Background and Aims: Black boys (6–8 years of age) were shown to have higher pulse wave velocity with potential early vascular compromise. We aimed to compare predefined urinary metabolites in black and white boys to explore associations of pulse wave velocity with these metabolites. Methods and Results: We included 40 white and 40 black apparently healthy boys between the ages of 6 and 8 years. Femoral pulse wave velocity was measured along with various metabolites using liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography-time of flight-mass spectrometry (GC-TOF-MS) methods. Pulse wave velocity and diastolic blood pressure were higher in the black compared to the white boys (both p ≤ 0.002). Isovalerylcarnitine was lower and 1-metylhistidine tended to be lower (p = 0.002 and p = 0.073, respectively), whereas L-proline levels tended to be higher (p = 0.079) in the black compared to the white boys. In single, partial, and multiple regression analyses, pulse wave velocity correlated inversely with β-alanine (β = –0.414; p = 0.008) and 1-methylhistidine (β = –0.347; p = 0.032) and positively with L-proline (β = 0.420; p = 0.008), threonic acid (β = 0.977; p = 0.033), and malonic acid (β = 0.348; p = 0.030) in black boys only. Conclusion: Our study is the first to discover the associations of pulse wave velocity with β-alanine, 1-methylhistidine, and L-proline in children from South Africa, which may suggest potential early compromise in cardiac protective metabolic pathways in black boys as young as 6 years of age.

Keywords:
β-Alanine, Cardiac protection, L-Proline, Metabolomics, Pulse wave velocity
1.
Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al: Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med 2016; 374: 2032–2043.
2.
Mosca L, Benjamin E, Berra K, Bezanson J, Dolor R, Lloyd-Jones D, et al: Effectiveness-based guidelines for the prevention of cardiovascular disease in women – 2011 update: a guideline from the American Heart Association. Circulation 2011; 123: 1–20.
3.
Afshin A, Penalvo J, Del Gobbo L, Kashaf M, Micha R, Morrish K, et al: CVD prevention through policy: a review of mass media, food/menu labeling, taxation/subsidies, built environment, school procurement, worksite wellness, and marketing standards to improve diet. Curr Cardiol Rep 2015; 17: 98.
4.
Mokwatsi GG, Schutte AE, Kruger R: Ethnic differences regarding arterial stiffness of 6–8-year-old black and white boys. J Hypertens 2017; 35: 960–967.
5.
Schutte AE, Huisman HW, Van Rooyen JM, De Ridder JH, Malan NT: Associations between arterial compliance and anthropometry of children from four ethnic groups in South Africa: the THUSA BANA Study. Blood Press 2003; 12: 97–103.
6.
Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, et al: A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet 2016; 388: 2665–2712.
7.
Djekic D, Nicoll R, Novo M, Henein M: Metabolomics in atherosclerosis. IJC Metab Endocr 2015; 8: 26–30.
8.
Lewis GD, Asnani A, Gerszten RE: Application of metabolomics to cardiovascular biomarker and pathway discovery. J Am Coll Cardiol 2008; 52: 117–123.
9.
Dunn WB, Erban A, Weber RJ, Creek DJ, Brown M, Breitling R, et al: Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics. Metabolomics 2013; 9: 44–66.
10.
Bouatra S, Aziat F, Mandal R, Guo AC, Wilson MR, Knox C, et al: The human urine metabolome. PLoS One 2013; 8:e73076.
11.
Stewart A M-JM, Olds T, De Ridder H: International Standards for Anthropometric Assessment. Lower Hutt, ISAK, 2011.
12.
Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, et al: Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens 2012; 30: 445–448.
13.
Faul F, Erdfelder E, Lang A-G, Buchner A: G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007; 39: 175–191.
14.
Wu H-C, Shiau C-Y, Chen H-M, Chiou T: Antioxidant activities of carnosine, anserine, some free amino acids and their combination. J Food Drug Anal 2003; 11: 148–153.
15.
McCarty MF, DiNicolantonio JJ: β-Alanine and orotate as supplements for cardiac protection. Open Heart 2014; 1:e000119.
16.
Ivanov V, Roomi MW, Kalinovsky T, Niedzwiecki A, Rath M: Anti-atherogenic effects of a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea phenolics in human aortic smooth muscle cells. J Cardiovasc Pharmacol 2007; 49: 140–145.
17.
Stvolinsky S, Dobrota D: Anti-ischemic activity of carnosine. Biochemistry (Mosc) 2000; 65: 849–855.
18.
Culbertson JY, Kreider RB, Greenwood M, Cooke M: Effects of beta-alanine on muscle carnosine and exercise performance: a review of the current literature. Nutrients 2010; 2: 75–98.
19.
Fu H, Katsumura Y, Lin M, Muroya Y, Hata K, Fujii K, et al: Free radical scavenging and radioprotective effects of carnosine and anserine. Radiat Phys Chem 2009; 78: 1192–1197.
20.
Mokhaneli MC, Fourie CMT, Botha S, Mels CMC: The association of oxidative stress with arterial compliance and vascular resistance in a bi-ethnic population: the SABPA study. Free Radic Res 2016; 50: 920–928.
21.
Williams P: Nutritional composition of red meat. Nutr Diet 2007; 64:S113–S119.
22.
Myint T, Fraser GE, Lindsted KD, Knutsen SF, Hubbard RW, Bennett HW: Urinary 1-methylhistidine is a marker of meat consumption in Black and in White California Seventh-day Adventists. Am J Epidemiol 2000; 152: 752–755.
23.
MacIntyre U, Kruger H, Venter C, Vorster H: Dietary intakes of an African population in different stages of transition in the North West Province, South Africa: the THUSA study. Nutr Res 2002; 22: 239–256.
24.
Phang JM, Pandhare J, Liu Y: The metabolism of proline as microenvironmental stress substrate. J Nutr 2008; 138: 2008S–2015S.
25.
Wu G, Bazer FW, Burghardt RC, Johnson GA, Kim SW, Knabe DA, et al: Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids 2011; 40: 1053–1063.
26.
LaRocca TJ, Gioscia-Ryan RA, Hearon CM, Seals DR: The autophagy enhancer spermidine reverses arterial aging. Mech Ageing Dev 2013; 134: 314–320.
27.
Karna E, Miltyk W, Wołczyński S, Pałka JA: The potential mechanism for glutamine-induced collagen biosynthesis in cultured human skin fibroblasts. Comp Biochem Physiol B Biochem Mol Biol 2001; 130: 23–32.
28.
Madeo F, Eisenberg T, Büttner S, Ruckenstuhl C, Kroemer G: Spermidine: a novel autophagy inducer and longevity elixir. Autophagy 2010; 6: 160–162.
29.
Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K: KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 2017; 45(D1):D353–D361.
30.
Zhao Y-J, Xu C-Q, Zhang W-H, Zhang L, Bian S-L, Huang Q, et al: Role of polyamines in myocardial ischemia/reperfusion injury and their interactions with nitric oxide. Eur J Pharmacol 2007; 562: 236–246.
31.
Moinard C, Cynober L, de Bandt J-P: Polyamines: metabolism and implications in human diseases. Clin Nutr 2005; 24: 184–197.
32.
Martin-Lorenzo M, Zubiri I, Maroto AS, Gonzalez-Calero L, Posada-Ayala M, de la Cuesta F, et al: KLK1 and ZG16B proteins and arginine-proline metabolism identified as novel targets to monitor atherosclerosis, acute coronary syndrome and recovery. Metabolomics 2015; 11: 2.
33.
Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, et al: Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet 2010; 3: 207–214.
34.
Batch BC, Shah SH, Newgard CB, Turer CB, Haynes C, Bain JR, et al: Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness. Metabolism 2013; 62: 961–969.
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.