Serial measures of circulating biomarkers of dairy fat and total and cause-specific mortality in older adults: the Cardiovascular Health Study

Background: Controversy has emerged about the benefits compared with harms of dairy fat, including concerns over long-term effects. Previous observational studies have assessed self-reported estimates of consumption or a single biomarker measure at baseline, which may lead to suboptimal estimation of true risk. Objective: The aim of this study was to investigate prospective associations of serial measures of plasma phospholipid fatty acids pentadecanoic (15: 0), heptadecanoic (17: 0), and trans-palmitoleic (trans-16: 1n-7) acids with total mortality, cause-specific mortality, and cardiovascular disease (CVD) risk among older adults. Design: Among 2907 US adults aged >= 65 y and free of CVD at baseline, circulating fatty acid concentrations were measured serially at baseline, 6 y, and 13 y. Deaths and CVD events were assessed and adjudicated centrally. Prospective associations were assessed by multivariate-adjusted Cox models incorporating time-dependent exposures and covariates. Results: During 22 y of follow-up, 2428 deaths occurred, including 833 from CVD, 1595 from non-CVD causes, and 1301 incident CVD events. In multivariable models, circulating pentadecanoic, heptadecanoic, and trans-palmitoleic acids were not significantly associated with total mortality, with extreme-quintile HRs of 1.05 for pentadecanoic (95% CI: 0.91, 1.22), 1.07 for heptadecanoic (95% CI: 0.93, 1.23), and 1.05 for trans-palmitoleic (95% CI: 0.91, 1.20) acids. Circulating heptadecanoic acid was associated with lower CVD mortality (extreme-quintile HR: 0.77; 95% CI: 0.61, 0.98), especially stroke mortality, with a 42% lower risk when comparing extreme quintiles of heptadecanoic acid concentrations (HR: 0.58; 95% CI: 0.35, 0.97). In contrast, heptadecanoic acid was associated with a higher risk of non-CVD mortality (HR: 1.27; 95% CI: 1.07, 1.52), which was not clearly related to any single subtype of non-CVD death. No significant associations of pentadecanoic, heptadecanoic, or trans-palmitoleic acids were seen for total incident CVD, coronary heart disease, or stroke. Conclusions: Long-term exposure to circulating phospholipid pentadecanoic, heptadecanoic, or trans-palmitoleic acids was not significantly associated with total mortality or incident CVD among older adults. High circulating heptadecanoic acid was inversely associated with CVD and stroke mortality and potentially associated with higher risk of non-CVD death.