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Circulating Markers of Inflammation and Endothelial Dysfunction Associated With Increased Progression of Internal

Hediyeh Baradaran¹, Adlin Pinheiro^2,3, Emelia J Benjamin^3,4,5

¹Department of Radiology and Imaging Sciences University of Utah Salt Lake City UT USA.

Journal of the American Heart Association

|November 17, 2025

Insights

Markers of inflammation and endothelial dysfunction are linked to increased carotid artery intima-media thickness (CIMT) progression. This study in the Framingham Heart Study cohort highlights key inflammatory markers associated with subclinical atherosclerosis.

Area of Science:

Cardiovascular Science
Biomarkers
Atherosclerosis Research

Background:

Subclinical atherosclerosis, indicated by carotid artery intima-media thickness (CIMT), is linked to cardiovascular and cerebrovascular diseases.
The association between circulating inflammatory markers and CIMT progression remains unclear.
This study investigates the relationship between inflammation, endothelial dysfunction markers, and CIMT progression in the Framingham Heart Study (FHS) cohort.

Purpose of the Study:

To determine if circulating markers of inflammation and endothelial dysfunction are associated with the progression of internal carotid artery intima-media thickness (ICIMT).
To examine the cross-sectional association between these markers and ICIMT.
To adjust for established vascular risk factors and baseline ICIMT in the analysis.

Main Methods:

Utilized multivariable linear regression to analyze data from 2264 participants in the Framingham Heart Study.
Assessed the association between specific circulating inflammatory markers and both cross-sectional ICIMT and ICIMT progression (rate of change in mm/y).
Primary analyses adjusted for age, sex, hypertension, diabetes, APOE4, BMI, and smoking; secondary analyses also adjusted for baseline ICIMT.

Main Results:

Higher baseline levels of C-reactive protein, lipoprotein-associated phospholipase A activity, and isoprostanes were significantly associated with increased ICIMT progression (p<0.05).
Cross-sectional analysis revealed significant associations between higher levels of interleukin-6, osteoprotegerin, and P-selectin with higher ICIMT.
The findings were adjusted for key vascular risk factors and baseline CIMT measurements.

Conclusions:

Specific circulating markers of inflammation and endothelial dysfunction are significantly associated with increased ICIMT.
These inflammatory markers are implicated in the progression of carotid atherosclerosis.
The results contribute to understanding the inflammatory pathways involved in cardiovascular disease development.

Read full analysis

Abstract

Background:

Circulating markers of inflammation may be associated with carotid artery intima-media thickness (CIMT), a marker of subclinical atherosclerosis associated with cardiovascular and cerebrovascular disease, although the exact relationship between these circulating markers of inflammation and progression of CIMT is unclear. We hypothesize that markers of circulating inflammation and endothelial dysfunction are associated with progression of CIMT in the FHS (Framingham Heart Study) cohort.

Methods:

Multivariable linear regression was used to assess the association between specific circulating markers of inflammation with cross-sectional internal CIMT (ICIMT) measurement and ICIMT progression defined as rate of change of intima-media thickness (mm/y) in the internal carotid artery. Our primary analyses adjusted for age, sex, hypertension, diabetes, APOE4, body mass index, and smoking at the time of baseline CIMT measurement. Secondary analyses additionally adjusted for baseline CIMT measurements.

Results:

We studied 2264 participants (mean age 57.2 years, 54% women). In our primary multivariable adjusted analysis, we observed that participants with higher baseline C-reactive protein (β=0.057 [95% CI, 0.012-0.102]; P=0.013), lipoprotein-associated phospholipase A activity (β=0.050 [95% CI, 0.006-0.094]; P=0.027), and isoprostanes (β=0.054 [95% CI, 0.013-0.101]; P=0.012) had significantly higher ICIMT progression, after adjusting for vascular risk factors and baseline CIMT. In a cross-sectional analysis at follow-up, we also observed that participants with higher levels of interleukin-6, osteoprotegerin, and P-selectin had significantly higher ICIMT.

Conclusions:

Specific markers of inflammation and endothelial dysfunction were associated with increased ICIMT and carotid atherosclerosis progression.

Keywords:

atherosclerosis carotid artery disease carotid plaque endothelial dysfunction inflammation

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