DESIGN NARRATIVE:

In the first five years of the study analyses were performed on food consumption data collected through semiquantitative food frequency questionnaires at baseline and during follow-up in the Nurses Health Study and Health Professionals Follow-up Study cohorts. Dietary patterns were derived from the food consumption data using factor analysis, cluster analysis, and dietary indexes (based on prevailing dietary recommendations). In addition, using existing datasets from dietary validation studies in sub-samples of the two cohorts, the reproducibility and validity of dietary patterns defined by factor/cluster analysis and dietary indexes were evaluated. Further, using prospectively collected and stored bloods in the NHS (n-32,826) during 1989-1990 and the HPFS (n-18,000) during 1993-1994, the investigators examined whether observed associations between dietary patterns and CHD were explained by (or mediated through) plasma biochemical measurements (including serum lipids, thrombotic factors, antioxidants, fasting insulin, and homocysteine levels) in a nested case-control design; and they assessed prospectively the relationship between dietary patterns and these biomarkers in the control samples.

The study was renewed in 2005 to apply novel statistical methods (such as confirmatory factor analysis and structural equation modeling) to validate various dietary patterns and examine their associations with risk of type 2 diabetes, cardiovascular disease and total mortality in two large ongoing cohort studies, the Nurses' Health Study (n=121,700) and Health Professionals' Follow-up Study (n=51,529). In addition to evaluating prevailing dietary recommendations, the study will also examine the role of the Mediterranean-type dietary pattern, the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, and the Atkins-type diet in predicting health outcomes. Using repeated measurements of diet, the study will examine the impact of changes in eating patterns and diet quality over time on subsequent risk of diabetes, CVD, and total mortality. In addition, it will examine relationships between major dietary patterns and novel plasma biomarkers of inflammation and endothelial function and whether such relationships are mediated through obesity. Finally, the study will test interactions between dietary patterns and individual single nucleotide polymorphisms (SNPs) and haplotypes of several promising candidate genes in the inflammation and endothelial dysfunction pathway on risk of coronary heart disease, including PPARa, PPARy, Adiponectin (AdipoQ), PON1, IL-6, TNF-a, ICAM-1, VCAM-1, E-Selectin, NOS3, ACE gene, and angiotensinogen (ANG) genes.