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 using samples from the Framingham Offspring Study. 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.
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
For milestone 1, we completed measurement of biomarkers of nutrient intake for WHI control (n=1224) and Women's Health Initiative (WHI) coronary heart disease (CHD) cases (n=1224). For milestone 2, the data indicate 6 principal components (dietary factors) explained >75% of the variation in dietary intakes and identified 3 Diet Clusters (DC); DC #1 is high in carbohydrate, vegetable protein, fiber, dietary vitamin K, folate and carotenoids, and supplemental calcium and vitamin D; DC #2 is high in total and animal protein, omega-3 fatty acids derived from fish (eicosapentaenoic and docosahexaenoic acids), and dietary vitamin D and calcium and DC #3 is high in energy, fat, linoleic, arachidonic, alpha-linolenic and trans fatty acids. DC #1 was associated with a lower CHD risk than DC #2 after adjusting for baseline body mass index (BMI), low density lipoprotein (LDL) cholesterol and energy intake. DC #3 was associated with a higher CHD risk than DC #2 although this difference did not remain significant after adjustment for BMI, systolic blood pressure, smoking, education and baseline LDL cholesterol level. Conditional logistic regression analysis confirmed that WHI participants with the highest values for DC #1 were at lower CHD risk. For milestone 3 we completed analysis for the measurement of plasma phytosterol, cholestanol and cholesterol precursor concentrations for the entire Framingham Offspring study. For milestone 4 we have first focused on a subgroup of the cohort, individuals diagnosed with established cardiovascular event (CVD) and/or >50% carotid stenosis and were not taking lipid lowering medication (cases, n=155 and matched controls, n=414). Cholesterol absorption markers were significantly higher, whereas cholesterol synthesis markers were significantly lower in CVD cases compared to controls, for both females and males. After controlling for standard risk factors, plasma indicators of cholesterol absorption (campesterol and sitosterol) were associated with increased CVD risk whereas indicators of cholesterol synthesis (cholestanol and desmosterol) were associated with decreased CVD risk. For milestone 5, with the exception of two participants, we completed the replicate glycemic index (GI) measures, using white bread and glucose as the test foods. Evaluated were 56 volunteers, recruited to differ by sex, age (18 to 85 y) and BMI (18.5 to 24.9, 25 to 29.9, 30 to 35 kg/m2). The mean (± SD) GI value for white bread was 63 ± 16. Intra-individual coefficient of variation (CV) ranged from 2% to 77%. The inter-individual CV was 25%. These data indicate that variability in GI value determinations is explained, in part, by differences in age, but not sex or BMI. The impact of this finding on estimates of associations between dietary GI and chronic disease risk assessment or management, especially with respect to CVD, needs to be considered. Subobjective 2 consists of 4 substudies; focused on total carbohydrate, protein, fat and fiber. We have completed ~50% of the GI challenges for studies 1 and 2, are focusing on completing the balance of the studies for subobjective 3B within the next year. See parent 1950-51000-072-00D for pubs.
1. Both long chain omega-6 and omega-3 polyunsaturated fatty acids decrease inflammatory response. Dietary long chain polyunsaturated fatty acids, both omega-3 (fish derived) and omega-6 (vegetable oil derived), are thought to have unique benefits with respect to heart disease prevention. Using a macrophage cell culture system, ARS-funded researchers from Tufts University in Boston, MA studied the mechanisms by which these polyunsaturated fatty acids alter inflammatory response and cholesterol accumulation. Exposure to long chain omega-6 and omega-3 polyunsaturated fatty acids elicited less inflammatory response than control cells or cells treated with saturated fatty acids, as indicated by lower levels of mRNA and secretion of inflammatory factors. In response to the various fatty acids, differences in cholesterol accumulation after exposure to minimally modified-LDL (source of cholesterol) and proteins controlling cellular cholesterol flux were modest. The results of this study confirm that diets rich in long chain polyunsaturated fatty acids, both from fish and vegetable oils, is beneficial in heart disease prevention.
2. Altering the ratio of dietary amino acids has little effect on heart disease risk factors. Information is conflicting about the effect of different dietary protein types on heart disease risk factors. One variable among protein types is their amino acid profile. Interest has focused on two amino acids, lysine and arginine, and the ratio of one to the other (termed Lys:Arg ratio). ARS-funded researchers from Tufts University in Boston, MA provided individuals with each of 2 diets in random order, one with a high Lys:Arg ratio and the other with a low Lys:Arg ratio. Most protein sources for the low Lys:Arg ratio diet was from plant foods, mainly nuts and legumes, and for the high Lys:Arg ratio diet was from animal foods, including dairy products, fish, eggs, poultry and beef. No significant differences were observed in plasma lipids or vascular function. The results of this study demonstrate that altering protein type has little effect on heart disease risk factors. These observations indicate researchers should direct their efforts to determining alternate diet modifications that will reduce heart disease risk.
3. More efficient absorbers of cholesterol are at increased risk of developing heart disease. Cholesterol balance is determined by the rate of cholesterol absorption and synthesis. The balance of the two can alter heart disease risk. In humans, it is difficult to directly measure these factors. ARS-funded researchers from Tufts University in Boston, MA measured validated surrogate markers of cholesterol absorption and synthesis in the Framingham Offspring Study Cycle-6 participants diagnosed with heart disease and matched control subjects. Plasma LDL-cholesterol concentrations were similar between the two groups. Cholesterol absorption markers were significantly higher, whereas cholesterol synthesis markers were significantly lower, in cases compared to controls. The results of this work indicate that some individuals are at increased risk of developing heart disease because they have high cholesterol absorption rates and do not adequately compensate by decreasing cholesterol synthesis rates. These findings indicate future work should be directed towards developing methods to identify this subgroup of the population early in life and identifying effective dietary approaches to decrease their heart disease risk.