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. 2018 Sep 1;108(3):476-484.
doi: 10.1093/ajcn/nqy117.

Serial Measures of Circulating Biomarkers of Dairy Fat and Total and Cause-Specific Mortality in Older Adults: The Cardiovascular Health Study

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Serial Measures of Circulating Biomarkers of Dairy Fat and Total and Cause-Specific Mortality in Older Adults: The Cardiovascular Health Study

Marcia C de Oliveira Otto et al. Am J Clin Nutr. .
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Abstract

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.

Figures

FIGURE 1
FIGURE 1
Structure of fatty acids found in dairy fat. Pentadecanoic (15:0) and heptadecanoic (17:0) acids are long-chain SFAs (no carbon-carbon double bonds) containing 15 and 17 carbon atoms respectively. trans-Palmitoleic acid (trans-16:1n–7) is a long-chain MUFA (one carbon-carbon double bond) containing 16 carbon atoms and 1 double bond in the trans configuration. Because mammals cannot synthesize odd-chain or trans-fatty acids in appreciable amounts, circulating concentrations of these fatty acids represent exogenous sources. Among different foods, the strongest correlations are seen for dairy consumption (r ∼ 0.7 based on 24-h recalls or 7-d food records). Biological properties, effects on physiologic risk factors, and relevant molecular pathways of these fatty acids remain mostly unknown.
FIGURE 2
FIGURE 2
Risk of total and cause-specific mortality according to quintiles of circulating dairy fatty acids in 2907 older US adults. Values are HRs (95% CIs) estimated by using multivariable Cox proportional hazards models including age (years), sex, race (white or nonwhite), education (less than high school, high school, some college degree or more), enrollment site (4 sites), time-varying smoking status (never, current, or former), alcohol (servings per week), leisure-time physical activity (kilocalories per week), BMI (kg/m2), drug-treated hypertension (yes or no), self-reported general health (excellent, very good, good, or fair/poor), circulating total trans-fatty acids (%), and self-reported consumption of dairy foods, dietary fiber, fruit, vegetables, and red meat. CVD, cardiovascular disease; Q, quintile.
FIGURE 3
FIGURE 3
Risk of CVD incidence according to quintiles of circulating dairy fatty acids in 2907 older US adults. Values are HRs (95% CIs) estimated by using multivariable Cox proportional hazards model including age (years), sex, race (white or nonwhite), education (less than high school, high school, some college degree or more), enrollment site (4 sites), time-varying smoking status (never, current, or former), alcohol (servings per week), leisure-time physical activity (kilocalories per week), BMI (kg/m2), drug-treated hypertension (yes or no), self-reported general health (excellent, very good, good, or fair/poor), circulating total trans-fatty acids (%), and self-reported consumption of dairy foods, dietary fiber, fruit, vegetables, and red meat. CHD, coronary heart disease; CVD, cardiovascular disease; Q, quintile.

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