cardiopulmonary stress test showed significantly lower exercise capacity in patients with cyanosis than in controls: maximal oxygen uptake (VO2max) 15.5±4.9 vs. 31.6±7.1 ml/kg/min (p=0.00001), maximum heart rate at peak exercise (HR max): 139.5±22.5 bpm vs. 176.6±12.1 (p=0.0001), VE/VCO2 slope: 46.4±10.1 vs. 27.3±2.9 (p=0.00001), forced vital capacity FVC: 3.1±1.1 l vs. 4.4±0.8 l (p=0.00001). Subjects with the evidence of pulmonary hypertension (PH+) had lower exercise capacity than those without (PH-): VO2max: 17.2±4.2 vs. 12.8±4.8 ml/kg/min (p=0.002), VE/VCO2: 43.7±11.1 vs. 50.9±6.4 (p=0.01), FVC: 3.46±1.05 l vs. 2.37±0.91 l (p=0.0002). Plasma BNP levels in the study group were higher than in controls: 122.4±106.7 vs. 21.1±20.2 pg/ml p=0.00001 and did not differ between PH+ and PH− groups (115.7±99.0 vs. 127.9±114.1 pg/ml p=0.78). Negative correlations between BNP levels and VO2max (r=−0.389, p=0.006), FVC (r=−0.395 p=0.005), FEV1 (r=−0.386 p=0.006), SO2 (r=−0.445 p=0.00001), and positive correlation between BNP level and VE/VCO2 (r=0.369 p=0.009) were found.

Abstract 3484: High Plasma Levels of Endogenous Free Dopamine Predict an Adverse Outcome in Patients with Heart Disease and Chronic Kidney Disease

Sympathetic activity is heightened in chronic kidney disease (CKD). The increased sympathetic activity is a risk of future cardiovascular disease (CVD) events. Dopamine, a precursor of norepinephrine biosynthesis, is metabolized in the kidney and excreted into urine, and its plasma levels are increased in renal dysfunction. Thus, we examined whether plasma levels of endogenous dopamine may be related to future CVD events in patients with CKD. A total of 840 patients in stable condition with chronic heart disease (622 patients with ischemic heart disease and 218 with non-ischemic heart disease) (586 patients with GFR ≥ 60 ml/min/1.73 m 2 [normal/mild CKD]; 153 patients with 60 &gt; GFR ≥ 30 [moderate CKD]; 101 patients with 30 &gt; GRF [advanced CKD]) were prospectively followed-up for 5 years or until one of the following CVD events: cardiac death, non-fatal myocardial infarction, unstable angina pectoris requiring unplanned revascularization, worsening heart failure requiring hospitalization, or stroke. Plasma levels of endogenous free dopamine at entry were measured by high-performance liquid chromatography. Patients with a higher stage of CKD had higher dopamine levels than patients with a lower stage (63.0 ± 5.5, 45.0 ± 5.1, and 26 ± 1.2 pg/mL, respectively, ρ = 0.54, p &lt; 0.0001 Spearman rank correlation test). During the follow-up period, 233 patients had CVD events (cardiac death in 54, myocardial infarction in 18, others events in 161) (113 events [19%] in normal/mild CKD, 64 [42%] in moderate CKD, and 56 [55%] in advanced CKD). In patients with moderate CKD and advanced CKD, higher dopamine levels (≥ 40 pg/mL, defined by ROC analysis) were the strongest predictor of CVD events (HR 2.1 and 3.3, 95% CI 1.2 – 3.7 and 1.5 – 7.2, p = 0.006 and 0.003, respectively) in a multivariate Cox hazards analysis using plasma norepinephrine and BNP levels, hypertension, and hyperlipidemia as covariates. In contrast, dopamine levels did not have predictive value in normal/mild CKD (HR 1.2, 95% CI 0.7 – 2.0, p = 0.5). High plasma levels of endogenous free dopamine are a risk factor for future CVD in patients with CKD independently of norepinephrine levels. Increases in plasma endogenous free dopamine levels may serve as a mechanistic link between CKD and CVD.

Abstract 1486: Activated Vitamin D Regresses Cardiac Hypertrophy and Attenuates Progression to Heart Failure in Dahl Salt-Sensitive Rats

HomeCirculationVol. 118, No. suppl_18Abstract 1486: Activated Vitamin D Regresses Cardiac Hypertrophy and Attenuates Progression to Heart Failure in Dahl Salt-Sensitive Rats Free AccessMeeting ReportAboutSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessMeeting ReportBasic ScienceCardiorenal Physiology/PathophysiologyAbstract 1486: Activated Vitamin D Regresses Cardiac Hypertrophy and Attenuates Progression to Heart Failure in Dahl Salt-Sensitive Rats Bhargavi Yalamarti, Qingen Ke, Natalya Bodyak, Isaac Stillman, Hector Tamez, S. A Karumanchi, Ravi Thadhani and Peter M Kang Bhargavi YalamartiBhargavi Yalamarti Search for more papers by this author , Qingen KeQingen Ke Search for more papers by this author , Natalya BodyakNatalya Bodyak Search for more papers by this author , Isaac StillmanIsaac Stillman Search for more papers by this author , Hector TamezHector Tamez Search for more papers by this author , S. A KarumanchiS. A Karumanchi Search for more papers by this author , Ravi ThadhaniRavi Thadhani Search for more papers by this author and Peter M KangPeter M Kang Search for more papers by this author Originally published28 Oct 2008https://doi.org/10.1161/circ.118.suppl_18.S_335-aCirculation. 2008;118:S_335AbstractVitamin D deficiency is a common but often unrecognized condition in patients with heart failure. We previously demonstrated that activated vitamin D (AVD) therapy prevents the progression of cardiac hypertrophy in Dahl salt sensitive (DSS) rats on a high salt (HS) diet ( PNAS2007; 104 :16810Google Scholar). Here we asked whether AVD can cause pre-existing cardiac hypertrophy to regress and/or attenuate the progression of heart failure.Methods: To generate cardiac hypertrophy, male DSS rats were fed a HS diet (6% NaCl) from 6 to 11 weeks of age. All animals develop compensated cardiac hypertrophy at 11 weeks, and baseline measurements were obtained (HS-C). The remaining animals divided into three groups:HS diet with vehicle injection x 4 weeks (HS+V)HS diet with paricalcitol (PC, 200ng IP 3x/wk) injection x 4 weeks (HS+PC)normal diet (ND). They were evaluated at 15 weeks.Results: Compared to hypertrophic baseline (HS-C), the HS+PC group showed a significant reduction in heart weight/tibial length (TL) ratio after 4 weeks (−10 %, p<0.05), whereas the HS+V and ND groups did not (both +2%, p=NS). There were similar reductions compared with baseline in septal and posterior wall thicknesses on echocardiograms (HS+PC: −18% and −20%, respectively, vs. 0% and 0% in HS+V, p<0.05). We also found a significant increase in the lung weight/TL ratio indicative of progressing heart failure in the HS+V group compared with baseline (+73%, p<0.05), which was reduced either by PC treatment or by changing to ND (−18% and −53%, p<0.05 for both). The attenuation of heart failure was also indicated by reductions in LV mass (−7% vs. +20%, p<0.05) and reduced fractional shortening (FS) (−15% vs. −35%, p<0.05) in PC compared to HS+V. Switching to ND, however, resulted in the attenuation of FS only (−11%, p<0.05). We also found a reduction of plasma BNP levels in HS+PC and ND compared to HS+V treated animals (−50% and −59%, P<0.05 for both), and, finally, significantly lower cardiomyocyte hypertrophy and intra-cardiac arteriolar diameter in HS+PC vs. HS+V treated animals.Conclusion: PC treatment resulted in the regression of pre-existing cardiac hypertrophy in DSS animals. Both PC treatment and a change to a normal diet attenuated the progression of clinical and biochemical signs of heart failure. Previous Back to top Next FiguresReferencesRelatedDetails October 28, 2008Vol 118, Issue suppl_18 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.118.suppl_18.S_335-a Originally publishedOctober 28, 2008 Advertisement

Statin therapy improve with exercise intolerance in patients with chronic heart failure?

Background: The 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (Statins) have pleiotrophic effects such as anti-inflammatory and anti-oxidant effects, which would be beneficial for patients with chronic heart failure(CHF). We investigated the correlation between statin therapy and exercise intolerance in CHF patients. Methods: Seventy-two patients who underwent cardiopulmonary exercise testing(CPX) were enrolled in this study. The patients were divided into three groups by the 13 patients with CHF on treatment with statin, 37 patients with CHF(statin not used), and 22 control(non CHF). Left ventricular ejection fraction(EF) were measured by echocardiogram. Plasma levels of BNP, interleukin-6(IL-6), tumor necrosis factor(TNF)-alpha were measured in all patients. Results: There were no significant differences in EF among both CHF groups. AT and Peak VO2 of statin CHF group was significantly higher than that in non-statin CHF group(p < 0.001, p < 0.02). TNF-alpha, IL-6 and BNP were significantly higher in the non-statin CHF group than in the statin group(p < 0.05, p < 0.01 p < 0.005, respectively). Futhermore, statin group, EF showed no significant negative correlation with TNF-alpha, IL-6, BNP whereas peak VO2 exhibited significant negative correlations with TNF-alpha(r = −0.51, p < 0.01), IL-6(r=−0.38, p < 0.05), BNP(r=−0.63, p < 0.01). Conclusion: These results suggest that statin therapy might improve with exercise intolerance in patients with chronic heart failure.

Osteoprotegerin and B-type natriuretic peptide in acute coronary syndromes with preserved systolic function: Relation to coronary artery disease extension

Objectives To analyze Osteoprotegerin (OPG), and BNP plasma levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. Methods 155 CAD patients were classified in four groups: stable angina (SA n = 42), unstable angina (UA n = 35) non-ST elevation myocardial infarction (NSTEMI n = 45) and control group ( n = 33), measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-,2-,3 or more vessels disease), and to the stenoses degree by Duke Jeopardy score. Results OPG levels were higher in patients with CAD respect to controls ( p < 0.0001). Patients with SA showed more elevated levels than controls (2.6 ± 1.2 vs 7.4 ± 5.0 pmol/l p < 0.01). However patients with UA and NSTEMI had higher OPG level with respect to SA patients (12.2 ± 7.8 and 11.6 ± 6.1 respectively pmol/l p < 0.001). A positive relation was found between OPG levels and coronary plaques extension by Duke Jeopardy score ( r = 0.65). BNP levels were higher in patients with UA/NSTEMI respect to controls and SA patients ( p < 0.001). Besides, BNP was significantly higher in patients with multi-vessels vs 1-vessel disease ( p < 0.001). Conclusions Patients with UA and NSTEMI show high OPG and BNP levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the CAD progression.

BNP in mitral valve restrictive annuloplasty for ischemic mitral regurgitation

Restrictive annuloplasty with undersized mitral rings is used to correct functional mitral regurgitation (MR) in patients with ischemic left ventricular dysfunction. Seventeen patients with severe coronary artery disease, previous myocardial infarction, moderate/severe functional MR and heart failure symptoms were prospectively evaluated. All patients received CABG associated with restrictive annuloplasty. Preoperatively and 6 months after the operation, clinical evaluation, echocardiography and blood sampling for BNP measurement were performed. Operative mortality occurred in 1 patient. MR degree decreased from 3.8 ± 0.3 to 1.0 ± 0.7 ( p < 0.01), LVEF increased from 36 ± 11% to 43 ± 8% ( p < 0.05), left ventricular end diastolic diameters changed from 54.7 ± 5.2 mm to 51.5 ± 5.8 mm ( p = 0.51). NYHA class improved from 2.94 ± 1.02 to 1.21 ± 0.42 ( p < 0.01). Mean plasma BNP levels decreased from 471 ± 248 pmol/l to 55.6 ± 52.8 pmol/l ( p < 0.05). Restrictive mitral annuloplasty is a safe procedure to be associated to CABG operation. We demonstrated mid-term reduction of BNP plasma values after MR correction thus suggesting the effectiveness of surgical treatment in modifying natural history of the disease.