New Link Between Cardiac Disease and Brain Injury

February 22, 2017

Researchers have established a new link between cardiac disease and small-vessel brain disease, which, they say, suggests that controlling cardiovascular risk factors could play a more important role than previously thought in preventing cognitive impairment.

The study, published online in JAMA Neurology on February 6, shows that both biomarkers of subclinical cardiac disease and clinically manifest cardiac disease are associated with cortical cerebral microinfarcts, a novel MRI marker of cerebral vascular disease.

"Hence, cardiac dysfunction should be targeted as a potentially modifiable factor to prevent CMI [cortical microinfarct]-related brain injury," the researchers conclude.

"We report the presence of cortical microinfarcts in elderly patients attending a memory clinic. These microinfarcts are evidence of disease of small vessels which perforate inner-brain areas that play an important role in cognition," lead author, Saima Hilal, PhD, Erasmus Medical Center, Rotterdam, the Netherlands, commented to Medscape Medical News.

"We have shown that these microinfarcts are now detectable in vivo on 3T MRI scans. We have reported a previous study in which we showed these microinfarcts were associated with cognitive dysfunction, and now we show that they are also associated with clinical and subclinical cardiac disease," Dr Hilal added. "So this gives a new possible mechanism linking heart disease to dementia."

Senior author, Christopher Chen, FRCP, National University of Singapore, pointed out that these microinfarcts are "relatively novel."

"We have known from postmortem studies that they are significantly linked with cognitive dysfunction and dementia above and beyond other ischemic lesions," he said. "But we haven't been able to see them on MRI in a living individual until very recently. So it has been hard to know how they develop and the underlying mechanisms on how they may contribute to cognitive dysfunction. Now we have shown in several papers that these microinfarcts can be visualized using MRI, and this is opening up a new area of research.

"We suggest that while amyloid and tau are markers of Alzheimer's-type dementia, these cerebral microinfarcts could be markers of vascular dementia, and being able to visualize these microinfarcts on MRI could become a powerful tool to investigate and treat patients with cognitive dysfunction," he added.

The current study was a cross-sectional analysis of 243 individuals (mean age, 72 years) attending a memory clinic. Of these individuals, 70 (28.8%) had cortical microinfarcts, and compared with participants with none of these lesions, those with cortical microinfarcts had a significantly higher prevalence of atrial fibrillation (rate ratio [RR], 1.62), ischemic heart disease (RR, 4.31), and congestive heart failure (RR, 2.05).

They also had significantly higher levels of N-terminal pro-brain natriuretic peptide (RR, 3.16) and high-sensitivity cardiac troponin T (RR, 2.17).

The link between levels of both cardiac biomarkers and the presence of cortical microinfarcts remained in multivariate models adjusted for demographics and vascular risk factors and after excluding patients with clinically manifest cardiac disease.

Dr Chen explained that while it is known that treating cardiovascular risk factors, such as hypertension, diabetes, and high cholesterol, reduces the risk for large-vessel cerebral disease (stroke), it has not been clear that treating heart failure or lowering subclinical markers of cardiac dysfunction may also help the brain.

"In this paper we show the first step in that direction: that heart failure and cardiac biomarkers are associated with small-vessel cerebral disease in the form of these microinfarcts. Thus, we have linked these cardiac risk factors to pathology in the brain that has been associated with dementia."

Dr Chen says the next step is to perform longitudinal studies to test whether the presence of these microinfarcts predicts the development of cognitive dysfunction, whether treating cardiovascular risk factors reduces the progression of cerebral microinfarcts, and whether this could prevent or delay cognitive dysfunction.

He noted that at present these microinfarcts are viewed as a research tool. "This is a relatively new field, and there are currently only a few specialists who know how to identify these microinfarcts on MRI. But in the future, as MRI technology becomes more sophisticated and if further studies validate our findings, then microinfarcts may become useful clinical tools."

Important Role

In an accompanying editorial, Robert J. Wityk, MD, emeritus, Johns Hopkins University School of Medicine, Baltimore, Maryland, writes, "The article by Hilal et al and others published in the recent literature suggest an important role of CMIs in epidemiologic studies of cerebrovascular disease, particularly with regard to cognitive dysfunction."

To Medscape Medical News, Dr Wityk added: "This paper is more proof of principle — another piece of information linking cardiac biomarkers with risk of cognitive dysfunction.

"It is too early for any clinical recommendations," he said. "More studies are needed on how these microinfarcts relate to dementia, and more specialists need to be trained to identify these microinfarcts on MRI, but these results do show that we can use available 3T MRI to study small-vessel disease of the brain in living patients, which in itself is an exciting finding."

This study was funded by grants from the Singapore National Medical Research Council. The authors have disclosed no relevant financial relationships.

JAMA Neurol. Published online February 6, 2017. Abstract, Editorial

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