Advertisement

Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis

  • Yoichi Inaba
  • Jennifer A. Chen
  • Steven R. Bergmann
Original Paper

Abstract

Background

We conducted a meta-analysis of observational studies which examined the association between flow-mediated dilatation (FMD) of brachial artery, a noninvasive measure of endothelial function, and future cardiovascular events.

Methods

Electronic databases were searched using a predefined search strategy. Data was independently abstracted on study characteristics, study quality, and outcomes by two reviewers. The multivariate relative risks, adjusted for confounding factors, were calculated from individual studies and then pooled using random-effects models. Statistical heterogeneity was evaluated using I2 statistics. Subgroup analyses and meta-regression analyses were conducted to assess the robustness of the meta-analysis. Publication bias was examined with funnel plot analysis and Egger’s test.

Results

Four population-based cohort studies and ten convenience-cohort studies, involving 5,547 participants, were included in the meta-analysis. The pooled relative risks of cardiovascular events per 1% increase in brachial FMD, adjusted for confounding risk factors, was 0.87 (95% CI, 0.83- 0.91). The significant associations between brachial FMD and cardiovascular events were consistent among all subgroups evaluated, suggesting the robustness of the meta-analysis. However, the presence of heterogeneity in study quality, the remaining confounding factors, and publication bias in the available literature prevent a definitive evaluation of the additional predictive value of brachial FMD beyond traditional cardiovascular risk factors.

Conclusions

The meta-analysis of heterogeneous studies with moderate methodological quality suggested that impairment of brachial FMD is significantly associated with future cardiovascular events. Further prospective randomized trials are warranted to confirm the efficacy of the usage of brachial FMD in the management of cardiovascular diseases.

Keywords

Endothelium Imaging Meta-analysis Vasodilation 

Abbreviations

CI

Confidence interval

FMD

Flow-mediated dilatation

SD

Standard deviation

Notes

Acknowledgments

The authors’ responsibilities were as follows—YI: selected studies, extracted and analyzed the data, performed the statistical analyses, wrote the manuscript, and takes responsibility for data integrity and accuracy of data analysis; JAC: designed the present study, selected studies, extracted and analyzed the data, and contributed to the writing of the manuscript; SRB: supervised the present study, contributed to the data interpretation and writing of the manuscript. All authors agreed on the final version of the manuscript. All authors have access to the data and a role in writing the manuscript.

Supplementary material

10554_2010_9616_MOESM1_ESM.docx (27 kb)
Supplementary material 1 (DOCX 26 kb)

References

  1. 1.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809CrossRefPubMedGoogle Scholar
  2. 2.
    Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115:1285–1295PubMedGoogle Scholar
  3. 3.
    Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695CrossRefPubMedGoogle Scholar
  4. 4.
    Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340:1111–1115CrossRefPubMedGoogle Scholar
  5. 5.
    Medline cohort study filter (2008) Search filters; 2008. Filter designed by knowledge information specialists from British Medical Journal. Accessed at www.clinicalevidence.com/ceweb/about/search_filters.jsp, on November 11, 2008
  6. 6.
    Downs SH, Black N (1998) The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 52:377–384CrossRefPubMedGoogle Scholar
  7. 7.
    Higgins JPT, Green S (eds) (2006) Cochrane handbook for systematic reviews of interventions 4.2.6 [updated September 2006]. In: The Cochrane Library, Issue 4, 2006. Wiley, ChichesterGoogle Scholar
  8. 8.
    Zhang J, Yu KF (1998) What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280:1690–1691CrossRefPubMedGoogle Scholar
  9. 9.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical studies. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  10. 10.
    Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309PubMedGoogle Scholar
  11. 11.
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMedGoogle Scholar
  12. 12.
    Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56:455–463CrossRefPubMedGoogle Scholar
  13. 13.
    Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMedGoogle Scholar
  14. 14.
    Venneri L, Poggianti E, Jambrik Z, Varga A, Palinkas A, Picano E (2007) The elusive prognostic value of systemic endothelial function in patients with chest pain syndrome. Int J Cardiol 119:109–111CrossRefPubMedGoogle Scholar
  15. 15.
    Neunteufl T, Heher S, Katzenschlager R, Wölfl G, Kostner K, Maurer G, Weidinger F (2000) Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 86:207–210CrossRefPubMedGoogle Scholar
  16. 16.
    Brevetti G, Silvestro A, Schiano V, Chiariello M (2003) Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle-brachial pressure index. Circulation 108:2093–2098CrossRefPubMedGoogle Scholar
  17. 17.
    Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA (2003) Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol 41:1769–1775CrossRefPubMedGoogle Scholar
  18. 18.
    Fathi R, Haluska B, Isbel N, Short L, Marwick TH (2004) The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol 43:616–623CrossRefPubMedGoogle Scholar
  19. 19.
    Katz SD, Hryniewicz K, Hriljac I, Balidemaj K, Dimayuga C, Hudaihed A, Yasskiy A (2005) Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation 111:310–314CrossRefPubMedGoogle Scholar
  20. 20.
    Patti G, Pasceri V, Melfi R, Goffredo C, Chello M, D’Ambrosio A, Montesanti R, Di Sciascio G (2005) Impaired flow-mediated dilation and risk of restenosis in patients undergoing coronary stent implantation. Circulation 111:70–75CrossRefPubMedGoogle Scholar
  21. 21.
    Frick M, Suessenbacher A, Alber HF, Dichtl W, Ulmer H, Pachinger O, Weidinger F (2005) Prognostic value of brachial artery endothelial function and wall thickness. J Am Coll Cardiol 46:1006–1010CrossRefPubMedGoogle Scholar
  22. 22.
    Meyer B, Mörtl D, Strecker K, Hülsmann M, Kulemann V, Neunteufl T, Pacher R, Berger R (2005) Flow-mediated vasodilation predicts outcome in patients with chronic heart failure: comparison with B-type natriuretic peptide. J Am Coll Cardiol 46:1011–1018CrossRefPubMedGoogle Scholar
  23. 23.
    Karatzis EN, Ikonomidis I, Vamvakou GD, Papaioannou TG, Protogerou AD, Andreadou I, Voidonikola PT, Karatzi KN, Papamichael CM, Lekakis JP (2006) Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation. Am J Cardiol 98:1424–1428CrossRefPubMedGoogle Scholar
  24. 24.
    Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM (2007) Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 115:2390–2397CrossRefPubMedGoogle Scholar
  25. 25.
    Shimbo D, Grahame-Clarke C, Miyake Y, Rodriguez C, Sciacca R, Di Tullio M, Boden-Albala B, Sacco R, Homma S (2007) The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis 192:197–203CrossRefPubMedGoogle Scholar
  26. 26.
    Rossi R, Nuzzo A, Origliani G, Modena MG (2008) Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women. J Am Coll Cardiol 51:997–1002CrossRefPubMedGoogle Scholar
  27. 27.
    Shechter M, Issachar A, Marai I, Koren-Morag N, Freinark D, Shahar Y, Shechter A, Feinberg MS (2009) Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Int J Cardiol 134:52–58CrossRefPubMedGoogle Scholar
  28. 28.
    Muiesan ML, Salvetti M, Paini A, Monteduro C, Galbassini G, Poisa P, Porteri E, Agabiti-Rosei C, Paderno V, Belotti E, Rizzoni D, Castellano M, Agabiti-Rosei E (2008) Prognostic role of flow-mediated dilatation of the brachial artery in hypertensive patients. J Hypertens 26:1612–1618CrossRefPubMedGoogle Scholar
  29. 29.
    Kallio K, Jokinen E, Raitakari OT, Hämäläinen M, Siltala M, Volanen I, Kaitosaari T, Viikari J, Rönnemaa T, Simell O (2007) Tobacco smoke exposure is associated with attenuated endothelial function in 11-year-old healthy children. Circulation 115:3205–3212CrossRefPubMedGoogle Scholar
  30. 30.
    Hamburg NM, Larson MG, Vita JA, Vasan RS, Keyes MJ, Widlansky ME, Fox CS, Mitchell GF, Levy D, Meigs JB, Benjamin EJ (2008) Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease. Am J Cardiol 101:82–88CrossRefPubMedGoogle Scholar
  31. 31.
    Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Rönnemaa T, Raitakari OT (2004) Interrelations between brachial endothelial function and carotid intima-media thickness in young adults: the cardiovascular risk in young Finns study. Circulation 110:2918–2923CrossRefPubMedGoogle Scholar
  32. 32.
    Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348:593–600CrossRefPubMedGoogle Scholar
  33. 33.
    Fichtlscherer S, Breuer S, Zeiher AM (2004) Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: further evidence for the existence of the “vulnerable” patient. Circulation 110:1926–1932CrossRefPubMedGoogle Scholar
  34. 34.
    Tonetti MS, D’Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J (2007) Treatment of periodontitis and endothelial function. N Engl J Med 356:911–920CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, B.V. 2010

Authors and Affiliations

  • Yoichi Inaba
    • 1
  • Jennifer A. Chen
    • 2
  • Steven R. Bergmann
    • 2
  1. 1.Division of Cardiovascular MedicineOregon Health and Science UniversityPortlandUSA
  2. 2.Division of CardiologyBeth Israel Medical CenterNew YorkUSA

Personalised recommendations