Dietary fatty acid intake, reflected by the endogenous fatty acid profile, has been associated with the pathogenesis and progression of cardiovascular diseases (CVD). Additional evidence is needed about the specific roles of individual fatty acids in the pathogenesis of inflammation, which is closely linked to CVD risk factors and interwined with oxidative stress and hemostatic dysfunction. It is also important to explore such relationships across the lifecycle. This dissertation, which includes four manuscripts, investigates the relations between fatty acids, biomarkers of inflammation (and oxidative stress and hemostasis), and cardiovascular health among different age groups. Specifically, the influences of adiposity and a genetic variant on the fatty acid/inflammation relations were also explored.
The first manuscript used data from a study of obesity, insulin resistance and CVD risk factors in adolescents. A cross-sectional analysis was conducted to examine whether overweight status modified the relations between serum phospholipid fatty acids from dairy fats (i.e. 15:0 and 17:0 fatty acids) and inflammation/oxidative stress among adolescents with a mean age of 15 years. Inverse associations were found between dairy fatty acids and three biomarkers of inflammation and oxidative stress among overweight adolescents, but not their normal weight counterparts. In additional analyses, we further examined the same study question on other fatty acids and observed similar effect modification of adiposity. Only in overweight adolescents, but not in normal adolescents, 18:0 and 20:3ù6 fatty acids were positively, while 20:4ù6 and 22:6ù3 fatty acids were inversely, related to inflammation/oxidative stress.
The second manuscript examined whether the cross-sectional relations between dietary intakes of polyunsaturated fatty acids (PUFA) and inflammation differed by genetic variant, peroxisome proliferator-activated receptor gamma (PPARã) Pro12Ala polymorphism. A biracial cohort of middle-aged adults enrolled in the year-20 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study was studied. In women, higher dietary intakes of 20:4ù6, 20:5ù3 and 22:6ù3 fatty acids were related to lower levels of IL-6 (an inflammatory biomarker) among Ala allele carriers. In contrast, these PUFA/IL-6 relations were positive among male Ala carriers, and absent among female Pro homozygotes. Male Pro homozygotes who consumed more 20:5ù3 and 22:6ù3 fatty acids tended to have a lower IL-6 level.
The last two manuscripts were both prospective studies using data from the Atherosclerosis Risk in Communities (ARIC) study, which enrolled middle-aged adults. This cohort has been followed since year 1987-89.
Manuscript 3 examined the interactions between dietary fatty acid intake and inflammatory/hemostatic factors in relation to incident coronary heart disease (CHD) and ischemic stroke (IS). Dietary intakes of 18:2ù6 and 20:4ù6 fatty acids were found to modify the associations between serum albumin and incident CHD/IS. The prediction of low serum albumin level, a potential inflammatory biomarker, on incident CHD/IS was attenuated with increasing intake of 18:2ù6 fatty acid or decreasing intake of 20:4ù6 fatty acid.
Manuscript 4 included 3,715 ARIC participants enrolled at the Minnesota field center who had plasma phospholipid fatty acid measurements. In manuscript 4, the focuse was to determine whether inflammation/hemostasis mediated the relation of phospholipid fatty acids with incident CHD and IS. Inflammation and hemostasis, represented by levels of factor VIIIc (VIIIc), white blood cell count (WBC) and fibrinogen, mediated the positive associations of 18:0 and 20:3ù6 fatty acids with incident CHD. A similar but less significant pattern was found for 16:1ù7 in relation to incident IS. Lower WBC, but not VIIIc or fibrinogen, partially explained the inverse relations of 17:0 and 20:4ù6 fatty acids with incident CHD.
In conclusion, this dissertation documents the associations between diverse fatty acids, inflammation and the development of CVD among different age-groups. The findings have enhanced the understanding of the health effects of individual fatty acids and the underlying mechanisms of fatty acid-inflammation-CVD relations, which are useful for advising food manufacturers and guiding CVD prevention.