Abstract
Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown. To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline. This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020. Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid. Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001). These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.
Highlights
With increasing life expectancy, the population of older adults is growing rapidly worldwide.[1]
Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions
These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events
Summary
The population of older adults is growing rapidly worldwide.[1]. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs), saturated fatty acids with 20 carbons or more, are integrated biomarkers of diet and metabolism that are associated with lower risk of heart failure,[3,4] atrial fibrillation,[5] and diabetes,[6,7,8] which are chronic diseases that contribute to unhealthy aging, and lower risk of sudden cardiac arrest[9] and total mortality.[10] These widely beneficial associations led us to hypothesize that higher circulating levels of VLSFAs may be broadly associated with a greater likelihood of healthy aging. We used data from the Cardiovascular Health Study (CHS), a cohort study of factors associated with risk of cardiovascular disease among older adults,[11] to examine the associations of plasma phospholipid levels of 3 circulating VLSFAs—arachidic acid (saturated fatty acid with 20 carbons), behenic acid (saturated fatty acid with 22 carbons), and lignoceric acid (saturated fatty acid with 24 carbons)—measured at the current study baseline and up to 2 more times during follow-up, with risk of an incident unhealthy aging event
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