Innovative research has begun to elucidate the role of individual fatty acids (FA) in human health. Historically, FA research has focused on broad categories of dietary fats, e.g. saturated, polyunsaturated, or monounsaturated fats, and relied on self-reported estimates from diet questionnaires. It is increasingly clear that such broad categorizations are estimated with error and, perhaps more importantly, obscure major differences in health effects of individual FA within these categories. Also, dietary estimates of fat intake provide little information on many other individual FA that in the human body are largely derived from endogenous metabolic processes rather than from direct dietary intake. Consequently, our prior work (R01- HL085710) has focused on circulating FA biomarkers that provide objective measures of exposure to both dietary and metabolic FA. We have found several key individual FA to be significantly associated with major cardiovascular disease (CVD) outcomes, including congestive heart failure (CHF), atrial fibrillation (AF), coronary heart disease (CHD), and stroke. Notably, we identified relations for FA that are largely derived from diet and FA largely derived from metabolic processes. Experimental studies support these findings, with effects of these and other individual FA on a variety of cellular functions and metabolic pathways. Together these results support key potential roles of individual FA in human health. Several fundamental questions remain. To date, all studies of FA biomarkers and CVD risk have utilized only a single baseline measure of exposure, typically among participants in middle-age. Because risk of CVD accelerates dramatically with age, these prior investigations of FA biomarkers in middle-age preclude strong inference on potential effects later in life. Our prior work in the Cardiovascular Health Study (CHS) thus focused on older men and women age 65 at baseline. Whereas this work produced several novel findings, the potential influence of FA on health much later in life, e.g., in the oldest of the old, average age 80- 85 and beyond, is not established. This represents a sizeable and rapidly growing segment of the US, in whom knowing how to prevent CVD and increase healthy aging is critical. Aging is marked by changes in diet, lifestyle, and metabolism, each of which influences circulating FA. Also, as with other risk factors, health effects of FA may vary with aging. Our prior work has confirmed that, for many individual FA, circulating levels change considerably over time. Thus, assessment of FA late in life is crucial to elucidate their potential influence on health in this population. This proposal will build upon and extend our prior work by assessing objective FA biomarkers in CHS at 6 years and 13 years after our initial measures to provide crucial insights into how specific individual dietary and endogenous FA relate to CVD and healthy aging later in life. This work will advance scientific understanding of how FA influence CVD, mortality, and healthy aging and inform innovative targets and interventions for lifestyle, policy, and drug treatment efforts later in life.

Public Health Relevance

Innovative research has begun to elucidate the role of individual fatty acids in human health, but no work has been performed in the oldest adults, age 80-85 and beyond, who represent a sizeable and rapidly growing segment of the US population. This proposal will build upon and extend our prior successful work by assessing the association of key individual circulating fatty acid biomarkers with risk of major cardiovascular diseases and healthy aging late in life, in the oldest adults. This research will advance scientific understandig of how fatty acids influence health later in life and will inform innovative targets and interventins for lifestyle, policy, and drug treatment efforts.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL085710-07
Application #
8681495
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Wright, Jacqueline
Project Start
2006-09-15
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
7
Fiscal Year
2014
Total Cost
$535,175
Indirect Cost
$140,208
Name
Tufts University
Department
None
Type
Other Domestic Higher Education
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Fretts, Amanda M; Mozaffarian, Dariush; Siscovick, David S et al. (2014) Plasma phospholipid saturated fatty acids and incident atrial fibrillation: the Cardiovascular Health Study. J Am Heart Assoc 3:e000889
Fretts, Amanda M; Mozaffarian, Dariush; Siscovick, David S et al. (2014) Plasma phospholipid and dietary ?-linolenic acid, mortality, CHD and stroke: the Cardiovascular Health Study. Br J Nutr 112:1206-13
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Wang, Qianyi; Imamura, Fumiaki; Lemaitre, Rozenn N et al. (2014) Plasma phospholipid trans-fatty acids levels, cardiovascular diseases, and total mortality: the cardiovascular health study. J Am Heart Assoc 3:
Wu, Jason H Y; Mozaffarian, Dariush (2014) ?-3 fatty acids, atherosclerosis progression and cardiovascular outcomes in recent trials: new pieces in a complex puzzle. Heart 100:530-3
Mozaffarian, Dariush; de Oliveira Otto, Marcia C; Lemaitre, Rozenn N et al. (2013) trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 97:854-61
Imamura, Fumiaki; Mukamal, Kenneth J; Meigs, James B et al. (2013) Risk factors for type 2 diabetes mellitus preceded by *-cell dysfunction, insulin resistance, or both in older adults: the Cardiovascular Health Study. Am J Epidemiol 177:1418-29
Mozaffarian, Dariush; Lemaitre, Rozenn N; King, Irena B et al. (2013) Plasma phospholipid long-chain ýý-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Ann Intern Med 158:515-25
Virtanen, Jyrki K; Siscovick, David S; Lemaitre, Rozenn N et al. (2013) Circulating omega-3 polyunsaturated fatty acids and subclinical brain abnormalities on MRI in older adults: the Cardiovascular Health Study. J Am Heart Assoc 2:e000305

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