Exploring metabolic and inflammatory abnormalities in rheumatoid arthritis patients developing stroke disease: a case-control study using electronic medical record data in northern China

  • Fangran Xin
  • Lingyu FuEmail author
  • Haina Liu
  • Yunwei Xu
  • Tingting Wei
  • Meng Chen
Original Article



Intend to investigate the roles of serum lipids, inflammatory markers, and serological status in rheumatoid arthritis and stroke patients by using case-control study.

Materials and methods

Clinical data were retrieved from the electronic medical record of the First Affiliated Hospital of China Medical University during January 2011 to March 2018. The obtained data were categorized into case groups and three control groups, in the ratios of 1:2, respectively, with all matching age and gender. Multinomial logistic regression analysis and restricted cubic spline were conducted examining the associations between serum lipids, inflammatory markers, serological status, and the risk of stroke among RA patients.


The present studies included 1057 study subjects. The elevated ESR, LDL-C levels, and much higher CRP levels ≥ 230 mg/L were independent risk factors for RA patients in developing stroke. Furthermore, we found that ESR and LDL-C levels could exhibit a linear association with the risk of comorbid stroke while CRP level had a nonlinearity association with stroke risk among RA patients.


A close monitoring is required for RA patients with dyslipidemia and elevated inflammatory markers, and the primary stroke preventive strategies should be directed against these risk factors.


Dyslipidemia Inflammatory marker Rheumatoid arthritis Serum lipids Stroke 



FRX analyzed and interpreted the data and drafted the manuscript. LYF designed the study. FRX, TTW, HNL, YWX and MC collected the data. LYF contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors have read and approved the final manuscript. FRX and LYF were the study guarantors.


This work was supported by grants from the Program of the National Natural Science Foundation of China (81673246).

Compliance with ethical standards



Supplementary material

10067_2019_4440_MOESM1_ESM.docx (36 kb)
ESM 1 (DOCX 35 kb)


  1. 1.
    Junbo Ge YX (2013) Internal Medicine. 8 ed. People’s Medical Publishing House, BeiJingGoogle Scholar
  2. 2.
    Zhanguo Li F (2009) Rheumatoid arthritis. 1 ed: People’s Medical Publishing HouseGoogle Scholar
  3. 3.
    Lévy LFB, Barnetche T, Schaeverbeke T (2008) Incidence and risk of fatal myocardial infarction and stroke events in rheumatoid arthritis patients: a systematic review of the literature. Clin Exp Rheumatol 26:67Google Scholar
  4. 4.
    Wiseman SJ, Ralston SH, Wardlaw JM (2016) Cerebrovascular disease in rheumatic diseases: a systematic review and meta-analysis. Stroke 47:4943–4950. Google Scholar
  5. 5.
    Mackey RH, Kuller LH, Deane KD, Walitt BT, Chang YF, Holers VM et al (2015) Rheumatoid arthritis, anti-cyclic citrullinated peptide positivity, and cardiovascular disease risk in the women’s health initiative. Arthritis Rheumatol 67:92311–92322.
  6. 6.
    Lindhardsen J, Gislason GH, Ahlehoff O, Madsen OR, Hansen PR.(2010) Increased risk of stroke and atrial fibrillation in rheumatoid arthritis - a nationwide cohort study. Eur Heart J 31156Google Scholar
  7. 7.
    Liou TH, Huang SW, Lin JW, Chang YS, Wu CW, Lin HW.(2014) Risk of stroke in patients with rheumatism: a nationwide longitudinal population-based study. Sci Rep.45110. doi:
  8. 8.
    Navarro-Millan I, Yang S, DuVall SL, Chen L, Baddley J, Cannon GW et al (2016) Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration. Ann Rheum Dis 75:2341–2347. CrossRefGoogle Scholar
  9. 9.
    Dursunoglu D, Evrengul H, Polat B, Tanriverdi H, Cobankara V, Kaftan A et al (2005) Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation. Rheumatol Int 25:4241–4245. CrossRefGoogle Scholar
  10. 10.
    Semb AG, Kvien TK, Aastveit AH, Jungner I, Pedersen TR, Walldius G et al (2010) Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study. Ann Rheum Dis 69:111996–112001. CrossRefGoogle Scholar
  11. 11.
    Zhang J, Chen L, Delzell E, Muntner P, Hillegass WB, Safford MM et al (2014) The association between inflammatory markers, serum lipids and the risk of cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 73:71301–71308. Google Scholar
  12. 12.
    Goodson NJ, Symmons DP, Scott DG (2005) Baseline levels of C reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year follow up study of a primary care-based inception cohort. Arthritis Rheum 52:2293–2299CrossRefGoogle Scholar
  13. 13.
    Huijun Sun TK, Ichikawa T, Hatakeyama K, Shiomi M, Zhang B, Kitajima S, Morimoto M, Watanabe T, Asada Y, Chen YE, Fan J (2005) C-reactive protein in atherosclerotic lesions: its origin and pathophysiological significance. Am J Pathol 167(4):1139–1148CrossRefGoogle Scholar
  14. 14.
    Arnett FC, Edworthy SM, Bloch DA (1988) The American Rheumatism Association 1987 Revised Criteria for the Classification of Rheumatoid Arthritis. Arthritis Rheum p. 315–24Google Scholar
  15. 15.
    Association CN.(2013) Diagnosis of various cerebrovascular diseases(1995). J Clin Exp Med 12:71Google Scholar
  16. 16.
    adults TjcopacoabliC (2012) Guidelines on Prevention and Treatment of Blood Lipid Abnormality in Chinese Adults. The joint committee on prevention and control of abnormal blood lipids in Chinese adultsGoogle Scholar
  17. 17.
    adults. TjcopacoabliC (2016) Guidelines on Prevention and Treatment of Blood Lipid Abnormality in Chinese Adults(2016 Revised). Guidelines and consensus. Chinese Circulation Journal: The joint committee on prevention and control of abnormal blood lipids in Chinese adultsGoogle Scholar
  18. 18.
    Wolfe F, Freundlich B, Straus WL (2003) Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. J Rheumatol 30:136–140Google Scholar
  19. 19.
    Ku IA, Imboden JB, Hsue PY, Ganz P (2009) Rheumatoid arthritis a model of systemic inflammation driving atherosclerosis. Circ J 73:6977–6985CrossRefGoogle Scholar
  20. 20.
    Nadareishvili Z, Michaud K, Hallenbeck JM, Wolfe F (2008) Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: a nested, case-control study. Arthritis Rheum 59:81090–81096. CrossRefGoogle Scholar
  21. 21.
    Liao KP, Liu J, Lu B, Solomon DH, Kim SC (2015) Association between lipid levels and major adverse cardiovascular events in rheumatoid arthritis compared to non-rheumatoid arthritis patients. Arthritis Rheum 67:82004–82010. Google Scholar
  22. 22.
    Myasoedova E, Crowson CS, Kremers HM, Roger VL, Fitz-Gibbon PD, Therneau TM et al (2011) Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis 70:3482–3487. CrossRefGoogle Scholar
  23. 23.
    Jurcut C, Jurcut R, Tanasescu C (2004) Cardiovascular risk and rheumatoid arthritis: from mechanisms of atherosclerosis to therapeutic approach. Rom J Int Med 42:4659–4669Google Scholar
  24. 24.
    Combe B, Cantagrel A, Goupille P, Bozonnat MC, Sibilia J, Eliaou JF et al (2003) Predictive factors of 5-year health assessment questionnaire disability in early rheumatoid arthritis. J Rheumatol 30:112344–112349Google Scholar
  25. 25.
    Guillemin F, Gerard N, van Leeuwen M, Smedstad LM, Kvien TK, van den Heuvel W (2003) Prognostic factors for joint destruction in rheumatoid arthritis: a prospective longitudinal study of 318 patients. J Rheumat 30:122585–122589Google Scholar
  26. 26.
    Del Rincon I, Williams K, Stern MP, Freeman GL, O'Leary DH, Escalante A (2003) Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 48:71833–71840. Google Scholar
  27. 27.
    Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE (2005) Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum 52:3722–3732. Google Scholar
  28. 28.
    Otterness IG (1994) The value of C-reactive protein measurement in rheumatoid arthritis. Semin Arthritis Rheum 24:291–104CrossRefGoogle Scholar
  29. 29.
    Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M et al (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:3499–3511Google Scholar
  30. 30.
    Hjeltnes G, Hollan I (2011) Anti-CCP and RF IgM: predictors of impaired endothelial function in rheumatoid arthritis patients. Scand J Rheumatol 40:6422–6427CrossRefGoogle Scholar
  31. 31.
    Curb JD, Abbott RD, Rodriguez BL, Sakkinen P, Popper JS, Yano K et al (2003) C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 107:152016–152020. CrossRefGoogle Scholar
  32. 32.
    Min Su TS (2011) The correlation between vascular endothelial dysfunction and serum inflammatory factors and serum lipid levels in patients with rheumatoid arthritis. Chin J Clin Lab Sci 29:4265.
  33. 33.
    Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695CrossRefGoogle Scholar
  34. 34.
    Greenberg JD, Kremer JM, Curtis JR, Hochberg MC, Reed G, Tsao P et al (2011) Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann Rheum Dis 70:4576–4582. CrossRefGoogle Scholar
  35. 35.
    Low AS, Lunt M, Mercer LK, Watson KD, Dixon WG, Symmons DP et al (2016) Association between ischemic stroke and tumor necrosis factor inhibitor therapy in patients with rheumatoid arthritis. Arthritis Rheum 68:61337–61345. Google Scholar
  36. 36.
    Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F (2002) Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 359:93131173–93131177. CrossRefGoogle Scholar
  37. 37.
    Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS (2005) Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol 52:2262–2267. Google Scholar
  38. 38.
    Sharma TS, Wasko MC, Tang X, Vedamurthy D, Yan X, Cote J et al (2016) Hydroxychloroquine use is associated with decreased incident cardiovascular events in rheumatoid arthritis patients. J Am Heart Assoc 5:1. CrossRefGoogle Scholar
  39. 39.
    Xie F, Yun H, Levitan EB, Muntner P, Curtis JR (2018) Tocilizumab and the risk for cardiovascular disease: a direct comparison among biologic disease-modifying antirheumatic drugs for rheumatoid arthritis patients. Arthritis Care Res.
  40. 40.
    Bili A, Tang X, Pranesh S, Bozaite R, Morris SJ, Antohe JL et al (2014) Tumor necrosis factor alpha inhibitor use and decreased risk for incident coronary events in rheumatoid arthritis. Arthritis Care Res 66:3355–3363. CrossRefGoogle Scholar
  41. 41.
    Barnabe C, Martin BJ, Ghali WA (2011) Systematic review and meta-analysis: anti-tumor necrosis factor alpha therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res 63:4522–4529. CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Fangran Xin
    • 1
  • Lingyu Fu
    • 1
    • 2
    Email author
  • Haina Liu
    • 3
  • Yunwei Xu
    • 2
  • Tingting Wei
    • 1
  • Meng Chen
    • 1
  1. 1.Department of Clinical Epidemiology and Evidence-based medicineThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Medical Record Management CenterThe First Affiliated Hospital, China Medical UniversityShenyangChina
  3. 3.Department of RheumatologyThe First Affiliated Hospital, China Medical UniversityShenyangChina

Personalised recommendations