Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Association of homocysteine with carotid atherosclerosis in hypertension

Abstract

Information on the association between homocysteine (HCY) levels and carotid atherosclerosis (CAS) in hypertension (HTN) is limited. A cross-sectional study was performed to examine the relationship of plasma HCY concentration with CAS in 1700 hypertensives (61.62 ± 12.16 year). The prevalence of CAS and carotid intima–media thickness (CIMT) progressively increased across quartiles of HCY levels (P < 0.001). Correlation analysis showed significantly positive correlation between HCY and CAS (r = 0.261, P < 0.001). In a logistic regression, HCY independently predicted the presence of CAS (OR 1.284, 95% CI 1.163–1.418). Further investigation revealed that interaction effect of HCY was substantial for gender (P for interaction 0.023), age (P for interaction <0.001) and smoking (P for interaction 0.025) on CAS. Thus, in hypertensives, those of male, aged ≥55 year and current smokers, in which HCY ≥ 13.49 μmol/L were more likely to suffer CAS, suggesting a role of HCY in the development and progression of CAS in these patients, and HCY determination should be recommended to better stratify the cardiovascular risk.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Flow chart of study selection.
Fig. 2: Percentage of CIMT grade stratified by quartile of HCY in HTN.

References

  1. Baszczuk A, Musialik K, Kopczyński J, Thielemann A, Kopczyński Z, Kęsy L, et al. Hyperhomocysteinemia, lipid and lipoprotein disturbances in patients with primary hypertension. Adv Med Sci. 2014;59:68–73.

    PubMed  Google Scholar 

  2. Ramasamy K, Mishra C. Commentary: role of hyperhomocysteinemia in proliferative diabetic retinopathy: a case-control study. Indian J Ophthalmol. 2018;66:1440.

    PubMed  PubMed Central  Google Scholar 

  3. McCully KS. Homocysteine and the pathogenesis of atherosclerosis. Expert Rev Clin Pharm. 2015;8:211–9.

    CAS  Google Scholar 

  4. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288:2015–22.

    Google Scholar 

  5. China Hypertension Prevention and Control Guidelines Revision Committee. China Guidelines for Prevention and Treatment of Hypertension 2010[J]. Chin J Hypertens. 2011;19:701–43.

    Google Scholar 

  6. Lim U, Cassano PA. Homocysteine and blood pressure in the Third National Health and Nutrition Examination Survey, 1988–1994[J]. Am J Epidemiol. 2002;156:1105–13.

    PubMed  Google Scholar 

  7. Tsai MY, Arnett DK, Eckfeldt JH, Williams RR, Ellison RC. Plasma homocysteine and its association with carotid intimal-medial wall thickness and prevalent coronary heart disease: NHLBI family heart study[J]. Atherosclerosis. 2000;151:519–24.

    CAS  PubMed  Google Scholar 

  8. Dietrich M, Jacques PF, Polak JF, Keyes MJ, Pencina MJ, Evans JC, et al. Segment-specific association between plasma homocysteine level and carotid artery intima-media thickness in the Framingham Offspring Study[J]. J Stroke Cerebrovasc Dis. 2011;20:155–61.

    PubMed  Google Scholar 

  9. Rundek T, Blanton SH, Bartels S, Dong C, Raval A, Demmer RT, et al. Traditional risk factors are not major contributors to the variance in carotid intima-media thickness[J]. Stroke. 2013;44:2101–8.

    PubMed  PubMed Central  Google Scholar 

  10. Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. International Society of Hypertension global hypertension practice guidelines. J Hypertens. 2020;38:982–1004.

    CAS  PubMed  Google Scholar 

  11. Lu JM, Endocrinology DO, Hospital PG. Updated key points of 2013 China guideline for type 2 diabetes. Chin J Diabetes. 2014;6:447–98.

    Google Scholar 

  12. Wang T, Xu G, Cai X, Gong J, Xie Q, Xie L. Association of homocysteine with carotid-femoral pulse wave velocity in a southern Chinese population. Aging. 2019;11:9709–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the european society of cardiology (ESC). Eur Heart J. 2007;28:1462–536.

    PubMed  Google Scholar 

  14. Kuo F, Gardener H, Dong C, Cabral D, Della-Morte D, Blanton SH, et al. Traditional cardiovascular risk factors explain the minority of the variability in carotid plaque. Stroke. 2012;43:1755–60.

    PubMed  PubMed Central  Google Scholar 

  15. Holmes MV, Newcombe P, Hubacek JA, Sofat R, Ricketts SL, Cooper J, et al. MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA. 2002;288:2023–31.

    Google Scholar 

  16. Nahid A, Morteza F, Abdohamid S. Evaluation of homocysteine level as a risk facor among patients with ischemic stroke and its subtypes. Iran J Med Sci. 2013;38:233–9.

    Google Scholar 

  17. Kong X, Huang X, Zhao M, Xu B, Xu R, Song Y, et al. Platelet count affects efficacy of folic acid in preventing first stroke. J Am Coll Cardiol. 2018;71:2136–46.

    CAS  PubMed  Google Scholar 

  18. Willeit K, Pechlaner R, Egger G, Weger S, Oberhollenzer M, Willeit J, et al. Carotid atherosclerosis and incident atrial fibrillation. Arterioscler Thromb Vasc Biol. 2013;33:2660–5.

    CAS  PubMed  Google Scholar 

  19. Duschek N, Ghai S, Sejkic F, Falkensammer J, Skrinjar E, Huber K, et al. Homocysteine improves risk stratification in patients undergoing endarterectomy for asymptomatic internal carotid artery stenosis. Stroke. 2013;44:2311–4.

    CAS  PubMed  Google Scholar 

  20. Bogdanski P, Miller-Kasprzak E, Pupek-Musialik D, Jablecka A, Lacinski M, Jagodzinski PP, et al. Plasma total homocysteine is a determinant of carotid intimamedia thickness and circulating endothelial progenitor cells in patients with newly diagnosed hypertension. Clin Chem Lab Med. 2012;50:1107–13.

    CAS  PubMed  Google Scholar 

  21. Okura T, Miyoshi K, Irita J, Enomoto D, Nagao T, Kukida M, et al. Hyperomocysteinemia is one of the risk factors associated with cerebrovascular stiffness in hypertensive patients, especially elderly males. Sci Rep. 2014;4:5663.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Catena C, Colussi G, Url-Michitsch M, Nait F, Sechi LA. Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension. J Am Soc Hypertens. 2015;9:167–75.

    CAS  PubMed  Google Scholar 

  23. Yang X, Zhou Y, Liu C, Gao X, Wang A, Guo Y, et al. Homocysteine and carotid plaque stability: a crosssectional study in Chinese adults. PLoS ONE. 2014;9:e94935.

    PubMed  PubMed Central  Google Scholar 

  24. Polak JF, Szklo M, Kronmal RA, Burke GL, Shea S, Zavodni AE, et al. The value of carotid artery plaque and intima-media thickness for incident cardiovascular disease: the multi-ethnic study of atherosclerosis. J Am Heart Assoc. 2013;2:e000087.

    PubMed  PubMed Central  Google Scholar 

  25. Polak JF, Pencina MJ, Meisner A, Pencina KM, Brown LS, Wolf PA, et al. Associations of carotid artery intima-media thickness (IMT) with risk factors and prevalence of cardiovascular disease: comparison of mean common artery IMT with maximum internal carotid artery IMT. J Ultrasound Med. 2010;29:1759–68.

    PubMed  PubMed Central  Google Scholar 

  26. Stangl V, Günther C, Jarrin A, Bramlage P, Moobed M, Staudt A, et al. Homocysteine inhibits TNF-alpha induced endothelial adhesion molecule expression and monocyte adhesion via nuclear factor-kappaB dependent pathway[J]. Biochem Biophys Res Commun. 2001;280:1093–100.

    CAS  PubMed  Google Scholar 

  27. Fryer RH, Wilson BD, Gubler DB, Fitzgerald LA, Rodgers GM. Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells[J]. Arterioscler Thromb. 1993;13:1327–33.

    CAS  PubMed  Google Scholar 

  28. Koohpeyma H, Goudarzi I, Elahdadi SM, Lashkarbolouki T, Shabani M. Postnatal administration of homocysteine induces cerebellar damage in rats: protective effect of folic acid. Neurotox Res. 2019;35:724–38.

    CAS  PubMed  Google Scholar 

  29. Ma SC, Zhang HP, Jiao Y, Wang YH, Zhang H, Yang XL, et al. Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by resveratrol. Mol Med Rep. 2018;17:5312–9.

    CAS  PubMed  Google Scholar 

  30. Xu R, Huang F, Wang Y, Liu Q, Lv Y, Zhang Q. Gender-and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China. Sci Rep. 2020;10:17401.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Cohen E, Margalit I, Shochat T, Goldberg E, Krause I. Gender differences in homocysteine concentrations, a population-based cross-sectional study. Nutr Metab Cardiovasc Dis. 2019;29:9–14.

    CAS  PubMed  Google Scholar 

  32. Saito M, Marumo K. The effects of homocysteine on the skeleton. Curr Osteoporos Rep. 2018;16:554–60.

    PubMed  Google Scholar 

  33. Proctor DN, O’ Brien PC, Atkinson EJ, Nair KS. Comparison of techniques to estimate total body skeletal muscle mass in people of different age groups. Am J Phys. 1999;277:489–95.

    Google Scholar 

  34. Graham MR, Grace FM, Boobier W, Hullin D, Kicman A, Cowan D, et al. Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse. Br J Sports Med. 2006;40:644–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Hak AE, Polderman KH, Westendorp ICD, Jakobs C, Hofman A, Witteman JCM, et al. Increased plasma homocysteine after menopause. Atherosclerosis. 2000;149:163–8.

    CAS  PubMed  Google Scholar 

  36. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409.

    PubMed  Google Scholar 

  37. Keller AC, Klawitter J, Hildreth KL, Christians U, Putnam K, Kohrt WM, et al. Elevated plasma homocysteine and cysteine are associated with endothelial dysfunction across menopausal stages in healthy women. J Appl Physiol. 2019;126:1533–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Tian J, Gu X, Sun Y, Ban X, Xiao Y, Hu S, et al. Effect of statin therapy on the progression of coronary atherosclerosis. BMC Cardiovasc Disord. 2012;12:70.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Noda H, Iso H, Irie F, Sairenchi T, Ohtaka E, Ohta H. Gender difference of association between LDL cholesterol concentrations and mortality from coronary heart disease amongst Japanese: the Ibaraki Prefectural Health Study. J Intern Med. 2010;267:576–87.

    CAS  PubMed  Google Scholar 

  40. Chen S, Wu P, Zhou L, Shen Y, Li Y, Song H. Relationship between increase of serum homocysteine caused by smoking and oxidative damage in elderly patients with cardiovascular disease. Int J Clin Exp Med. 2015;8:4446–54.

    PubMed  PubMed Central  Google Scholar 

  41. Singh D. Effect of cigarette smoking on serum homocysteine and vitamin B12 level in male population of Udaipur. Biochem Anal Biochem. 2016;5:3.

    Google Scholar 

Download references

Acknowledgements

The authors thank the participants and participating physicians from The First Affiliated Hospital of Fujian Medical University, China.

Funding

This work was supported by National Natural Science Foundation of China [Grant Number: 82170355].

Author information

Authors and Affiliations

Authors

Contributions

Ai Chen and Liangdi Xie participated in the conception and design of this work. Ai Chen and Weibin Wu collected the clinical data. Ai Chen and Jin Gong contributed to the data analysis and interpretation. Guoyan Xu and Ying Han provided with the study materials and patients. Liangdi Xie revised and provided critical comments. All authors approved the manuscript

Corresponding author

Correspondence to Liangdi Xie.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Our study was in accordance with the ethical standards formulated in the Helsinki Declaration, and the protocol was approved by Branch for Medical Research and Clinical Technology Application, Ethics Committee of the First Affiliated Hospital of Fujian Medical University (IEC-FOM-013-2.0). Informed consent was obtained from all patients involved.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, A., Wu, W., Gong, J. et al. Association of homocysteine with carotid atherosclerosis in hypertension. J Hum Hypertens (2022). https://doi.org/10.1038/s41371-022-00665-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41371-022-00665-1

Search

Quick links