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Heart Failure Protein Tied to Brain Atrophy

— NT-proBNP seen as link between heart disease and brain shrinkage

MedpageToday

CHICAGO -- Levels of N-terminal pro b-type natriuretic peptide (NT-proBNP), currently used as a biomarker for heart failure, were correlated with subtle changes in brain structure including gray matter loss, researchers said here.

The findings suggest that, in patients with heart disease, clinicians should be aware of the possibility of subclinical but progressive neurological dysfunction, according to a PhD candidate at Erasmus University Medical Center in Rotterdam, The Netherlands, who presented the findings of an imaging study at the Radiological Society of North America meeting.

Compared with the lowest tertile of NT-proBNP in serum, community-dwelling people (mean age 56.6) in the highest tertile had smaller total brain volumes (P=0.040), smaller gray matter volume (P=0.008), and more white matter lesions (P=0.002), Zonneveld and colleagues found.

"The brain volume loss was predominantly in the gray matter," Zonneveld said at a press conference here. "Our work implies implies that the heart and brain are intimately linked, even in presumably healthy individuals, and informs us importantly about development of disease as we age."

She told app that the ongoing, longitudinal Rotterdam Study will follow the participants, and researchers may some day be able to show definitely that the heart damage indicated by NT-proBNP levels truly predicts dementia or strokes.

"Heart and brain diseases are big problems in aging individuals and are expected to grow even more," she said "We know that myocardial infarction, heart failure, and atrial fibrillation are associated with an increased risk of stroke and dementia. Our study investigates whether the heart-brain link is present at an earlier stage of disease."

Zonneveld and colleagues analyzed data from 2,432 participants in the Rotterdam Study. About 57.4% of the participants in the current study were women. Participants with overt heart disease, dementia, and stroke were excluded from the analysis.

The participants underwent brain MRI with diffusion tensor imaging (DTI). They also had blood drawn to measure levels of NT-proBNP.

"NT-proBNP is released into the bloodstream in response to myocardial wall stress," Zonneveld explained. "Studies have demonstrated that NT-proBNP provides information on cardiac dysfunction even in the absence of overt heart disease."

The researchers evaluated the brain MRI results for markers of early brain disease, including a loss of brain volume, microstructural changes, and white matter lesions, which indicate areas of cells that have been damaged by injury or disease.

"DTI gives us information on the microstructural organization of the brain's white matter," Zonneveld said. "It is thought that microstructural brain changes precede brain changes, such as white matter lesions."

The results of DTI showed that participants with higher NT-proBNP levels had worse microstructural organization within the white matter. A statistical analysis revealed that higher NT-proBNP levels were also associated with smaller total brain volume and larger white matter lesion volume.

In commenting on the study, , of Stanford University School of Medicine in Stanford, Calif., told app that "when we do MRI of the brains of patients, we often see these while matter spots and we never know exactly what they represent. We know that the older you get, the more of those you see. So maybe some of these white matter lesions are related to cardiac dysfunction."

However, he added that it has not yet been shown that these changes relate to stroke or dementia, although future longitudinal studies may show that.

Zonneveld said it is "important for cardiologists to know that in cases where they see heart disease, they should be aware that brain disease can occur as well." She said that cost-effectiveness studies should be performed to determine it NT-proBNP should be included in screening studies.

Disclosures

Zonneveld disclosed no relevant relationships with industry.

Primary Source

Radiological Society of North America

Zonneveld H, et al "Subclinical cardiac dysfunction relates to imaging markers of subclinical brain disease in the general population" RSNA 2015; Abstract SST09-01.