Advertisement

Rheumatology International

, Volume 38, Issue 7, pp 1179–1190 | Cite as

Coronary flow reserve in systemic rheumatic diseases: a systematic review and meta-analysis

  • Gian Luca ErreEmail author
  • Giorgio Buscetta
  • Panagiotis Paliogiannis
  • Arduino Aleksander Mangoni
  • Ciriaco Carru
  • Giuseppe Passiu
  • Angelo Zinellu
Systematic Review

Abstract

Coronary flow reserve (CFR), a measure of both obstructive coronary artery disease and microvascular dysfunction, has been evaluated in systemic rheumatic diseases (RDs), but a comprehensive critical appraisal of the available evidence is lacking. The objective of this study is to conduct a systematic review and meta-analysis of studies with small sample size investigating the associations between the presence of RDs and CFR to increase statistical power and accuracy. PubMed, Web of Science, Scopus, and Google Scholar, from inception to March 2018, were searched for studies reporting on CFR in RDs in comparison to healthy subjects. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. Meta-regressions and sensitivity analyses assessed study heterogeneity by type of RDs, age, traditional cardiovascular risk factors, systemic inflammation, and methodology used to evaluate CFR. Twenty-one studies (709 RDs patients and 650 healthy controls) were included in the meta-analysis. Pooled results showed that CFR values were significantly lower in patients with RDs than in healthy controls (SMD = − 1.51, 95% CI − 1.91, − 1.11; p < 0.001; I2 = 90.1%, p < 0.001). The between-group differences in CFR were not associated with inflammatory burden, age, lipids, body mass index, blood pressure, or assessment methods. Patients with prevalent autoimmune features (e.g., systemic lupus erythematosus) showed a significantly lower CFR when compared to patients with mixed autoimmune and autoinflammatory features (e.g., psoriatic arthritis). This meta-analysis showed a significant impairment in CFR in patients with RDs with respect to the general population. Differences in pathogenetic mechanisms may influence the severity of CFR impairment in RDs.

Keywords

Coronary flow reserve Atherosclerosis Rheumatic diseases Connective tissue diseases Rheumatoid arthritis Behcet’s disease 

Abbreviations

ADE

Adenosine

AS

Ankylosing spondylitis

BD

Behcet’s disease

BMI

Body mass index

CMR

Cardiac magnetic resonance

CI

95% Confidence intervals

CFR

Coronary flow reserve

CRP

C-reactive protein

CTDs

Connective tissue diseases

DBP

Diastolic blood pressure

DPD

Dipyridamole

ESR

Erythrocyte sedimentation rate

HDL

High-density lipoprotein

HR

Heart rate

MHC

Major histocompatibility complex

LDL

Low-density lipoprotein

PET

Positron emission tomography

RDs

Rheumatic diseases

RA

Rheumatoid arthritis

SBP

Systolic blood pressure

SSc

Systemic sclerosis

SMD

Standardized mean differences

TTE

Trans-thoracic stress echocardiography

Notes

Author contributions

GLE and AZ designed the study. GLE and AZ searched databases and performed the selection of studies; GLE, AZ, and AAM wrote the manuscript; PP and AZ analyzed the data; GB, CC, and GP contributed to writing and critically uprising the manuscript and approved the last version.

Funding

No grant support was utilized for this study.

Compliance with ethical standards

Conflict of interest

The authors report no relationships that could be construed as a conflict of interest.

References

  1. 1.
    Palazzo C, Ravaud JF, Papelard A, Ravaud P, Poiraudeau S (2014) The burden of musculoskeletal conditions. PLoS One 9:e90633CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Prasad M, Hermann J, Gabriel SE, Weyand CM, Mulvagh S, Mankad R et al (2015) Cardiorheumatology: cardiac involvement in systemic rheumatic disease. Nat Rev Cardiol 12:168–176CrossRefPubMedGoogle Scholar
  3. 3.
    Erre GL, Piras A, Mura S, Mundula N, Piras M, Taras L (2016) Asymmetric dimethylarginine and arterial stiffness in patients with rheumatoid arthritis: a case–control study. J Int Med Res 44:76–80CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Erre GL, Piga M, Fedele AL, Mura S, Piras A, Cadoni ML et al (2018) Prevalence and determinants of peripheral microvascular endothelial dysfunction in rheumatoid arthritis patients: a multicenter cross-sectional study. Mediators Inflamm.  https://doi.org/10.1155/2018/6548715 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Erre GL, Sanna P, Zinellu A, Ponchietti A, Fenu P, Sotgia S et al (2011) Plasma asymmetric dimethylarginine (ADMA) levels and atherosclerotic disease in ankylosing spondylitis: a cross-sectional study. Clin Rheumatol 30:21–27CrossRefPubMedGoogle Scholar
  6. 6.
    Agca R, Heslinga SC, van Halm VP, Nurmohamed MT (2016) Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders. Heart 102:790–795CrossRefPubMedGoogle Scholar
  7. 7.
    O’Sullivan M, Bruce IN, Symmons DPM (2016) Cardiovascular risk and its modification in patients with connective tissue diseases. Best Pract Res Clin Rheumatol 30:81–94CrossRefPubMedGoogle Scholar
  8. 8.
    Taqueti VR, Shaw LJ, Cook NR, Murthy VL, Shah NR, Foster CR et al (2017) Excess cardiovascular risk in women relative to men referred for coronary angiography is associated with severely impaired coronary flow reserve, Not obstructive disease clinical perspective. Circulation 135:566–577CrossRefPubMedGoogle Scholar
  9. 9.
    Schelbert HR (2012) FFR and coronary flow reserve: friends or foes? JACC Cardiovasc Imaging 5:203–206CrossRefPubMedGoogle Scholar
  10. 10.
    Nakazato R, Heo R, Leipsic J, Min JK (2014) CFR and FFR assessment with PET and CTA: strengths and limitations. Curr Cardiol Rep 16:484CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cortigiani L, Rigo F, Gherardi S, Bovenzi F, Picano E, Sicari R (2010) Implication of the continuous prognostic spectrum of Doppler echocardiographic derived coronary flow reserve on left anterior descending artery. Am J Cardiol 105:158–162CrossRefPubMedGoogle Scholar
  12. 12.
    Montisci R, Vacca A, Garau P, Colonna P, Ruscazio M, Passiu G et al (2003) Detection of early impairment of coronary flow reserve in patients with systemic sclerosis. Ann Rheum Dis 62:890–893CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Sulli A, Ghio M, Bezante GP, Deferrari L, Craviotto C, Sebastiani V et al (2004) Blunted coronary flow reserve in systemic sclerosis. Rheumatology 43:505–509CrossRefPubMedGoogle Scholar
  14. 14.
    D’Andrea A, Stisi S, Caso P, Uccio FS, Bellissimo S, Salerno G et al (2007) Associations between left ventricular myocardial involvement and endothelial dysfunction in systemic sclerosis: noninvasive assessment in asymptomatic patients. Echocardiography 24:587–597CrossRefPubMedGoogle Scholar
  15. 15.
    Hirata K, Kadirvelu A, Kinjo M, Sciacca R, Sugioka K, Otsuka R et al (2007) Altered coronary vasomotor function in young patients with systemic lupus erythematosus. Arthritis Rheumatol 56:1904–1909CrossRefGoogle Scholar
  16. 16.
    Caliskan M, Gullu H, Yilmaz S, Ciftci O, Erdogan D, Dursun R et al (2008) Cardiovascular prognostic value of vascular involvement in Behcet’s disease. Int J Cardiol 125:428–430CrossRefPubMedGoogle Scholar
  17. 17.
    Caliskan M, Gullu H, Yilmaz S, Erdogan D, Unler GK, Ciftci O et al (2007) Impaired coronary microvascular function in familial Mediterranean fever. Atherosclerosis 195:e161–e167CrossRefGoogle Scholar
  18. 18.
    Ciftci O, Yilmaz S, Topcu S, Caliskan M, Gullu H, Erdogan D et al (2008) Impaired coronary microvascular function and increased intima-media thickness in rheumatoid arthritis. Atherosclerosis 198:332–337CrossRefPubMedGoogle Scholar
  19. 19.
    Recio-Mayoral A, Mason JC, Kaski JC, Rubens MB, Harari OA, Camici PG (2009) Chronic inflammation and coronary microvascular dysfunction in patients without risk factors for coronary artery disease. Eur Heart J 30:1837–1843CrossRefPubMedGoogle Scholar
  20. 20.
    Turiel M, Atzeni F, Tomasoni L, de Portu S, Delfino L, Bodini BD et al (2009) Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients. Rheumatology 48:834–839CrossRefPubMedGoogle Scholar
  21. 21.
    Alexanderson E, Cruz P, Vargas A, Meave A, Ricalde A, Talayero JA et al (2007) Endothelial dysfunction in patients with antiphospholipid syndrome assessed with positron emission tomography. J Nucl Cardiol 14:566–572CrossRefPubMedGoogle Scholar
  22. 22.
    Atzeni F, Sarzi-Puttini P, Sitia S, Tomasoni L, Gianturco L, Battellino M et al (2011) Coronary flow reserve and asymmetric dimethylarginine levels: new measurements for identifying subclinical atherosclerosis in patients with psoriatic arthritis. J Rheumatol 38:1661–1664CrossRefPubMedGoogle Scholar
  23. 23.
    Ishimori ML, Martin R, Berman DS, Goykhman P, Shaw LJ, Shufelt C et al (2011) Myocardial ischemia in the absence of obstructive coronary artery disease in systemic lupus erythematosus. JACC Cardiovasc Imaging 4:27–33CrossRefPubMedGoogle Scholar
  24. 24.
    Yılmaz S, Caliskan M, Kulaksızoglu S, Ciftci O, Caliskan Z, Gullu H et al (2012) Association between serum total antioxidant status and coronary microvascular functions in patients with SLE. Echocardiography 29:1218–1223CrossRefPubMedGoogle Scholar
  25. 25.
    Turiel M, Gianturco L, Ricci C, Sarzi-Puttini P, Tomasoni L, Colonna V de G et al (2013) Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross-sectional study. Arthritis Care Res 62:274–280CrossRefGoogle Scholar
  26. 26.
    Atzeni F, Sarzi-Puttini P, Signorello MC, Gianturco L, Stella D, Boccassini L et al (2014) New parameters for identifying subclinical atherosclerosis in patients with primary Sjögren’s syndrome: a pilot study. Clin Exp Rheumatol 32:361–368PubMedGoogle Scholar
  27. 27.
    Ikonomidis I, Tzortzis S, Andreadou I, Paraskevaidis I, Katseli C, Katsimbri P et al (2014) Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis. Circ Cardiovasc Imaging 7:619–628CrossRefPubMedGoogle Scholar
  28. 28.
    Mahfouz RA, Mostafa T, Fahmy DS (2014) Impact of the neutrophil-to-lymphocyte ratio on coronary flow reserve and incipient myocardial dysfunction in patients with psoriatic arthritis. J Arthritis 3:1–5CrossRefGoogle Scholar
  29. 29.
    Faccini A, Agricola E, Oppizzi M, Margonato A, Galderisi M, Sabbadini MG et al (2015) Coronary microvascular dysfunction in asymptomatic patients affected by systemic sclerosis—limited vs. diffuse form. Circ J 79:825–829CrossRefPubMedGoogle Scholar
  30. 30.
    Kakuta K, Dohi K, Sato Y, Yamanaka T, Kawamura M, Ogura T et al (2016) Chronic inflammatory disease is an independent risk factor for coronary flow velocity reserve impairment unrelated to the processes of coronary artery calcium deposition. J Am Soc Echocardiogr 29:173–180CrossRefPubMedGoogle Scholar
  31. 31.
    Mavrogeni S, Bratis K, Koutsogeorgopoulou L, Karabela G, Savropoulos E, Katsifis G et al (2017) Myocardial perfusion in peripheral Raynaud’s phenomenon. Evaluation using stress cardiovascular magnetic resonance. Int J Cardiol 228:444–448CrossRefPubMedGoogle Scholar
  32. 32.
    Gyllenhammar T, Kanski M, Engblom H, Wuttge DM, Carlsson M, Hesselstrand R et al (2018) Decreased global myocardial perfusion at adenosine stress as a potential new biomarker for microvascular disease in systemic sclerosis: a magnetic resonance study. BMC Cardiovasc Disord 18:16CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Crea F, Camici PG, Bairey Merz CN (2014) Coronary microvascular dysfunction: an update. Eur Heart J 35:1101–1111CrossRefPubMedGoogle Scholar
  34. 34.
    Alexánderson E, Ochoa JM, Calleja R, Juárez-Rojas JG, Prior JO, Jácome R et al (2010) Endothelial dysfunction in systemic lupus erythematosus: evaluation with 13N-ammonia PET. J Nucl Med 51:1927–1931CrossRefPubMedGoogle Scholar
  35. 35.
    Steyers CM, Miller FJ (2014) Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci 15:11324–11349CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Boin F, Erre GL, Posadino AM, Cossu A, Giordo R, Spinetti G et al (2014) Oxidative stress-dependent activation of collagen synthesis is induced in human pulmonary smooth muscle cells by sera from patients with scleroderma-associated pulmonary hypertension. Orphanet J Rare Dis 9:123CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    von Scholten BJ, Hansen CS, Hasbak P, Kjaer A, Rossing P, Hansen TW (2016) Cardiac autonomic function is associated with the coronary microcirculatory function in patients with type 2 diabetes. Diabetes 65:3129–3138CrossRefGoogle Scholar
  38. 38.
    Adlan AM, Lip GYH, Paton JFR, Kitas GD, Fisher JP (2014) Autonomic function and rheumatoid arthritis: a systematic review. Semin Arthritis Rheum 44:283–304CrossRefPubMedGoogle Scholar
  39. 39.
    Stojanovich L, Milovanovich B, de Luka SR, Popovich-Kuzmanovich D, Bisenich V, Djukanovich B et al (2007) Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjögren syndrome and other autoimmune diseases. Lupus 16:181–185CrossRefPubMedGoogle Scholar
  40. 40.
    McGonagle D, McDermott MF (2006) A proposed classification of the immunological diseases. PLoS Med 3:e297CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ait-Oufella H, Salomon BL, Potteaux S, Robertson A-KL, Gourdy P, Zoll J et al (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12:178–180CrossRefPubMedGoogle Scholar
  42. 42.
    Suciu CF, Prete M, Ruscitti P, Favoino E, Giacomelli R, Perosa F (2018) Oxidized low density lipoproteins: the bridge between atherosclerosis and autoimmunity. Possible implications in accelerated atherosclerosis and for immune intervention in autoimmune rheumatic disorders. Autoimmun Rev 17:366–375CrossRefPubMedGoogle Scholar
  43. 43.
    Erre GL, Piga M, Carru C, Angius A, Carcangiu L, Piras M et al (2015) Global microRNA profiling of peripheral blood mononuclear cells in patients with Behcet’s disease. Clin Exp Rheumatol 33(6 Suppl 94):72–79Google Scholar
  44. 44.
    Piga M, Paladini F, Lai S, Erre G, Passiu G, Carcassi C et al (2012) Genetics of Behçet’s disease in Sardinia: two distinct extended HLA haplotypes harbour the B*51 allele in the normal population and in patients. Clin Exp Rheumatol 30:S51PubMedGoogle Scholar
  45. 45.
    Seyahi E, Ugurlu S, Cumali R, Balci H, Ozdemir O, Melikoglu M et al (2008) Atherosclerosis in Behçet’s Syndrome. Semin Arthritis Rheum 38:1–12CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.UOC Reumatologia, Dipartimento di Medicina Clinica e SperimentaleAzienda Ospedaliero-Universitaria di Sassari e Università di SassariSassariItaly
  2. 2.Dipartimento di Scienze BiomedicheUniversità degli Studi di SassariSassariItaly
  3. 3.Department of Clinical Pharmacology, College of Medicine and Public HealthFlinders University and Flinders Medical CentreAdelaideAustralia

Personalised recommendations