Serum non-esterified fatty acids, carotid artery intima-media thickness and flow-mediated dilation in older adults: The Cardiovascular Health Study (CHS)

Authors: HUANG, NEIL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BUZKOVA, PETRA - University Of Washington; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DJOUSSE, LUC - Harvard Medical School; KIZER, JORGE - San Francisco Va Medical Center; MUKAMAL, KENNETH - Beth Israel Deaconess Medical Center; POLAK, JOSEPH - Tufts Medical Center; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/29/2021
Publication Date: 8/31/2021
Citation: Huang, N.K., Buzkova, P., Matthan, N., Djousse, L., Kizer, J.R., Mukamal, K., Polak, J.F., Lichtenstein, A.H. 2021. Serum non-esterified fatty acids, carotid artery intima-media thickness and flow-mediated dilation in older adults: The Cardiovascular Health Study (CHS). Nutrients. 13(9):3052. https://doi.org/10.3390/nu13093052.
DOI: https://doi.org/10.3390/nu13093052

Interpretive Summary: Two measures of blood vessel health are common carotid artery intima-media thickness (IMT) and flow-mediated dilation (FMD). Elevated carotid IMT and diminished FMD are indicators of elevated risk of heart disease (subclinical atherosclerosis), before symptoms develop. Elevated IMT and diminished FMD are prevalent among older adults. High serum total non-esterified fatty acid (NEFA) concentrations are used as indicators of subclinical atherosclerosis. Whether this is due to total serum NEFA concentration or specific individual NEFA has yet to be determined. To this end we tested the hypothesis that some but not all individual NEFAs are associated with measures of carotid IMT and FMD and subsequent subclinical atherosclerosis. To test this hypothesis we measured 35 individual NEFAs in Cardiovascular Health Study participant samples. We found that the non-esterified trans fatty acid and conjugated linoleic acid (trans-18:2 CLA) was positively associated with carotid IMT among participants with, but not in participants without subclinical atherosclerosis. Non-esterified cis-palmitoleic acid (16:1n-7c) was positively associated with FMD among participants without, but not with subclinical atherosclerosis. No significant associations were observed between NEFAs and plaque thickness, estimated from the IMT measures. These data indicate that in older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for subclinical atherosclerosis.

Technical 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 [beta (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.