Metabolic phenotyping for discovery of urinary biomarkers of diet, xenobiotics and blood pressure in the INTERMAP Study: An overview

The etiopathogenesis of cardiovascular diseases (CVDs) is multifactorial. Adverse blood pressure (BP) is a major independent risk factor for epidemic CVD affecting ∼40% of the adult population worldwide and resulting in significant morbidity and mortality. Metabolic phenotyping of biological fluids has proven its application in characterizing low-molecular-weight metabolites providing novel insights into gene-environmental-gut microbiome interaction in relation to a disease state. In this review, we synthesize key results from the INTERnational study of MAcro/micronutrients and blood Pressure (INTERMAP) Study, a cross-sectional epidemiologic study of 4680 men and women aged 40-59 years from Japan, the People's Republic of China, the United Kingdom and the United States. We describe the advancements we have made regarding the following: (1) analytical techniques for high-throughput metabolic phenotyping; (2) statistical analyses for biomarker identification; (3) discovery of unique food-specific biomarkers; and (4) application of metabolome-wide association studies to gain a better understanding into the molecular mechanisms of cross-cultural and regional BP differences.