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Identifying a metabolomics profile associated with masked hypertension in two independent cohorts: Data from the African-PREDICT and SABPA studies

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Abstract

Individuals with masked hypertension (MHT) have a greater risk of adverse cardiovascular outcomes than normotensive (NT) individuals. Exploring metabolomic differences between NT and MHT individuals may help provide a better understanding of the etiology of MHT. We analyzed data from 910 young participants (83% NT and 17% MHT) (mean age 24 ± 3 years) from the African-PREDICT and 210 older participants (63% NT and 37% MHT) from the SABPA (mean age 42 ± 9.6 years) studies. Clinic and ambulatory blood pressures (BPs) were used to define BP phenotypes. Urinary amino acids and acylcarnitines were measured using liquid chromatography time-of-flight mass spectrometry in SABPA and liquid chromatography tandem mass spectrometry in the African-PREDICT studies. In the SABPA study, amino acids (leucine/isoleucine, valine, methionine, phenylalanine), free carnitine (C0-carnitine), and acylcarnitines C3 (propionyl)-, C4 (butyryl)-carnitine and total acylcarnitine) were higher in MHT than NT adults. In the African-PREDICT study, C0- and C5-carnitines were higher in MHT individuals. With unadjusted analyses in NT adults from the SABPA study, ambulatory SBP correlated positively with only C3-carnitine. In MHT individuals, positive correlations of ambulatory SBP with leucine/isoleucine, valine, methionine, phenylalanine, C0-carnitine and C3-carnitine were evident (all p < 0.05). In the African-PREDICT study, ambulatory SBP correlated positively with C0-carnitine (r = 0.101; p = 0.006) and C5-carnitine (r = 0.195; p < 0.001) in NT adults and C5-carnitine in MHT individuals (r = 0.169; p = 0.034). We demonstrated differences between the metabolomic profiles of NT and MHT adults, which may reflect different stages in the alteration of branched-chain amino acid metabolism early on and later in life.

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References

  1. Global Burden of Disease 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1223–49.

    Article  Google Scholar 

  2. Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 International society of hypertension global hypertension practice guidelines. Hypertension. 2020;75:1334–57.

    Article  CAS  PubMed  Google Scholar 

  3. Cuspidi C, Tadic M, Grassi G. How to unmask masked hypertension: The role of office aortic blood pressure. Hypertens Res. 2021;44:256–8.

    Article  PubMed  Google Scholar 

  4. Antza C, Vazakidis P, Doundoulakis I, Bouras E, Haidich AB, Stabouli S, et al. Masked and white coat hypertension, the double trouble of large arteries: a systematic review and meta-analysis. J Clin Hypertens. 2020;22:802–11.

    Article  Google Scholar 

  5. Cuspidi C, Facchetti R, Quarti-Trevano F, Sala C, Tadic M, Grassi G, et al. Incident left ventricular hypertrophy in masked hypertension. Hypertension. 2019;74:56–62.

    Article  CAS  PubMed  Google Scholar 

  6. Sekoba NP, Kruger R, Labuschagne P, Schutte AE. Left ventricular mass independently associates with masked hypertension in young healthy adults: The African-PREDICT study. J Hypertens. 2018;36:1689–96.

    Article  CAS  PubMed  Google Scholar 

  7. Tientcheu D, Ayers C, Das SR, McGuire DK, de Lemos JA, Khera A, et al. Target organ complications and cardiovascular events associated with masked hypertension and white-coat hypertension: analysis from the Dallas Heart Study. J Am Coll Cardiol. 2015;66:2159–69.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Thompson JE, Smith W, Ware LJ, C MCM, van Rooyen JM, Huisman HW, et al. Masked hypertension and its associated cardiovascular risk in young individuals: The African-PREDICT study. Hypertens Res. 2016;39:158–65.

    Article  CAS  PubMed  Google Scholar 

  9. Palla M, Saber H, Konda S, Briasoulis A. Masked hypertension and cardiovascular outcomes: an updated systematic review and meta-analysis. Integr Blood Press Control. 2018;11:11–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang D-Y, Guo Q-H, An D-W, Li Y, Wang J-G. A comparative meta-analysis of prospective observational studies on masked hypertension and masked uncontrolled hypertension defined by ambulatory and home blood pressure. J Hypertens. 2019;37:1775–85.

    Article  CAS  PubMed  Google Scholar 

  11. Stergiou GS, Asayama K, Thijs L, Kollias A, Niiranen TJ, Hozawa A, et al. Prognosis of white-coat and masked hypertension: International Database of HOme blood pressure in relation to Cardiovascular Outcome. Hypertension. 2014;63:675–82.

    Article  CAS  PubMed  Google Scholar 

  12. Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of hypertension: The Mosaic Theory and beyond. Circ Res. 2021;128:847–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tzoulaki I, Iliou A, Mikros E, Elliott P. An overview of metabolic phenoty** in blood pressure research. Curr Hypertens Rep. 2018;20:78 https://doi.org/10.1007/s11906-018-0877-8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chakraborty S, Mandal J, Yang T, Cheng X, Yeo J-Y, McCarthy CG, et al. Metabolites and hypertension: Insights into hypertension as a metabolic disorder. Hypertension. 2020;75:1386–96.

    Article  CAS  PubMed  Google Scholar 

  15. McGarrah RW, Crown SB, Zhang G-F, Shah SH, Newgard CB. Cardiovascular metabolomics. Circ Res. 2018;122:1238–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9:311–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Guasch-Ferré M, Hruby A, Toledo E, Clish CB, Martínez-González MA, Salas-Salvadó J, et al. Metabolomics in prediabetes and diabetes: A systematic review and meta-analysis. Diabetes Care. 2016;39:833–46.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Schutte AE, Gona PN, Delles C, Uys AS, Burger A, Mels CM, et al. The African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT): Design, recruitment and initial examination. Eur J Prev Cardiol. 2019;26:458–70.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Malan L, Hamer M, Frasure-Smith N, Steyn HS, Malan NT. Cohort Profile: Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) prospective cohort study. Int J Epidemiol. 2014;44:1814–22.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mels CMC, Schutte AE, Erasmus E, Huisman HW, Schutte R, Fourie CMT, et al. l-Carnitine and long-chain acylcarnitines are positively correlated with ambulatory blood pressure in humans: The SABPA Study. Lipids. 2013;48:63–73.

    Article  CAS  PubMed  Google Scholar 

  21. Ekoru K, Murphy G, Young E, Delisle H, Jerome C, Assah F, et al. Deriving an optimal threshold of waist circumference for detecting cardiometabolic risk in sub-Saharan Africa. Int J Obes. 2018;42:487–94.

    Article  Google Scholar 

  22. Yang W-Y, Thijs L, Zhang Z-Y, Asayama K, Boggia J, Hansen TW, et al. Evidence-based proposal for the number of ambulatory readings required for assessing blood pressure level in research settings: an analysis of the IDACO database. Blood Press. 2018;27:341–50.

    Article  PubMed  Google Scholar 

  23. De Beer D, Mels CM, Schutte AE, Louw R, Delles C, Kruger RJN, et al. Left ventricular mass and urinary metabolomics in young black and white adults: the African-PREDICT study. Nutr Metab Cardiovasc Dis. 2020;30:2051–62.

    Article  PubMed  Google Scholar 

  24. Mels CM, Delles C, Louw R, Schutte AEJJoh. Central systolic pressure and a nonessential amino acid metabolomics profile: the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension. J Hypertens. 2019;37:1157–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. van Deventer CA, Lindeque JZ, van Rensburg PJ, Malan L, van der Westhuizen FH, Louw R. Use of metabolomics to elucidate the metabolic perturbation associated with hypertension in a black South African male cohort: the SABPA study. J Am Soc Hypertens. 2015;9:104–14.

    Article  PubMed  Google Scholar 

  26. Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N. Eng J Med. 2010;362:800–11.

    Article  CAS  Google Scholar 

  27. Minkler PE, Stoll MS, Ingalls ST, Kerner J, Hoppel CL. Validated method for the quantification of free and total carnitine, butyrobetaine, and acylcarnitines in biological samples. Anal Chem. 2015;87:8994–9001.

    Article  CAS  PubMed  Google Scholar 

  28. Newgard CB. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab. 2012;15:606–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wu G. Amino acids: Metabolism, functions, and nutrition. Amino acids. 2009;37:1–17.

    Article  PubMed  Google Scholar 

  30. Zhang Z-Y, Monleon D, Verhamme P, Staessen JA. Branched-chain amino acids as critical switches in health and disease. Hypertension. 2018;72:1012–22.

    Article  CAS  PubMed  Google Scholar 

  31. van Vliet S, Burd NA, van Loon LJ. The skeletal muscle anabolic response to plant- versus animal-based protein consumption. J Nutr. 2015;145:1981–91.

    Article  PubMed  Google Scholar 

  32. Merz B, Frommherz L, Rist MJ, Kulling SE, Bub A, Watzl B. Dietary pattern and plasma BCAA-variations in healthy men and women-results from the KarMeN Study. Nutrients. 2018;10:623 https://doi.org/10.3390/nu10050623.

    Article  CAS  PubMed Central  Google Scholar 

  33. Ye Z, Wang S, Zhang C, Zhao Y. Coordinated modulation of energy metabolism and inflammation by branched-chain amino acids and fatty acids. Front Endocrinol. 2020;11:617 https://doi.org/10.3389/fendo.2020.00617.

    Article  Google Scholar 

  34. Flores-Guerrero JL, Groothof D, Connelly MA, Otvos JD, Bakker SJL, Dullaart RPF. Concentration of branched-chain amino acids is a strong risk marker for incident hypertension. Hypertension. 2019;74:1428–35.

    Article  CAS  PubMed  Google Scholar 

  35. Tobias DK, Lawler PR, Harada PH, Demler OV, Ridker PM, Manson JE, et al. Circulating branched-chain amino acids and incident cardiovascular disease in a prospective cohort of US women. Circ Genom Precis Med. 2018;11:e002157–e002157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ruiz-Canela M, Toledo E, Clish CB, Hruby A, Liang L, Salas-Salvadó J, et al. Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED Trial. Clin Chem. 2016;62:582–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sciarretta S, Volpe M, Sadoshima J. Mammalian target of rapamycin signaling in cardiac physiology and disease. Circ Res. 2014;114:549–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Latimer MN, Sonkar R, Mia S, Frayne IR, Carter KJ, Johnson CA, et al. Branched chain amino acids selectively promote cardiac growth at the end of the awake period. J Mol Cell Cardiol. 2021;157:31–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gao X-M, Wong G, Wang B, Kiriazis H, Moore X-L, su Y, et al. Inhibition of mTOR reduces chronic pressure-overload cardiac hypertrophy and fibrosis. J Hypertens. 2006;24:1663–70.

    Article  CAS  PubMed  Google Scholar 

  40. Wongkittichote P, Ah Mew N, Chapman KA. Propionyl-CoA carboxylase – A review. Mol Genet Metab. 2017;122:145–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sharma S, Black SM. Carnitine homeostasis, mitochondrial function, and cardiovascular disease. Drug Disco Today Dis Mech. 2009;6:e31–e39.

    Article  CAS  Google Scholar 

  42. Brunt VE, Gioscia-Ryan RA, Casso AG, VanDongen NS, Ziemba BP, Sapinsley ZJ, et al. Trimethylamine-N-Oxide promotes age-related vascular oxidative stress and endothelial dysfunction in mice and healthy humans. Hypertension. 2020;76:101–12.

    Article  CAS  PubMed  Google Scholar 

  43. Brunt VE, Casso AG, Gioscia-Ryan RA, Sapinsley ZJ, Ziemba BP, Clayton ZS, et al. Gut microbiome-derived metabolite Trimethylamine N-Oxide induces aortic stiffening and increases systolic blood pressure with aging in mice and humans. Hypertension. 2021;78:499–511.

    Article  CAS  PubMed  Google Scholar 

  44. Lopaschuk GD, Ussher JR, Folmes CDL, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010;90:207–58.

    Article  CAS  PubMed  Google Scholar 

  45. de las Fuentes L, Herrero P, Peterson LR, Kelly DP, Gropler RJ, Dávila-Román VG. Myocardial fatty acid metabolism: Independent predictor of left ventricular mass in hypertensive heart disease. Hypertension. 2003;41:83–7.

    Article  Google Scholar 

  46. Stühlinger MC, Tsao PS, Her J-H, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway. Circulation. 2001;104:2569–75.

    Article  PubMed  Google Scholar 

  47. Yang R, Dong J, Zhao H, Li H, Guo H, Wang S, et al. Association of branched-chain amino acids with carotid intima-media thickness and coronary artery disease risk factors. PLoS One. 2014;9:e99598.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kauko A, Palmu J, Jousilahti P, Havulinna A, Salomaa V, Niiranen T. Associations between circulating metabolites and arterial stiffness. J Hum Hypertens. 2021;35:809–11.

    Article  PubMed  Google Scholar 

  49. Hänninen M-RA, Niiranen TJ, Puukka PJ, Kesäniemi YA, Kähönen M, Jula AM. Target organ damage and masked hypertension in the general population: the Finn-Home study. J Hypertens. 2013;31:1136–43.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to all individuals who voluntarily participated in the SABPA and African-PREDICT studies. The dedication of the support and research staff as well as students at the Hypertension Research and Training Clinic at the North-West University are also duly acknowledged. The SABPA study would not have been possible without collaboration with the Department of Education, North-West Province, South Africa. Images were obtained from Servier Medical Art (smart.servier.com).

Funding

With regard to the African-PREDICT study, the research funded in this manuscript is part of an ongoing larger research project financially supported by the South African Medical Research Council (SAMRC) with funds from National Treasury under its Economic Competitiveness and Support Package; the South African Research Chairs Initiative (SARChI) of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (GUN 86895); SAMRC with funds received from the South African National Department of Health, GlaxoSmithKline R&D (Africa Non-Communicable Disease Open Lab grant), the UK Medical Research Council and with funds from the UK Government’s Newton Fund; and corporate social investment grants from Pfizer (South Africa), Boehringer-Ingelheim (South Africa), Novartis (South Africa), the Medi Clinic Hospital Group (South Africa) and in-kind contributions of Roche Diagnostics (South Africa). Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors, and therefore, the NRF does not accept any liability in this regard. The SABPA study was supported by the National Research Foundation, South Africa; the North-West University, Potchefstroom, South Africa; and the Metabolic Syndrome Institute, France.

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Correspondence to Carina Mels.

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Strauss-Kruger, M., Kruger, R., Jansen Van Vuren, E. et al. Identifying a metabolomics profile associated with masked hypertension in two independent cohorts: Data from the African-PREDICT and SABPA studies. Hypertens Res 45, 1781–1793 (2022). https://doi.org/10.1038/s41440-022-01010-2

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