Atherosclerosis is the underlying cause of myocardial infarction (MI) and numerous environmental and genetic factors contribute to its development. Despite advances in our understanding of atherogenesis, many uncertainties on the relationship between diet and cardiovascular disease (CVD) risk remain. Chapter 1 reviews the biologic mechanisms for the effects of dietary fats on CVD risk, including effects on serum lipids, vascular function, chronic inflammation, and thrombosis.
Chapters 2 and 3 examine the effects of sex, ethnicity, and genetic variation on the associations between specific types of dietary fat and CVD risk and atherosclerosis. Among 53,120 Latino and African-American men and women in the Multiethnic Cohort Study, greater intakes of monounsaturated fat and marine-derived long-chain n-3 polyunsaturated fatty acids were associated with lower risk of MI. Greater intakes of saturated fat and n-6 polyunsaturated fat were associated with higher risk of MI among Latinos. Among 1,827 healthy subjects who participated in one of four randomized controlled atherosclerosis trials, atherosclerosis measured using carotid intima-media thickness (CIMT) was not associated with promoter polymorphisms for 5-lipoxygenase, an inflammatory gene in the overall sample. However, there were significant gene-environment interactions such that homozygosity for shorter 5-lipoxygenase promoter alleles was atherogenic among users of lipid-lowering medication or individuals with low dietary intake of linoleic acid, the intermediate-chain n-6 polyunsaturated fatty acid that comprised the majority of energy intake from polyunsaturated fats. Taken together, these findings suggest that nutritional recommendations for prevention of cardiovascular-disease may need to account for differences in the relationship between diet and cardiovascular disease across population subgroups. Further investigation is needed to understand the interactions between diet, inflammation, and other factors underlying atherosclerosis and cardiovascular disease.
Chapter 4 validates Multiethnic Cohort Study self-reports of physician-diagnosed MI and other conditions through comparison with a statewide database of California hospital discharge diagnoses. The sensitivity of self-reports ranged from 59 to 93% and was higher for chronic conditions (such as hypertension, diabetes, and cancers) than for acute events (such as MI, stroke, hip fracture, and cholecystectomy). Sensitivity of self-reports also varied by sex, ethnicity, age, education, length of the hospital stay, and illness severity.
|Advisor:||Mack, Wendy J.|
|Commitee:||Allayee, Hooman, Crimmins, Eileen, Henderson, Brian E., Hodis, Howard N., Monroe, Kristine|
|School:||University of Southern California|
|Department:||Preventive Medicine (Health Behavior Research)|
|School Location:||United States -- California|
|Source:||DAI-B 71/01, Dissertation Abstracts International|
|Keywords:||Atherosclerosis, Cardiovascular disease, Dietary fats, Lipoxygenase|
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