NUTRITION AND CARDIOVASCULAR HEALTH
Jean Mayer Human Nutrition Research Center On Aging
2012 Annual Report
1a. Objectives (from AD-416):
LAB: LIPID METABOLISM
1. To determine the effect of altering dietary composition by restricting carbohydrates, fats, glycemic load, or total calories on plasma lipoproteins, blood pressure, glucose homeostasis, and body weight, cardiovascular risk factors in overweight and obese subjects under controlled feeding conditions and in the free-living state.
2. Develop and test an interactive program to provide an optimal diet and exercise program for middle-aged and elderly overweight and obese subjects for weight loss and heart disease reduction.
3. Observe the interactions of nutritional factors, especially intake of calories, types of fat, types of carbohydrate, level of physical activity, and different genetic factors on lipoprotein subspecies, obesity, metabolic syndrome, inflammatory markers, and heart disease risk in overweight and obese subjects and subjects with premature cardiovascular disease as compared to age- and gender-matched control subjects within populations.
4. Determine the in vitro and in vivo effects of dietary fatty acids, cholesterol, carbohydrates, hormone levels, hormonal replacement, B vitamins, cholesterol biosynthesis inhibition and cholesteryl ester transfer protein inhibition on lipoprotein metabolism and gene expression, and inflammation in human liver cells (HepG2) and in human subjects under metabolic ward conditions using stable isotopes.
LAB: CARDIOVASCULAR NUTRITION
1. Assess the relationship between plasma biomarkers of nutrient intake and heart
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):
LAB: LIPID METABOLISM
In the next 5 years the Lipid Metabolism Laboratory will continue to test optimal lifestyle strategies for the prevention of coronary heart disease (CHD). Human intervention studies will assess effects of supplementation with omega 3 fatty acids and plant sterols versus placebo on CHD risk factors, caloric restriction in older overweight subjects using diet either low or high in glycemic load on CHD risk factors, and an aggressive lifestyle and omega 3 fatty acid supplementation program in overweight subjects with CHD versus usual care on CHD risk factors, cognitive function, and change in coronary atheroma. Population studies will examine the interaction of diet as assessed by questionnaires, genetics as assessed by genotyping, and biochemical markers of insulin resistance, inflammation, and alterations in lipoprotein particles on CHD risk and cognitive decline in participants in the Framingham Heart Study (original cohort and offspring). Human metabolic studies will examine the effects of diets low in animal fat and cholesterol with or without fish versus average American diets on lipoprotein metabolism. We will also examine the effects of estrogens and niacin on human plasma lipoprotein metabolism. Cell studies will examine the mechanisms of action of different fatty acids on the expression of specific genes involved in reverse cholesterol transport in human liver cells and in macrophages. Our overall objectives are to develop optimal lifestyle strategies for the prevention of CHD.
LAB: CARDIOVASCULAR NUTRITION
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:
This progress report includes the work of two subordinate projects at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-072-01S (Lipoproteins and nutrition) and 1950-51000-072-02S (Diet and biomarkers of cardiovascular health)
Furusyo, N., Koga, T., Ai, M., Otokozawa, S., Kohzuma, T., Ikezaki, H., Schaefer, E., Hayashi, J. 2011. Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese population study: results from the Kyushu and Okinawa Populaiton Study (KOPS). Diabetologia. 54(12):3028-3036.
Sorci-Thomas, M., Zabalawi, M., Bharadwaj, M., Wilhelm, A., Owen, J., Asztalos, B., Bhat, S., Thomas, M. 2012. Dysfunctional HDL containing L159R apoA-I leads to exacerbation of atherosclerosis in hyperlipidemic mice. Biochimica et Biophysica Acta. 1821(3):502-512.
Akao, H., Polisecki, E., Kajinami, K., Trompet, S., Robertson, M., Ford, I., Jukema, J., De Craen, A., Westendorp, R., Shepherd, J., Packard, C., Buckleyi, B., Schaefer, E. 2012. Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly. Atherosclerosis. 220(2):413-417.
Van Himbergen, T., Beiser, A., Ai, M., Seshadri, S., Otokozawa, S., Au, R., Thongtang, N., Wolf, P., Schaefer, E. 2012. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Archives of Neurology. DOI: 10.1001/archneurol.2011.670.
De La Llera Moya, M., Mcgillicuddy, F., Hinkle, C., Byrne, M., Joshi, M., Nguyen, V., Tabita-Martinez, J., Wolfe, M., Badellino, K., Pruscino, L., Mehta, N., Asztalos, B., Reilly, M. 2012. Inflammation modulates human HDL composition and function in vivo. Atherosclerosis. 222(2):390-394.
Lamon-Fava, S., Marcovina, S., Albers, J., Kennedy, H., Deluca, C., White, C., Cupples, L., Mcnamara, J., Seman, L., Bongard, V., Schaefer, E. 2011. Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study. Journal of Lipid Research. 52(6):1181-1187.
Sun, J., Strauch, C., Keenan, H., Monnier, V., Cavallerano, J., Doria, A., Asztalos, B., Aiello, L., Schaefer, E., King, G., Sell, D. 2011. Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration. Diabetes Care. 34(4):968-974.
Akao, H., Polisecki, E., Kajinami, K., Trompet, S., Robertson, M., Ford, I., Jukema, J., De Craen, A., Westendorp, R., Shepherd, J., Packard, C., Buckley, B., Schaefer, E. 2012. KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly. Atherosclerosis. 220(2):456-462.
Mooijaart, S., Sattar, N., Trompet, S., Polisecki, E., De Craen, A., Schaefer, E., Jahn, S., Van Himbergen, T., Welsh, P., Ford, I., Stott, D., Westendorp, R. 2011. C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study. PLoS One. 6(9):e23890.
Rosenson, R., Brewer Jr., H., Chapman, M., Fazio, S., Hussain, M., Konush, A., Krauss, R., Otvos, J., Remaley, A., Schaefer, E. 2012. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clinical Chemistry. 57(3):392-410.
Kuang, Y., Paulson, K., Lichtenstein, A., Lamon-Fava, S. 2012. Regulation of the expression of key genes involved in HDL metabolism by unsaturated fatty acids. British Journal of Nutrition. DOI: 10.1017/S0007114511006854.
Diffenderfer, M., Brousseau, M., Millar, J., Barrett, P., Nartsupha, C., Schaefer, P., Wolfe, M., Dolnikowski, G., Rader, D., Schaefer, E. 2012. Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism. Journal of Lipid Research. 53(6):1190-1199.
Sankaranarayanan, S., Kellner-Weibel, G., De La Llera-Moya, M., Phillios, M., Asztalos, B., Bittman, R., Rothblat, G. 2011. A sensitive assay for ABCA1-mediated cholesterol efflux using BODIPY-cholesterol. Journal of Lipid Research. 52(12):2332-2340.
Asztalos, B. 2010. High-density lipoprotein particles, coronary heart disease, and niacin. Clinical Lipidology. 4(5):405-410.
Schaefer, E., Gleason, J.A., Dansinger, M.L. 2009. Dietary fructose and glucose differentially affect lipid and glucose homeostasis. Journal of Nutrition. 139(6):1257S-1262S.
Masumi, A., Otokozawa, S.M., Asztalos, B.F., Nakajima, K., Jones, P., Schaefer, E. 2008. Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels. American Journal of Cardiology. 10:315-318.
Van Himbergen, T.M., Matthan, N.R., Resteghini, N.A., Otokozawa, S., Jones, P., Schaefer, E. 2009. Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers. Journal of Lipid Research. 50:730-739.
Lamon-Fava, S., Herrington, D.M., Reboussin, D.M., Sherman, M., Horvath, K.V., Cupples, A.L., White, C., Demissie, S., Schaefer, E.J., Asztalos, B.F. 2008. Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically defined disease in post-menopausal women. Arteriosclerosis Thrombosis and Vascular Biology. 28(3):575-579.
Otokozawa, S., Ai, M., Van Himbergen, T., Asztalos, B.F., Tanaka, A., Stein, E.A., Jones, P.H., Schaefer, E. 2009. Effects of intensive atorvastatin and rosuvastatin treatment on apolipoprotein B-48 and remnant lipoprotein cholesterol levels. Atherosclerosis. 205(1):197-201.
Lamon-Fava, S., Asztalos, B.F., Howard, T.D., Reboussin, D.M., Horvath, K., Schaefer, E.J., Herrington, D.M. 2009. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clinical Endocrinology. 72(2):169-175.
Lecker, J.L., Matthan, N.R., Billheimer, J.T., Rader, D.J., Lichtenstein, A.H. 2011. Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids. Lipids in Health and Disease. 186:1-10.
Djousse, L., Matthan, N.R., Lichtenstein, A.H., Gaziano, J.M. 2012. Red blood cell membrane concentration of cis-palmitoleic and cis-vaccenic acids and risk of coronary heart disease. American Journal of Cardiology. PMID:22579341.
Van Horn, L., Tian, L., Neuhouser, M., Howard, B., Eaton, C., Snetselaar, L., Matthan, N., Lichtenstein, A. 2012. Dietary patterns are associated with disease risk among participants in the women's health initiative observational study. Journal of Nutrition. 142:284-291.
Trikalinos, T., Moorthy, D., Chung, M., Yu, W., Lee, J., Lichtenstein, A., Lau, J. 2012. Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations. Journal of Clinical Epidemiology. 65(1):16-29.
Baker, K., Matthan, N., Lichtenstein, A.H., Niu, J., Guermazi, A., Roemer, F., Grainger, A., Nevitt, M., Clancy, M., Lewis, C. 2012. Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study. Osteoarthritis and Cartilage. 20(5):382-387.
Rao, G., Burke, L., Spring, B., Ewing, L., Lichtenstein, A., Turk, M., Cormier, M., Spence, J.D., Coons, M. 2011. New and emerging weight management strategies for busy ambulatory settings: a scientific statement from the American Heart Association. Circulation. 124:1182-1203.
Ai, M., Otokozawa, S., Asztalos, B., White, C., Cupples, L., Nakajima, K., Lamon-Fava, S., Wilson, P., Matsuzawa, Y., Schaefer, E. 2011. Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham Offspring Study. Atherosclerosis. 217(2):543-548.
Farina, E., Kiel, D., Roubenoff, R., Schaefer, E., Cupples, L., Tucker, K. 2012. Plasma phosphatidylcholine concentrations of polyunsaturated fatty acids are differentially associated with hop bone mineral density and hip fracture in older adults: The Framingham Osteoporosis Study. Journal of Bone and Mineral Research. 27(5):1222-1230.
Dillard, A., Matthan, N., Lichtenstein, A. 2011. THP-1 macrophage lipid accumulation unaffected by fatty acid double bond geometric or positional configuration. Nutrition Research. 31(8):625-630.