Novel Nutritional and Lifestyle Factors for Cardiometabolic Risk in Prospective Cohorts and Randomized Clinical Trial

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide. Great advances have been made in identifying important cardiometabolic risk factors. More recently, emerging evidence has suggested several novel etiology pathways for CVD-of particular importance are gut microbiota and amino acids. In addition, despite that higher circulating adiponectin has been associated with reduced cardiometabolic risk in prospective studies, its role in the context of dietary intervention remains unclear. This has motivated my three dissertation projects in the identification of novel cardiometabolic risk factors related to the aforementioned pathways in prospective cohorts and randomized clinical trial. Bowel movement frequency has been correlated with gut microbiota composition and other cardiometabolic risk factors. In Chapter one, we investigate whether bowel movement frequency is prospectively associated with risk of incident CVD and mortality in the Nurses’ Health Study. Compared to women with daily bowel movements, more frequent bowel movements were significantly associated with elevated cardiovascular risk, which may be partly explained by body mass index and diabetes. Increased bowel movement frequency was associated with a modest increase in the risk of total mortality independent of traditional risk factors. Metabolomics profiling has identified circulating concentrations of glutamine, glutamate, and glutamine-to-glutamate ratio associated with risk of developing CVD and other cardiometabolic abnormalities. Chapter two prospectively examines dietary intakes of glutamine, glutamate, and their ratio in relation to total mortality and cause-specific mortality in the Nurses’ Health Study and Health Professionals Follow-up Study. Data from two cohorts consistently showed that dietary intakes of glutamine and glutamine-to-glutamate ratio were inversely related to mortality particularly cardiovascular mortality, independent of other dietary and lifestyle factors. The beneficial effects of weight-loss diet interventions on improvement of cardiometabolic risk may be partly through modulating secretion of adiponectin. Chapter three assesses the effects of long-term weight-loss diets with different compositions of macronutrients on longitudinal changes in circulating adiponectin concentrations and how such changes, if they exist, affect cardiometabolic risk. In the 2-year Preventing Overweight Using Novel Dietary Strategies Trial, long-term interventions by weight-loss diets varying in macronutrients similarly increased circulating adiponectin, which might particularly improve body adiposity, abdominal fat distribution, and lipid profile.