Longitudinal lipidomic signature of carotid atherosclerosis in American Indians: Findings from the Strong Heart Family Study

Guanhong Miao; Oliver Fiehn; Mingjing Chen; Ying Zhang; Jason G Umans; Elisa T Lee; Barbara V Howard; Mary J Roman; Richard B Devereux; Jinying Zhao

doi:10.1016/j.atherosclerosis.2023.117265

Longitudinal lipidomic signature of carotid atherosclerosis in American Indians: Findings from the Strong Heart Family Study

Atherosclerosis. 2023 Oct:382:117265. doi: 10.1016/j.atherosclerosis.2023.117265. Epub 2023 Sep 2.

Authors

Affiliations

¹ Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.
² West Coast Metabolomics Center, University of California, Davis, CA, USA.
³ Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ MedStar Health Research Institute, Hyattsville, MD, USA; Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USA.
⁵ Weill Cornell Medical College, New York, NY, 10065, USA.
⁶ Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA. Electronic address: jzhao66@ufl.edu.

PMID: 37722315
DOI: 10.1016/j.atherosclerosis.2023.117265

Abstract

Background and aims: Dyslipidemia is an independent risk factor for atherosclerosis and atherosclerotic cardiovascular disease (ASCVD). To date, a comprehensive assessment of individual lipid species associated with atherosclerosis is lacking in large-scale epidemiological studies, especially in a longitudinal setting. We investigated the association of circulating lipid species and its longitudinal changes with carotid atherosclerosis.

Methods: Using liquid chromatograph-mass spectrometry, we repeatedly measured 1542 lipid species in 3687 plasma samples from 1918 unique American Indians attending two visits (mean ∼5 years apart) in the Strong Heart Family Study. Carotid atherosclerotic plaques were assessed by ultrasonography at each visit. We identified lipids associated with prevalence or progression of carotid plaques, adjusting age, sex, BMI, smoking, hypertension, diabetes, and eGFR. Then we examined whether longitudinal changes in lipids were associated with changes in cardiovascular risk factors. Multiple testing was controlled at false discovery rate (FDR) < 0.05.

Results: Higher levels of sphingomyelins, ether-phosphatidylcholines, and triacylglycerols were significantly associated with prevalence or progression of carotid plaques (odds ratios ranged from 1.15 to 1.34). Longitudinal changes in multiple lipid species (e.g., acylcarnitines, phosphatidylcholines, triacylglycerols) were associated with changes in cardiometabolic traits (e.g., BMI, blood pressure, fasting glucose, eGFR). Network analysis identified differential lipid networks associated with plaque progression.

Conclusions: Baseline and longitudinal changes in multiple lipid species were significantly associated with carotid atherosclerosis and its progression in American Indians. Some plaque-related lipid species were also associated with risk for CVD events.

Keywords: American Indians; Carotid atherosclerosis; Lipidomics; Subclinical atherosclerosis.