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United States Department of Agriculture

Agricultural Research Service

Research Project: DIET AND BIOMARKERS OF CARDIOVASCULAR HEALTH

Location: Human Nutrition Research Center on Aging

2013 Annual Report


1a.Objectives (from AD-416):
1.Assess the relationship between plasma biomarkers of nutrient intake and heart health.

2. Characterize the relationship between plasma markers of cholesterol homeostasis, dietary intake and intestinal cholesterol absorption protein genotypes, and heart health.

3. Assess the value of glycemic index (GI) as a component of dietary guidance to promote heart health and decrease the risk of chronic diseases associated with aging.

4. Assess the relationship between the red blood cell fatty acid profiles and indicators of heart health in subjects consuming diets enriched in trans fatty acids derived from ruminant fat and partially-hydrogenated vegetable oils.

5. Assess the efficacy of a comprehensive family centered lifestyle modification program – Family Weight Study (FamWtStudy) – using biomarkers of nutrient intake and cardiovascular risk factors in family member pairs (female parent/guardian and child) after initiation of a comprehensive year long program.

6. Assess the influence in human subjects of dietary 16- and 18-carbon fatty acids on cardiovascular risk factors.


1b.Approach (from AD-416):
In the next 5 years the Cardiovascular Nutrition Laboratory will assess the relationship between cardiovascular health and biomarkers of nutrient intake relative to food frequency data using Women’s Health Initiative samples by measuring nutrient intake biomarkers (plasma phospholipid trans fatty acids, eicosapentaenoic acid and docosahexaenoic acid, and phylloquinone and dihydrophylloquinone) and relating these data to cardiovascular health; identifying dietary patterns from food frequency questionnaire data and relating to cardiovascular health; and developing an algorithm using these data that best predicates cardiovascular health; assess the relationship between biomarkers of cholesterol homeostasis and modifiers thereof using plasma samples from the Framingham Offspring Study by measuring plasma cholesterol absorption (sitosterol, campesterol, cholestanol) and biosynthesis (desmosterol, lathosterol, squalene) marker concentrations and relating these data to cardiovascular health as modified by dietary intake and selected genotypes; and evaluate glycemic index (GI) as a component of dietary guidance to decrease chronic diseases risk by determining the reproducibility and variability of GI value determinations in volunteers differing in BMI, age, and gender; assessing the effect of macronutrient amounts and combinations, and fiber on GI and glycemic load (GL) value determinations; and determining the effect of macronutrient composition (carbohydrate, fat, and protein) of a prior meal (“second meal” effect) on GI and GL value determinations.


3.Progress Report:

Our aim is to compare the predictive value of data derived from self-reported measures of food intake – food frequency questionnaires, and objective measures of food intake – plasma markers, as indicators of heart disease risk. We analyzed validated Women’s Health Initiative food frequency questionnaire data and plasma nutrient biomarkers for cases with confirmed heart disease and controls matched for age, enrollment date, race/ethnicity, and absence of heart disease. Plasma dihydrophylloquinone, the phospholipid fatty acids 20:3n-6 and 22:5n-6 were positively associated with heart disease risk, while the very long chain phospholipid omega-3 fatty acids 20:5n-3, 22:5n-3 and 22:6n-3, were negatively associated with heart disease risk. Among FFQ-derived variables, only 22:5n-3 was negatively associated with CHD risk. These associations were partly explained by alterations in endogenous fatty acid metabolism, demonstrated by lower stearoyl-CoA-desaturase and higher delta-6-desaturase indexes. Our objective was to determine the impact of acculturation status on dietary intake and CVD risk in Chinese Americans. Higher dominant culture identification was associated with higher 15:0 (dairy fat), 18:1n-7T (partially-hydrogenated fat) and lycopene (tomatoes) concentrations, while higher ethnic culture identification was associated with higher plasma phylloquinone (vegetable oil) and isoflavone (soy) concentrations. Plasma LDL-cholesterol was positively associated with 20:4n-6 (meat) and inversely associated with lutein and zeaxanthin (green leafy vegetable) concentrations. Higher acculturation status is associated with dietary patterns that more closely resemble the typical U.S. diet. Some data suggest that a difference in cholesterol homeostasis is predictive of heart disease events. We tested this hypothesis in 2616 women and men from the Framingham Offspring Study by measuring markers of cholesterol absorption (campesterol, sitosterol, cholestanol) and synthesis (squalene, desmosterol, lathosterol) and comparing them to 10-year heart disease incidence. In both women and men, lower cholesterol absorption was associated with higher triglyceride and lower HDL cholesterol concentrations, whereas lower cholesterol synthesis was associated with higher LDL cholesterol concentrations. In women only, lower cholesterol synthesis and absorption were associated with higher non–HDL cholesterol concentrations. Using Cox proportional hazards model adjusting for standard CVD risk factors, squalene concentrations were associated with lower HCHD in women. In contrast, squalene concentrations were associated with higher HCHD in men. Our aim was to determine whether differences in body composition affected glucose homeostasis and calculated glycemic index (GI) values in response to a single food challenge. Intra-individual reproducibility (within the same individual) and inter-individual variability (among individuals) of GI value determinations for white bread and glucose, in 63 healthy men and women aged 18 to 85 years with a wide range in body mass index (BMI, 18.5 - 35 kg/m2). Each participant underwent 3 sets of food challenges in random order. The mean (+/- SD) GI value for white bread was 62 +/- 15. The average coefficient of variation for intra-individual was 42% and inter-individual was 25%. No significant association was observed between the GI value for white bread and sex or BMI. After adjustment for age, GI value was positively associated with whole body total fat, and trunk total fat and negatively associated with whole body lean muscle mass, trunk lean muscle, whole body lean muscle+ bone mineral content, and trunk lean muscle+bone mineral content.


4.Accomplishments
1. Positive association between circulating cis-palmitoleic acid and heart disease risk. Although previous studies have suggested associations between plasma palmitoleic acid, a monounsaturated fatty acid, and heart disease risk factors, including blood pressure, inflammation and insulin resistance, little is known about the relation of palmitoleic acid and heart disease risk. In collaboration with researchers at Harvard Medical School, Boston, MA, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts found that higher levels of circulating levels of cis-palmitoleic acid was associated with higher heart disease risk. These data suggest that not all fatty acids within a class, in this case monounsaturated fatty acids, should be assumed to have similar effects on heart disease risk. These data also suggest that in addition to dietary intake, in vitro synthesis/modification of fatty acids may influence fatty acid profiles.

2. Plasma biomarkers of food intake are better predictors of heart disease risk than self-reported data. Diet quality is an important determinant of heart disease risk. Uncertainty in estimating food intake can affect heart disease risk estimates and obscure disease-risk associations. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts demonstrated that higher plasma levels of dihydrophylloquinone (marker for partially-hydrogenated fat/trans fatty acids), saturated fat (marker for meat and dairy fat) and very long chain omega-3 fatty acid ( marker for fish) were more robust predictors of heart disease risk than similar measures determined using self-reported food frequency questionnaires. These data support efforts to increase fish intake and develop alternative vegetable oils that can replace partially-hydrogenated fat in the diet.

3. Postprandial lipid response to standard carbohydrates challenges. Prior studies assessing the metabolic effects of different types of dietary carbohydrate have focused on their glycemic response and plasma glucose without taking other cardiometabolic risk factors into consideration. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts demonstrated that a sugar solution (glucose) resulted in higher plasma glucose concentrations and more rapid decline in plasma glucose concentrations than white bread, with little difference in plasma postprandial total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. These data suggest that with regard to heart disease risk factors there was little difference between the two types of refined carbohydrate, glucose and white bread. These data also suggest that more emphasis should be placed on other less refined sources of carbohydrate in the diet.

4. Cholesterol homeostasis markers are not predictors of heart disease risk and differ on the basis of sex. Available data are inconsistent regarding the predictive value of cholesterol homeostasis markers and heart disease risk. To address this issue, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts measured plasma cholesterol homeostasis marker concentrations in the Framingham Offspring cohort (cycle.
6)and related the values to incident heart disease events. They determined that the markers, both absorption and synthesis, were not predictive of heart disease events in either women or men. They found that there were significant sex differences in the 10-year prognostic value of cholesterol synthesis markers and heart disease, indicating the need for judicious interpretation of these marker data.

5. Relationship between stearidonic acid and heart disease risk. Current recommendations for heart disease risk reduction include consuming at least two fish meals per week to ensure adequate intake of the very long chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosapentaenoic acid. A large proportion of individuals in the U.S. do not comply with this recommendation. A strain of soybeans has recently been developed that is rich in stearidonic acid (SDA), a plant-based n-3 fatty acid. Some of the SDA can be converted to EPA. In collaboration with researchers at Harvard Medical School, Boston, MA, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, at Boston, Massachusetts addressed the question of whether conversion from SDA to EPA is necessary by assessing the association between circulating SDA levels and heart disease risk. They found no significant relationship, suggesting that for SDA to be biologically active it has to first be converted, in vivo, to EPA. This work supports a potential role of the newly developed high SDA soybean oils and heart disease risk reduction.


Last Modified: 8/27/2014
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