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Morten Schou,
Finn Gustafsson,
Lars Videbaek,
Helge Andersen,
Jens Toft,
Ole Nyvad,
Henrik Ryde,
Lars Fog,
Jens C H Jensen,
Olav W Nielsen,
Soren Lind-Rasmussen,
Jawdat Abdulla, Per R Hildebrandt
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ABSTRACT: AIMS: This study was designed to evaluate a new NT-proBNP monitoring concept in outpatients with systolic heart failure (HF). METHODS AND RESULTS: This was a multicentre, prospective randomized open-label blinded endpoint study. A total of 407 systolic HF patients were allocated to either clinical management (n = 208) or clinical management + NT-proBNP monitoring (n = 199) and followed for 2.5 years. If NT-proBNP increased >30%, a clinical checklist was completed and treatment initiated. The patients were matched at randomization and were 73 years old, 25% were females, 85% were NYHA class I-II, LVEF was 30%, and NT-proBNP 1955 pg/mL. NT-proBNP monitoring did not improve outcome, the hazard ratio for the primary composite endpoint (death or a cardiovascular admission) being 0.96 [95% confidence interval (CI) 0.71-1.29, P = 0.766]. NT-proBNP monitoring did not induce a significant change in the pharmacological strategy (P > 0.05 for all comparisons). In patients in whom NT-proBNP increased >30% (25% of the patients) during follow-up, a higher frequency of admission (69% vs. 47%, P = 0.002), a higher number of admission days (14 vs. 5 days, P = 0.003) and number of admissions (2 vs. 1, P = 0.009), and a lower quality of life (P = 0.032) and a poorer functional class (37% vs. 18% in NYHA class III-IV, P < 0.001) were observed. CONCLUSIONS: Adding serial measurements of NT-proBNP to optimal clinical management was not associated with a change in pharmacological strategy and did not improve outcome. However, survivors in whom NT-proBNP increased >30% showed a poorer functional class, clinical outcome, and quality of life.Trial registrationwww.centerwatch: 173491 (NorthStar).
European Journal of Heart Failure 03/2013; · 4.90 Impact Factor
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Morten Schou,
Finn Gustafsson,
Lars Videbaek,
Chr Tuxen,
Niels Keller,
Jens Handberg,
Anne Sejr Knudsen,
Geert Espersen,
John Markenvard,
Kenneth Egstrup,
Hans Ulriksen, Per R Hildebrandt
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ABSTRACT: Background
Outpatient follow-up in specialized heart failure clinics (HFCs) is recommended by current guidelines and implemented in most European countries, but the optimal duration of HFC programmes has not been established. Nor is it known whether all or only high-risk patients, e.g. identified by NT-proBNP, might benefit from an extended HFC follow-up.Methods and resultsIn a multi-centre setting, we randomly assigned 921 clinically stable systolic heart failure (HF) outpatients on optimal medical therapy to undergo either an extended follow-up in the HFC (n = 461) or referral back to their general practitioner (GP) (n = 460). The primary composite endpoint was death or a cardiovascular admission. Secondary endpoints included mortality, an HF admission, quality of life, number of days admitted, and number of admissions. The median age of the patients was 69 years; 23% were females; the median left ventricular ejection fraction was 0.30; and the median NT-proBNP was 801 pg/mL; 89% were in NYHA class I-II. The median follow-up was 2.5 years. Time-to-event did not differ between groups (HFC vs. GP) (HR: 1.17, 95% CI: 0.95-1.45, P = 0.149). The two groups did not differ with respect to any of the secondary endpoints at the follow-up (P> 0.05 for all). In high-risk patients identified by NT-proBNP ≥1000 pg/mL, no benefit from HFC follow-up was found (P = 0.721).Conclusion
Irrespective of the level of NT-proBNP stable HF patients on optimal medical therapy do not benefit from long-term follow-up in a specialized HFC in a publicly funded universal access healthcare system. Heart failure patients on optimal medical therapy with mild or moderate symptoms are safely managed by their personal GP.Trial Registration: www.Centerwatch.com: 173491 (NorthStar).
European Heart Journal 08/2012; · 10.48 Impact Factor
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ABSTRACT: Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤ 45% were enrolled in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro-B-type natriuretic peptide was measured at baseline. Mean age was 71 years, 29% were women, 62% had coronary artery disease (CAD), mean left ventricular ejection fraction was 31%, and 57% had abnormal level of hs-cTnT. During 4.4 years of follow-up, 211 (51%) patients died. In multivariate Cox regression models, hs-cTnT was categorized as quartiles or dichotomized by the 99th percentile of a healthy population. Adjusted hazard ratios for all-cause mortality for quartiles 2 to 4, with quartile 1 as reference, were 1.4 (95% confidence interval 0.9 to 2.4, p = 0.16) for quartile 2, 1.7 (0.9 to 2.5, p = 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4 and 1.7 (1.2 to 2.5, p = 0.003) for abnormal versus normal level of hs-cTnT. In patients without CAD, quartile 4 of hs-cTnT was associated with an adjusted hazard ratio of 6.8. In conclusion, hs-cTnT is increased in most outpatients with chronic systolic HF and carries prognostic information beyond clinical parameters and amino-terminal pro-B-type natriuretic peptide. Increased hs-cTnT indicated a particularly deleterious prognosis in patients without CAD.
The American journal of cardiology 05/2012; 110(4):552-7. · 3.58 Impact Factor
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ABSTRACT: We evaluated the applicability and prognostic importance of oral glucose tolerance testing (OGTT) among outpatients with systolic heart failure (SHF).
Consecutive patients with SHF and left ventricular ejection fraction (LVEF) ≤ 45% referred to a heart failure clinic (n= 413) were included in this study. An OGTT was conducted in patients without a history of diabetes. Information on NYHA class, aetiology of SHF, LVEF, treatment, and biochemical parameters were collected at baseline. The survival status was obtained after a median follow-up time of 591 days. Of the 413 patients, 82 (20%) had known diabetes. Of the remaining 331 patients, 227 (69%) agreed to undergo an OGTT. Among the tested subjects, 136 (60%) were classified as having normal glucose tolerance (NGT), 51 (23%) impaired glucose tolerance (IGT), and 40 (18%) newly diagnosed diabetes. Assuming a similar prevalence of unrecognized diabetes among the patients who refused OGTT, the prevalence of diabetes in the total population was 34%. If only fasting blood glucose had been used, 16 of the 40 newly diagnosed diabetic patients would have been undiagnosed. During follow-up, 24 (29%) patients with known diabetes, 6 (15%) of the newly diagnosed diabetic patients, 9 (18%) of those with IGT, and 13 (9%) patients with NGT died. Patients with diabetes had higher mortality rate compared with non-diabetic patients [multivariate hazard ratio 1.89 (1.02-3.59); P = 0.047].
It is feasible to perform diabetes screening using OGTT in outpatients with SHF. A substantial proportion of patients tested were found to have unrecognized diabetes. The presence of diabetes was associated with a higher mortality rate.
European Journal of Heart Failure 03/2011; 13(3):319-26. · 4.90 Impact Factor
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ABSTRACT: This study was designed to assess whether pharmacologically treated depression was associated with increased mortality risk in systolic heart failure (SHF) patients.
Patients (n=3346) with SHF (left ventricular ejection fraction ≤ 0.45) and primarily New York Heart Association (NYHA) classes II-III (78%) were recruited from a clinical database used in 20 heart failure clinics in Denmark. The association between pharmacologically treated depression identified by at least one prescription of an antidepressant and mortality risk was evaluated.
Follow-up time was 540 days (range: 30-1600 days). 539 patients died. For 243 patients (7%) an antidepressant had been prescribed at least once. In a Cox Proportional Hazard Model, pharmacologically treated depression was associated with a 49% increased mortality risk (Hazard ratio: 1.49, 95% confidence interval: 1.03-2.16) after adjustment for traditional confounders. Three months after the baseline visit in the heart failure clinic, these patients received lower doses of beta-blockers than patients without antidepressant therapy (p=0.006). Female sex (p<0.001) and NYHA classes III-IV (p=0.007) were associated with the prescription of an antidepressant.
Our analyses suggest that pharmacologically treated depression is associated with a 49% increased mortality risk, and that these high-risk patients receive lower doses of beta-blockers than patients with no antidepressant therapy.
International journal of cardiology 02/2010; 146(1):64-7. · 7.08 Impact Factor
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ABSTRACT: In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt-proBNP), related to hemodynamic cardiovascular risk factors, high sensitivity C-reactive protein (hsCRP), related to metabolic cardiovascular risk factors and urine albumin/creatinine ratio (UACR), related to hemodynamic as well as metabolic risk factors. In healthy subjects with a 10-year risk of cardiovascular death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified a larger subgroup of 16% with high cardiovascular risk in which primary prevention may be advised despite low-moderate cardiovascular risk based on HeartScore. Furthermore, combined use of high UACR or high Nt-proBNP in subjects with known cardiovascular disease or diabetes identified a large subgroup of 48% with extremely high cardiovascular risk who should be referred for specialist care to optimize treatment.
Current Vascular Pharmacology 02/2010; 8(1):134-9. · 2.90 Impact Factor
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ABSTRACT: To assess the rates of death or hospitalization in outpatients with heart failure (HF) followed in multidisciplinary, nurse-based HF clinics and to compare the rates with published data from the literature. A second aim was to identify risk factors for death or hospital admission.
A total of 4012 consecutive outpatients referred for HF management in 18 Danish HF clinics were included. Clinical data were collected prospectively. Outcome data were obtained from a validated, national registry. Mean follow-up time was 580 days. The mean age of patients was 69 years, 83% had left ventricular systolic dysfunction and 52% had been hospitalized within 90 days prior to referral to the HF clinic. The 6 and 12 month rates of hospitalization or death were 31 and 42%. Hospitalization or death was significantly predicted by age 1.12 (1.05-1.19), diabetes 1.21 (1.03-1.42), serum creatinine 1.03 (1.02-1.04), NYHA III and IV 1.32 (1.15-1.52), and hospitalization prior to referral to the HF clinic 1.81 (1.57-2.08).
Event rates in this cohort were lower than most published data from HF clinic populations. Factors such as advanced age, NYHA class, and prior hospitalization predict poor outcome in patients managed in multidisciplinary HF clinics.
European Journal of Heart Failure 03/2009; 11(4):413-9. · 4.90 Impact Factor
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Morten Schou,
Finn Gustafsson,
Lars Videbaek,
John Markenvard,
Hans Ulriksen,
Henrik Ryde,
Jens C H Jensen,
Tonny Nielsen,
Anne S Knudsen,
Christian D Tuxen, [......],
Per J Sørensen,
Geert Espersen,
Søren Lind-Rasmussen,
Niels Keller,
Kenneth Egstrup,
Olav W Nielsen,
Jawdat Abdulla,
Ole Nyvad,
Jens Toft, Per R Hildebrandt
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ABSTRACT: Randomized clinical trials have shown that newly discharged and symptomatic patients with chronic heart failure (CHF) benefit from follow-up in a specialized heart failure clinic (HFC). Clinical stable and educated patients are usually discharged from the HFC when on optimal therapy. It is unknown if risk stratification using natriuretic peptides could identify patients who would benefit from longer-term follow-up. Furthermore, data on the use of natriuretic peptides for monitoring of stable patients with CHF are sparse.
The aims of this study are to test the hypothesis that clinical stable, educated, and medical optimized patients with CHF with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels > or = 1,000 pg/mL benefit from long-term follow-up in an HFC and to assess the efficacy of NT-proBNP monitoring.
A total of 1,250 clinically stable, medically optimized, and educated patients with CHF will be enrolled from 18 HFCs in Denmark. The patients will be randomized to treatment in general practice, to a standard follow-up program in the HFC, or to NT-proBNP monitoring in the HFC. The patients will be followed for 30 months (median).
Data will be collected from 2006 to 2009. At present (March 2008), 720 patients are randomized. Results expect to be presented in the second half of 2010.
This article outlines the design of the NorthStar study. If our hypotheses are confirmed, the results will help cardiologists and nurses in HFCs to identify patients who may benefit from long-term follow-up. Our results may also indicate whether patients with CHF will benefit from adding serial NT-proBNP measurements to usual clinical monitoring.
American heart journal 10/2008; 156(4):649-55. · 4.65 Impact Factor
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ABSTRACT: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated the impact of age and sex on their prognostic performance in a subgroup of 1994 apparently healthy individuals without diabetes, previous stroke or myocardial infarction, who did not receive any cardiovascular, antidiabetic or lipid-lowering medication.
In 1993-1994 we recorded cardiovascular risk factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years.
In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P < 0.05) and age (P < 0.05), respectively. The effect of logUACR was not significantly modulated by age or sex. Log(hsCRP)/SD did not predict CEP in women, but did predict CEP in 41 plus 51-year-old men [hazard ratio (HR) 1.71; 95% confidence interval, 1.1-2.6; P < 0.05] and 61 plus 71-year-old men (HR 1.64; 1.3-2.2; P < 0.001). Log(Nt-proBNP)/SD predicted CEP in 61 plus 71-year-old women (HR 1.74; 1.2-2.5; P < 0.01) and in 61 plus 71-year-old men (HR 1.58; 1.3-2.0; P < 0.001).
Elevated hsCRP, reflecting early atherosclerosis, predicted CEP even in 41 plus 51-year-old men. Elevated Nt-proBNP, reflecting subclinical cardiovascular damage, predicted CEP in 61 plus 71-year-old subjects. Elevated UACR, reflecting endothelial dysfunction as well as microvascular damage, predicted events independently of age and sex, but primarily in 61 plus 71-year-old subjects.
Journal of Hypertension 01/2008; 26(1):26-34. · 4.02 Impact Factor
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ABSTRACT: N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and anemia are predictors of outcome in systolic heart failure. It is currently unclear how these 2 markers interact in particular with regard to the prognostic information carried by each risk marker. We therefore tested the hypothesis that anemia (World Health Organization criteria, hemoglobin levels <7.5 mmol/L for women and <8.0 mmol/L for men) and NT-pro-BNP are associated and evaluated how a possible association affects the prognostic value of each risk marker. Clinical data from 345 patients with systolic heart failure were obtained prospectively at the baseline visit to our heart failure clinic (inclusion criterion left ventricular ejection fraction <0.45, no exclusion criteria). Follow-up was 30 months (median), and 70 events (mortality) occurred. Prevalence of anemia was 27%. In a multivariate logistic regression model, anemia (p = 0.041) was closely associated with NT-pro-BNP levels above the median (1,381 pg/ml) after adjustment for traditional confounders (left ventricular ejection fraction, age, body mass index, atrial fibrillation, chronic kidney disease). In an adjusted Cox proportional hazard model, the 2 parameters were associated with mortality after adjustment for traditional confounders (hazard ratio for anemia 1.73, 95% confidence interval 1.06 to 2.83, p = 0.029; hazard ratio for NT-pro-BNP >1,381 pg/ml 2.68, 95% confidence interval 1.58 to 4.66, p <0.001). Patients with anemia and high NT-pro-BNP levels had a fivefold increased risk for mortality (hazard ratio 4.77, 95% confidence interval 2.47 to 9.18, p <0.001). In conclusion, anemia is closely associated with NT-pro-BNP in patients with systolic heart failure, and anemia and NT-pro-BNP carry independent prognostic information. Patients with anemia and high levels of NT-pro-BNP have a markedly increased mortality risk.
The American Journal of Cardiology 11/2007; 100(10):1571-6. · 3.37 Impact Factor
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ABSTRACT: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR.
We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using multiple linear regression models.
Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P <0.0001), and left ventricular ejection fraction (P <0.0001) were associated with log(NT-proBNP). After adjustment for GFR estimated by the Cockcroft and Gault equation, the parameter estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFR(MDRD)), the parameter estimates for age (P = 0.0674) changed markedly and became insignificant, but BMI (P = 0.0067) remained significant and unchanged. The eGFR(MDRD) is adjusted for body surface area, which may explain the difference.
In CHF patients, the effect of age on NT-proBNP is associated with estimates for GFR derived from serum creatinine, and the significance of the effects of BMI on NT-proBNP depends on the method by which GFR is estimated.
Clinical Chemistry 11/2007; 53(11):1928-35. · 7.91 Impact Factor
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ABSTRACT: Glycated hemoglobin A1c (HbA1c) is a measure of the average blood glucose levels over 2 months and is minimally affected by acute hyperglycemia often observed in myocardial infarction (MI). In a large population of high-risk patients with MI, we examined the prognostic impact of HbA1c in patients with and without a history of diabetes.
In the OPTIMAAL trial, patients with MI complicated with heart failure were randomized to losartan or captopril. Of the 2841 patients who had HbA1c measured at randomization, 495 (17%) reported a history of diabetes. The remaining patients without diabetes history were stratified into 3 categories according to HbA1c level: HbA1c, <4.9% (n = 1642); HbA1c, 4.9% to 5.1% (n = 432); and HbA1c, >5.1% (n = 272). Mean follow-up time was 2.5 years.
Mortality rate during follow-up was 18% in patients with a history of diabetes. Increasing HbA1c levels were associated with higher mortality rate among patients without diabetes history (13% in patients with HbA1c <4.9%, 17% in patients with HbA1c 4.9%-5.1%, 22% in patients with HbA1c >5.1%). Among patients with no prior history of diabetes, a 1% absolute increase in HbA1c level at baseline resulted in a 24% increase in mortality, whereas the level of HbA1c had no impact on mortality among the patients with well-known diabetes (multivariate analyses).
In this high-risk MI population, HbA1c level was a potent predictor of mortality in patients without previously known diabetes.
American heart journal 09/2007; 154(3):470-6. · 4.65 Impact Factor
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ABSTRACT: N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore, a clinically useful algorithm for risk stratification based on NT-proBNP as a continuous variable has not yet been described. We therefore evaluated NT-proBNP as a risk marker for mortality and hospitalization and developed a simple algorithm for risk stratification based on NT-proBNP as a continuous variable.
Data from 345 patients with chronic heart failure were collected prospectively in our heart failure clinic, and the patients were followed for 28 months (median). Seventy patients died, and 201 patients were hospitalized. Cox proportional hazard models for mortality and hospitalization were constructed with NT-proBNP as a dichotomous (median 1381 pg/mL) and a continuous variable (log2 NT-proBNP).
Patients with supramedian levels of NT-proBNP had a 2.40-fold (95% CI 1.40-4.10) increased risk for mortality and 1.71-fold (95% CI 1.24-2.36) increased risk for hospitalization. The effect of doubling NT-proBNP on adjusted hazard ratios was 1.56 (95% CI 1.32-1.85) for mortality and 1.19 (95% CI 1.09-1.31) for hospitalization. We observed a curvilinear relationship between NT-proBNP and risk for mortality and hospitalization in the whole range of NT-proBNP.
N-terminal pro-brain natriuretic peptide predicts risk for hospitalization and mortality. A simple algorithm indicates that every time NT-proBNP is doubled, estimated hazard ratio for death increases by a factor of 1.56 (56%) and by a factor of 1.19 (19%) for hospitalization. Finally, the relationship between NT-proBNP and risk is curvilinear if NT-proBNP is considered as a continuous variable.
American heart journal 08/2007; 154(1):123-9. · 4.65 Impact Factor
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ABSTRACT: Serum N-terminal pro-brain natriuretic peptide (Nt-proBNP), high sensitivity (hs)-C-reactive protein, and urine albumin/creatinine ratio (UACR) are cardiovascular (CV) risk markers in the general population. The aim of this study was to determine whether they predicted CV events independently of established CV risk factors and whether they did so in an additive fashion.
In a population-based sample of 2656 individuals, 41, 51, 61, and 71 years old, we measured UACR, serum Nt-proBNP, hs-C-reactive protein, insulin, lipids and plasma glucose, clinic blood pressures, body composition, left ventricular (LV) mass index, and ejection fraction (EF) by echocardiography and pulse wave velocity. During the following 9.4 years, the combined CV endpoint (CEP) of CV death (136), non-fatal stroke, or non-fatal myocardial infarction occurred in 219 subjects. After adjustment for established CV risk factors using Cox-regression analyses, CEP and CV death were predicted by log(Nt-proBNP)/SD [hazard ratio (HR) = 1.58 and HR = 1.80, both P < 0.001] and by log(UACR)/SD (HR = 1.44 and HR = 1.52, both P < 0.001) in an additive fashion, but not by log(hs-C-reactive protein)/SD (HR = 1.17, P = 0.06 and HR = 1.13, NS). CV risk functions were constructed on the basis of Cox-regression analyses. Inclusion of Nt-proBNP and UACR did not increase the area under the receiver-operating characteristic plots.
Serum Nt-proBNP and UACR, but not hs-C-reactive protein, predicted CV events after adjustment for established CV risk factors including LV EF and relative wall thickness. However, more studies in relevant subgroups are needed before Nt-proBNP and UACR can be recommended for risk prediction in the general population to select subjects for primary prevention.
European Heart Journal 07/2007; 28(11):1374-81. · 10.48 Impact Factor
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ABSTRACT: Here, the aim is to assess long-term clinical variation (CV) of N-terminal pro-brain natriuretic peptide (NT-proBNP) in stable chronic heart failure (CHF) patients. The proposed use of NT-proBNP for monitoring of CHF patients will require accurate information about long-term CV of the peptide.
Medication, biochemical variables, and NYHA class were recorded at 1-year and 2-year follow-up in patients treated in our heart failure clinic. Only patients without changes in medication and the NYHA class who were not hospitalized or died in the period from first follow-up to 12 months after the second follow-up were included. A total of 78 patients fulfilled the criteria, and year-to-year CV was calculated to 30% (median) (range: 0-111%) (% changes range: -87 to 397%). Log transformation of NT-proBNP (skewed to the right) reduced the year-to-year CV to 4.7% (range: 0-22%) (% changes range: -18 to 38%).
Long-term CV of plasma concentrations of NT-proBNP in stable CHF patients is 30%, but the variation is substantial. Therefore, high long-term CV of NT-proBNP does not necessarily carry prognostic significance within the subsequent 12 months. Plasma concentrations of NT-proBNP followed a lognormal distribution, and the low CV of log(NT-proBNP) indicate that NT-proBNP levels are constant during stable conditions.
European Heart Journal 02/2007; 28(2):177-82. · 10.48 Impact Factor
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ABSTRACT: The usefulness of brain-natriuretic-peptide (BNP) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) for monitoring of chronic heart failure (CHF) patients has been questioned because of high levels of unexplained variation.
Week-to-week total variance (CV(T)), unexplained variation (CV(I)), reference change values (RCV), index of individualities (IOI) and number of samples (N) with week-to-week intervals needed to estimate the underlying homeostatic set point (+/-15%) for BNP and NT-proBNP were calculated in pre-specified stable CHF patients.
We measured plasma concentrations of BNP and NT-proBNP, clinical and laboratory variables in 20 CHF patients with a 7-days interval. Only patients considered to be in steady state were included. The CV(I) was 15% (BNP) and 8% (NT-proBNP). CV(T) was 16% (BNP) and 8% (NT-proBNP) and RCV was 43% (BNP) and 23% (NT-proBNP). IOI was 0.14 for BNP and 0.03 for NT-proBNP and N was 1 for BNP and 1 for NT-proBNP.
Our data demonstrate that unexplained variation of BNP and NT-proBNP is low in CHF patients during steady state, which is a prerequisite for the use of these peptides for monitoring of the disease.
European Journal of Heart Failure 02/2007; 9(1):68-74. · 4.90 Impact Factor
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ABSTRACT: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that losartan-based treatment reduced risk of the composite endpoint of cardiovascular death, stroke and myocardial infarction compared with atenolol-based treatment in patients with hypertension and left ventricular hypertrophy with similar office blood pressure (BP) reduction. Our aim was to investigate the effect of losartan- and atenolol-based treatment on 24-h ambulatory BP and heart rate (HR) in LIFE.
In 110 patients, 24-h ambulatory BP and heart rate were recorded at baseline and 1 year after randomization.
Ambulatory BP was comparably reduced throughout the 24-h period after 1 year of losartan- vs atenolol-based antihypertensive treatment. Office and ambulatory BP were comparably reduced in the follow-up period. Early morning surge in BP was similar between groups. Non-dipping status was more frequent in the losartan group (p = 0.01). From baseline to Year 1 the 24-h HR profile for the losartan group was unchanged, but, as expected, there was a significant decrease in daytime HR in the atenolol group, which was not as large during early night-time.
There were no differences in 24-h BP burden and HR that could explain the difference in outcome in favor of losartan vs atenolol in the LIFE study.
Blood Pressure 02/2007; 16(6):392-7. · 1.43 Impact Factor
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ABSTRACT: N-terminal pro-brain natriuretic peptide (Nt-proBNP) and high-sensitivity C-reactive protein (hsCRP) are cardiovascular risk markers in various populations, but are not well examined in hypertension. Therefore, we wanted to investigate whether high Nt-proBNP or hsCRP predicted the composite endpoint of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction independently of traditional cardiovascular risk factors and the urine albumin: creatinine ratio (UACR), which is a well established cardiovascular risk factor in hypertension.
In 945 hypertensive patients from the LIFE study with electrocardiographic left ventricular (LV) hypertrophy, we measured traditional cardiovascular risk factors including electrocardiography, morning UACR, hsCRP by immunoturbidimetry assay and Nt-proBNP by immunoassay after 2 weeks of placebo treatment. During 55 months' follow-up 80 patients suffered a composite endpoint.
HsCRP as well as Nt-proBNP above the median values of 3.0 mg/l and 170 pg/ml, respectively, was associated with a higher incidence of composite endpoint (13.1 versus 3.8%, P < 0.01, and 11.5 versus 5.4%, P < 0.01). In Cox regression analyses, standardized log(hsCRP)/SD predicted a composite endpoint [hazard ratio (HR) 1.3 per SD = 0.47 log(mg/l), P < 0.05] after adjustment for traditional cardiovascular risk factors, but not after further adjustment for UACR. Standardized log(Nt-proBNP)/SD predicted a composite endpoint after adjustment for traditional cardiovascular risk factors [HR 1.9 per SD = 0.49 log(pg/ml), P < 0.05] as well as after further adjustment for UACR [HR 1.5 per SD = 0.49 log(pg/ml), P < 0.01]. Log(Nt-proBNP) added significantly to the Cox regression models using traditional cardiovascular risk factors with and without UACR (both P < 0.001).
Nt-proBNP predicted a composite endpoint after adjustment for traditional risk factors, UACR and a history of diabetes or cardiovascular disease and added significantly to the prediction of composite endpoint, whereas hsCRP did not.
Journal of Hypertension 08/2006; 24(8):1531-9. · 4.02 Impact Factor
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ABSTRACT: Renal metabolism of the cardiac marker NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) has been suggested. Therefore, we determined the renal extraction ratios of NT-proBNP and its bioactive coproduct brain natriuretic peptide (BNP) at rest and during exercise. In addition, the cerebral ratios were evaluated. Ten young healthy men were investigated at baseline, during moderate cycle exercise (heart rate: 140, Borg scale: 14-15), and in the recovery with BNP and NT-proBNP measured from the brachial artery and the jugular and renal veins, and the renal and cerebral extraction ratios (Ext-Ren and Ext-Cer, respectively) were calculated. Cardiac output, stroke volume, heart rate, mean arterial pressures, and estimated glomerular filtration were determined. BNP and NT-proBNP were extracted by the kidneys but not by the brain. We observed no effect of exercise. The mean values (+/- SE) of Ext-Ren of NT-proBNP were similar (0.19 +/- 0.05, 0.21 +/- 0.06, and 0.12 +/- 0.03, respectively) during the three sessions (P > 0.05). Also the Ext-Ren of BNP were similar (0.18 +/- 0.07, 0.15 +/- 0.11, and 0.14 +/- 0.06, respectively; P > 0.05). There were no significant differences between Ext-Ren of BNP and NT-proBNP during the three sessions (P > 0.05). The Ext-Cer of both peptides varied insignificantly between -0.21 +/- 0.15 and 0.11 +/- 0.08. The renal extraction ratio of both BNP and NT-proBNP is approximately 0.15-0.20. There is no cerebral extraction, and short-term moderate exercise does not affect these values. Our findings suggest that the kidneys extract BNP and NT-proBNP to a similar extent in healthy young men.
Journal of Applied Physiology 11/2005; 99(5):1676-80. · 3.75 Impact Factor
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ABSTRACT: Secretion of natriuretic peptides is related to cardiac wall stress and influenced by the renin-angiotensin system. Therefore, we investigated the influence of blood pressure (BP) reduction with losartan versus atenolol on N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP).
In 183 patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy, enrolled in the LIFE Study, we measured BP and serum Nt-proANP and Nt-proBNP by immunoassay after 2 weeks of placebo treatment and after 1, 2, 4, 6, 12, 24, 36 and 48 months of randomized treatment with losartan- or atenolol-based antihypertensive regimens.
There was no significant difference in BP at any time point between the two treatment groups. In patients treated with losartan, median Nt-proANP decreased gradually throughout the study, reaching significance after 6 months of treatment (1125-1060 pmol/l, P < 0.001), and Nt-proBNP decreased within the first month (24.7-18.7 pmol/l, P < 0.01) and stayed reduced throughout the study. During losartan-based antihypertensive treatment, Nt-proANP and Nt-proBNP as a percentage of baseline values were correlated to reductions in systolic BP (r = 0.11, P < 0.01 and r = 0.10, P = 0.01) and diastolic BP (r = 0.17, P < 0.001 and r = 0.07, P = 0.09). In atenolol-treated patients, Nt-proANP (1100-1640 pmol/l, P < 0.001) and Nt-proBNP (20.0-37.7 pmol/l, P < 0.001) increased during the first month, and remained elevated throughout the study. During atenolol-based antihypertensive treatment, changes in Nt-proANP (r = -0.16, P < 0.001) and Nt-proBNP (r = -0.07, P = 0.08) were negatively related to change in heart rate.
Nt-proANP and Nt-proBNP were reduced in parallel with BP in losartan-treated patients whereas they increased in parallel with decreased heart rate in atenolol-treated patients.
Journal of Hypertension 06/2005; 23(5):1083-90. · 4.02 Impact Factor
