Skip to main content
SpringerLink
Log in

Decreased Flow-Mediated Dilatation in Patients with Systemic Lupus Erythematosus: a Meta-analysis

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Premature atherosclerosis, the hallmark of cardiovascular diseases, has been found to be a significant cause of late deaths in systemic lupus erythematosus (SLE) patients. Therefore, early identification of atherosclerosis before the overt disease is curial for the management program of SLE. Flow-mediated dilatation (FMD%) is a reliable, noninvasive, easy to use, reproducible, and pathogenically relevant index for early atherosclerosis. In recent years, a number of studies have been performed to compare the mean FMD% difference between patients with SLE and healthy controls. However, these studies have shown inconclusive or even contradictory findings. In this study, to derive a more precise comparison of FMD% difference between SLE patients and healthy controls, a meta-analysis was performed. Databases were searched to identify all available studies comparing FMD% between SLE patients and healthy controls. The study eligibility criteria were cohort or case–control studies with data on both patients diagnosed with SLE and healthy controls, and use of high-resolution ultrasonography to detect FMD. Random effect meta-analysis was conducted to evaluate the overall mean FMD% difference between the two groups. Publication bias was detected by funnel plot and Egger’s test. Meta-regression analysis was performed to investigate the potential influencing factors on FMD% difference. Of the 434 articles initially identified, 22 were finally included in the meta-analysis. Compared to healthy controls, SLE patients had significantly lower FMD% (standardized mean difference, −1.19; 95 % CI, −1.63, −0.74; P < 0.001). There was significant heterogeneity among these studies (I 2 = 94.3 %, P < 0.001), which was mainly due to variations in disease duration of SLE patients. The funnel plot showed a skewed shape, indicating a marked publication bias, which was further supported by the Egger’s test (P = 0.006). However, after the correction for potential publication bias by using the trim-and-fill method, the main results for all studies combined were still significant (P < 0.001). Taken together, these findings support the current evidence on a higher cardiovascular burden in SLE and support using FMD% as a surrogate for premature atherosclerosis in SLE patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Au, K., M.K. Singh, V. Bodukam, et al. 2011. Atherosclerosis in systemic sclerosis: a systematic review and meta-analysis. Arthritis and Rheumatism 63: 2078–2090.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Telles, R.W., C.C. Lanna, A.J. Sousa, et al. 2013. Progression of carotid atherosclerosis in patients with systemic lupus erythematosus. Clinical Rheumatology 32: 1293–1300.

    Article  PubMed  Google Scholar 

  3. Frieri, M. 2012. Accelerated atherosclerosis in systemic lupus erythematosus: role of proinflammatory cytokines and therapeutic approaches. Current Allergy and Asthma Reports 12: 25–32.

    Article  CAS  PubMed  Google Scholar 

  4. Kiani, A.N., W.S. Post, L.S. Magder, et al. 2011. Predictors of progression in atherosclerosis over 2 years in systemic lupus erythematosus. Rheumatology (Oxford) 50: 2071–2079.

    Article  Google Scholar 

  5. Deo, S.S., A.R. Chogle, K.J. Mistry, et al. 2012. Increased prevalence of subclinical atherosclerosis in rheumatoid arthritis patients of Indian descent. Experimental and Clinical Cardiology 17: 20–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Kobayashi, H., J.T. Giles, J.F. Polak, et al. 2010. Increased prevalence of carotid artery atherosclerosis in rheumatoid arthritis is artery-specific. Journal of Rheumatology 37: 730–739.

    Article  PubMed  Google Scholar 

  7. Avalos, I., Y.H. Rho, C.P. Chung, et al. 2008. Atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Clinical and Experimental Rheumatology 26: S5–S13.

    CAS  PubMed  Google Scholar 

  8. Wolfe, F., B. Freundlich, and W.L. Straus. 2003. Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. Journal of Rheumatology 30: 36–40.

    PubMed  Google Scholar 

  9. Hettema, M.E., D. Zhang, K. de Leeuw, et al. 2008. Early atherosclerosis in systemic sclerosis and its relation to disease or traditional risk factors. Arthritis Research and Therapy 10: R49.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Khurma, V., C. Meyer, G.S. Park, et al. 2008. A pilot study of subclinical coronary atherosclerosis in systemic sclerosis: coronary artery calcification in cases and controls. Arthritis and Rheumatism 59: 591–597.

    Article  CAS  PubMed  Google Scholar 

  11. Hettema, M.E., H. Bootsma, and C.G. Kallenberg. 2008. Macrovascular disease and atherosclerosis in SSc. Rheumatology (Oxford) 47: 578–583.

    Article  CAS  Google Scholar 

  12. Szucs, G., O. Timar, Z. Szekanecz, et al. 2007. Endothelial dysfunction precedes atherosclerosis in systemic sclerosis—relevance for prevention of vascular complications. Rheumatology (Oxford) 46: 759–762.

    Article  CAS  Google Scholar 

  13. Hansson, G.K. 2005. Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine 352: 1685–1695.

    Article  CAS  PubMed  Google Scholar 

  14. Rho, Y.H., C.P. Chung, A. Oeser, et al. 2009. Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis and Rheumatism 61: 1580–1585.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. McMahon, M., J. Grossman, J. FitzGerald, et al. 2006. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis and Rheumatism 54: 2541–2549.

    Article  CAS  PubMed  Google Scholar 

  16. O'Neill, S.G., I. Giles, A. Lambrianides, et al. 2010. Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus. Arthritis and Rheumatism 62: 845–854.

    Article  PubMed  Google Scholar 

  17. Piper, M.K., K. Raza, S.L. Nuttall, et al. 2007. Impaired endothelial function in systemic lupus erythematosus. Lupus 16: 84–88.

    Article  CAS  PubMed  Google Scholar 

  18. Tyrrell, P.N., J. Beyene, B.M. Feldman, et al. 2010. Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arteriosclerosis, Thrombosis, and Vascular Biology 30: 1014–1026.

    Article  CAS  PubMed  Google Scholar 

  19. Yeboah, J., J.R. Crouse, F.C. Hsu, et al. 2007. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 115: 2390–2397.

    Article  PubMed  Google Scholar 

  20. Hochberg, M.C. 1997. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and Rheumatism 40: 1725.

    Article  CAS  PubMed  Google Scholar 

  21. Whitlock, R.P., S. Chan, P.J. Devereaux, et al. 2008. Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: a meta-analysis of randomized trials. European Heart Journal 29: 2592–2600.

    Article  PubMed  Google Scholar 

  22. DerSimonian, R., and N. Laird. 1986. Meta-analysis in clinical trials. Controlled Clinical Trials 7: 177–188.

    Article  CAS  PubMed  Google Scholar 

  23. Higgins, J.P., and S.G. Thompson. 2002. Quantifying heterogeneity in a meta-analysis. Statistics in Medicine 21: 1539–1558.

    Article  PubMed  Google Scholar 

  24. Higgins, J.P., S.G. Thompson, J.J. Deeks, et al. 2003. Measuring inconsistency in meta-analyses. BMJ 327: 557–560.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Sterne, J.A., and M. Egger. 2001. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. Journal of Clinical Epidemiology 54: 1046–1055.

    Article  CAS  PubMed  Google Scholar 

  26. Egger, M., G. Davey Smith, M. Schneider, et al. 1997. Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–634.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Peters, J.L., A.J. Sutton, D.R. Jones, et al. 2007. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Statistics in Medicine 26: 4544–4562.

    Article  PubMed  Google Scholar 

  28. Lima, D.S., E.I. Sato, V.C. Lima, et al. 2002. Brachial endothelial function is impaired in patients with systemic lupus erythematosus. Journal of Rheumatology 29: 292–297.

    PubMed  Google Scholar 

  29. El-Magadmi, M., H. Bodill, Y. Ahmad, et al. 2004. Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women. Circulation 110: 399–404.

    Article  PubMed  Google Scholar 

  30. Rajagopalan, S., E.C. Somers, R.D. Brook, et al. 2004. Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Blood 103: 3677–3683.

    Article  CAS  PubMed  Google Scholar 

  31. Wright, S.A., F.M. O'Prey, D.J. Rea, et al. 2006. Microcirculatory hemodynamics and endothelial dysfunction in systemic lupus erythematosus. Arteriosclerosis, Thrombosis, and Vascular Biology 26: 2281–2287.

    Article  CAS  PubMed  Google Scholar 

  32. Karadag, O., M. Calguneri, E. Atalar, et al. 2007. Novel cardiovascular risk factors and cardiac event predictors in female inactive systemic lupus erythematosus patients. Clinical Rheumatology 26: 695–699.

    Article  PubMed  Google Scholar 

  33. Svenungsson, E., A. Cederholm, K. Jensen-Urstad, et al. 2008. Endothelial function and markers of endothelial activation in relation to cardiovascular disease in systemic lupus erythematosus. Scandinavian Journal of Rheumatology 37: 352–359.

    Article  CAS  PubMed  Google Scholar 

  34. Valdivielso, P., J.J. Gomez-Doblas, M. Macias, et al. 2008. Lupus-associated endothelial dysfunction, disease activity and arteriosclerosis. Clinical and Experimental Rheumatology 26: 827–833.

    CAS  PubMed  Google Scholar 

  35. Aizer, J., E.W. Karlson, L.B. Chibnik, et al. 2009. A controlled comparison of brachial artery flow mediated dilation (FMD) and digital pulse amplitude tonometry (PAT) in the assessment of endothelial function in systemic lupus erythematosus. Lupus 18: 235–242.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Cypiene, A., M. Kovaite, A. Venalis, et al. 2009. Arterial wall dysfunction in systemic lupus erythematosus. Lupus 18: 522–529.

    Article  CAS  PubMed  Google Scholar 

  37. Ghosh, P., A. Kumar, S. Kumar, et al. 2009. Subclinical atherosclerosis and endothelial dysfunction in young South-Asian patients with systemic lupus erythematosus. Clinical Rheumatology 28: 1259–1265.

    Article  PubMed  Google Scholar 

  38. Soltesz, P., H. Der, G. Kerekes, et al. 2009. A comparative study of arterial stiffness, flow-mediated vasodilation of the brachial artery, and the thickness of the carotid artery intima-media in patients with systemic autoimmune diseases. Clinical Rheumatology 28: 655–662.

    Article  PubMed  Google Scholar 

  39. Zhang, C.Y., L.J. Lu, F.H. Li, et al. 2009. Evaluation of risk factors that contribute to high prevalence of premature atherosclerosis in Chinese premenopausal systemic lupus erythematosus patients. Journal of Clinical Rheumatology 15: 111–116.

    Article  PubMed  Google Scholar 

  40. Cypiene, A., J. Dadoniene, R. Rugiene, et al. 2010. The influence of mean blood pressure on arterial stiffening and endothelial dysfunction in women with rheumatoid arthritis and systemic lupus erythematosus. Medicina (Kaunas, Lithuania) 46: 522–530.

    Google Scholar 

  41. Mak, A., P.A. Robless, L. Gong, et al. 2010. Endothelial reactivity predicts bone mineral density (BMD) in patients with systmeic lupus erythematosus (SLE). International Journal of Rheumatic Diseases 13: 124–125.

    Article  Google Scholar 

  42. Ahmadi, B., Z.S. Bonakdar, S.M. Hashemi, et al. 2011. Endothelial dysfunction in Iranian lupus patients. Rheumatology International 31: 27–31.

    Article  PubMed  Google Scholar 

  43. Mak, A., L.H. Ling, R.C.M. Ho, et al. 2011. Lumbar spine bone mineral density predicts endothelial reactivity in patients with systemic lupus erythematosus. Clinical and Experimental Rheumatology 29: 261–268.

    CAS  PubMed  Google Scholar 

  44. Stalc, M., M. Tomsic, M.K. Jezovnik, et al. 2011. Endothelium-dependent and independent dilation capability of peripheral arteries in patients with systemic lupus erythematosus and antiphospholipid syndrome. Clinical and Experimental Rheumatology 29: 616–623.

    CAS  PubMed  Google Scholar 

  45. Gaber, R., N. Kotb, E. Kassem, et al. 2011. Association of circulating endothelial cells with flow mediated vasodilation and disease activity in patients with systemic lupus erythematosus. European Heart Journal Cardiovascular Imaging 12: ii158.

    Google Scholar 

  46. El-Banawy, H.S., E.W. Gaber, D.A. Maharem, et al. 2012. Angiopoietin-2, endothelial dysfunction and renal involvement in patients with systemic lupus erythematosus. Journal of Nephrology 25: 541–550.

    Article  CAS  PubMed  Google Scholar 

  47. Somers, E.C., W. Zhao, E.E. Lewis, et al. 2012. Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients. PLoS One 7: e37000.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Parker, B., A. Al-Husain, P. Pemberton, et al. 2013. Suppression of inflammation reduces endothelial microparticles in active systemic lupus erythematosus. Annals of the Rheumatic Diseases 73: 1144–1150.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Valer, P., B. Paul, B. Eugenia, et al. 2013. Annexin A5 as independent predictive biomarker for subclinical atherosclerosis and endothelial dysfunction in systemic lupus erythematosus patients. Clinical Laboratory 59: 359–367.

    CAS  PubMed  Google Scholar 

  50. Manzi, S., E.N. Meilahn, J.E. Rairie, et al. 1997. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. American Journal of Epidemiology 145: 408–415.

    Article  CAS  PubMed  Google Scholar 

  51. Roman, M.J., B.A. Shanker, A. Davis, et al. 2003. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. New England Journal of Medicine 349: 2399–2406.

    Article  CAS  PubMed  Google Scholar 

  52. Masoura, C., C. Pitsavos, K. Aznaouridis, et al. 2011. Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis. Atherosclerosis 214: 129–138.

    Article  CAS  PubMed  Google Scholar 

  53. Inaba, Y., J.A. Chen, and S.R. Bergmann. 2010. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. International Journal of Cardiovascular Imaging 26: 631–640.

    Article  PubMed  Google Scholar 

  54. Nikpour, M., D. Gladman, and M. Urowitz. 2013. Premature coronary heart disease in systemic lupus erythematosus: what risk factors do we understand? Lupus 22: 1243–1250.

    Article  CAS  PubMed  Google Scholar 

  55. Hopkins, N.D., G. Stratton, T.M. Tinken, et al. 2009. Relationships between measures of fitness, physical activity, body composition and vascular function in children. Atherosclerosis 204: 244–249.

    Article  CAS  PubMed  Google Scholar 

  56. Reis-Neto, E.T., A.E. Silva, C.M. Monteiro, et al. 2013. Supervised physical exercise improves endothelial function in patients with systemic lupus erythematosus. Rheumatology (Oxford) 52: 2187–2195.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81102192, 81373073), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20113420120008), as well as the Grants for Scientific Research of BSKY (No. XJ201014) from Anhui Medical University.

Conflict of Interest

None of the authors has any potential financial conflict of interest related to this manuscript.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People’s Republic of China

    De-Guang Wang, Rui-Xue Leng, Jing Ni, Han Cen, Hai-Feng Pan & Dong-Qing Ye

  2. Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

    De-Guang Wang

  3. Department of Medicine, HeFei Vocational and Technical College, MuShan Road, ChaoHu, Anhui, 238000, China

    Xiao-Wu Tang

  4. Department of Maternal, Child and Adolescent Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China

    Ye Fan

  5. Department of Preventive Medicine, School of Public Health, Anhui Medical University, Hefei, China

    Sen-Miao Deng

  6. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Chao Wang

Authors
  1. De-Guang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Wu Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ye Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rui-Xue Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jing Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sen-Miao Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Han Cen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hai-Feng Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dong-Qing Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hai-Feng Pan or Dong-Qing Ye.

Additional information

De-Guang Wang, Xiao-Wu Tang, and Ye Fan contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, DG., Tang, XW., Fan, Y. et al. Decreased Flow-Mediated Dilatation in Patients with Systemic Lupus Erythematosus: a Meta-analysis. Inflammation 37, 2067–2075 (2014). https://doi.org/10.1007/s10753-014-9940-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-014-9940-z

KEY WORDS

Search

Navigation