Integrated Dynamics of Oxidative Stress, Atherogenic Lipids, and Vascular Inflammation in Early-Stage Hypertensive Patients
DOI:
https://doi.org/10.64229/rs10p547Keywords:
Hypertension, Adolescents, Metabolic profile, Dyslipidemia, Inflammatory markersAbstract
Background: Hypertension (HTN) in young adults is increasingly prevalent and frequently accompanied by subclinical metabolic and vascular abnormalities that predispose affected individuals to future cardiovascular disease. Oxidative stress, dyslipidemia, endothelial dysfunction, and low-grade inflammation are central to early hypertensive (HTN) pathophysiology, yet their interactions remain incompletely characterized. Methods: This cross-sectional case-control study included 110 HTN and 60 normotensive (NORM) participants aged 20-45 years recruited from tertiary hospitals in Ekiti State, Nigeria. Sociodemographic, anthropometric, and clinical data were collected. Circulating biomarkers of oxidative stress, antioxidant defense, endothelial function, inflammation, purine metabolism, insulin regulation, and lipid profile were measured using colorimetric and ELISA methods. Appropriate parametric and non-parametric statistical analyses were applied. Results: HTN participants exhibited significantly higher systolic and diastolic blood pressure (DBP), body weight, and body mass index (BMI) compared with controls (P<0.01). They showed marked oxidative stress and endothelial dysfunction, evidenced by reduced heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS), alongside elevated xanthine oxidase (XO), uric acid, iron, adenosine deaminase (ADA), vascular endothelial growth factor (VEGF), and plasminogen activator inhibitor-1 (P<0.00001). An atherogenic lipid profile was observed, including higher total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and TC/HDL ratio, with reduced high-density lipoprotein (HDL) (P<0.00001). Circulating insulin levels were higher in HTN participants compared with NORM controls, consistent with insulin resistance. Correlation analyses revealed predominantly weak and non-significant associations between HO-1 and individual biomarkers. Conclusions: Early-stage HTN in young adults is characterized by coexisting oxidative stress, dyslipidemia, endothelial dysfunction, elevated insulin, metabolic dysregulation, and vascular inflammation, underscoring the need for early, integrative preventive strategies.
References
[1]McEvoy JW, McCarthy CP, Bruno RM, Brouwers S, Canavan MD, Ceconi C, et al. 2024 ESC guidelines for the management of elevated blood pressure and hypertension. European Heart Journal, 2024, 45(38), 3912-4018. DOI: 10.1093/eurheartj/ehae178
[2]Chen N, Fan F, Geng J, Yang Y, Gao Y, Jin H, et al. Evaluating the risk of hypertension in residents in primary care in Shanghai, China with machine learning algorithms. Frontiers in Public Health, 2022, 10, 984621. DOI: 10.3389/fpubh.2022.984621
[3]Zhang M, Xia X, Wang Q, Pan Y, Zhang GY, Wang Z. Application of machine learning algorithms in predicting new onset hypertension: a study based on the China Health and Nutrition Survey. Environmental Health and Preventive Medicine, 2025, 30, 3. DOI: 10.1265/ehpm.24-00270
[4]AlKaabi LA, Ahmed LS, Attiyah MFA, Abdel-Rahman ME. Predicting hypertension using machine learning: Findings from Qatar Biobank Study. PLoS One, 2020, 15(10), e0240370. DOI: 10.1371/journal.pone.0240370
[5]Ranadive SM, Dillon GA, Mascone SE, Alexander LM. Vascular health triad in humans with hypertension not the usual suspects. Frontiers in Physiology, 2021, 12, 746278. DOI: 10.3389/fphys.2021.746278
[6]Chai SS, Goh KL, Cheah WL, Chang YHR, Ng GW. Hypertension prediction in adolescents using anthropometric measurements: Do machine learning models perform equally well? Applied Sciences, 2022, 12(3), 1600. DOI: 10.3390/app12031600
[7]Krzemińska J, Wronka M, Młynarska E, Franczyk B, Rysz J. Arterial hypertension oxidative stress and inflammation. Antioxidants, 2022, 11(1): 172. DOI: 10.3390/antiox11010172
[8]Amponsah-Offeh M, Diaba‐Nuhoho P, Speier S, Morawietz H. Oxidative stress, antioxidants and hypertension. Antioxidants, 2023, 12(2), 281. DOI: 10.3390/antiox12020281
[9]Aboukhater D, Morad B, Nasrallah N, Nasser SA, Sahebkar A, Kobeissy F, et al. Inflammation and hypertension: Underlying mechanisms and emerging understandings. Journal of Cellular Physiology, 2023, 238(6), 1148-1159. DOI: 10.1002/jcp.31019
[10]Islam MM, Alam MJ, Maniruzzaman M, Ahmed NAMF, Ali MS, Rahman MJ, et al. Predicting the risk of hypertension using machine learning algorithms: A cross sectional study in Ethiopia. PLoS One, 2023, 18(8), e0289613. DOI: 10.1371/journal.pone.0289613
[11]Jeong E, Yun D, Baek Y, Kim H, Lee HG. Antihypertensive effects of the combined extract of Sorghum bicolor, Vigna angularis, and Eleusine coracana in spontaneously hypertensive rats. Scientific Reports, 2024, 14(1), 803. DOI: 10.1038/s41598-024-51364-5
[12]Kario K, Okura A, Hoshide S, Mogi M The WHO Global report 2023 on hypertension warning the emerging hypertension burden in globe and its treatment strategy. Hypertension Research, 2024, 47(5), 1099-1102. DOI: 10.1038/s41440-024-01622-w
[13]Caminiti R, Carresi C, Mollace R, Macrì R, Scarano F, Oppedisano F, et al. The potential effect of natural antioxidants on endothelial dysfunction associated with arterial hypertension. Frontiers in Cardiovascular Medicine, 2024, 11, 1345218. DOI: 10.3389/fcvm.2024.1345218
[14]Tanase DM, Apostol AG, Costea CF, Tarniceriu CC, Tudorancea I, Maranduca MA, et al. Oxidative stress in arterial hypertension (HTN): The nuclear factor erythroid factor 2-related factor 2 (Nrf2) pathway, implications and future perspectives. Pharmaceutics, 2022, 14(3), 534. DOI: 10.3390/pharmaceutics14030534
[15]Rahut DB, Mishra R, Sonobe T, Timilsina RR. Prevalence of prehypertension and hypertension among the adults in South Asia: A multinomial logit model. Frontiers in Public Health, 2023, 10, 1006457. DOI: 10.3389/fpubh.2022.1006457
[16]Olalekan SO, Okwute PG, Osonuga IO, Adegbesan BO, Ezima EN, Adeyemi IM. Clinical relevance of nutraceuticals in hypertension management: mechanisms, efficacy, and integration into therapeutic protocols. Bulletin of the National Research Centre, 2025, 49(1), 35. DOI: 10.1186/s42269-025-01329-z
[17]Goorani S, Zangene S, Imig JD. Hypertension: A continuing public healthcare issue. International Journal of Molecular Sciences, 2024, 26(1), 123. DOI: 10.3390/ijms26010123
[18]Nguyen BA, Alexander MR, Harrison DG. Immune mechanisms in the pathophysiology of hypertension. Nature Reviews Nephrology, 2024, 20(8), 530. DOI:10.1038/s41581-024-00838-w
[19]Camargo LL, Rios FJ, Montezano AC, Touyz RM. Reactive oxygen species in hypertension. Nature Reviews Cardiology, 2025, 22, 20-37. DOI: 10.1038/s41569-024-01062-6
[20]Aboukhater D, Morad B, Nasrallah N, Nasser SA, Sahebkar A, Kobeissy F, et al. Inflammation and hypertension: Underlying mechanisms and emerging understandings. Journal of Cellular Physiology. 2023, 238(6), 1148-1159. DOI: 10.1002/jcp.31019
[21]Amponsah-Offeh M, Diaba-Nuhoho P, Speier S, Morawietz H. Oxidative stress, antioxidants and hypertension. Antioxidants, 2023, 12(2), 281. DOI: 10.3390/antiox12020281
[22]Dabrowska E, Narkiewicz K. Hypertension and dyslipidemia: The two partners in endothelium-related crime. Current Atherosclerosis Reports, 2023, 25(9), 605-612. DOI: 10.1007/s11883-023-01132-z
[23]Guzik TJ, Nosalski R, Maffia P, Drummond GR. Immune and inflammatory mechanisms in hypertension. Nature Reviews Cardiology, 2024, 21(6), 396-416. DOI: 10.1038/s41569-023-00964-1
[24]Zhang Z, Zhao L, Zhou X, Meng X, Zhou X. Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets. Frontiers in Immunology, 2023, 13, 1098725. DOI: 10.3389/fimmu.2022.1098725
[25]Durante A, Mazzapicchi A, Baiardo Redaelli M. Systemic and cardiac microvascular dysfunction in hypertension. International Journal of Molecular Sciences, 2024, 25(24), 13294. DOI: 10.3390/ijms252413294
[26]Arendshorst WJ, Vendrov AE, Kumar N, Ganesh SK, Madamanchi NR. Oxidative stress in kidney injury and hypertension. Antioxidants, 2024, 13(12), 1454. DOI: 10.3390/antiox13121454
[27]Hao XM, Liu Y, Hailaiti D, Gong Y, Zhang XD, Yue BN, et al. Mechanisms of inflammation modulation by different immune cells in hypertensive nephropathy. Frontiers in Immunology, 2024, 15, 1333170. DOI: 10.3389/fimmu.2024.1333170
[28]Chen Y, Lv T, Lin W, Meng T, Sui Y, Chen S. J-shaped association of neutrophil-to-lymphocyte ratio with all-cause and cardiovascular mortality in stroke survivors. Frontiers in Neurology, 2025, 16, 1473802. DOI: 10.3389/fneur.2025.1473802
[29]Liu M, Chen R, Zheng Z, Xu S, Hou C, Ding Y, et al. Mechanisms of inflammatory microenvironment formation in cardiometabolic diseases: molecular and cellular perspectives. Frontiers in Cardiovascular Medicine, 2025, 11, 1529903. DOI: 10.3389/fcvm.2024.1529903
[30]Mroz T, Griffin M, Cartabuke R, Laffin L, Russo-Alvarez G, Thomas G, et al. Predicting hypertension control using machine learning. PLoS One, 2024, 19(3), e0299932. DOI: 10.1371/journal.pone.0299932
[31]Zhang M, Xia X, Wang Q, Pan Y, Zhang G, Wang Z. Application of machine learning algorithms in predicting new onset hypertension: China health and nutrition survey. Environmental Health and Preventive Medicine, 2025, 30, 3. DOI: 10.1265/ehpm.24-00270
[32]Mantovani A, Garlanda C. Humoral innate immunity and acute-phase proteins. The New England Journal of Medicine, 2023, 388(5), 439-452. DOI: 10.1056/NEJMra2206346
[33]Rios FJ, de Ciuceis C, Georgiopoulos G, Lazaridis A, Nosalski R, Pavlidis G, et al. Mechanisms of vascular inflammation and potential therapeutic targets: ESH position paper on small arteries. Hypertension, 2024, 81(6), 1218-1232. DOI: 10.1161/HYPERTENSIONAHA.123.22483
[34]Rahut DB, Mishra R, Sonobe T, Timilsina RR. Prevalence of prehypertension and hypertension among the adults in South Asia: A multinomial logit model. Frontiers in Public Health, 2023, 10, 1006457. DOI: 10.3389/fpubh.2022.1006457
[35]Musilanga N, Nasib H, Mwakibolwa A, Jackson G, Nhanga C, Kijusya K. Burden and determinants of self-reported high blood pressure among women of reproductive age in Tanzania: Evidence from 2022 Tanzania demographic and health survey. PLoS One, 2025, 20(2), e0314901. DOI: 10.1371/journal.pone.0314901
[36]Zhong X, Yu J, Jiang F, Chen H, Wang Z, Teng J, et al. A risk prediction model based on machine learning for early cognitive impairment in hypertension: Development and validation study. Frontiers in Public Health, 2023, 11, 1143019. DOI: 10.3389/fpubh.2023.1143019
[37]Mancusi C, Izzo R, di Gioia G, Losi MA, Barbato E, Morisco C. Insulin resistance the hinge between hypertension and type 2 diabetes. High Blood Pressure & Cardiovascular Prevention, 2020, 27(6), 515-526. DOI: 10.1007/s40292-020-00408-8
[38]Sakr HF, Sirasanagandla SR, Das S, Bima A, Elsamanoudy AZ. Insulin resistance and hypertension: mechanisms involved and modifying factors for effective glucose control. Biomedicines, 2023, 11(8), 2271. DOI: 10.3390/biomedicines11082271
[39]Sinha S, Haque M. Insulin resistance is cheerfully hitched with hypertension. Life, 2022, 12(4), 564. DOI: 10.3390/life12040564
[40]Ranadive SM, Dillon GA, Mascone SE, Alexander LM. Vascular health triad in humans with hypertension not the usual suspects. Frontiers in Physiology, 2021, 12, 746278. DOI: 10.3389/fphys.2021.746278
[41]Chennupati R, Solga I, Wischmann P, Dahlmann P, Celik FG, Pacht D, et al. Chronic anemia is associated with systemic endothelial dysfunction. Frontiers in Cardiovascular Medicine, 2023, 10, 1099069. DOI: 10.3389/fcvm.2023.1099069
[42]Borghi C, Agnoletti D, Cicero AFG, Lurbe E, Virdis A. Uric acid and hypertension: a review of evidence and future perspectives for the management of cardiovascular risk. Hypertension, 2022, 79(9), 1927-1936. DOI: 10.1161/HYPERTENSIONAHA.122.17956
[43]An L, Wang Y, Liu L, Miao C, Xu L, Wang G, et al. High serum uric acid is a risk factor for arterial stiffness in a Chinese hypertensive population: a cohort study. Hypertension Research, 2024, 47(6), 1512-1522. DOI: 10.1038/s41440-024-01591-0
[44]Huang L, Liu Z, Zhang H, Li D, Li Z, Huang J, et al. The Association between serum lipid profile levels and hypertension grades: A Cross-sectional study at a health examination center. High Blood Pressure & Cardiovascular Prevention, 2025, 32(1), 87-98. DOI: 10.1007/s40292-024-00683-9
[45]Tassew WC, Woldie SS, Ferede YA, Zeleke AM, Nigussie A. Dyslipidemia and associated factors among hypertensive patients in Ethiopia: a systematic review and meta-analysis. BMC Cardiovasc Disord, 2025, 25(1), 367. DOI: 10.1186/s12872-025-04808-3
[46]Wang W, Li X, Lv D, Wu X, Xie F, Xie W, et al. Analyzing lipid profiles and dyslipidemia prevalence in hypertensive patients: a cross-sectional study from primary community health institutions. Frontiers in Medicine, 2024, 11, 1425414. DOI: 10.3389/fmed.2024.1425414
[47]O'Rourke SA, Shanley LC, Dunne A. The Nrf2-HO-1 system and inflammaging. Frontiers in Immunology, 2024, 15, 1457010. DOI: 10.3389/fimmu.2024.1457010
[48]Ryter SW. Heme oxygenase-1: An anti-inflammatory effector in cardiovascular, lung, and related metabolic disorders. Antioxidants, 2022, 11(3), 555. DOI: 10.3390/antiox11030555
[49]Kuwabara M, Ae R, Kosami K, Kanbay M, Andres-Hernando A, Hisatome I, et al. Current updates and future perspectives in uric acid research, 2024. Hypertension Research, 2024, 48(2), 867. DOI: 10.1038/s41440-024-02031-9
[50]Maruhashi T, Higashi Y. Is uric acid a causal risk factor of arterial stiffness in patients with hypertension? Hypertension Research, 2024, 47(6), 1570-1572. DOI: 10.1038/s41440-024-01637-3
[51]Hahn D, Shin SH, Bae J. Natural antioxidant and anti-inflammatory compounds in foodstuff or medicinal herbs inducing heme oxygenase-1 expression. Antioxidants, 2020, 9(12), 1191. DOI: 10.3390/antiox9121191
[52]Liu H, Liu K, Zhang K, Zong C, Yang H, Li Y, et al. Early neurological deterioration in patients with acute ischemic stroke: A prospective multicenter cohort study. Therapeutic Advances in Neurological Disorders, 2023, 16, 17562864221147743. DOI: 10.1177/17562864221147743
[53]Shrestha J, Limbu KR, Chhetri RB, Paudel KR, Hansbro PM, Oh YS, et al. Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1. International Journal of Biological Sciences, 2024, 20(12), 4888. DOI: 10.7150/ijbs.98846
[54]Chen W, Zhang Y, Chen J, Dong S, Wu X, Wu Y, et al. Heme oxygenase-1 modulates macrophage polarization through endothelial exosomal miR-184-3p and reduces sepsis-induce lung injury. International Journal of Nanomedicine, 2025, 20, 5039-5057. DOI: 10.2147/IJN.S506830
[55]Lianos EA, Detsika MG. Immune-related functions of heme oxygenase-1. Antioxidants, 2023, 12(7), 1322. DOI: 10.3390/antiox12071322
[56]Nitti M, Furfaro AL, Mann GE. Dependent bilirubin generation in vascular cells: A role in preventing endothelial dysfunction in local tissue microenvironment? Frontiers in Physiology, 2020, 11, 23. DOI: 10.3389/fphys.2020.00023
Downloads
Published
Issue
Section
License
Copyright (c) 2026 MUSA Maijidda Abubakar (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
