Cardiovascular disease (CVD) and type 2 diabetes (T2DM) are among the leading causes of death in the world and in the US. Hispanics are the largest ethnic population in the US, and they are a diverse population that varies in national origin, socioeconomic characteristics, heritage groups, and cultural histories. Nevertheless, the combination of all these genetic, social, and environmental factors contributes to the differences in the CVD risk observed between populations and the extent of the independent contribution of the genetic admixture to CVD remains understudied.Moreover, it is well known that dietary patterns vary across Hispanic heritage groups and that diet influences chronic inflammation through the modulation of the levels of inflammatory markers (i.e., cytokines, acute-phase proteins, soluble adhesion molecules, and cytokine receptors), as well as lipids and glucose. Chronic inflammation in turn contributes to the pathogenesis of CVD by increasing the progression of atherosclerosis plaque and in the modulation of endothelial function, and to the pathogenesis of T2DM by increasing insulin resistance, β-cell dysfunction, and apoptosis. The dietary inflammatory index (DII®) is a scoring algorithm that allows us to categorize individuals’ diets on a continuum from maximally anti-inflammatory to maximally pro-inflammatory based on the consumption of 45 food components.
Furthermore, it has been established that other factors such as genetic variations or obesity can modify the metabolic response to nutrients and dietary patterns in some ethnic groups, and they also can alter the relationship between diet-associated inflammation and some health outcomes. Previous studies found that the effect of certain dietary patterns or nutrients on inflammation differs depending on the proportion of Amerindian ancestry of the participants or on the presence of some genetic variations. Also, it has been reported that the association between the DII® or inflammatory factors and chronic diseases is stronger or only significant in participants with overweight/obesity but not in participants with normal weight.
The first chapter of this dissertation evaluated the association between CVD and the relative proportion of sub-Saharan African (AFR), Amerindian (AMI), and European (EUR) admixture in a subset of 5,195 participants of the Women’s Health Initiative (WHI) who self-identify as Hispanic American and have been genotyped. The analyses included adjustments for known risk factors for CVD such as socioeconomic status, physical activity, smoking, alcohol intake, body mass index (BMI), hypertension, hypercholesterolemia, and diabetes. Results from adjusted regression models showed that among WHI Hispanic women, EUR ancestry was significantly associated with a lower risk of CVD, AFR was associated with an increased risk of CVD, AMI was not statistically significantly associated with CVD risk and the incidence of CVD in Hispanic women was driven more by modifiable factors than genetic admixture. These findings highlight the need to account for genetic admixture in CVD studies of participants from diverse backgrounds. Also, the known CVD risk factors and lifestyle-related risk factors explained most of the variation in the risk of CVD. As these factors play an important role on the pathologic pathway between genetics and CVD development so they should be considered when designing interventions or preventive strategies in Hispanic populations.
The second chapter of this dissertation evaluated the association between the DII® and CVD in a subset of 3,469 women who participated in the WHI, and who self-identified as Hispanic. The analyses included adjustments for known risk factors for CVD such as age, socioeconomic status, physical activity, smoking, alcohol intake, acculturation, Amerindian ancestry, BMI, diabetes, hypercholesterolemia, and hypertension. Additionally, this chapter evaluated the effect of obesity as an effect modifier of the association between the DII® and CVD. Results from the adjusted Cox regression models showed that among postmenopausal Hispanic women without obesity, higher inflammatory diets were associated with higher risk of CVD. When nutritional supplements were considered in the calculation of the DII® its association with CVD was not statistically significant. Additional research is needed to understand how to promote long-term heart-healthy dietary habits to reduce inflammation and prevent CVD in at-risk women.
The third chapter of this dissertation evaluated the association between the DII® and energy-adjusted DII (E-DII®) with the risk of incident diabetes in a subset of 3,165 women who participated in the WHI, and who self-identified as Hispanic. The analyses included adjustments for known risk factors for T2DM such as age, socioeconomic status, physical activity, smoking, alcohol intake, acculturation, Amerindian ancestry, BMI, family history of diabetes, hypercholesterolemia, and hypertension. Additionally, this chapter evaluated the effect of obesity as an effect modifier of the association between the DII® and incident diabetes and the interaction between the genetic admixture and DII® scores. Results from adjusted Cox regression models showed that E-DII® scores were associated with a higher risk of T2DM (HR 1.09; 95% CI: 1.03, 1.15). Neither obesity nor the ancestry proportions interacted with the DII® scores (p=0.91 and p>0.20). The E-DII had a stronger correlation with diet quality than the DII. Understanding of the pathophysiological link between diet, inflammation and T2DM in Hispanic women can be used for the development and evaluation of future lifestyle interventions to help reduce the burden, morbidity, and mortality of T2DM in this population.
Findings from this dissertation indicated that genetic factors and the inflammatory potential of the diet participate in the pathophysiologic process of CVD and T2DM. EUR ancestry was associated with a lower risk of CVD and AFR ancestry showed a trend for increased risk of CVD. Also, increases in the inflammatory potential of the diet were associated a with higher risk of CVD in women without obesity and a higher risk of diabetes in all Hispanic women. More studies are necessary for a better understanding of the determinants of health in Hispanic populations to be able to develop interventions that reduce health disparities in this population.