Skip to main content
Log in

Status of hyperhomocysteinemia in China: results from the China Stroke High-risk Population Screening Program, 2018

  • Research Article
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

A nationwide survey was conducted from October 2018 to September 2019 to assess the prevalence of hyperhomocysteinemia (Hhcy) and its influencing factors in China. A standardized questionnaire was used to collect information. Hhcy was defined as the level of serum homocysteine (HCY) ⩾ 15.0µmol/L. The H-type hypertension (HHYP) was defined as hypertension with an elevated serum HCY 15.0µmol/L). Finally, 110 551 residents ⩾ 40 years of age from 31 provinces in the mainland of China were included. Overall, the median serum HCY level was 10.9µmol/L (interquartile range 7.9–15.1). A total of 28 633 participants (25.9%) were defined as Hhcy. The Hhcy prevalence ranged from 7.9% in Shanghai to 56.8% in Tianjin. The data showed that serum HCY levels were associated with age, male gender, cigarette smoking, hypertension, diabetes, ethnicity, endurance in exercise (inverse), and fruit and vegetable intake (inverse). In addition, 15 486 participants were defined as HHYP, and the rate was 14.0%. HHYP was an independent predictor of stroke with an adjusted odds ratio of 1.752 (95% CI 1.338–2.105). The geographical distribution pattern of the Hhcy epidemic reflects dynamic differences, and national strategies should be carried out to further improve the care of patients with Hhcy across China.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. The GBD 2016 Lifetime Risk of Stroke Collaborators. Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016. N Engl J Med 2018; 379: 2429–2437

    Article  Google Scholar 

  2. Wu S, Wu B, Liu M, Chen Z, Wang W, Anderson CS, Sandercock P, Wang Y, Huang Y, Cui L, Pu C, Jia J, Zhang T, Liu X, Zhang S, Xie P, Fan D, Ji X, Wong KL, Wang L; China Stroke Study Collaboration. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol 2019; 18(4): 394–405

    Article  PubMed  Google Scholar 

  3. Wang W, Jiang B, Sun H, Ru X, Sun D, Wang L, Wang L, Jiang Y, Li Y, Wang Y, Chen Z, Wu S, Zhang Y, Wang D, Wang Y, Feigin VL; NESS-China Investigators. Prevalence, incidence, and mortality of stroke in China: results from a nationwide population-based survey of 480 687 adults. Circulation 2017; 135(8): 759–771

    Article  PubMed  Google Scholar 

  4. Chao BH, Yan F, Hua Y, Liu JM, Yang Y, Ji XM, Peng B, Zhao GG, Wang YJ, Kang DZ, Wang YL. Stroke prevention and control system in China: CSPPC-Stroke Program. Int J Stroke 2021; 16(3): 265–272

    Article  PubMed  Google Scholar 

  5. Wang Z, Chen Z, Zhang L, Wang X, Hao G, Zhang Z, Shao L, Tian Y, Dong Y, Zheng C, Wang J, Zhu M, Weintraub WS, Gao R; China Hypertension Survey Investigators. Status of hypertension in China: results from the China hypertension survey, 2012–2015. Circulation 2018; 137(22): 2344–2356

    Article  PubMed  Google Scholar 

  6. Lu J, Lu Y, Wang X, Li X, Linderman GC, Wu C, Cheng X, Mu L, Zhang H, Liu J, Su M, Zhao H, Spatz ES, Spertus JA, Masoudi FA, Krumholz HM, Jiang L. Prevalence, awareness, treatment, and control of hypertension in China: data from 1.7 million adults in a population-based screening study (China PEACE Million Persons Project). Lancet 2017; 390(10112): 2549–2558

    Article  PubMed  Google Scholar 

  7. Zheng L, Sun Z, Li J, Zhang R, Zhang X, Liu S, Li J, Xu C, Hu D, Sun Y. Pulse pressure and mean arterial pressure in relation to ischemic stroke among patients with uncontrolled hypertension in rural areas of China. Stroke 2008; 39(7): 1932–1937

    Article  PubMed  Google Scholar 

  8. Bundy JD, He J. Hypertension and related cardiovascular disease burden in China. Ann Glob Health 2016; 82(2): 227–233

    Article  PubMed  Google Scholar 

  9. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999; 354(9176): 407–413

    Article  CAS  PubMed  Google Scholar 

  10. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288 (16): 2015–2022

    Article  Google Scholar 

  11. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999; 19(1): 217–246

    Article  CAS  PubMed  Google Scholar 

  12. Refsum H, Ueland PM, Nygárd O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998; 49(1): 31–62

    Article  CAS  PubMed  Google Scholar 

  13. Yang B, Fan S, Zhi X, Wang Y, Wang Y, Zheng Q, Sun G. Prevalence of hyperhomocysteinemia in China: a systematic review and meta-analysis. Nutrients 2014; 7(1): 74–90

    Article  PubMed  PubMed Central  Google Scholar 

  14. Li Z, Guo X, Chen S, Zheng L, Yang H, Sun G, Yu S, Li W, Zhou L, Wang J, Hu W, Sun Y. Hyperhomocysteinemia independently associated with the risk of hypertension: a cross-sectional study from rural China. J Hum Hypertens 2016; 30(8): 508–512

    Article  CAS  PubMed  Google Scholar 

  15. van Beynum IM, Smeitink JA, den Heijer M, te Poele Pothoff MT, Blom HJ. Hyperhomocysteinemia: a risk factor for ischemic stroke in children. Circulation 1999; 99(16): 2070–2072

    Article  CAS  PubMed  Google Scholar 

  16. Zhang Y, Huo Y. Hypertension with elevated homocysteine—H-type hypertension. Adv Cardiovasc Dis 2011; 32: 3–6

    Google Scholar 

  17. Hu DY, Xu XP. Prevention of stroke relies on valid control “H” type hypertension. Chin J Intern Med (Zhonghua Nei Ke Za Zhi) 2008; 47(12): 976–977 (in Chinese)

    Google Scholar 

  18. Zhang Q, Qiu DX, Fu RL, Xu TF, Jing MJ, Zhang HS, Geng HH, Zheng LC, Wang PX. H-type hypertension and C reactive protein in recurrence of ischemic stroke. Int J Environ Res Public Health 2016; 13(5): 477

    Article  PubMed Central  Google Scholar 

  19. Guan T, Ma J, Li M, Xue T, Lan Z, Guo J, Shen Y, Chao B, Tian G, Zhang Q, Wang L, Liu Y. Rapid transitions in the epidemiology of stroke and its risk factors in China from 2002 to 2013. Neurology 2017; 89(1): 53–61

    Article  PubMed  Google Scholar 

  20. Jacobsen DW. Homocysteine and vitamins in cardiovascular disease. Clin Chem 1998; 44(8): 1833–1843

    Article  CAS  PubMed  Google Scholar 

  21. Zhang J, Liu Y, Wang A, Wang D, Jiang R, Jia J, Chen S, Zhao X. Association between H-type hypertension and asymptomatic extracranial artery stenosis. Sci Rep 2018; 8(1): 1328

    Article  PubMed  PubMed Central  Google Scholar 

  22. Cattaneo M. Hyperhomocysteinemia, atherosclerosis and thrombosis. Thromb Haemost 1999; 81(2): 165–176

    Article  CAS  PubMed  Google Scholar 

  23. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002; 325 (7374): 1202–1206

    Article  PubMed  PubMed Central  Google Scholar 

  24. Pang H, Han B, Fu Q, Hao L, Zong Z. Association between homocysteine and conventional predisposing factors on risk of stroke in patients with hypertension. Sci Rep 2018; 8(1): 3900

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang CY, Chen ZW, Zhang T, Liu J, Chen SH, Liu SY, Han LY, Hui ZH, Chen YM. Elevated plasma homocysteine level is associated with ischemic stroke in Chinese hypertensive patients. Eur J Intern Med 2014; 25(6): 538–544

    Article  CAS  PubMed  Google Scholar 

  26. Han L, Wu Q, Wang C, Hao Y, Zhao J, Zhang L, Fan R, Liu Y, Li R, Chen Z, Zhang T, Chen S, Ma J, Liu S, Peng X, Duan S. Homocysteine, ischemic stroke, and coronary heart disease in hypertensive patients: a population-based, prospective cohort study. Stroke 2015; 46(7): 1777–1786

    Article  CAS  PubMed  Google Scholar 

  27. Faraci FM, Lentz SR. Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke 2004; 35(2): 345–347

    Article  PubMed  Google Scholar 

  28. Austin RC, Lentz SR, Werstuck GH. Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differ 2004; 11(Suppl 1): S56–S64

    Article  CAS  PubMed  Google Scholar 

  29. Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, Tanji N, Ferran LJ Jr, Kohl B, Rao V, Kisiel W, Stern DM, Schmidt AM. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 2001; 107(6): 675–683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354(15): 1567–1577

    Article  CAS  PubMed  Google Scholar 

  31. Gao X, Bermudez OI, Tucker KL. Plasma C-reactive protein and homocysteine concentrations are related to frequent fruit and vegetable intake in Hispanic and non-Hispanic white elders. J Nutr 2004; 134(4): 913–918

    Article  CAS  PubMed  Google Scholar 

  32. Broekmans WM, Klöpping-Ketelaars IA, Schuurman CR, Verhagen H, van den Berg H, Kok FJ, van Poppel G. Fruits and vegetables increase plasma carotenoids and vitamins and decrease homocysteine in humans. J Nutr 2000; 130(6): 1578–1583

    Article  CAS  PubMed  Google Scholar 

  33. Chrysohoou C, Panagiotakos DB, Pitsavos C, Zeimbekis A, Zampelas A, Papademetriou L, Masoura C, Stefanadis C. The associations between smoking, physical activity, dietary habits and plasma homocysteine levels in cardiovascular disease-free people: the ‘ATTICA’ study. Vasc Med 2004; 9(2): 117–123

    Article  PubMed  Google Scholar 

  34. Alomari MA, Khabour OF, Gharaibeh MY, Qhatan RA. Effect of physical activity on levels of homocysteine, folate, and vitamin B12 in the elderly. Phys Sportsmed 2016; 44(1): 68–73

    Article  PubMed  Google Scholar 

  35. Dankner R, Chetrit A, Dror GK, Sela BA. Physical activity is inversely associated with total homocysteine levels, independent of C677T MTHFR genotype and plasma B vitamins. Age (Dordr) 2007; 29(4): 219–227

    Article  CAS  Google Scholar 

  36. Albert MA, Glynn RJ, Buring JE, Ridker PM. Relation between soluble intercellular adhesion molecule-1, homocysteine, and fibrinogen levels and race/ethnicity in women without cardiovascular disease. Am J Cardiol 2007; 99(9): 1246–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jacques PF, Rosenberg IH, Rogers G, Selhub J, Bowman BA, Gunter EW, Wright JD, Johnson CL. Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr 1999; 69(3): 482–489

    Article  CAS  PubMed  Google Scholar 

  38. Wang J, Zhang L, Wang F, Liu L, Wang H; China National Survey of Chronic Kidney Disease Working Group. Prevalence, awareness, treatment, and control of hypertension in China: results from a national survey. Am J Hypertens 2014; 27(11): 1355–1361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Qin X, Li J, Cui Y, Liu Z, Zhao Z, Ge J, Guan D, Hu J, Wang Y, Zhang F, Xu X, Wang X, Xu X, Huo Y. Effect of folic acid intervention on the change of serum folate level in hypertensive Chinese adults: do methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms affect therapeutic responses? Pharmacogenet Genomics 2012; 22(6): 421–428

    Article  CAS  PubMed  Google Scholar 

  40. Ma L, Li L, Tang Z. Epidemiological characteristics of hyperhomocysteinemia and H-type hypertension in the elderly in Beijing, China. Clin Exp Hypertens 2017; 39(7): 640–644

    Article  CAS  PubMed  Google Scholar 

  41. Chen Z, Wang F, Zheng Y, Zeng Q, Liu H. H-type hypertension is an important risk factor of carotid atherosclerotic plaques. Clin Exp Hypertens 2016; 38(5): 424–428

    Article  PubMed  Google Scholar 

  42. Li J, Jiang S, Zhang Y, Tang G, Wang Y, Mao G, Li Z, Xu X, Wang B, Huo Y. H-type hypertension and risk of stroke in chinese adults: a prospective, nested case-control study. J Transl Int Med 2015; 3(4): 171–178

    Article  PubMed  PubMed Central  Google Scholar 

  43. Li T, Liu X, Diao S, Kong Y, Duan X, Yang S, Liu S, Fang Q, Cai X. H-type hypertension is a risk factor for cerebral small-vessel disease. BioMed Res Int 2020; 2020: 6498903

    PubMed  PubMed Central  Google Scholar 

  44. Li T, Zhu J, Fang Q, Duan X, Zhang M, Diao S, Zhou Y, Yang S, Kong Y, Cai X. Association of H-type hypertension with stroke severity and prognosis. BioMed Res Int 2018; 2018: 8725908

    PubMed  PubMed Central  Google Scholar 

  45. Lu ZH, Li J, Li XL, Ding M, Mao CJ, Zhu XY, Liu CF. Hypertension with hyperhomocysteinemia increases the risk of early cognitive impairment after first-ever ischemic stroke. Eur Neurol 2019; 82(4–6): 75–85

    Article  CAS  PubMed  Google Scholar 

  46. Hu S, Ren L, Wang Y, Zhang R, Zhao X, Liu L, Li W, Wang Y. Homocysteine-lowering therapy and early functional outcomes of ischemic patients with H-type hypertension: a retrospective analysis of CNSR. Australas Phys Eng Sci Med 2015; 38(4): 785–791

    Article  PubMed  Google Scholar 

  47. Zhao M, Wang X, He M, Qin X, Tang G, Huo Y, Li J, Fu J, Huang X, Cheng X, Wang B, Hou FF, Sun N, Cai Y. Homocysteine and stroke risk: modifying effect of methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention. Stroke 2017; 48 (5): 1183–1190

    Article  CAS  PubMed  Google Scholar 

  48. Finkelstein JD, Martin JJ. Homocysteine. Int J Biochem Cell Biol 2000; 32(4): 385–389

    Article  CAS  PubMed  Google Scholar 

  49. Bissoli L, Di Francesco V, Ballarin A, Mandragona R, Trespidi R, Brocco G, Caruso B, Bosello O, Zamboni M. Effect of vegetarian diet on homocysteine levels. Ann Nutr Metab 2002; 46(2): 73–79

    Article  CAS  PubMed  Google Scholar 

  50. Appel LJ, Miller ER3rd, Jee SH, Stolzenberg-Solomon R, Lin PH, Erlinger T, Nadeau MR, Selhub J. Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study. Circulation 2000; 102(8): 852–857

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We express our gratitude to all the China Stroke Data Center Platform Hospitals that made this work possible. This study was supported by grants from the Special Plan of the Ministry of Science and Technology of the People’s Republic of China (No. Z135080000022), CAMS Innovation Fund for Medical Science (Nos. 2017-I2M-1-016 and 2019-I2M-2-006), Natural Science Foundation of Tianjin (No. 19JCYBJC26600), China Postdoctoral Science Foundation (Nos. 2019M660921 and 2020T130436), and Science Foundation for Post Doctorate Research of the Beijing (Nos. 2017-ZZ-123 and 2020-ZZ-005). The funding organizations had no role in the study’s design and concept; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xunming Ji or Longde Wang.

Additional information

Compliance with ethics guidelines

Wenjun Tu, Feng Yan, Baohua Chao, Xunming Ji, and Longde Wang declare no conflict of interest. The Ethics Committee of Capital Medical University Xuanwu Hospital approved the trial protocol according to the Declaration of Helsinki (1964). Written Informed consent was obtained from all participants before entering the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tu, W., Yan, F., Chao, B. et al. Status of hyperhomocysteinemia in China: results from the China Stroke High-risk Population Screening Program, 2018. Front. Med. 15, 903–912 (2021). https://doi.org/10.1007/s11684-021-0871-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-021-0871-4

Keywords

Navigation