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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

2012 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:

Objective estimates of dietary patterns may be better predictors of heart disease risk than subjective estimates. Our aim was to compare the predictive value of a self-reported assessment for dietary patterns, a food frequency questionnaire (FFQ), and objective measures of dietary patterns (plasma biomarkers of nutrient intake) as indicators of heart disease risk. To achieve this aim we completed analysis of the validated Women’s Health Initiative food frequency questionnaire data and plasma nutrient biomarkers for a sub-set of post-menopausal women who participated in the Women’s Health Initiative Observational Study; 1214 cases with confirmed heart disease and 1214 controls matched for age, enrollment date, race/ethnicity, and absence of heart disease at baseline. The nutrient biomarkers assessed were: phylloquinone, an indicator of vegetable intake, dihydrophylloquinone (dhK), an indicator of partially-hydrogenated fat intake, and plasma phospholipid [PL] fatty acid profiles. Plasma dhK and plasma PL-saturated fatty acids were associated with higher, and plasma PL omega-3 fatty acids (eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid) were associated with lower heart disease risk, whereas only FFQ derived docosahexaenoic acid intake was associated with lower heart disease risk. From these data we concluded that plasma nutrient biomarkers were more robust predictors of heart disease than dietary intake and may be useful as an objective screening tool to assess heart disease risk in large cohort studies.

Some data suggest that a difference in cholesterol homeostasis, estimated using markers of cholesterol absorption and synthesis, is predictive of cardiovascular disease (CVD) 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 incidence of CVD. In both women and men, lower cholesterol absorption marker concentrations were associated with higher triglyceride and lower high density lipoprotein (HDL)-cholesterol (C) concentrations, whereas lower cholesterol synthesis markers were associated with higher low density lipoprotein (LDL)-C concentrations. After controlling for potential confounders, body mass index (BMI), systolic blood pressure, smoking, education, medication/hormone use, family history of CVD/diabetes and leisure physical activity, squalene concentrations were associated with a lower 10-year CVD risk in women whereas squalene and lathosterol concentrations were associated with a higher CVD risk in men. Cholesterol absorption markers were not predictive in women or men. From these data we conclude that although cholesterol synthesis biomarkers have prognostic value for predicting 10-year CVD risk, there are significant sex differences that should be factored into their use.

Although previous studies have suggested an association between plasma palmitoleic and cis-vaccenic acids and coronary heart disease (CHD) risk the relationship between palmitoleic acid and CHD risk was untested. We analyzed red blood cell (RBC) fatty acid patterns in samples from the Physicians' Health Study. Of note, both palmitoleic and cis-vaccenic acids are synthesized endogenously. After adjusting for demographics, anthropometric, lifestyle factors and co-morbidity, higher RBC cis-palmitoleic acid levels was associated with higher CHD risk, whereas higher RBC cis-vaccenic acid levels were associated with lower CHD risk. These data suggest that RBC cis-palmitoleic acid and cis-vaccenic acid may be biomarkers of CHD risk in men.

Glycemic Index (GI) has been proposed as a useful indicator of dietary quality, with lower values associated with lower risk of chronic disease. The approach used to determine GI values for individual foods does not take gender, age or BMI into consideration. The blood glucose response to 50 g of carbohydrate is expressed relative to the blood glucose response to 50 g of oral glucose as assessed by area under the curve over a 2-hour period. To assess potential variability in GI values among subjects on the basis of gender, age and BMI we determined the GI value of white bread in 60 women and men stratified among three BMI ranges (18.0-24.9, 25.0-29.9, 30.0-35.0) and two age ranges (18.0-49.9, 50.0-85.0 years). In women, mean GI values ranged from 0.52 to 0.71. For women in the lowest and highest BMI categories, GI values were lower in younger than older women. This difference was not seen in women in the intermediate BMI category. For men in the lowest BMI category, GI values were lower in younger than older men. This difference was not seen in men in the intermediate and highest BMI categories. Preliminary data indicate that plasma insulin concentrations did not account for the differences observed. Plasma HOMA-IR (measure of insulin resistance) values were similar on the basis of gender, age and BMI.


4.Accomplishments
1. Women’s Health Initiative Observational Study predicts disease risk through diet patterns. Heart disease is the leading cause of death in women. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, Massachusetts, addressed the experimental question of whether habitual dietary patterns are predictive of heart disease risk in post-menopausal women. Analyzed were diet records of 2448 women, half of whom were diagnosed with heart disease and half of whom were similar in age and race/ethnicity, and did not have heart disease at baseline. We found that women whose dietary patterns were characterized by higher intakes of vegetables and fruits and took supplemental calcium and vitamin D were at the lowest risk of developing heart disease. These data support efforts to increase vegetable and fruit intake in the U.S. population.

2. Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids. Fish derived n-3 fatty acids have been associated with decreased risk of heart disease in humans. To define the mechanism associated with these beneficial effects of n-3 fatty acids, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, Massachusetts, compared the effects of fish derived n-3 fatty acids with vegetable oil derived n-6 fatty acids in a common animal model, the F1B hamster. Our results indicated that in contrast to previous assumptions the F1B hamster does not respond to dietary fatty acids in a manner similar to humans. To determine the mechanisms by which n-3 fatty acids decrease heart disease risk in humans an alternate experimental model must be developed.


Last Modified: 9/10/2014
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