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Plasma NT-proBNP and white matter hyperintensities in type 2 diabetic patients

Henrik Reinhard1*, Ellen Garde2, Arnold Skimminge2, Per Åkeson2, Thomas Zoëga Ramsøy27, Kaj Winther3, Hans-Henrik Parving45, Peter Rossing1 and Peter K Jacobsen16

Author Affiliations

1 Steno Diabetes Center, Gentofte, Denmark

2 Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark

3 Department of Clinical Biochemistry, Frederiksberg University Hospital, Frederiksberg, Denmark

4 Department of Medical Endocrinology, University Hospital of Copenhagen, Copenhagen, Denmark

5 Faculty of Health Science, Aarhus University, Aarhus, Denmark

6 The Heart Centre, Rigshospitalet & University of Copenhagen, Copenhagen, Denmark

7 Decision Neuroscience Research Group, Dept. of Marketing, Copenhagen Business School, Frederiksberg, Denmark

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Cardiovascular Diabetology 2012, 11:119  doi:10.1186/1475-2840-11-119

Published: 3 October 2012


Elevated plasma N-terminal (NT)-proBNP from the heart as well as white matter hyperintensities (WMH) in the brain predict cardiovascular (CV) mortality in the general population. The cause of poor prognosis associated with elevated P-NT-proBNP is not known but WMH precede strokes in high risk populations. We assessed the association between P-NT-proBNP and WMH or brain atrophy measured with magnetic resonance imaging (MRI) in type 2 diabetic patients, and age-matched controls.

We measured P-NT-proBNP(ng/l) in 20 diabetic patients without prior stroke but with(n = 10) or without(n = 10) asymptomatic coronary artery disease(CAD) in order to include patients with a wide-ranging CV risk profile. All patients and 26 controls had a 3D MRI and brain volumes(ml) with WMH and brain parenchymal fraction(BPF), an indicator of brain atrophy, were determined.

P-NT-proBNP was associated with WMH in linear regression analysis adjusted for CV risk factors(r = 0.94, p = 0.001) and with BPF in univariate analysis(r = 0.57, p = 0.009). Patients divided into groups of increased P-NT-proBNP levels were paralleled with increased WMH volumes(geometric mean[SD];(2.86[5.11] ml and 0.76[2.49] ml compared to patients with low P-NT-proBNP 0.20[2.28] ml, p = 0.003)) and also when adjusted for age, sex and presence of CAD(p = 0.017). The association was strengthened by CV risk factors and we did not find a common heart or brain specific driver of both P-NT-proBNP and WMH. Patients and particular patients with CAD had higher WMH, however no longer after adjustment for age and sex.

P-NT-proBNP was associated with WMH in type 2 diabetic patients, suggesting a linkage between heart and brain disease.

Type 2 diabetes; Plasma NT-proBNP; 3-D magnetic resonance imaging; White matter hyperintensities; Brain parenchymal fraction