Subclinical Atherosclerosis, CVD Risk Factors Tied To Brain Hypometabolism

Middle-aged adults with subclinical atherosclerosis and cardiovascular risk factors such as hypertension, diabetes, high cholesterol, and inactivity may be at increased risk for cerebral hypotension that's tied to cognitive impairment, a study suggests.

Researchers examined data on 547 asymptomatic adults (mean age 50.3 years, 82% male) with subclinical atherosclerosis. All the participants had positron emission tomography (PET) scans, and researchers used F-fluorodeoxyglucose (FDG) uptake and voxel-wise analysis to determine the association between cerebral metabolism and cardiovascular risk factors.

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Overall, participants' median 30-year Framingham Risk Score was 24.2% and these scores were inversely associated with global brain FDG uptake (beta -0.15). Higher Framingham scores had the strongest correlation with reduced FDG uptake in the angular and middle/inferior temporal gyri in the parietotemporal region.

Among the cardiovascular risk factors examined in the study, hypertension appeared to have the strongest association with global cerebral hypometabolism; the effect size for this association was moderate but highly significant (d=0.36), the study team reports in the Journal of the American College of Cardiology.

"We had already detected short-term progression of early subclinical atherosclerosis in abdominal aorta, carotid, iliac, and femoral territories in a substantial proportion of apparently healthy middle-aged men and women," said senior study author Dr. Valentin Fuster, general director of the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) in Madrid and director of the Cardiovascular Institute and physician-in-chief at the Mount Sinai Medical Center in New York City.

"It is not surprising that this finding is correlated to the findings in the brain," Dr. Fuster said by email.

Total plaque burden was associated with cerebral hypometabolism, but no association between global brain FDG uptake and total atheroma plaque burden was seen.

Carotid plaque burden was inversely associated with lower FDG uptake even after adjusting for total plaque burden, the analysis also found.

One limitation of the study is that researchers lacked data on the cognitive status of individual participants. Effect sizes of the main outcomes in this population of middle-aged asymptomatic patients were also relatively small, the study team points out.

The study population was also exclusively Caucasian, limiting generalizability.

"Whether atherosclerosis directly causes brain hypometabolism is unclear," said Dr. Neal Parikh, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York City, who coauthored an editorial comment accompanying the study.

At this point, the bulk of evidence suggests that hypertension is the most important modifiable risk factor, Dr. Parikh said by email. Clinicians should work with patients to help them achieve and maintain normal blood pressure, which can reduce the risk of a range of health problems including heart disease, stroke and cognitive impairment, Dr. Parikh said.

"The main take-home message for clinicians is that uncontrolled vascular risk factors in mid-life should not be dismissed," Dr. Parikh added. "There is a large body of evidence showing that vascular risk factors in midlife influence health in later life."

—Lisa Rapaport

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