2006 Annual Report 1.What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? Why does it matter? Cardiovascular disease is the leading cause of death and disability in Americans. The risk of developing cardiovascular disease increases dramatically with age. Prevention is far more efficacious and cost-effective than treatment. Although we know that diet can play an important role in maintaining cardiovascular health, our understanding of the absolute impact of individual dietary components in this process is far from complete. Similarly, our understanding of diet/gene interactions, especially as they contribute to variability in response to dietary modification, is in its infancy. The focus of the Cardiovascular Nutrition Laboratory is to investigate dietary strategies intended to maintain cardiovascular health; develop a screening tool for the early identification of individuals at high-risk of developing cardiovascular disease; and expand our understanding at a biochemical level of how diet alters measures of cardiovascular disease risk. Research is conducted to assess the efficacy of selectively bred and genetically modified vegetable oils, new sources of plant sterols, and soy protein on cardiovascular disease risk factors. The laboratory is also working to determine the impact of diet and genotype on cholesterol homeostasis and cardiovascular health in the Framingham Offspring Study; and to relate diet-induced changes in cardiovascular disease risk factors to functional changes in gene expression and atherosclerotic lesion formation in animal models and cell culture. The objectives are to test novel dietary interventions aimed at improving biological markers of cardiovascular health, defining diet/gene interactions that might mitigate nutrition interventions and determine more accurate approaches to identify high-risk individuals for early and intensive dietary intervention to maintain cardiovascular health with advancing age. The results of this work are relevant to the general United States (US) population and relate to the following program components within the National Program 107 - Human Nutrition: 6 – Prevention of obesity and disease: relationship between diet, genetics, and lifestyle, and 7 – Health promoting properties of plant and animal foods. 2.List by year the currently approved milestones (indicators of research progress) Objective 1: Examine the efficacy of selectively bred and genetically modified vegetable oils and new sources of plant sterols on cardiovascular disease risk factors in middle-aged and older hypercholesterolemic female and male subjects. Objective 2: Determine the effect of soy protein on cardiovascular risk factors in middle-aged and older hypercholesterolemic female and male subjects. Objective 3: Determine the impact of diet and genotype on cholesterol homeostasis and cardiovascular health in the Framingham Offspring Study – Cycle 6. Objective 4: Relate diet-induced changes in plasma lipid and lipoprotein levels to functional changes in gene expression and atherosclerotic lesion formation in Golden-Syrian hamsters. Milestones: 2005 1. Determine the effect of genetically modified and selectively breed soybean oils on cardiovascular disease risk factors. Objective 1 2. Determine the effect of plant sterols with and without very long chain omega-3 fatty acids on cardiovascular disease risk factors. Objective 1 3. Determine the effect soybean derived foods on cardiovascular disease risk factors. Objective 2 4. Begin measures of surrogate markers of cholesterol homeostasis in case and matched control subjects. Objective 3 5. Begin to relate measures of cholesterol homeostasis to the incidence of cardiovascular disease and carotid stenosis. Objective 3 6. Determine the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in Golden Syrian Hamsters. Objective 4 2006 1. Complete studies on the effect of genetically modified and selectively breed soybean oils on cardiovascular disease risk factors. Objective 1 2. Complete studies on the effect of plant sterols with and without very long chain omega-3 fatty acids on cardiovascular disease risk factors. Objective 1 3. Complete studies on the effect soybean derived foods on cardiovascular disease risk factors. Objective 2 4. Continue work relating measures of cholesterol homeostasis to incidence of cardiovascular disease and carotid stenosis in case and matched control subjects. Objective 3 5. Begin to establish adult normal ranges for phytosterol, cholestanol and cholesterol precursor levels using samples collected during Cycle 6 of the Framingham Offspring Study. Objective 3 6. Continue determining the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in Golden Syrian Hamsters. Objective 4 7. Begin to determine the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in LDL knockout mice. Objective 4 2007 1. Complete work on relating measures of cholesterol homeostasis to incidence of cardiovascular disease and carotid stenosis in case and matched control subjects. Objective 3 2. Continue work to establish adult normal ranges for phytosterol, cholestanol and cholesterol precursor levels using samples collected during Cycle 6 of the Framingham Offspring Study. Objective 3 3. Begin work to define the relationship between phytosterol, cholestanol and cholesterol precursor levels and plasma lipid, lipoprotein and apolipoprotein levels. Objetive 3 4. Begin work to define the relationship between phytosterol, cholestanol and cholesterol precursor levels and selected dietary intake data (macronutrients, cholesterol, fatty acids, fiber and antioxidant supplements). Objective 3 5. Continue work determining the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in Golden Syrian Hamsters. Objective 4 6. Continue studies to determine the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in LDL knockout mice. Objective 4 2008 1. Continue establishing adult normal ranges for phytosterol, cholestanol and cholesterol precursor levels using samples collected during Cycle 6 of the Framingham Offspring Study. Objective 3 2. Continue defining the relationship between phytosterol, cholestanol and cholesterol precursor levels and plasma lipid, lipoprotein and apolipoprotein levels. Objective 3 3. Continue defining the relationship between phytosterol, cholestanol and cholesterol precursor levels and selected dietary intake data (macronutrients, cholesterol, fatty acids, fiber and antioxidant supplements). Objective 3 4. Continue determining the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in Golden Syrian Hamsters. Objective 4 5. Continue determining the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in LDL knockout mice. Objective 4 2009 1. Complete studies determining adult normal ranges for phytosterol, cholestanol and cholesterol precursor levels using samples collected during Cycle 6 of the Framingham Offspring Study. Objective 3 2. Continue work defining the relationship between phytosterol, cholestanol and cholesterol precursor levels and plasma lipid, lipoprotein and apolipoprotein levels. Objetive 3 3. Continue work defining the relationship between phytosterol, cholestanol and cholesterol precursor levels and selected dietary intake data (macronutrients, cholesterol, fatty acids, fiber and antioxidant supplements). Objective 3 4. Continue work determining the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in Golden Syrian Hamsters. Objective 4 5. Continue work determining the effect of dietary fatty acids on mRNA abundance of genes involved with the metabolism of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol in LDL knockout mice. Objective 4 4a.List the single most significant research accomplishment during FY 2006. Novel Soybean Oils and Cardiovascular Risk Factors. We completed studies on the effect of selectively bred and genetically modified soybean oils on cardiovascular disease risk factors in middle-aged and older hypercholesterolemic female and male subjects. The purpose of this work was to determine whether the forms of soybean oils with modified fatty acid profiles that have been produced recently to improve stability and functional characteristics of native soybean oil and to substitute for hydrogenated fat, have beneficial effects of plasma lipoprotein levels and other heart disease risk factors. Thirty subjects (16 female and 14 male) over age 50 years with low-density lipoprotein (LDL) cholesterol concentrations greater than 130 mg/dL at screening were fed each of five experimental diets provided in random order for 35 day periods each. Diets contained the same foods and provided 30 percent energy as fat, of which 2/3 was either native soybean oil, low saturated fatty acid soybean oil, high oleic acid soybean oil, low alpha-linolenic acid soybean oil or partially-hydrogenated soybean oil. Results: Plasma phospholipid patterns reflected the predominant fat in the diet. LDL cholesterol concentrations and total cholesterol/HDL cholesterol ratio were highest after subjects consumed the partially-hydrogenated relative to the other soybean oil enriched diets. When we removed partially-hydrogenated soybean oil from the analysis, there was little difference among the native and the other soybean oils in LDL cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglyceride, Lp(a) and CRP concentrations, or LDL cholesterol/apoB or and HDL cholesterol/ apoA-I ratios. From these data we concluded that all of the newer fatty acid modified varieties of soybean oils result in more favorable lipoprotein profiles compared to the partially-hydrogenated form. These may provide a viable option for reformulation of products to reduce the content of trans fatty acids. This work is closely aligned with National Program 107 – Human Nutrition program component 5 – Health Promoting Properties of Plant and Animal Foods. 4b.List other significant research accomplishment(s), if any. Palm, Partially Hydrogenated Soybean Oil, Soybean Oil and Canola Oil and Cardiovascular Risk Factors. We completed studies on the effect of palm oil relative to soybean oil, partially hydrogenated soybean oil and canola oil on cardiovascular disease risk factors in middle-aged and older hypercholesterolemic female and male subjects. We sought to determine whether palm oil is an acceptable substitute for partially hydrogenated soybean oil as assessed on the basis of plasma lipoprotein levels and other heart disease risk factors. The effects of these two fats were assessed relative to soybean oil, rich in polyunsaturated fatty acids and canola oil, rich in monounsaturated fatty acids. Fifteen subjects over the age of 50 years with low-density lipoprotein (LDL) cholesterol concentrations greater than 130 mg/dL at screening were fed each of five experimental diets provided in random order for 35 day periods each (partially-hydrogenated soybean, soybean, palm, or canola; 2/3 fat, 20% energy). Plasma fatty acid profiles, lipids, lipoproteins, apo AI, apo B, Lp(a), glucose, insulin, HDL subfractions, and indicators of lipoprotein metabolism (HDL cholesterol fractional esterification rate, and CETP, PLTP and paraoxonase activities) were measured at the end of each phase. Results: Plasma fatty acid profiles reflected the major source of dietary fat. Partially-hydrogenated soybean and palm oils resulted in higher LDL cholesterol and apo B concentrations than soybean and canola. There was no significant effect of palm oil relative to the other dietary fats on the total cholesterol/HDL ratio. HDL3 cholesterol was higher after palm oil relative to partially-hydrogenated and soybean oils. Differences attributable to dietary fat in measures of glucose and HDL intravascular processing were small. Palm and partially-hydrogenated soybean oils, relative to soybean and canola oils, adversely altered the lipoprotein profile in moderately hyperlipidemic subjects without significantly affecting HDL intravascular processing markers. This work is closely aligned with National Program 107 – Human Nutrition program component 5 – Health Promoting Properties of Plant and Animal Foods. 4c.List significant activities that support special target populations. None. 4d.Progress report. None. 5.Describe the major accomplishments to date and their predicted or actual impact. The first major accomplishment of the Cardiovascular Nutrition Laboratory over the life of the project includes work related to Milestone 4 (2005): Cholesterol homeostasis. In a case-controlled study of Framingham Offspring Study participants with coronary heart disease and carotid stenosis, cardiovascular health was associated with lower absorption rates and paradoxically higher synthesis rates of cholesterol. These surrogate markers of cardiovascular health were better predictors of risk than plasma lipid levels. These data provide support for using surrogate markers of cholesterol homeostasis as risk factor measures, in addition to those currently in place (i.e., plasma lipids, C-reactive protein [CRP] levels) to assess an individual’s risk for cardiovascular health and will promote cost effective and targeted diagnostic and treatment modalities. Corn oil (low in trans fatty acid) is currently being use in the commercial preparation of savory snacks as a replacement for hydrogenated fat (high trans fatty acids). The impact of these two oils was assessed in moderately hypercholesterolemic postmenopausal females and older males. The fats were tested under conditions where they contributed a relatively high amount (20%) of the dietary fat and were incorporated into various food items throughout the day. Scientists observed a significant decrease in total and LDL cholesterol levels, in both the fasting and non-fasting states among subjects consuming diets prepared with the test corn oil relative to the hydrogenated fat. These results suggest that encouraging the food industry to displace trans fatty acid-containing hydrogenated fats with fats low in trans fatty acids may have a beneficial effect with respect to cardiovascular health. This work was related to Milestone 1, (2005, 2006): Dietary variables that alter cardiovascular disease risk. Metabolic study of selectively bred and genetically modified oils. These accomplishments will have the following potential benefits by providing a basis with which to formulate more efficacious public health dietary guidelines to maintain cardiovascular health for both the general population and high-risk individuals. They can also be used to design more accurate tools for identifying individuals at increased risk of developing cardiovascular disease at an early age, thereby fostering an economically sound model of prevention and maintenance of cardiovascular health rather than treatment of disease. This information can be used to relate cholesterol homeostasis regulation to dietary intake data and specific genotypes associated with lipoprotein metabolism to provide a better understanding of the environmental and genetic influences determining cardiovascular health, and to increase our understanding at a basic level of how specific dietary modifications alter the metabolic parameters that favor cardiovascular health at the genetic level. These accomplishments relate to the National Program 107 - Human Nutrition components, 5 – Health Promoting Properties of Plant and Animal Foods, and 6 - Prevention of Obesity and Disease: Relationship between Diet, Genetics, and Lifestyle. 6.What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end-user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? These research findings have been published in peer-reviewed journals and have been presented to the scientific community at a number of meetings including the American Heart Association’s symposium on Obesity, Lifestyle and Lifestyle, the 2006 Women’s Cardiac Health Conference of the Massachusetts Medical Society, the Nutrition and Health: State of the Science & Clinical Applications at Columbia University, and the American Diabetes Association’s annual meeting. 7.List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: List your peer reviewed publications below). Chicago Daily Tribune, October 11, 2005, By Ronald Kotulak, Eating fish slows loss of memory, study says The Miami Herald, October 16, 2005, By Amy Driscoll, Trim calories and pump up nutrition-packed fruits and veggies to help hold back the hands of time The Boston Globe, October 24, 2005, By Beth Daley, Fish warnings taken too far The New York Times, October 31, 2005, By Alexei Barrionuevo, An Apple a Day for Health? Mars Recommends Two Bars of Chocolate Real Simple, October 2005, By Mary Desmond Pinkowish, Check the label Parade Magazine, November 13, 2005, Victuals vs. Vitamins MedPage Today, November 17, 2005, By Peggy Peck, AHA: Fish Oil Plus Statin Reduces Coronary Events MedPage Today, November 22, 2005, By Katrina Woznicki, Chocolate Makers Fortify Cocoa Snacks for Health CBS4 News, November 22, 2005, Reporter Paula Ebben, New Food Labels Help ID Carbs, Whole Grains CBS4 Boston, Nov 23, 2005, Reporter Dr. Mallika Marshall, Can It Be True? Chocolate That's Good For You? Nutrition Action Health Letter, November 2005, By Bonnie Liebman, Cover Story: Antioxidants: Still Hazy After All These Years Nutrition Action Health Letter, November 2005, By Bonnie Liebman, Cover Story: Beyond Vitamins CBS13, CA, December 1, 2005, Healthcheck: Chocolate Bar Good For Your Heart? Toledo Blade, December 5, 2005, By Luke Shockman, Trans fat: 'Zero' foods add up: Experts say manufacturers should have to list even traces of the substance MedPage Today, December 7, 2005, By Katrina Woznicki, IOM Report Says TV Advertisers Influences Children's Eating Habits WCCO, MN, December 8, 2005, Reporter Dennis Douda, 'Healthy' Chocolate Bar Could Tax Your Diet WFRV, CBS 5, Boston, December 8, 2005, Reporter Lisa Malak National Public Radio, December 15, 2005, Host Renee Montagne TheBostonChannel.com, December 22, 2005, New Food Label Requirements To Go Into Effect: Trans Fat Content To Be Added To Labels U.S. News & World Report, December 26, 2005, By Kerry Hannon, Have a Daily Dose of Omega-3: From food to floss: how to stay in good shape in 2006 and beyond The New York Times, December 28, 2005, By Melanie Warner, Marketing Fortified Food to Those Leery of Drugs HealthDay via Gannett News Service, December 30, 2005, By Janice Billingsley, Trans fat food labels are coming SeaFood Business, December 2005, By Steven Hedlund, Medical miracle: omega-3 WebMD, January 6, 2006, By Kathleen Zelman Medpage Today, January 13, 2006, By Katrina Woznicki, Fat Viewed by Americans as Less of Stigma Newsweek, January 16, 2006, By Anne Underwood, The Nature of Nutrients: Are you really getting all the vitamins, minerals and fatty acids you need? The Los Angeles Times, January 23, 2006, By Rosie Mestel, Zero guilt? Not on your life. 'No trans fat' doesn't mean low-fat. It might even mean more fat. USA Today, January 23, 2006, By Kim Painter, Today's mailbag National Public Radio, January 24, 2006, Reporter Allison Aubrey, Host Renee Montagne, Study: Fish Oil May Not Help Prevent Cancer HealthScout News (South Africa), January 30, 2006, Don't skip breakfast Medwise News / Fashion Monitor (Toronto Canada), January 31, 2006, Cholesterol Lowering Margarines Don't Promise Miracles International Food Information Council Food Insight Newsletter, January/February 2006, Make the Most Out of Dietary Fats Information: Keep the Trans AND Saturated Fats Down The New York Times, February 10, 2006, To the Editor: Re "Low-Fat Diets Flub a Test" (editorial, Feb. 9): The News Journal (Delaware), February 14, 2006, By In-Sung Yoo, Snacks claim health benefits of chocolate The Washington Post, February 14, 2006, By Sally Squires, Chewing the Low-Fat Results The News-Times, February 16, 2006, By Robert Miller, Area doctors still stick to low-fat diet message WebMD, February 17, 2006, By R. Morgan Griffin, The New Low-Cholesterol Diet: Soy WebMD, February 22, 2006, By Salynn Boyles, Low-Salt Diet May Not Cut Heart Risk: More Deaths Seen With Sodium Restriction USA Today, February 27, 2006, By Elizabeth Weise, Pattern for health is tried and true: Amid conflicting diet headlines, experts advise staying the course Bottom Line's Daily Health News, February 28, 2006, SPILLING THE BEANS ON BEANS O, The Oprah Magazine, February 2006, By Alison Motluk, The Drug Detectives: Women who make sure your medication is safe Eating Well, February 2006, By Peter Jaret, The Food-Cancer Connection Delicious Living, February 2006, By Cheryl Sternman Rule, How diet can help you heal after a heart attack or cardiac surgery Harvard Health Letter, February 2006, Take two candy bars and call me in the morning? Adding plant sterols and flavanols to chocolate doesn't make candy bars a health food. Doc News, March 1, 2006, By Joene Hendry , Healthful Fiber Findings Often Forgotten: Benefits include lowering CVD risk, normalizing glucose The Los Angeles Times, March 6, 2006, By Hilary E. MacGregor, Chocolate, with benefits? Forget the nuts and caramel. Candy makers are packing sweets with heart-healthy ingredients WebMD, March 7, 2006, By Louise Chang, Coffee May Up Heart Risks for Some U.S. News & World Report, March 8, 2006, By Christopher J. Gearon, Retirement: Five tips for the next 20 years Tribune Media Services, March 8, 2006, By Bev Bennett, Nutritious fish on a fast track Scout News Service, March 12, 2006, By Steven Reinberg, Folic Acid Supplements Won't Lower Heart-Attack Risk Associated Press, March 15, 2006, Tofu, oatmeal can help lower cholesterol: Study finds strict soy, nut, fiber diet can be as effective as drugs Scout News Service, March 16, 2006, By Kathleen Doheny, Foods Fortified With Folic Acid May Cut Stroke Risk The Washington Post, March 21, 2006, By Sally Squires, Portfolio Diet: Tough to Stay Invested In The Los Angeles Times, March 27, 2006, By Denise Gellene, Makin' better bacon: Scientists use genetic engineering to make pigs rich in healthy fat The New York Times, March 27, 2006, By Gina Kolata The New York Times, March 28, 2006, Corrections: For the Record Orlando Sentinel, March 28, 2006, By Robyn Shelton, Anti-cholesterol diet unlikely to spark fad Harvard Heart Letter, March 2006, Eating your way to lower cholesterol Science News, April 1, 2006, By Christen Brownlee, Pigging Out Healthfully: Engineered pork has more omega-3s Prevention.com, April 11, 2006, Oh No, It's Frankenfat! Associated Press, April 18, 2006, By Jamie Stengle, A yo-yo sized lesson in portion control Health Day News, April 24, 2006, By Ed Edelson, Heavy Coffee Drinking Doesn't Hurt the Heart: No risk of heart disease found in two long-term studies The Los Angeles Times, May 8, 2006, By Hilary E. MacGregor, Fab bean or has-been? Chicago Tribune, May 17, 2006, By Janet Helm, When fats are good; Time to rethink the low-fat mantra in favor of healthful oils and fats USA Today (Weekend magazine), May 21, 2006, By Jean Carper, A guide to better health with the AHA Shape Magazine, May 2006, By Connie Harikul, The latest on what makes a diet healthy O, The Oprah Magazine, May 2006, By Allison Motluck, More Omega-3s, Please Women’s Health, June 6, 2006, By Lisa Draver, Food labels can stump even the smartest eater. Here's our cheat sheet for the back of the box Tribune Media Services, June 8, 2006, By Bev Bennett, Fish is a Fast Meal, and It’s Good for You American Public Radio- Marketplace, June 8, 2006, Host Helen Palmer, Wendy's gets leaner MSN Health and Fitness, June 8, 2006, By Rich Maloof, Reality Check Health Centers: Cholesterol-High cholesterol is within your power to control. Health Day News, June 13, 2006, By Ed Edelson, Fish Oil Won't Fix Abnormal Heart Rhythms: Study Fitcommerce.com, June 14, 2006, Hear Me Roar, Time For Change -- Understanding Women's Heart Disease Eating Well, June/July 2006, By Peter Jaret, Soy Reconsidered; Is the magic bean a magic bullet? The Chicago Tribune, June 18, 2006, Extra-crispy chicken and deep-fried panic WebMD, June 19, 2006, By Daniel DeNoon, Lifestyle Vital to New Heart Diet: American Heart Association: Good Food, Exercise Best Way to Health NBC Newsfeed, June 19, 2006, HealthWatch Health Day News, June 19, 2006, By Kathleen Doheny, Veggies Do a Heart Good: Mice fed 30% vegetable diet were thinner with clearer arteries, study found Heartwire, June 19, 2006, New AHA diet recommendations also emphasize lifestyle, but focus is still mostly on trimming the fat Investor’s Business Daily, June 19, 2006, Issues & Insights: Let Them Eat Whatever MedPage Today, June 20, 2006, By Peggy Peck, AHA Recommends Less Fat and Sugar and More Exercise Associated Press, June 20, 2006, By Marilynn Marchione, Guidelines call for limits on trans fats: The American Heart Association lends its support to a dietary crackdown. The Detroit News, June 20, 2006, By Kimberly Hayes Taylor, The ABCs of the vitamin debate: Should you take dietary supplements? Physicians disagree over conflicting studies. Review Publications Lapointe, A., Balk, E.M., Lichtenstein, A.H. 2006. Gender differences in plasma lipid response to dietary fat. Nutrition Reviews. 64(5):234-249. Dorfman, S.E., Lichtenstein, A.H. 2006. Dietary fatty acids differentially modulate messenger rna abundance of low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme a reductase, and microsomal triglyceride transfer protein in golden-syrian hamsters. Metabolism. 55(5):635-641. Jordan, H.S., Chung, M., Lichtenstein, A.H., Lathrop, D.A., Lau, J., Matthan, N. 2005. A systematic review and meta-analysis of the impact of omega-3 fatty acids on selected arrhythmia outcomes in animal models. Metabolism. 54(12):1557-65. Lichtenstein, A.H. 2005. Hyperlipidaemia. In: Caballero, B., Allen, L., Prentice, A. editors. Encyclopedia of Human Nutrition. 2nd edition. Kidlington, Oxford, U.K., Elsevier, Ltd., p. 491-498. Matthan, N.R., Jalbert, S.M., Dolnikowski, G., Welty, F.K., Schaefer, E., Lichtenstein, A.H. 2005. Trl, idl, and ldl apoliproprotein b-100 and hdl apolipoprotein a-i kinetics as a function of age and menopausal status. Arteriosclerosis Thrombosis and Vascular Biology. 25(8):1691-1696. Erkkila, A.T., Herrington, D.M., Mozaffarian, D., Lichtenstein, A.H. 2005. Cereal fiber and whole-grain intake are associated with reduced progression of coronary-artery atherosclerosis in postmenopausal women with coronary artery disease. American Heart Journal. 150(1):94-101. Lichtenstein, A. 2005. Dietary effects of cardiovascular risk factors. In: Brundy, Scott, Editor. Atlas of Atherosclerosis: Risk Factors and Treatment. 4th Edition. Philadelphia, PA: Current Medicine, LLC. p. 124-146. Wang, C., Harris, W.S., Chung, M., Lichtenstein, A.H., Blak, E.M., Kupelnick, B., Jordan, H.S., Lau, J. 2006. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. American Journal of Clinical Nutrition. 84(1):5-17.