The next five years of this basic investigative program are committed to accomplishing a new set of aims for the unique INTERMAP international metabolomics research on multiple urinary metabolites related to blood pressure (BP) and BP associated traits (nutritional, sociodemographic, anthropomorphic, biomedical) - a program conceived, opened up, and developed by its senior cooperating Principal Investigators in London and Chicago. During the years of the currently ongoing funded NHLBI grant (Feb. 1, 2007 - - Jan. 31, 2011), 66 urinary metabolites (44 of known chemical composition) have been identified, based on the strategic approach set down in the prior (2006) grant application. This strategy entailed paired sampling of the 10,000+ urinary specimens from the 4,630 INTERMAP participants, based on traits related to BP - - e.g., lower and higher vegetable protein intake and Na/K intake;African Americans and Other Americans;northern and southern Chinese, obese and lean. For each contrasting pair of samples, the urinary nuclear magnetic resonance (NMR) spectra already in hand (7100 peaks/spectrum) underwent metabolomewide scanning to identify the urinary metabolic pattern and its specific metabolites discriminating the pair. Further, per this research strategy, 7 of the 44 known metabolites were quantified in both urine specimens of all 4,630 participants;of these, 5 related to BP - - alanine directly, formate, hippurate, 4 cresyl sulphate, phenyl acetyl glutamine inversely. During the next years, this proven strategy is to be serially utilized to accomplished the new set of specific aims derived from recent INTERMAP research findings on nutrient - BP relations, i.e., identification of urinary metabolomic patterns/specific metabolites distinguishing INTERMAP participants with lower and higher intakes of: glutamic acid, glycine, omega-3/omega-6 PFA and their specific PFAs, oleic acid/MFA, dietary Ca, Mg, P, non-heme Fe. Further, characterize metabolites of unknown chemical structure. Further, quantify - - in all 10,000+ INTERMAP urine specimens - - selected metabolites so identified, and assess their relations to BP. For these purposes the projected research is relying not only on the extensive high-quality data already in hand on the 4,630 INTERMAP participants (women and men ages 40-59 from 17 population samples - - 4 in Japan;3, People's Republic of China;2, UK;8, USA). In addition, as appropriate for the foregoing purposes, the basic data set is to be extended/enhanced with analyses by ultra performance liquid chromatography - time of flight - mass spectroscopy (UPLC - TOF - MS) to complement the metabolic profiling already achieved with NMR. With the data analyses thereby achieved, INTERMAP anticipates adding a new dimension of research information and achieving a qualitative advance in knowledge - - of potential importance both practically and theoretically - - on the etiophatogenesis of population wide adverse BP levels (prehypertensive and hypertensive).

Public Health Relevance

This research program uses extensive high-quality data for 4,630 women and men ages 40-59 from 17 random samples of populations in China, Japan, the United Kingdom, and the United States: data on 83 nutrients;urinary sodium, potassium, calcium, magnesium, 23 amino acids;multiple metabolites identified by modern biochemical/biophysical metabolomic techniques;sociodemographic, anthropomorphic, and biomedical data. The focus is on identification of metabolites in the urine that relate to blood pressure (BP) and BP-associated traits (nutritional, sociodemographic, anthropomorphic, biomedical). The data serve to clarify how lifestyles and other human traits influence the pathways/mechanisms leading to the epidemic of prehypertension and hypertension - - data that can help to prevent and control adverse BP, key risk factor for heart disease and stroke.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-PSE-J (02))
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Loria, Catherine
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Northwestern University at Chicago
Public Health & Prev Medicine
Schools of Medicine
United States
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Chan, Q; Stamler, J; Brown, I J et al. (2014) Relation of raw and cooked vegetable consumption to blood pressure: the INTERMAP Study. J Hum Hypertens 28:353-9
Stamler, Jeremiah; Brown, Ian J; Yap, Ivan K S et al. (2013) Dietary and urinary metabonomic factors possibly accounting for higher blood pressure of black compared with white Americans: results of International Collaborative Study on macro-/micronutrients and blood pressure. Hypertension 62:1074-80
Oude Griep, Linda M; Wang, Huifen; Chan, Queenie (2013) Empirically-derived dietary patterns, diet quality scores, and markers of inflammation and endothelial dysfunction. Curr Nutr Rep 2:97-104
Oude Griep, Linda M; Stamler, Jeremiah; Chan, Queenie et al. (2013) Association of raw fruit and fruit juice consumption with blood pressure: the INTERMAP Study. Am J Clin Nutr 97:1083-91
Loo, Ruey Leng; Chan, Queenie; Brown, Ian J et al. (2012) A comparison of self-reported analgesic use and detection of urinary ibuprofen and acetaminophen metabolites by means of metabonomics: the INTERMAP Study. Am J Epidemiol 175:348-58
Heinzmann, Silke S; Brown, Ian J; Chan, Queenie et al. (2010) Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption. Am J Clin Nutr 92:436-43
Chadeau-Hyam, Marc; Ebbels, Timothy M D; Brown, Ian J et al. (2010) Metabolic profiling and the metabolome-wide association study: significance level for biomarker identification. J Proteome Res 9:4620-7
Yap, Ivan K S; Angley, Manya; Veselkov, Kirill A et al. (2010) Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res 9:2996-3004
Bictash, Magda; Ebbels, Timothy M; Chan, Queenie et al. (2010) Opening up the "Black Box": metabolic phenotyping and metabolome-wide association studies in epidemiology. J Clin Epidemiol 63:970-9
Martin, Francois-Pierre J; Sprenger, Norbert; Yap, Ivan K S et al. (2009) Panorganismal gut microbiome-host metabolic crosstalk. J Proteome Res 8:2090-105

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