natriuretic-peptide--brain and Acromegaly

Acromegaly is associated with an increased risk of fatal and non-fatal cardiovascular (CV) events. Controlling acromegaly decreases, but does not normalize this risk. Brain natriuretic peptide (BNP) assessment is used in the general population for the diagnosis of heart failure and to predict ischemic recurrences and mortality. This is a retrospective, longitudinal, monocenter study that evaluates the role of serum N-terminal fragment of BNP (NT-pro-BNP) for predicting CV events in acromegaly patients.. Serum NT-pro-BNP levels were measured in 76 patients with acromegaly (23 males, 57.7±1.5 years), and compared with other predictors of CV events. NT-pro-BNP cut-off value discriminating the occurrence of CV events was determined by ROC analysis. CV events were recorded during a follow-up of 78.6±6.4 months.. CV events occurred in 9.2% of patients. Mean log(NT-pro-BNP) concentration was higher in patients who experienced CV events than in those who did not (p<0.01) and in patients who died due to CV events than in those who died due to other causes (p<0.01). Based on the ROC curve, a cut-off value of 91.55 pg/mL could predict CV events (OR 19.06). Log(NT-pro-BNP) was lower in surgically treated patients by surgery (p<0.05), and in those cured by neurosurgery (p<0.02).. High NT-pro-BNP value is an independent middle-term predictor of fatal or non-fatal CV events in patients with acromegaly. According to this parameter, surgically treated patients show lower CV risk than those managed with medical therapy, especially if the disease is cured.

Topics: Acromegaly; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; ROC Curve

Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems.

Topics: Acromegaly; Angiotensin-Converting Enzyme 2; Animals; Blood Pressure; Body Composition; Body Weight; Cattle; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Glucose; Glucose Tolerance Test; Growth Hormone; Homeostasis; Hypertension; Insulin; Kidney Glomerulus; Male; Mice; Mice, Transgenic; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Renin-Angiotensin System; Systole; Time Factors

Patients with active acromegaly have an increased prevalence of cardiomyopathy and heart failure but a less than expected risk of coronary artery disease, considering the frequent association of diabetes mellitus and hypertension. We examined whether changes in high-sensitive C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) might contribute to this phenomenon.. Two hundred patients of the Belgian acromegaly registry (AcroBel) were divided in two groups: active disease (IGF1 Z-score >2; n=95) and controlled disease (IGF1 Z-score ≤2; n=105). Serum levels of hs-CRP and NT-proBNP were measured and correlated with BMI, blood pressure, fasting lipids, fasting glucose and insulin, HbA1c, IGF1, interleukin 6 (IL6), adiponectin, and sE-selectin. In a subset of acromegaly patients, hs-CRP, IL6, and NT-proBNP levels were also compared with those/the values of an age-, gender-, and BMI-matched reference group.. Patients with active acromegaly had significantly lower levels of hs-CRP (median (interquartile range), 0.5 mg/l (0.1, 0.9) vs 1.3 mg/l (0.5, 4.1); P<0.001) and NT-proBNP, (47.0 ng/l (26.0, 86.0) vs 71.0 ng/l (43.0, 184.0); P<0.001) compared with patients with controlled acromegaly. Compared with the reference population, hs-CRP was not different in controlled acromegaly but significantly lower in active acromegaly (median, 0.4 mg/l (0.1, 0.8) vs 1.4 mg/l (0.8, 2.9); P<0.001), while NT-proBNP was similar in active acromegaly but significantly higher in controlled acromegaly (66.5 ng/l (40.0, 119.5) vs 50.8 ng/l (26.5, 79.7); P<0.001).. Patients with active acromegaly have significantly lower values of NT-proBNP and hs-CRP compared with patients with controlled disease and even lower values of hs-CRP compared with control subjects.

Topics: Acromegaly; Adult; Aged; Belgium; Blood Pressure; Body Mass Index; C-Reactive Protein; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Registries

Long-term treatment of acromegaly prevents aggravation and reverses associated heart disease. A previous study has shown a temporary increase in serum levels of the N-terminal fraction of pro B-type natriuretic peptide (NT-proBNP) suggesting an initial decline in cardiac function when treatment of acromegaly is initiated. This was a three months prospective study investigating short-term cardiac effects of treatment in acromegalic patients. Cardiac function was evaluated by the gold standard method cardiac magnetic resonance imaging (CMRI) and circulating levels of B-type natriuretic peptides (BNP and NT-proBNP). CMRI was performed at baseline and after 3 months of treatment. Levels of IGF-I, BNP and NT-proBNP were measured after 0, 1, 2 and 3 months. Eight patients (5 males and 3 females, mean age 53 ± 12 years (range 30-70)) and 8 matched healthy control subjects were included. Median IGF-I Z-score decreased from 4.5 (range 2.5-6.4) to 2.3 (-0.1 to 3.3). At baseline the patients had increased left ventricle mass index (LVMI) compared to control subjects (ΔLVMI 35 g/m(2) (95% CI 8-63 g/m(2), P = 0.016). After 3 months of treatment there was an increase in end-diastolic volume index EDVI (ΔEDVI 9 mL/m(2) (95% CI 3-14), P = 0.007) and an increase in levels of BNP (median (ranges) 7 (0.58-286) vs. 20 (1-489) pg/mL, P = 0.033) and of NT-proBNP (63 (20-1004) vs. 80 (20-3391) pg/mL, P = 0.027). Assessed by the highly sensitive and precise CMRI method, 3 months treatment of acromegaly resulted in an increase in EDVI, and increased levels of BNP and NT-proBNP suggesting an initial decrease in cardiac function.

Topics: Acromegaly; Adult; Aged; Case-Control Studies; Female; Heart; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Octreotide; Peptide Fragments; Prospective Studies; Somatostatin

The mechanisms of acromegalic cardiomyopathy are not clearly understood. Brain natriuretic peptide (BNP) and N-terminal fragment of its pro-hormone (NT-proBNP) are released by the cardiac ventricles and increase in heart failure. In the present study, we aimed to evaluate serum NT-proBNP levels in acromegalic patients and determine a relationship between NT-proBNP levels and echocardiographic parameters.. Twenty-two newly diagnosed acromegalic patients [mean age 38.85 ± 11.06 yr; body mass index (BMI): 28.51 ± 3.48 kg/m2] and 26 age- and BMI-matched healthy control subjects (mean age 32.9 ± 12.6 yr; BMI: 26.2 ± 5.3 kg/m2) were included in the study. Standard oral glucose tolerance test (OGTT) was performed. Serum NT-proBNP and GH were measured at the beginning of the OGTT (0 min). Body fat analyses were measured by bioelectrical impedance. Echocardiography was used in cardiac evaluations.. The mean NT-proBNP level in the acromegalic group was not significantly different from the control subjects (55.89 ± 46.64 pg/ml in acromegaly vs 28.76 ± 22.13 pg/ml in control subjects). There were no correlations between the serum NTproBNP, GH, and IGF-I levels. Echocardiography revealed significantly increased left ventricular end-diastolic diameter (p=0.008), interventricular septum thickness (p=0.009), left atrium (p=0.029), and right ventricle diameter (p=0.027) in the acromegalic group.. NT-proBNP levels were found to be slightly higher in acromegalic patients as an indicator of heart failure, but the increase was not statistically significant. Although these cardiac structural changes in newly diagnosed acromegalic patients are present, the normal level of NT-proBNP shows that NT-proBNP may not be a good indicator in acromegaly.

Topics: Acromegaly; Adolescent; Adult; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Acromegaly is associated with increased morbidity and mortality from cardiovascular disease. Inflammatory markers, such as C-reactive protein and leucocyte count, haemostatic markers, such as fibrinogen and factor VIII and cardiac hypertrophy marker, B-type natriuretic peptide, have emerged as important cardiovascular risk markers in the general population. The objective of this study was to assess the serum levels of conventional, inflammatory, haemostatic markers and NT-pro BNP in mostly non-diabetic normotensive patients with acromegaly, as well as the effect of 6 months of octreotide LAR therapy on these markers. We studied 12 patients with active acromegaly, 12 patients in whom remission of acromegaly had been achieved by surgery and 12 healthy control subjects matched for age, gender and body mass index. At baseline fasting blood was obtained for measurements of GH, IGF-1, glucose, insulin, lipids, lipoprotein (a), C-reactive protein, leucocyte count, fibrinogen, factor VIII and NT-pro BNP. After baseline evaluation, patients with active acromegaly were treated with octreotide LAR for 24 weeks. At 24 weeks, measurements were repeated as on baseline. Insulin resistance index and fibrinogen levels were higher in patients with active acromegaly than patients and subjects in control groups. CRP, leucocyte count, factor VIII and NT-pro BNP were similar in the three groups. Octreotide LAR reduced GH, IGF-1 and insulin resistance index but did not alter levels of CRP and NT-pro BNP.

Topics: Acromegaly; Adult; Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Delayed-Action Preparations; Factor VIII; Fibrinogen; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Lipids; Longitudinal Studies; Middle Aged; Natriuretic Peptide, Brain; Octreotide; Peptide Fragments; Time Factors; Treatment Outcome

Acromegaly is associated with hypertrophic cardiomyopathy, hypertension and subsequent congestive heart failure. Impairment of cardiac function has also been associated with growth hormone deficiency (GHD). B-type natriuretic peptides (BNPs) have emerged as strong diagnostic and prognostic risk markers. They are cardioprotective hormones that compensate heart disease by promoting natriuresis and modulation of cardiac hypertrophy in response to volume expansion and ventricular wall stretch.. To investigate N-terminal pro-BNP (NT-proBNP) in patients with GH disturbances before and after treatment, and in healthy gender- and age-matched controls.. Ten acromegalic patients (age 48 +/- 12 years) and 10 patients with GHD (age 41 +/- 14 years) were studied. None had symptoms or signs of cardiovascular disease except for hypertension. Serum NT-proBNP was measured before and 3, 6, 12 and 24 months after treatment.. Baseline NT-proBNP was lower in acromegalic patients [median (interquartile range) 24.3 (17.8-33.0) pg/ml] than in 20 healthy matched controls [57.9 (35.4-92.2) pg/ml; P < 0.001]. NT-proBNP increased during treatment (P = 0.002), concomitant with a decrease in IGF-I (P < 0.001). After 3 months of treatment NT-proBNP peaked, with a fourfold increase to 96.4 (57.8-113.2) pg/ml. NT-proBNP did not differ in patients with GHD compared with controls (P = 0.19), and did not change during treatment (P = 0.39).. Untreated patients with acromegaly had low NT-proBNP levels that increased fourfold after treatment. This is in contrast to other conditions with cardiac hypertrophy. Further studies are required to determine the significance of this novel finding in relation to acromegalic cardiac disease.

Topics: Acromegaly; Adult; Aged; Analysis of Variance; Antineoplastic Agents, Hormonal; Biomarkers; Case-Control Studies; Female; Follow-Up Studies; Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Middle Aged; Natriuretic Peptide, Brain; Octreotide; Peptide Fragments; Peptides, Cyclic; Protein Precursors; Retrospective Studies; Somatostatin; Statistics, Nonparametric

Increased cardiac insulin-like growth factor (IGF)-I production is associated with physiological cardiac hypertrophy in athletes, and IGF-I has been recognized as a cardioprotective agent in experimental animal studies. On the other hand, acromegaly which is characterized by an excess of IGF-I has been linked to impaired cardiac function.. Both the relationship between the serum levels of IGF-I and brain natriuretic peptide (BNP), which is released from the cardiac ventricles in response to ventricular stress, and that between IGF-I and the concentrations of the plasma amino-terminal propeptide of procollagen type III (P-III-P), which is associated with myocardial fibrosis, were evaluated in 19 patients after surgical treatment for acromegaly. Echocardiography revealed that left ventricular systolic function and dimensions were within normal range in all patients. Significant inverse correlations were found between IGF-I and the BNP (r=-0.5, p=0.02) and P-III-P levels (r=-0.62, p=0.005).. We observed an inverse significant relationship between IGF-I and both the BNP and P-III-P value in surgically treated acromegaly patients. These observations suggest that appropriate levels of IGF-I have beneficial cardioprotective effects after surgery in patients with acromegaly.

Topics: Acromegaly; Cardiotonic Agents; Endomyocardial Fibrosis; Female; Heart Ventricles; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Prospective Studies; Ventricular Function, Left