Asymptomatic Coronary Plaque Linked to White Matter Lesions

Nancy A. Melville

October 28, 2019

ST. LOUIS — The presence of coronary artery atherosclerotic plaque is significantly associated with increased white matter hyperintensity volume in the brain — specifically the periventricular region, new research suggests. This occurs even in healthy individuals who are at risk for coronary artery disease (CAD) but are asymptomatic.

Using data from the ongoing Genetic Study of Atherosclerosis Risk (GeneSTAR) study, the results suggest that CAD may also "have differential associations with lesions in different locations," the investigators note.

"Our findings are novel because they consider the different locations of the white matter disease, which has not been done before; and our cohort is also unique," lead author Michelle C. Johansen, MD, from Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News.

"The GeneSTAR cohort enables us to look at younger individuals who have a family history of CAD but no manifestations of disease," Johansen added.

The findings were presented here at ANA 2019: 144th Annual Meeting of the American Neurological Association.

Unknown Mechanisms

White matter hyperintensity, or lesions, has increasingly been shown to be associated with cognition as well as overall function. Although CAD is known to be linked with white matter lesions, understanding of mechanisms and significance of location in the brain is lacking.

To evaluate these issues, the investigators turned to GeneSTAR, an ongoing prospective study designed to identify genetic and biological risk factors in families with early-onset CAD.

They identified 782 asymptomatic individuals who had family members with premature CAD, meaning they were younger than the age of 60 years. These participants (58% women; 39% black; mean age, 51 years) were eligible for coronary computed tomography angiography (CTA) and brain MRI.

Analyzing biomarkers of CAD and MRI, and after controlling for traditional risk factors such as hypertension and diabetes, the researchers found a significant association between CAD atherosclerotic plaque volume and white matter hyperintensity. In fact, there was an increase in total white matter hyperintensity volume of 0.08% for each 1% increase in total cardiac plaque volume (95% confidence interval [CI], 0.05 - 0.11).

Participants showing any coronary plaque had white matter hyperintensity volumes that were as much as 58% greater than those without any plaque (β, 0.46; 95% CI, 0.28 - 0.63).

Looking at the specific location of hyperintensities, the researchers found that for each 1% increase in total cardiac plaque there was a 5.0% larger deep white matter hyperintensity (95% CI, 4.66 - 5.42), a 5.1% increase in periventricular white matter hyperintensity volume (95% CI, 4.71 - 5.51), and a 2.75% greater cuff volume.

Compared with the other regions, periventricular white matter hyperintensity volume was significantly greater than cuff volume (P < .001) and deep white matter hyperintensity (P = .001).

Independent Risk Factor?

Focusing on coronary CTA showed larger lesion volumes in all locations among the participants with any coronary CTA plaque compared with those without plaque.

Again, the associations were the strongest in the periventricular region. Compared with the association between coronary CTA plaque and deep white matter hyperintensity (β, 5.01; 95% CI, 4.67 - 5.34), the association with CTA was greater for periventricular white matter hyperintensity (β, 5.46; 95% CI, 5.08 - 5.85; P = .009) but was lower for increased cuff volume (β, 2.22; 95% CI, 1.88 - 2.56; P < .001).

Importantly, the study helps distinguish CAD as an independent risk factor for white matter hyperintensity, Johansen said. "If this was all due to shared vascular risk factors then we should not have found an association," she explained.

The higher association in the periventricular area also suggests a possible unique interaction with coronary plaque, she noted.

"It is plausible that there is a difference in the way the different areas of the brain are impacted by asymptomatic CAD, whether through a flow phenomenon or perhaps the cerebrovasculature is differentially affected by CAD," Johansen said.

However, she pointed out that the findings don't necessarily show a causal role.

"We cannot say that CAD caused these white matter hyperintensity changes, but rather it is important to realize and recognize that there might be something else mechanistically occurring that leads to these changes," Johansen said.

"Intriguing Findings"

The findings offer important insights into the potential interplay between CAD and the brain, Costantino Iadecola, MD, professor of neurology and director and chair of the Feil Family Brain and Mind Research Institute in New York City, told Medscape Medical News when asked for comment.

"The interest of this paper is that the white matter lesions were associated with coronary artery disease independent of vascular risk factors, such as hypertension," said Iadecola, who was not involved with the research.

"In this population of individuals at genetic risk, the data may suggest a general vasculopathy on genetic basis, which manifests itself with coronary artery disease in the heart and small vessel disease in the brain," he said.

Iadecola added that the higher concentration in periventricular white matter is also notable.

"The periventricular white matter is at risk for hypoxia-ischemia and vascular pathology, since it is supplied by the terminal fields of two separate arterial territories. Furthermore, the vessels of this brain region are prone to occlusion and other pathologies which may underlie the white matter hyperintensities," he said.

Study limitations he cited include a lack of data on factors that could paint a bigger picture, including the genetic makeup of the individuals, such as exam/genome sequencing, and ApoE status.

Other factors that could help further understanding of the findings include "the impact on cardiac function, cerebral blood flow, and blood-brain permeability, as well as cognitive function," Iadecola said.

"The white matter hyperintensity/cognition should be correlated to these variables to provide a more mechanistic interpretation of these intriguing findings," he concluded.

The study received funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences, and the National Heart, Lung, and Blood Institute. Johansen receives funding through the American Heart Association Mentored Career Development Award and the KL2 Career Development Award. Iadecola has reported no relevant financial relationships.

ANA 2019: 144th Annual Meeting of the American Neurological Association. Abstract M297. Presented October 14, 2019.

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