Abstract

Backgrounds and aims: Elevated common carotid artery intima-media thickness (carotid IMT) and diminished flow-mediated dilation (FMD) are early subclinical indicators of atherosclerosis. Serum total non-esterified fatty acid (NEFA) concentrations have been positively associated with subclinical atherosclerosis. The relations between individual NEFA, carotid IMT and FMD have as yet to be assessed. Methods: We investigated the associations between fasting serum individual NEFA, carotid IMT and FMD among Cardiovascular Health Study (CHS) participants with (n = 255 for carotid IMT, 301 for FMD) or without (n = 1314 for carotid IMT, 1462 for FMD) known atherosclerotic cardiovascular disease (ASCVD). Using archived samples (fasting) collected from 1996–1997 (baseline), 35 individual NEFAs were measured using gas chromatography. Carotid IMT and estimated plaque thickness (mean of maximum internal carotid IMT) were determined in 1998–1999. FMD was measured in 1997–1998. Linear regression adjusted by the Holm-Bonferroni method was used to assess relations between individual NEFA, carotid IMT and FMD. Results: In multivariable adjusted linear regression models per SD increment, the non-esterified trans fatty acid conjugated linoleic acid (trans-18:2 CLA) was positively associated with carotid IMT [β (95% CI): 44.8 (19.2, 70.4), p = 0.025] among participants with, but not without, ASCVD [2.16 (−6.74, 11.5), p = 1.000]. Non-esterified cis-palmitoleic acid (16:1n-7c) was positively associated with FMD [19.7 (8.34, 31.0), p = 0.024] among participants without, but not with ASCVD. No significant associations between NEFAs and estimated plaque thickness were observed. Conclusions: In older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for arteriopathy.

Highlights

  • Cardiovascular disease (CVD) is the most common and leading cause of morbidity and mortality in the US [1]

  • The aims of this study were to assess the relations of fasting serum individual non-esterified fatty acid (NEFA) with carotid IMT and flow-mediated dilation (FMD), and as a secondary outcome, estimated plaque thickness, in the Cardiovascular Health Study (CHS) cohort

  • In individuals with Atherosclerotic cardiovascular disease (ASCVD), the non-esterified trans FA18:2CLA was positively associated with carotid IMT, and there was a trend towards significance for two other trans species

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Summary

Introduction

Cardiovascular disease (CVD) is the most common and leading cause of morbidity and mortality in the US [1]. Inflammation and disorders of lipoprotein metabolism are positively associated with carotid IMT [5]. Flow-mediated dilation (FMD) is a noninvasive measure of endothelial function and considered a reflection of endothelial nitric oxide synthase (eNOS). Diminished FMD is positively associated with impaired eNOS activity and CVD risk [6,7,8]. Both FMD and carotid IMT have been associated with risk of clinical cardiovascular disease in the Cardiovascular Health Study [6,9]

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