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Utility of the amino-terminal fragment of pro-brain natriuretic peptide in plasma for the evaluation of cardiac dysfunction in elderly patients in primary health care
Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
Sahlgren Academy at Gothenburg University, Gothenburg, Sweden.
Department of Medicine, Sahlgrenska University Hospital-Östra, Gothenburg, Sweden.
Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0001-6353-8041
2003 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 49, no 8, 1337-1346 p.Article in journal (Refereed) Published
Abstract [en]

Background: The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure.

Methods: We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction ≤40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern.

Results: Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormali-ties had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations.

Conclusions: Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.

Place, publisher, year, edition, pages
2003. Vol. 49, no 8, 1337-1346 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-26758DOI: 10.1373/49.8.1337Local ID: 11356OAI: diva2:247308
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-09-26Bibliographically approved
In thesis
1. Heart failure in primary health care: special emphasis on natriuretic peptides in the elderly
Open this publication in new window or tab >>Heart failure in primary health care: special emphasis on natriuretic peptides in the elderly
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: This thesis focuses on heart failure among elderly patients in the community who usually are not included in studies on heart failure. The heart failure syndrome is an increasing problem in Western society. Severe heart failure is often easy to diagnose compared with light to moderate heart failure, which is more frequent in patients in the community,

Doppler echocardiography is the most commonly used method to objectively verify an abnormal cardiac function, mostly the systolic function. One goal of this thesis was to evaluate both the systolic and diastolic functions. Another goal was a study of the possible utility of the B-type natriuretic peptide, BNP (brain natriuretic peptide), and the amino terminal fragment of its precursor, proBNP (N-terminal proBNP) as tools in the diagnosis of heart failure in elderly patients.

Methods: In a primary health care setting, 510 elderly patients (age range 65-82 years) with symptoms and signs possibly associated with heart failure were examined concerning patient history, ongoing pharmacological treatment, clinical examination, chest x-ray, electrocardiogram, Doppler echo cardiography, and selected biochemical measurements of blood samples. Additionally, the natriuretic peptide BNP and the aminoterminal fragment of proBNP were analyzed for a possible influence of gender, age, impaired cardiac function assessed using Doppler echocardiography, other diseases, and phannacological treatment. We followed our study population for six years, carefully registering mortality with death certificates. This information was used in analyzing the risk of cardiovascular death based on Cox proportional hazard regression. We present a model for estimating the risk of cardiovascular death in the individual patient.

Results: Almost half of our study population [mean age 73 (SD 6) years] with symptoms of possible heart failure had signs of impaired cardiac function on Doppler echocardiography. Half of these individuals had isolated impairment of the diastolic function. Almost two thirds of the elderly patients who had an ejection fraction of less than 40% did not receive treatment with ACE inhibitors, one of the cornerstones in the treatment of heart failure.

BNP and N-terminal proBNP were equally effective in detecting impaired cardiac function. As a response to increased filling pressure they probably provide earlier information on the haemodynamic situation than Doppler echocardiography does.

In these elderly patients, functional class (NYHA class III: 7 times increased risk), in vivo examination by Doppler echo cardiography (EF<30%: 8 times increased risk) and the in vitro measurement of plasma BNP (>27.8 pmol/L: 11 times increased risk) and N-terminal proBNP (>109 pmol/L: 7 times increased risk) could be used as prognostic determinants in assessing the risk of cardiovascular death.

Conclusion: The results indicate that a focused patient history and clinical examination provides important information that is often sufficient for the prognostic evaluation of a patient with heart failure symptoms. Additional information may be obtained with Doppler echo cardiographic examination and measurement of plasma BNP or N-terminal proBNP. The relationship between BNPIN-terminal proBNP concentration and risk of cardiovascular death may be analysed to define decision limits for the concentrations of these peptides as regards further diagnostic procedures and/or phannaceutical treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2003. 111 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 819
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-27454 (URN)12107 (Local ID)91-7373-508-6 (ISBN)12107 (Archive number)12107 (OAI)
Public defence
2003-11-06, Hälsans Hus, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-17Bibliographically approved

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