Abstract Details

Title Association of Plasma NfL Levels with Risk of Cardiovascular Disease in the Framingham Heart Study

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S33 - Cerebrovascular Disease: Basic Sciences and Cohort Studies (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background Neurofilament light chain is a protein that forms the neuron cytoskeleton. Higher levels in blood signal neuronal injury in several conditions including stroke, dementia, multiple sclerosis, and amyotrophic lateral sclerosis. Whether plasma NfL levels are a risk marker for future cardiovascular disease is unknown.

Objective To investigate the association of circulating neurofilament light chain levels with the incidence of cardiovascular disease.

Design/Methods Plasma NfL levels were measured from participants enrolled in the community-based Framingham Heart Study Offspring and OMNI1 cohorts using a high sensitivity single molecule array analysis. Using multivariable Cox regression, natural log-transformed plasma NfL levels at baseline were related to the incidence of cardiovascular disease (coronary heart disease, heart failure, stroke, angina, and claudication), and its individual components, over a mean±SD of 5.5±1.6 years follow-up. All models were adjusted for age, sex, and cohort (Offspring or OMNI1).

Results

Among the 2,048 included participants (mean±SD age 69±8 years, 58% women), there were 175 (8.5%) incident cardiovascular events over the study period (2011-2019). Higher plasma NfL levels (per unit of the natural log of the protein level) were associated with an increased risk of cardiovascular disease (hazard ratio [HR]=1.43, 95% confidence interval [CI]=1.05-1.95), coronary heart disease (n=67; HR=1.56, 95%CI=1.00-2.41), and heart failure (n=91; HR=1.67, 95%CI=1.13-2.47), but not stroke (n=60; HR=1.00, 95%CI=0.56-1.78). Associations were non-significant when models were further adjusted for renal function, body mass index, race, current smoking, diabetes, systolic blood pressure, antihypertensive treatment, and high-density lipoprotein level.

Conclusions Circulating levels of the NfL protein were associated with future risk of all cardiovascular disease, coronary heart disease, and heart failure in minimally adjusted models. NfL is a biomarker of neuronal injury and may also be a risk marker for the onset of cardiac disease. Ongoing research will determine the adjusted risk factors that specifically attenuate this association.

Authors/Disclosures
Hugo Javier Aparicio, MD, MPH (Boston University) PRESENTER	Dr. Aparicio has received research support from American Academy of Neurology. Dr. Aparicio has received research support from Alzheimer's Association. Dr. Aparicio has received research support from National Institutes of Health. Dr. Aparicio has received personal compensation in the range of $10,000-$49,999 for serving as a expert panelist for the Memory & Healthy Aging Program with Cedars-Sinai.
Jayandra Himali	No disclosure on file
Dibya Himali	No disclosure on file
Jose R. Romero, MD (Boston University School of Medicine - Boston Medical Center)	The institution of Dr. Romero has received research support from NIH/NIA.
Vasileios-Arsenios Lioutas, MD (Beth Israel Deaconess Medical Center, Department of Neurology)	Dr. Lioutas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Qmetis. Dr. Lioutas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mindray. The institution of Dr. Lioutas has received research support from NIH. The institution of Dr. Lioutas has received research support from Alzheimer's Association.
Matthew Pase, PhD (Monash University)	Dr. Pase has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzheimer's Disease Drug Discovery Foundation.
Claudia L. Satizabal, PhD (UT Health San Antonio)	The institution of Dr. Satizabal has received research support from NIH and TARCC.
Alexa Beiser	No disclosure on file
	No disclosure on file
Sudha Seshadri, MD, FAAN (Glenn Biggs Institute for Alzheimer'S and Neurodegenerative Diseases)	Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Seshadri has received research support from NIH. The institution of Dr. Seshadri has received research support from Alzheimer Association.