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04-08-2017 | Systemic lupus erythematosus | Article

Endothelial dysfunction in systemic lupus erythematosus – a case-control study and an updated meta-analysis and meta-regression

Journal: Scientific Reports

Authors: Anselm Mak, Nien Yee Kow, Herbert Schwarz, Lingli Gong, Sen Hee Tay, Lieng Hsi Ling

Publisher: Nature Publishing Group UK

Abstract

Endothelium-dependent flow-mediated dilation (ED-FMD), a biophysical marker of endothelial dysfunction, is apparently impaired in patients with systemic lupus erythematosus (SLE) but such observation is inconsistent. Here, we assessed and compared the brachial artery ED-FMD (baED-FMD) using ultrasonography between SLE patients without cardiovascular disease and healthy controls (HC) matched for age, gender and body mass index. We then performed a comprehensive meta-analysis of case-control studies which compared baED-FMD between SLE patients and HC by determining the effect size of baED-FMD as standardized mean difference (SMD). Factors associated with the effect size were explored by mixed-model meta-regression. Seventy one SLE patients and 71 HC were studied. SLE patients had lower baED-FMD than HC (3.72 ± 2.8% vs 4.63 ± 3.1%, p = 0.032). Meta-analysis of 25 case-control studies involving 1,313 SLE patients and 1,012 HC with the random effects model revealed lower baED-FMD in SLE patients compared to HC (SMD −1.077, p < 0.001). The presence of diabetes mellitus (p = 0.04747), higher diastolic blood pressure (p = 0.044), renal involvement (p = 0.027) and aspirin use (p = 0.001) were associated with more discrepant baED-FMD between both groups. In conclusion, SLE patients naïve of cardiovascular disease have impaired endothelial function. Diabetes mellitus, renal disease and diastolic hypertension are major contributors of endothelial dysfunction in SLE patients.

Chambers, S. A., Allen, E., Rahman, A. & Isenberg, D. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatology (Oxford). 48, 673–5 (2009).CrossRefPubMed

Mak, A., Cheung, M. W. L., Chiew, H. J., Liu, Y. & Ho, R. C. M. Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s. Semin Arthritis Rheum. 41, 830–839 (2012).CrossRefPubMed

Bruce, I. N., Gladman, D. D. & Urowitz, M. B. Premature atherosclerosis in systemic lupus erythematosus. Rheum Dis Clin North Am. 26, 257–78 (2000).CrossRefPubMed

Manzi, S. et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 145, 408–415 (1997).CrossRefPubMed

Asanuma, Y. et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med. 349, 2407–15 (2003).CrossRefPubMed

Doria, A. et al. Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus. Ann Rheum Dis. 62, 1071–7 (2003).CrossRefPubMedPubMedCentral

Inoue, T. & Node, K. Vascular failure: A new clinical entity for vascular disease. J Hypertens. 24, 2121–30 (2006).CrossRefPubMed

Korkmaz, H. & Onalan, O. Evaluation of endothelial dysfunction: flow-mediated dilation. Endothelium. 15, 157–63 (2008).CrossRefPubMed

Halcox, J. P. et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation. 106, 653–8 (2002).CrossRefPubMed

10.

Matsuzawa, Y. & Lerman, A. Endothelial dysfunction and coronary artery disease: assessment, prognosis, and treatment. Coron. Artery Dis. 25, 713–24 (2014).CrossRefPubMedPubMedCentral

11.

Hochberg, M. C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 40, 1725 (1997).CrossRefPubMed

12.

Ibañez, D., Gladman, D. D., Touma, Z., Nikpour, M. & Urowitz, M. B. Optimal frequency of visits for patients with systemic lupus erythematosus to measure disease activity over time. J Rheumatol. 38, 60–3 (2011).CrossRefPubMed

13.

Gladman, D. D. et al. The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum. 40, 809–13 (1997).CrossRefPubMed

14.

Parra, S. et al. Circulating FABP4 is a marker of metabolic and cardiovascular risk in SLE patients. Lupus. 23, 245–54 (2014).CrossRefPubMed

15.

Mak, A. et al. Lumbar spine bone mineral density predicts endothelial reactivity in patients with systemic lupus erythematosus. Clin Exp Rheumatol. 29, 261–268 (2011).PubMed

16.

Stein, J. H. et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr. 21, 93–111 (2008).CrossRefPubMed

17.

Pigott, T. D. Handling missing data. The handbook of research synthesis and meta-analysis. 2nd ed. New York: Russell Sage Foundation. 399–416 (2009)

18.

Fletcher, J. What is heterogeneity and is it important? Br Med J. 334, 94–6 (2007).CrossRef

19.

DerSimonian, R. & Laird, N. Meta-analysis in clinical trials. Control Clin Trials. 7, 177–88 (1986).CrossRefPubMed

20.

Thompson, S. G. & Higgins, J. P. How should meta-regression analyses be undertaken and interpreted? Stat Med. 21, 1559–73 (2002).CrossRefPubMed

21.

Stroup, D. F. et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 283, 2008–12 (2000).CrossRefPubMed

22.

Moher, D. et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet. 354, 1896–900 (1999).CrossRefPubMed

23.

Wells, G. B. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Ottawa Hospital Research Institute. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

24.

Mak, A., Liu, Y. & Ho, R. C. Endothelium-dependent but not endothelium-independent flow-mediated dilation is significantly reduced in patients with systemic lupus erythematosus without vascular events: a metaanalysis and metaregression. J Rheumatol. 38, 1296–303 (2011).CrossRefPubMed

25.

Piper, M. K. et al. Impaired endothelial function in systemic lupus erythematosus. Lupus. 16, 84–8 (2007).CrossRefPubMed

26.

Cypiene, A. et al. Arterial wall dysfunction in systemic lupus erythematosus. Lupus. 18, 522–9 (2009).CrossRefPubMed

27.

Ghosh, P. et al. Subclinical atherosclerosis and endothelial dysfunction in young South-Asian patients with systemic lupus erythematosus. Clin Rheumatol. 28, 1259–65 (2009).CrossRefPubMed

28.

Johnson, S. R. et al. Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations. Lupus. 13, 590–3 (2004).CrossRefPubMed

29.

Karadag, O. et al. Novel cardiovascular risk factors and cardiac event predictors in female inactive systemic lupus erythematosus patients. Clin Rheumatol. 26, 695–9 (2007).CrossRefPubMed

30.

Zhang, C. Y. et al. Evaluation of risk factors that contribute to high prevalence of premature atherosclerosis in Chinese premenopausal systemic lupus erythematosus patients. J Clin Rheumatol. 15, 111–6 (2009).CrossRefPubMed

31.

Valdivielso, P. et al. Lupus-associated endothelial dysfunction, disease activity and arteriosclerosis. Clin Exp Rheumatol. 26, 827–33 (2008).PubMed

32.

Svenungsson, E. et al. Endothelial function and markers of endothelial activation in relation to cardiovascular disease in systemic lupus erythematosus. Scand J Rheumatol. 37, 352–9 (2008).CrossRefPubMed

33.

Lima, D. S., Sato, E. I., Lima, V. C., Miranda, F. Jr. & Hatta, F. H. Brachial endothelial function is impaired in patients with systemic lupus erythematosus. J Rheumatol. 29, 292–7 (2002).PubMed

34.

Wright, S. A. et al. Microcirculatory hemodynamics and endothelial dysfunction in systemic lupus erythematosus. Arterioscler Thromb Vasc Biol. 26, 2281–7 (2006).CrossRefPubMed

35.

Kiss, E. et al. Reduced flow-mediated vasodilation as a marker for cardiovascular complications in lupus patients. J Autoimmun. 27, 211–7 (2006).CrossRefPubMed

36.

Rajagopalan, S. et al. Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Blood. 103, 3677–83 (2004).CrossRefPubMed

37.

Ahmadi, B., Bonakdar, Z. S., Hashemi, S. M., Sadrkabir, S. M. & Karimifar, M. Endothelial dysfunction in Iranian lupus patients. Rheumatol Int. 31, 27–31 (2011).CrossRefPubMed

38.

Cypienė, A. et al. The influence of mean blood pressure on arterial stiffening and endothelial dysfunction in women with rheumatoid arthritis and systemic lupus erythematosus. Medicina (Kaunas). 46, 522–30 (2010).PubMed

39.

Conti, F. et al. Subclinical atherosclerosis in systemic lupus erythematosus and antiphospholipid syndrome: focus on β2GPI-specific T cell response. Arterioscler Thromb Vasc Biol. 34, 661–8 (2014).CrossRefPubMed

40.

Barsalou, J. et al. Impact of Disease Duration on Vascular Surrogates of Early Atherosclerosis in Childhood-Onset Systemic Lupus Erythematosus. Arthritis Rheumatol. 68, 237–46 (2016).CrossRefPubMed

41.

Mikołajczyk, T. P. et al. Heterogeneity of peripheral blood monocytes, endothelial dysfunction and subclinical atherosclerosis in patients with systemic lupus erythematosus. Lupus. 25, 18–27 (2016).CrossRefPubMed

42.

Somers, E. C. et al. Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients. PLoS One. 7, e37000 (2012).ADSCrossRefPubMedPubMedCentral

43.

Parker, B. et al. Suppression of inflammation reduces endothelial microparticles in active systemic lupus erythematosus. Ann Rheum Dis. 73, 1144–50 (2014).CrossRefPubMed

44.

Aizer, J. et al. 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, 235–42 (2009).CrossRefPubMedPubMedCentral

45.

El-Banawy, H. S., Gaber, E. W., Maharem, D. A. & Matrawy, K. A. Angiopoietin-2, endothelial dysfunction and renal involvement in patients with systemic lupus erythematosus. J Nephrol. 25, 541–550 (2012).CrossRefPubMed

46.

Sincer, İ. et al. Association between serum total antioxidant status and flow-mediated dilation in patients with systemic lupus erythematosus: an observational study. Anatol J Cardiol. 15, 913–8 (2015).CrossRefPubMedPubMedCentral

47.

Apurba, B. P. et al. Study of endothelial dysfunction and its correlation with disease activity in systemic lupus erythematosus patients without conventional cardiovascular risk factors. Indian J Rheumatol. 6, 178–84 (2011).CrossRef

48.

Valer, P., Paul, B., Eugenia, B. & Camelia, B. Annexin A5 as independent predictive biomarker for subclinical atherosclerosis and endothelial dysfunction in systemic lupus erythematosus patients. Clin Lab. 59, 359–67 (2013).CrossRefPubMed

49.

Mak, A., & Kow, N. Y. Imbalance between endothelial damage and repair: a gateway to cardiovascular disease in systemic lupus erythematosus. Biomed Res Int. 178721 (2014).

50.

Di Minno, M. N. et al. Clinical assessment of endothelial function in patients with rheumatoid arthritis: A meta-analysis of literature studies. Eur J Intern Med. 26, 835–42 (2015).CrossRefPubMed

51.

Ridker, P. M., Hennekens, C. H., Buring, J. E. & Rifai, N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 342, 836–43 (2000).CrossRefPubMed

52.

Mak, A., Cheung, M. W., Cheak, A. A. & Ho, R. C. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford). 49, 281–8 (2010).CrossRefPubMed

53.

Ghiadoni, L. et al. Prognostic value of flow-mediated dilation in patients with systemic lupus erythematosus: a pilot prospective cohort study. Atherosclerosis. 236, 381–4 (2014).CrossRefPubMed

Medicine Matters Rheumatology

Abstract