Alterations in Serum Vanillylmandelic Acid Levels in patients With Hypertension: A Case-Control Study
Serum Vanillylmandelic Acid Levels
DOI:
https://doi.org/10.63939/j8gqak63Keywords:
VMA, Hypertension, Hyperlipidemia, Catecholamines, Obesity, AgeingAbstract
Background: The metabolic abnormalities and sympathetic activity are linked to hypertension. Catecholamine metabolism can be inferred indirectly from vanillylmandelic acid (VMA), which is the last metabolite of norepinephrine and epinephrine. However, it is unclear how serum VMA levels relate to antihypertensive medication, age, body weight, and hyperlipidemia in hypertensive individuals. Aim: The purpose of this study was to evaluate the connection between serum VMA levels and hyperlipidemia, age, body mass index, and antihypertensive medication in men with hypertension and healthy controls. Methods: Ninety men between the ages of thirty and fifty-nine were recruited from Al-Sader Teaching Hospital in Najaf to participate in case-control research. Of them, sixty had hypertension and thirty appeared healthy. The presence or absence of hyperlipidemia, treatment status (newly diagnosed or on antihypertensive medication), and body mass index were used to further categorize the hypertensive subjects. ELISA was used to measure the levels of serum VMA. The t-test and one-way analysis of variance (ANOVA) were used to compare groups; p < 0.05 was deemed statistically significant. Results: Compared to healthy controls, hypertension patients had considerably higher serum VMA levels (p < 0.0001). VMA concentrations were highest in hypertensive patients who also had hyperlipidemia, and they increased with age. VMA levels were higher in newly diagnosed individuals than in those on antihypertensive medication. Furthermore, serum VMA levels rose gradually in all BMI groups, with obese individuals showing the highest levels. Conclusions: Increased sympathetic activity and altered catecholamine metabolism may be the cause of elevated blood VMA levels in hypertensive men, especially those with hyperlipidemia, obesity, advanced age, and recently diagnosed hypertension. More longitudinal investigations are required to confirm the clinical importance of serum VMA as a possible measure of cardiometabolic risk in hypertension.
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References
1. World Health Organization. Global report on hypertension 2025: high stakes—turning evidence into action. Geneva: World Health Organization; 2025.
2. Swarup S, Ahmed I, Grigorova Y, Zeltser R. Metabolic syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
3. Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med. 2003;139(9):761-776.
4. Saxena T, Ali AO, Saxena M. Pathophysiology of essential hypertension: an update. Expert Rev Cardiovasc Ther. 2018;16(12):879-887.
5. Seravalle G, Grassi G. Sympathetic nervous system and hypertension: new evidences. Auton Neurosci. 2022;238:102954.
6. Berends AMA, Eisenhofer G, Fishbein L, van der Horst-Schrivers ANA, Kema IP, Links TP, et al. Intricacies of the molecular machinery of catecholamine biosynthesis and secretion by chromaffin cells of the normal adrenal medulla and in pheochromocytoma and paraganglioma. Cancers (Basel). 2019;11(8):1121.
7. Abd-Allah NM, Hassan FH, Esmat AY, Hammad SA. Age dependence of the levels of plasma norepinephrine, aldosterone, renin activity and urinary vanillylmandelic acid in normal and essential hypertensives. Biol Res. 2004;37(1):95-106.
8. Bima C, Lopez C, Tuli G, Munarin J, Maccario M, De Sanctis L. Prevention and management of hypertensive crises in children with pheochromocytoma and paraganglioma. Front Endocrinol (Lausanne). 2024;15:1460320. doi:10.3389/fendo.2024.1460320.
9. Engberink MF, Brink EJ, van Baak MA, Gans ROB, Navis G, Bakker SJL. Dietary protein, blood pressure and renal function in renal transplant recipients. Nutr Cardiovasc Health Ren Transplant Recipients. 2013;1:41.
10. Willows JW, Blaszkiewicz M, Townsend KL. The sympathetic innervation of adipose tissues: regulation, functions, and plasticity. Compr Physiol. 2023;13:4985-5021.
11. Clayton TL, Fitch A, Bays HE. Obesity and hypertension: Obesity Medicine Association (OMA) clinical practice statement (CPS) 2023. Obes Pillars. 2023;8:100083.
12. Bigalke JA, Young BE, Cleveland EL, Fadel PJ, Carter JR. Aging and sympathetic transduction to blood pressure in humans: methodological and physiological considerations. Am J Physiol Heart Circ Physiol. 2024;326(1):H148-H157.
13. Parati G, Amir A, Refaat Abd El Meguid K, Sabbour H, Centonze C, Tsabedze N, et al. Managing the patient with hypertension and elevated heart rate in the routine care setting: expert opinion and narrative review. Curr Med Res Opin. 2026;42(6):1093-1111. doi:10.1080/03007995.2026.2682073.
14. Kamal S, Lappin SL. Biochemistry, catecholamine degradation. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545235/
15. Grassi G, Drager LF. Sympathetic overactivity, hypertension and cardiovascular disease: state of the art. Curr Med Res Opin. 2024;40(Suppl 1):5-13.
16. Shantsila A, et al. Influence of age on respiratory modulation of muscle sympathetic nerve activity, blood pressure and baroreflex function in humans. Exp Physiol. 2015;100(9):1039-1051.
17. D'Souza AW, Klassen SA, Badrov MB, Lalande S, Shoemaker JK. Aging is associated with enhanced central but impaired peripheral arms of the sympathetic baroreflex arc. J Appl Physiol (1985). 2022;133(2):349-360. doi:10.1152/japplphysiol.00045.2022.
18. Ahmadian M, et al. Fatty acids promote uncoupled respiration via ATP/ADP carriers in white adipocytes. Nat Metab. 2026;8(3):572-586.
19. Jiang M, Stifel U, Blüher M, Lefebvre H, Bornstein SR, Bechmann N. Adrenal-adipose tissue crosstalk in health and disease. Eur J Endocrinol. 2025;193(6):R83-R96. doi:10.1093/ejendo/lvaf252.
20. Khalil H, Zeltser R. Antihypertensive medications. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
21. Park J, Hamanaka A, Park I, Abdelhady HG. Chronic β-blockade and systemic homeostasis: molecular integration of cardiorenal and immune pathways, a narrative review. Biomolecules. 2025;15(12):1653. doi:10.3390/biom15121653.
22. Pongwattanapakin K, Care C, Sitticharoon C, Wilasrusmee KT, Keadkraichaiwat I, Maikaew P, et al. Interplay between key metabolic hormones, metabolic factors, renal function, and heart rate variability in humans with obesity. Sci Rep. 2025;15(1):37873. doi:10.1038/s41598-025-21757-1.
23. Patel M, Braun J, Lambert G, Kameneva T, Keatch C, Lambert E. Central mechanisms in sympathetic nervous dysregulation in obesity. J Neurophysiol. 2023;130:1414-1424. doi:10.1152/jn.00254.2023.
24. Evans LC, Dayton A, Osborn JW. Renal nerves in physiology, pathophysiology and interoception. Nat Rev Nephrol. 2025;21(1):57-69.

