Plasma N-terminal Pro-atrial Natriuretic Peptide Research Articles

Association between glomerular filtration rate and plasma N-terminal pro-atrial natriuretic peptide concentration in dogs.

To investigate the association between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate in dogs. Dogs were classified into four categories by bodyweight. Dogs were divided into four groups (Groups 1 to 4) based on glomerular filtration rate estimates using plasma iohexol clearance per bodyweight category. Generalised linear models were built to explore the relationship between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate and the effect of confounders on plasma N-terminal pro-atrial natriuretic peptide concentration. Fifty-three dogs were included (Group 1, 25; Group 2, seven; Group 3, five; and Group 4, 16). The medians (interquartile range) N-terminal pro-atrial natriuretic peptide concentrations for Groups 1 to 4 were 7224 pg/mL (4766 to 10,254 mg/dL), 8958 pg/mL (4935 to 11,271 mg/dL), 9280 pg/mL (9195 to 10,384 mg/dL) and 12,683 pg/mL (9133 to 19,217 mg/dL), respectively. Group 4, estimated to have the highest reduction in glomerular filtration rate, had a higher plasma N-terminal pro-atrial natriuretic peptide concentration than Groups 1 to 3. Based on the final generalised linear model, influencing factors for plasma N-terminal pro-atrial natriuretic peptide concentration were plasma iohexol clearance (-0.136; 95% confidence interval, -0.227 to -0.046) and bodyweight (-0.058; 95% confidence interval, -0.098 to -0.018). N-terminal pro-atrial natriuretic peptide concentration is associated with the glomerular filtration rate.

Associations of atrial natriuretic peptide with measures of insulin and adipose depots.

Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post-challenge insulin in AA adults is associated with lower plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). A secondary purpose was to explore associations between NT-proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic-euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT-proANP with measures of insulin and adipose depots. Lower NT-proANP concentrations in AA participants was not independent of 30-min insulin area under the curve (AUC). NT-proANP was inversely associated with 30-min insulin AUC in AA participants, and with fasting insulin and HOMA-IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT-proANP in EA participants. Higher post-challenge insulin may contribute to lower ANP concentrations in AA adults.

Plasma N-terminal pro-atrial natriuretic peptide concentrations are affected by dehydration in healthy dogs.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations may be affected by the hydration status. This study aimed to evaluate the effect of dehydration on plasma NT-proANP and NT-proBNP concentrations in healthy dogs. This prospective study included five clinically healthy dogs. Furosemide was administered intravenously at 2-4 mg/kg every 1-2 hours until completion of the dehydration model. The dehydration model was considered complete when weight loss was ≥5% and findings of dehydration on physical examination were observed. Plasma NT-proANP and NT-proBNP concentrations were compared at three-time points: before the dehydration model was created (point 1), at the completion of the dehydration model (point 2), and when dehydration was judged to have improved (point 3). Association between plasma NT-proANP and NT-proBNP concentrations, and each clinical variable (physical examination, blood pressure, blood chemistry, blood gases, and echocardiography) was assessed using linear regression analysis. Plasma NT-proANP concentration decreased significantly from point 2 to point 1 (p < 0.05), whereas plasma NT-proBNP concentration showed a decreasing trend but did not differ significantly between points 1 and 2. Plasma NT-proANP concentration correlated significantly with body weight (R2 = 0.178) and plasma NT-proBNP concentration (R2 = 0.284) (p < 0.05, respectively), and plasma NT-proBNP concentration correlated significantly with electrolytes (sodium, R2 = 0.439; potassium, R2 = 0.444; and chloride, R2 = 0.419), and echocardiographic parameters [diastolic left ventricular internal diameter (LVIDd) R2 = 0.519; weight-standardized LVIDd, R2 = 0.535] (p < 0.01, respectively). The plasma NT-proANP concentrations decreased with dehydration. However, the plasma NT-proBNP concentration did not change with mild dehydration and reflected left ventricular morphology.

Abstract P157: Racial Differences In Atrial Natriuretic Peptide And Insulin

Low circulating concentrations of the natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). As a group, African Americans (AA) have lower NP levels and are disproportionately burdened by T2D. Insulin, which is higher in AA, has been shown to regulate NP concentration by increasing the NP clearance receptor. This secondary analysis tests the hypothesis that higher insulin in AA will be associated with lower levels of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). Participants were 120 AA and European American (EA) men and women ages 19-45 years. Measures of insulin, including fasting insulin and insulin total and incremental area under the curve (AUC and iAUC, respectively, at 30 and 120 m), were derived from an oral glucose tolerance test (OGTT). Insulin sensitivity (SI Clamp ) was assessed using the euglycemic glucose clamp. NT-proANP was measured from fasting samples obtained during the OGTT. Differences in NT-proANP by race was evaluated with analysis of covariance while adjusting for age, sex, and BMI. Linear regression models were used to examine associations between NT-proANP and insulin measures while adjusting for age, sex, race, and BMI. Relative to EA, AA had higher insulin concentrations, lower insulin sensitivity, and lower NT-proANP levels (p&lt;0.05). Fasting insulin and 30 m insulin AUC were inversely associated with NT-proANP (p=0.02, p=0.02, and p=0.04, respectively). These results suggest that the lower NT-proANP observed in AA is related to higher insulin. Future research is needed to investigate the relationship between insulin, ANP, and the NP clearance receptor, particularly in populations at risk for chronic disease.

Comparison of N-terminal pro-atrial natriuretic peptide and three cardiac biomarkers for discriminatory ability of clinical stage in dogs with myxomatous mitral valve disease.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.

Correlation between corin, N-terminal pro-atrial natriuretic peptide and neonatal adverse prognostic in hypertensive disorders of pregnancy.

Atrial natriuretic peptide (ANP) regulates water-salt balance and blood pressure by promoting renal sodium and water excretion. Our study was to investigate plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and corin in hypertensive disorders of pregnancy (HDP) patients. Furthermore, the relationship between corin/NT-proANP and neonatal adverse prognosis were evaluated. Seventy-seven HDP patients and forty-eight normotensive women as control group were recruited. Clinical characteristic and plasma were collected. Plasma NT-proANP and corin were determined by ELISA. Gestational age, neonatal weight and APGAR scores were recorded. Statistical analysis was conducted. NT-proANP and corin were significantly increased in HDP group compared with that of control (P<0.05). NT-proANP and corin were significantly elevated in HDP patients who suffered from premature delivery (P<0.05). Both NT-proANP and corin were negatively associated with delivery time, neonatal weight and APGAR scores in HDP group. Multiple regressions demonstrated that NT-proANP and corin were independent risk factor of delivery time, neonatal weight and APGAR scores. Plasma NT-proANP and corin were significantly increased in HDP. NT-proANP and corin were associated with neonatal adverse events in HDP patients. Thus, NT-proANP and corin may become new biomarkers for evaluating severity of pregnancy and neonatal adverse events in HDP patients.

Gender difference of association between plasma N-terminal pro-atrial natriuretic peptide and metabolic syndrome.

The natriuretic peptides (NPs) system, and mainly atrial natriuretic peptide (ANP), plays a key role in human metabolism and cardiometabolic disorders. Due to differences in NP levels and in prevalence of metabolic syndrome (MetS) between men and women, we aimed to explore the gender difference of association between N-terminal pro-atrial natriuretic peptide (NT-proANP) and MetS in a general population in China. Participants' weight, height, waist circumference, blood pressure, plasma NT-proANP, and other traditional biomarkers were measured. Multivariate logistic regression models were used to determine the association between plasma NT-proANP and MetS, and the odds ratio (OR) and 95% confidence interval (CI) were calculated for men and women, respectively. Among 2203 participants, 1361 (61.78%) were women, 687(30.77%) participants had MetS, and the average age was 53years. Women had a higher level of NT-proANP than men. However, adjusted logistic regression demonstrated that men in the upper quartile group of NT-proANP had 0.60 (95% CI 0.39-0.92) times the risk of having MetS, while women in the upper quartile group had 1.10 (95% CI 0.77-1.56) times the risk of having MetS compared to the lower quartile group. Furthermore, with the increase of the level of NT-proANP, the ORs showed a declining trend in men (P = 0.017), but it was not statistically significant among women (P = 0.700). There are gender differences in the relationship between NT-proANP and MetS, while an inverse association between plasma NT-proANP and MetS in men suggests that higher levels of NT-proANP may be a protective factor for MetS.

Atrial natriuretic peptide predicts disease progression and digital ulcers development in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients. Seventy patients were enrolled (64 women and six men; mean age 56.7 ± 14 years) with a disease duration of 11.1 ± 8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan-Meier and Cox regression analyses. Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development. Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.

Left atrial ejection fraction and outcomes in heart failure with preserved ejection fraction

The aim of this study was to determine whether left atrial ejection fraction (LAEF) quantified with cardiovascular magnetic resonance (CMR) was different between heart failure with preserved ejection fraction (HFpEF) and controls, and its relation to prognosis. As part of our single-centre, prospective, observational study, 188 subjects (HFpEF n = 140, controls n = 48) underwent phenotyping with contrast-enhanced CMR, transthoracic echocardiography, blood sampling and six-minute walk testing. LAEF was calculated using the biplane method. Atrial fibrillation (AF) was present in 43 (31%) of HFpEF subjects. Overall, LAEF (%) was lower in HFpEF patients inclusive of AF (32 ± 16) or those in sinus rhythm alone (41 ± 12) compared to controls (51 ± 11), p < 0.0001. LAEF correlated inversely with maximal and minimal left atrial volumes indexed (r = − 0.602, r = − 0.762), and plasma N-terminal pro-atrial natriuretic peptide (r = − 0.367); p < 0.0001. During median follow-up (1429 days), there were 67 composite events of all-cause death or hospitalization for heart failure (22 deaths, 45 HF hospitalizations) in HFpEF. Lower LAEF (below median) was associated with an increased risk of composite endpoints (Log-Rank: all p = 0.028; sinus p = 0.036). In multivariable Cox regression analysis, LAEF (adjusted hazard ratio [HR] 0.767, 95% confidence interval [CI] 0.591–0.996; p = 0.047) and indexed extracellular volume (HR 1.422, CI 1.015–1.992; p = 0.041) were the only parameters that remained significant when added to a base prognostic model comprising age, prior HF hospitalization, diastolic blood pressure, lung disease, NYHA, six-minute-walk-test-distance, haemoglobin, creatinine and B-type natriuretic peptide. CMR-derived LAEF is lower in HFpEF compared to healthy controls and is a strong prognostic biomarker.

A4190 Relationship between plasma N-terminal pro-atrial natriuretic peptide and Corin levels and disease severity in patients with pregnancy induced hypertension

Objectives: We investigate the plasma N-terminal atrial natriuretic peptide (NT-proANP) and corin in pregnancy induced hypertension (PIH) and studies the correlation between plasma NT-proANP/ corin levels and adverse events. Methods: A total of 77 PIH who admitted in hospital were enrolled. 48 normotensive pregnancies in the same gestational weeks were chosen as control. Clinical characteristics were collected. Plasma was collected for laboratory examination Results: NT-proANP and corin was significantly increased in PIH compared with control (P = 0.003 and P < 0.001). The association between plasma NT-proANP/corin and the adverse event demostrated that 1) In PIH, NT-proANP and corin were increased significantly in preterm compared with that in full-term birth (P < 0.001 and P = 0.023); 2) Weeks of gestation in PIH patients were dramatically reduced compared with control, and it was negative correlated to NT-proANP and corin (R = −0.487, P < 0.001 and R = −0.383, P = 0.000); 3) The weight of newborns in PIH was significantly lower than that in control, and it was negatively correlated with NT-proANP and corin (R = −0.487, P < 0.001 and R = −0.383, P = 0.001); 4) The APGARP score of PIH was significantly lower than that of control, and it was negatively correlated with NT-proANP (R = −0.359, P = 0.001). NT-proANP/Corin and target organ function demonstrated that 1) The eGFR of PIH was significantly lower than that of control (P < 0.001), and it was negatively correlated with NT-proANP and corin (R = −0.490, P < 0.001 and R = −0.415, P < 0.001); 2) The urinary protein in PIH was significantly increased than that in control (P < 0.001), and it was positively correlated with NT-proANP and corin (R = 0.386, P = 0.001 and R = 0.401, P < 0.001). Conclusion: The plasma NT-proANP and corin was increased in PIH, and both of them may associate with the severity of PIH.

A8162 Relationship between plasma N-terminal pro-atrial natriuretic peptide and Corin levels and dyslipidemia in patients with pregnancy induced hypertension

A8162 Relationship between plasma N-terminal pro-atrial natriuretic peptide and Corin levels and dyslipidemia in patients with pregnancy induced hypertension

Plasmatic levels of N-terminal pro-atrial natriuretic peptide in preeclamptic patients and healthy normotensive pregnant women

Background and objectiveTo compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women. MethodsA cases–controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected 1h after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters. ResultsPlasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26]pg/ml) showed a significant difference when compared with patients in group B (mean 0.55 [0.07]pg/ml; p<0.001). There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (p=ns). A cut-off value of 0.66ng/ml had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%. ConclusionPreeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis.

Concentraciones plasmáticas de fragmento N-terminal del propéptido natriurético auricular plasmático en pacientes con preeclampsia y embarazadas normotensas sanas

Background and objectiveTo compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women. MethodsA cases-controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected one hour after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters. ResultsPlasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26] pg/mL) showed a significant difference when compared with patients in group B (mean 0.55 [0.07] pg/mL; P<.001]. There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (P=ns). A cut-off value of 0.66ng/mL had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%. ConclusionPreeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis.

Assessment of left atrial volume and function by real time three-dimensional echocardiography in obese patients.

To evaluate left atrial (LA) volume and functions in obese subjects using real time three-dimensional echocardiography (RT3DE) and also the relationship between LA mechanical functions and N-terminal pro-atrial natriuretic peptide (NT-proANP). This study included 40 obese (26 females and 14 males, mean age 51.9years) and 40 normal weight subjects (23 females and 16 males, mean age 53.5years) with normal coronary angiograms. All the study participants underwent RT3DE to assess LA volume and mechanical function. Plasma NT-proANP was determined by ELISA method. There was no significant difference between groups in left ventricular (LV) diameters and ejection fraction, which reflect LV systolic function. However, transmitral deceleration time, isovolumetric relaxation time, and peak late diastolic tissue Doppler velocity values, which reflect LV diastolic function, were found to be significantly higher in obese subjects when compared with controls. LA maximum volume (LAVmax), LAVmax index (LAVI), LA minimal volume (LAVmin), before atrial contraction volume (LAVpreA), LA active emptying volume, LA total emptying volume, and LA active emptying fraction, which reflect LA reservoir and pump functions, were also higher in obese subjects when compared with controls. LA passive emptying fraction was significantly lower in obese subjects than in controls. NT-proANP levels were similar between groups. There were positive correlations between NT-proANP level and LAVI, LAVmax, LAVmin, LAVpreA, and LA total and active emptying volumes. Left atrial mechanical functions and volumes are impaired in obese subjects. These findings may be regarded as early markers of subclinical cardiac failure in obese subjects who have not yet exhibited any clinical evidence of cardiovascular disease.

Circulating Atrial Natriuretic Peptide Genetic Association Study Identifies a Novel Gene Cluster Associated with Reduced NT-proANP, Increased Stroke and Higher Diastolic Blood Pressure

The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility.

A corin variant identified in hypertensive patients that alters cytoplasmic tail and reduces cell surface expression and activity.

Corin is a membrane-bound protease that regulates blood pressure by activating the natriuretic peptides. CORIN variants have been associated with hypertension and heart disease in African Americans. In this study, we conducted targeted exome sequencing and identified an insertion variant, c.102_103insA, in exon 1 of the CORIN gene. Analysis of two independent cohorts showed that the variant was preferentially present in hypertensive patients (38/795 or 4.78% vs. 4/632 or 0.63% in normal individuals, p = 4.14E-6). The insertion shifted the reading frame, resulting in a corin variant with a truncated cytoplasmic tail. In cell-based studies, the corin variant exhibited poor trafficking in the Golgi, reduced cell surface expression and zymogen activation, and low natriuretic peptide processing activity. Compared with normal individuals with the wild-type allele, individuals with the variant allele had lower levels of plasma corin [0.59 ± 0.07 ng/mL (n = 25) vs. 0.91 ± 0.02 ng/mL (n = 215), p<0.001] and higher levels of plasma N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) [2.39 ± 3.6 nmol/L (n = 21) vs. 0.87 ± 0.6 nmol/L (n = 48), p = 0.005]. These results indicate that the variant altered corin structure and impaired the natriuretic peptide processing activity in vivo. The results highlight corin defects as an important underlying mechanism in hypertension.

Circulating atrial natriuretic peptide genetic association study identifies a novel gene cluster associated with stroke in whites.

The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility. Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55±8% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004). This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation is related to lower NT-proANP levels, higher blood pressures, and an increased risk of stroke in the general community.

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease

ObjectivesTo evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. AnimalsSeventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. MethodsProspective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. ResultsThe hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6–12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6–12.6 months), compared to 54 months (46 – infinity) for dogs with concentrations ≤1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥3/6). ConclusionsThe risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.

GW24-e2957 Efficacy of ivabradine in combination with metoprolol versus uptitration of metoprolol in patients after Q-wave myocardial infarction with early left ventricular systolic dysfunction

ObjectivesThe purpose of the study was to evaluate the effect of combination of ivabradine with metoprolol tartrate versus uptitration of metoprolol tartrate on left ventricular (LV) systolic function and plasma...

Higher aldosterone and lower N-terminal proatrial natriuretic peptide as biomarkers of salt sensitivity in the community

Salt sensitivity, a trait characterized by a pressor blood pressure response to increased dietary salt intake, has been associated with higher rates of cardiovascular target organ damage and cardiovascular disease events. Recent experimental studies have highlighted the potential role of the natriuretic peptides and aldosterone in mediating salt sensitivity. Prospective cohort study. We evaluated 1575 non-hypertensive Framingham Offspring cohort participants (mean age 55 ± 9 years, 58% women) who underwent routine measurements of circulating aldosterone and N-terminal proatrial natriuretic peptide (NT-ANP) and assessment of dietary sodium intake. Participants were categorized as potentially 'salt sensitive' if their serum aldosterone was >sex-specific median but plasma NT-ANP was ≤sex-specific median value. Dietary sodium intake was categorized as lower versus higher (dichotomized at the sex-specific median). We used multivariable linear regression to relate presence of salt sensitivity (as defined above) to longitudinal changes (Δ) in systolic and diastolic blood pressure on follow-up (median four years). Participants who were 'salt sensitive' (N = 437) experienced significantly greater increases in blood pressure (Δ systolic, +4.4 and +2.3 mmHg; Δ diastolic, +1.9 and -0.3 mmHg; on a higher versus lower sodium diet, respectively) as compared to the other participants (Δ systolic, +2.8 and +1.0 mmHg; Δ diastolic, +0.5 and -0.2 mmHg; on higher versus lower sodium diet, respectively; P = 0.033 and P = 0.0127 for differences between groups in Δ systolic and Δ diastolic blood pressure, respectively). Our observational data suggest that higher circulating aldosterone and lower NT-ANP concentrations may be markers of salt sensitivity in the community. Additional studies are warranted to confirm these observations.