Skip to main content

Advertisement

SpringerLink
Log in

A critical view on cardiovascular risk in systemic sclerosis

  • Pathology Review
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Systemic Sclerosis (SSc) is an autoimmune disorder characterized by microvascular injury and diffuse fibrosis of the skin and internal organs. While macrovascular disease and higher risk for cardiovascular events are well documented in other systemic rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, the presence and extent of atherosclerosis among patients with SSc is yet to be established. Primary cardiac involvement, due to impairment of coronary microvascular circulation and myocardial fibrosis, considerably affects prognosis and life expectancy of individuals with SSc, representing one of the leading causes of death in this population. On the other hand the existence and prevalence of atherosclerotic coronary disease remains an issue of debate as studies comparing structural and morphological markers of atherosclerosis and cardiovascular events between SSc patients and the general population have yielded controversial results. The aim of this review is to summarize recent literature about the prevalence of cardiovascular disease in SSc, review the surrogate markers of CVD that have been evaluated and examine whether common pathogenic mechanisms exist between SSc and macrovascular disease.

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

Similar content being viewed by others

References

  1. Barnes J, Mayes MD (2012) Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr Opin Rheumatol 24:165–170

    Article  PubMed  Google Scholar 

  2. Chifflot H et al (2008) Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthritis Rheum 37:223–235

    Article  PubMed  Google Scholar 

  3. Gabrielli A et al (2009) Scleroderma. N Engl J Med 360:1989–2003

    Article  CAS  PubMed  Google Scholar 

  4. Dimitroulas T, Giannakoulas G, Karvounis H, Settas L, Kitas GD (2012) Systemic sclerosis-related pulmonary hypertension: unique characteristics and future treatment targets. Curr Pharm Des 18:1457–1464

    Article  CAS  PubMed  Google Scholar 

  5. Cannarile F et al (2015) Cardiovascular disease in systemic sclerosis. Ann Transl Med 3:8

    PubMed  PubMed Central  Google Scholar 

  6. Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD (2011) Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int 31(11):1409–1417

    Article  PubMed  Google Scholar 

  7. Sherer Y, Shoenfeld Y (2006) Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat Clin Pract Rheumatol 2:99–106

    Article  CAS  PubMed  Google Scholar 

  8. Kitas GD, Gabriel SE (2011) Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis 70:8–14

    Article  PubMed  Google Scholar 

  9. Hollan I et al (2013) Cardiovascular disease in autoimmune rheumatic diseases. Autoimmun Rev 12:1004–1015

    Article  CAS  PubMed  Google Scholar 

  10. Nurmohamed MT, Heslinga M, Kitas GD (2015) Cardiovascular comorbidity in rheumatic diseases. Nat Rev Rheumatol 11:693–704

    Article  CAS  PubMed  Google Scholar 

  11. Gonzalez A, Maradit Kremers H, Crowson CS, Ballman KV, Roger VL, Jacobsen SJ et al (2008) Cardiovascular risk factors confer the same risk for cardiovascular outcomes in rheumatoid arthritis patients as in non-rheumatoid arthritis patients? Ann Rheum Dis 67:64–69

    Article  CAS  PubMed  Google Scholar 

  12. Zegos T, Kitas G, Dimitroulas T (2016) Cardiovascular risk in rheumatoid arthritis: assessment, management and next steps. Ther Adv Musculoskelet Dis 8:86–101

    Article  Google Scholar 

  13. Faccini A, Kaski JC, Camici PG (2016) Coronary microvascular dysfunction in chronic nflammatory rheumatoid diseases. Eur Heart J 37:1799–1806

    Article  PubMed  Google Scholar 

  14. Sharma A, Gopalakrishnan D, Kumar R, Vijayvergiya R, Dogra S (2013) Metabolic syndrome in psoriatic arthritis patients: a cross-sectional study. Int J Rheum Dis 16:667–673

    Article  PubMed  Google Scholar 

  15. Medina G et al (2003) Increased carotid artery intima-media thickness may be associated with stroke in primary antiphospholipid syndrome. Ann Rheum Dis 62:607–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Westlake SL, Colebatch AN, Baird J, Kiely P, Quinn M, Choy E et al (2010) The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford) 49:295–307

    Article  CAS  Google Scholar 

  17. Sandoo A, van Zanten JJ, Toms TE, Carroll D, Kitas GD (2012) Anti-TNFα therapy transiently improves high density lipoprotein cholesterol levels and microvascular endothelial function in patients with rheumatoid arthritis: a pilot study. BMC Musculoskelet Disord 13:127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kiortsis DN, Mavridis AK, Vasakos S, Nikas SN, Drosos AA (2005) Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis 64:765–766

    Article  CAS  PubMed  Google Scholar 

  19. Stavropoulos-Kalinoglou A, Metsios GS, Panoulas VF, Nightingale P, Koutedakis Y, Kitas GD (2012) Anti-tumour necrosis factor alpha therapy improves insulin sensitivity in normal-weight but not in obese patients with rheumatoid arthritis. Arthritis Res Ther 14:R160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gasparyan AY, Ayvazyan L, Cocco G, Kitas GD (2012) Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research. Curr Pharm Des 18:1543–1555

    Article  CAS  PubMed  Google Scholar 

  21. Nurmohamed MT, Kitas G (2011) Cardiovascular risk in rheumatoid arthritis and diabetes: how does it compare and when does it start? Annals of the rheumatic diseases. Ann Rheum Dis 70:881–883

    Article  PubMed  Google Scholar 

  22. Dimitroulas T, Sarafidis P, Roma V, Karagiannopoulou G, Kapoulas S, Dimitroula H et al (2010) Scleroderma renal crisis accompanied by new-onsetpulmonary arterial hypertension: an acute systemic endothelial injury? Casereport and literature. Inflamm Allergy Drug Targets 9:313–318

    Article  CAS  PubMed  Google Scholar 

  23. Simeón-Aznar CP, Fonollosa-Plá V, Tolosa-Vilella C, Espinosa-Garriga G, Campillo-Grau M, Ramos-Casals M et al Spanish Scleroderma Study Group (SSSG); Autoimmune Diseases Study Group (GEAS); Spanish Society of Internal Medicine (SEMI) (2015) Registry of the Spanish Network for systemic sclerosis: survival, prognostic factors, and causes of death. Medicine (Baltimore) 94:e1728

  24. Nussinovitch U, Shoenfeld Y (2011) Atherosclerosis and macrovascular involvement in systemic sclerosis: myth or reality. Autoimmun Rev 10:259–266

    Article  PubMed  Google Scholar 

  25. Psarras A et al (2014) Giant cell arteritis and systemic sclerosis: a rare overlap syndrome. Rheumatol Rep 6:1

    Article  Google Scholar 

  26. Hupp SL (1989) Giant cell arteritis associated with progressive systemic sclerosis. J Clin Neuroophthalmol 9:126–130

    CAS  PubMed  Google Scholar 

  27. Jacobsen S et al (1998) Mortality and causes of death of 344 Danish patients with systemic sclerosis (scleroderma). Br J Rheumatol 37:750–755

    Article  CAS  PubMed  Google Scholar 

  28. Hesselstrand R et al (1998) Mortality and causes of death in a Swedish series of systemic sclerosis patients. Ann Rheum Dis 57:682–686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tyndall AJ et al (2010) Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69:1809–1815

    Article  PubMed  Google Scholar 

  30. Dave AJ et al (2014) Atherosclerotic cardiovascular disease in hospitalized patients with systemic sclerosis: higher mortality than patients with lupus and rheumatoid arthritis. Arthritis Care Res (Hoboken) 66:323–327

    Article  Google Scholar 

  31. Man A et al (2013) The risk of cardiovascular disease in systemic sclerosis: a population-based cohort study. Ann Rheum Dis 72:1188–1193

    Article  PubMed  Google Scholar 

  32. Ngian GS et al (2012) Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis. Ann Rheum Dis 71:1980–1983

    Article  PubMed  Google Scholar 

  33. Ngian GS et al (2011) Cardiovascular disease in systemic sclerosis–an emerging association? Arthritis Res Ther 13:237

    Article  PubMed  PubMed Central  Google Scholar 

  34. Aviña-Zubieta JA, Man A, Yurkovich M, Huang K, Sayre EC, Choi HK (2016) Early cardiovascular disease after the diagnosis of systemic sclerosis. Am J Med 129:324–331

    Article  PubMed  Google Scholar 

  35. D’Angelo WA et al (1969) Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 46:428–440

    Article  PubMed  Google Scholar 

  36. Youssef P et al (1995) Limited scleroderma is associated with increased prevalence of macrovascular disease. J Rheumatol 22:469–472

    CAS  PubMed  Google Scholar 

  37. Komocsi A et al (2010) Overlap of coronary disease and pulmonary arterial hypertension in systemic sclerosis. Ann Rheum Dis 69:202–205

    Article  CAS  PubMed  Google Scholar 

  38. Derk CT, Jimenez SA (2007) Acute myocardial infarction in systemic sclerosis patients: a case series. Clin Rheumatol 26:965–968

    Article  PubMed  Google Scholar 

  39. Khurma V et al (2008) A pilot study of subclinical coronary atherosclerosis in systemic sclerosis: coronary artery calcification in cases and controls. Arthritis Rheum 59:591–597

    Article  CAS  PubMed  Google Scholar 

  40. Tarek G et al (2006) Coronary angiographic findings in asymptomatic systemic sclerosis. Clin Rheumatol 25:487–490

    Article  Google Scholar 

  41. Lekakis J et al (1998) Short-term estrogen administration improves abnormal endothelial function in women with systemic sclerosis and Raynaud’s phenomenon. Am Heart J 136:905–912

    Article  CAS  PubMed  Google Scholar 

  42. Sherer Y et al (2007) Early atherosclerosis and autoantibodies to heat-shock proteins and oxidized LDL in systemic sclerosis. Ann N Y Acad Sci 1108:259–267

    Article  CAS  PubMed  Google Scholar 

  43. Bartoli F et al (2007) Angiotensin-converting enzyme I/D polymorphism and macrovascular disease in systemic sclerosis. Rheumatology (Oxford) 46:772–775

    Article  CAS  Google Scholar 

  44. Bartoli F et al (2007) Flow-mediated vasodilation and carotid intima-media thickness in systemic sclerosis. Ann N Y Acad Sci 1108:283–290

    Article  PubMed  Google Scholar 

  45. Kaloudi O et al (2007) Circulating levels of Nepsilon-(carboxymethyl)lysine are increased in systemic sclerosis. Rheumatology (Oxford) 46:412–416

    Article  CAS  Google Scholar 

  46. Kumar U, Verma N, Kumar AK, Hari S, Yadav R, Sreenivas V et al (2010) Endothelial dysfunction in Indian patients with systemic sclerosis[abstract]. Ann Rheum Dis 69(Suppl 3):692

    Google Scholar 

  47. Tsifetaki N et al (2010) Subclinical atherosclerosis in scleroderma patients. Scand J Rheumatol 39:326–329

    Article  CAS  PubMed  Google Scholar 

  48. Hettema ME, Zhang D, de Leeuw K, Stienstra Y, Smit AJ, Kallenberg CG, Bootsma H (2008) Early atherosclerosis in systemic sclerosis and its relation to disease or traditional risk factors. Arthritis Res Ther 10:R49

    Article  PubMed  PubMed Central  Google Scholar 

  49. Roustit M et al (2008) Discrepancy between simultaneous digital skin microvascular and brachial artery macrovascular post-occlusive hyperemia in systemic sclerosis. J Rheumatol 35:1576–1583

    PubMed  PubMed Central  Google Scholar 

  50. Piccione MC et al (2011) Early identification of vascular damage in patients with systemic sclerosis. Angiology 62:338–343

    Article  PubMed  Google Scholar 

  51. Liu J et al (2011) Preferential macrovasculopathy in systemic sclerosis detected by regional pulse wave velocity from wave intensity analysis: comparisons of local and regional arterial stiffness parameters in cases and controls. Arthritis Care Res (Hoboken) 63:579–587

    Article  Google Scholar 

  52. Ho M et al (2000) Macrovascular disease and systemic sclerosis. Ann Rheum Dis 59:39–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Schiopu E et al (2014) Prevalence of subclinical atherosclerosis is increased in systemic sclerosis and is associated with serum proteins: a cross-sectional, controlled study of carotid ultrasound. Rheumatology (Oxford) 53:704–713

    Article  CAS  Google Scholar 

  54. Ozen G, Inanc N, Unal AU, Korkmaz F, Sunbul M, Ozmen M et al (2016) Subclinical Atherosclerosis in systemic sclerosis: not less frequent than rheumatoid arthritis and not detected with cardiovascular risk indices. Arthritis Care Res (Hoboken) 2016 Feb 11 [Epub ahead of print]

  55. Szucs G 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 

  56. Rollando D et al (2010) Brachial artery endothelial-dependent flow-mediated dilation identifies early-stage endothelial dysfunction in systemic sclerosis and correlates with nailfold microvascular impairment. J Rheumatol 37:1168–1173

    Article  PubMed  Google Scholar 

  57. Stucker M et al (2000) Macroangiopathy of the upper extremities in progressive systemic sclerosis. Eur J Med Res 5:295–302

    CAS  PubMed  Google Scholar 

  58. Trostle DC et al (1988) Renal vascular histology and morphometry in systemic sclerosis. A case-control autopsy study. Arthritis Rheum 31:393–400

    Article  CAS  PubMed  Google Scholar 

  59. Stafford L et al (1998) Distribution of macrovascular disease in scleroderma. Ann Rheum Dis 57:476–479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dimitroulas T, Giannakoulas G, Karvounis H, Garyfallos A, Settas L, Kitas GD (2014) Micro- and macro-vascular treatment targets in scleroderma heart disease. Curr Pharm 20:536–544

    Article  CAS  Google Scholar 

  61. Zakopoulos NA et al (2003) Systemic sclerosis is not associated with clinical or ambulatory blood pressure. Clin Exp Rheumatol 21:199–204

    CAS  PubMed  Google Scholar 

  62. Zeng Y et al (2012) Macrovascular involvement in systemic sclerosis: evidence of correlation with disease activity. Clin Exp Rheumatol 30(2 Suppl 71):S76–S80

    PubMed  Google Scholar 

  63. Lippi G et al (2006) Lipoprotein[a] and the lipid profile in patients with systemic sclerosis. Clin ChimActa 364(1–2):345–348

    Article  CAS  Google Scholar 

  64. Borba EF et al (2005) Lipoprotein profile in limited systemic sclerosis. Rheumatol Int 25:379–383

    Article  CAS  PubMed  Google Scholar 

  65. Abraham DJ, Distler O (2007) How does endothelial cell injury start? The role of endothelin in systemic sclerosis. Arthritis Res Ther 9(Suppl 2):S2

    Article  PubMed  PubMed Central  Google Scholar 

  66. Abraham DJ, Krieg T, Distler O (2009) Overview of pathogenesis of systemic sclerosis. Rheumatology (Oxford)48(Suppl 3):iii3-7

  67. Assaly R et al (2001) Initial evidence of endothelial cell apoptosis as a mechanism of systemic capillary leak syndrome. Chest 120:1301–1308

    Article  CAS  PubMed  Google Scholar 

  68. Muro Y et al (2009) An evaluation of the efficacy of the toe brachial index measuring vascular involvement in systemic sclerosis and other connective tissue diseases. Clin Exp Rheumatol 27(3 Suppl 54):26–31

    CAS  PubMed  Google Scholar 

  69. Sgonc R et al (2000) Endothelial cell apoptosis in systemic sclerosis is induced by antibody-dependent cell-mediated cytotoxicity via CD95. Arthritis Rheum 43:2550–2562

    Article  CAS  PubMed  Google Scholar 

  70. Fernández-Codina A, Simeón-Aznar CP, Pinal-Fernandez I, Rodríguez-Palomares J, Pizzi MN, Hidalgo CE (2015) Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival. Rheumatol Int 2015 Oct 25 [Epub ahead of print]

  71. Muresan L, Petcu A, Pamfil C, Muresan C, Rinzis M, Mada RO (2016) Cardiovascular profiles of scleroderma patients arrhythmias and conduction disorders. Acta Reumatol Port 41:26–39

    CAS  PubMed  Google Scholar 

  72. Cannarile F, Valentini V, Mirabelli G, Alunno A, Terenzi R, Luccioli F (2015) Cardiovascular disease in systemic sclerosis. Ann Transl Med 3:8

    PubMed  PubMed Central  Google Scholar 

  73. Fernandes F et al (2003) Cardiac remodeling in patients with systemic sclerosis with no signs or symptoms of heart failure: an endomyocardial biopsy study. J Card Fail 9:311–317

    Article  PubMed  Google Scholar 

  74. Lekakis J, Mavrikakis M, Emmanuel M, Prassopoulos V, Papazoglou S, Papamichael C et al (1997) Cold-induced coronary Raynaud’s phenomenon in patients with systemic sclerosis. Clin Exp Rheumatol 16:135–140

    Google Scholar 

  75. Gustafsson R, Kazzam E, Mannting F, Waldenström A, Hällgren R (1989) Cold-induced reversible myocardial ischaemia in systemic sclerosis. The Lancet 334:475–479

    Article  Google Scholar 

  76. Long A, Duffy G, Bresnihan B (1986) Reversible myocardial perfusion defects during cold challenge in scleroderma. Rheumatology 25:158–161

    Article  CAS  Google Scholar 

  77. Mueller KA, Mueller II, Eppler D, Zuern CS, Seizer P, Kramer U (2015) Clinical and histopathological features of patients with systemic sclerosis undergoing endomyocardial biopsy. PLoS ONE 10:e0126707

    Article  PubMed  PubMed Central  Google Scholar 

  78. Kahan A, Nitenberg A, Foult JM, Amor B, Menkes CJ, Devaux JY et al (1985) Decreased coronary reserve in primary scleroderma myocardial disease. Arthritis Rheum 28:637–646

    Article  CAS  PubMed  Google Scholar 

  79. Follansbee WP, Curtiss EI, Medsger TA Jr, Steen VD, Uretsky BF, Owens GR (1984) Rodnan GP (1984) Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma. NEJM 310:142–148

    Article  CAS  PubMed  Google Scholar 

  80. Desai CS, Lee DC, Shah SJ (2011) Systemic sclerosis and the heart: current diagnosis and management. Curr Opin Rheumatol 23:545–554

    Article  PubMed  PubMed Central  Google Scholar 

  81. Can I, Onat AM, Aytemir K, Akdogan A, Ureten K, Kiraz S et al (2009) Detecting subclinical biventricular impairment in scleroderma patients by use of pulsed-wave tissue Doppler imaging. Tex Heart Inst J 1:36

    Google Scholar 

  82. Schattke S, Knebel F, Grohmann A, Dreger H, Kmezik F, Riemekasten G et al (2010) Early right ventricular systolic dysfunction in patients with systemic sclerosis without pulmonary hypertension: a Doppler Tissue and Speckle Tracking echocardiography study. Cardiovasc Ultrasound 8:1

    Article  Google Scholar 

  83. Dimitroulas T, Giannakoulas G, Papadopoulou K, Karvounis H, Dimitroula H, Koliakos G et al (2010) Early detection of cardiac involvement in systemic sclerosis assessed by tissue-Doppler echocardiography: relationship with neurohormonal activation and endothelial dysfunction. J Rheumatol 37:993–999

    Article  PubMed  Google Scholar 

  84. Mavrogeni S, Sfikakis PP, Dimitroulas T, Koutsogeorgopoulou L, Karabela G, Katsifis G et al (2015) Imaging patterns of cardiovascular involvement in mixed connective tissue disease evaluated by cardiovascular magnetic resonance. Inflamm Allergy Drug Targets 4:111–116

    Google Scholar 

  85. Barison A et al (2015) Early myocardial and skeletal muscle interstitial remodelling in systemic sclerosis: insights from extracellular volume quantification using cardiovascular magnetic resonance. Eur Heart J Cardiovasc Imaging 16:74–80

    Article  PubMed  Google Scholar 

  86. Ntusi NA, Piechnik SK, Francis JM, Ferreira VM, Rai AB, Matthews PM et al (2014) Subclinical myocardial inflammation and diffuse fibrosis are common in systemic sclerosis—a clinical study using myocardial T1-mapping and extracellular volume quantification. J Cardiovasc Magn Reson 16:21

    Article  PubMed  PubMed Central  Google Scholar 

  87. Mavrogeni S, Bratis K, Karabela G et al (2015) Cardiovascular Magnetic Resonance Imaging clarifies cardiac pathophysiology in early, asymptomatic diffuse systemic sclerosis. Inflamm Allergy Drug Targets 14:29–36

    Article  CAS  PubMed  Google Scholar 

  88. Mavrogeni SI, Kitas GD, Dimitroulas T, Sfikakis PP, Seo P, Gabriel S et al (2016) Cardiovascular magnetic resonance in rheumatology: current status and recommendations for use. Int J Cardiol 217:135–148

    Article  PubMed  Google Scholar 

  89. Hachulla E, Gressin V, Guillevin L et al (2005) Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum 52:3792–3800

    Article  PubMed  Google Scholar 

  90. Hunzelmann N, Genth E, Krieg T et al (2008) The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford) 47:1185–1192

    Article  CAS  Google Scholar 

  91. Avouac J, Airò P, Meune C et al (2010) Prevalence of pulmonary hyper- tension in systemic sclerosis in European Caucasians and metaana- lysis of 5 studies. J Rheumatol 37:2290–2298

    Article  PubMed  Google Scholar 

  92. Phung S, Strange G, Chung LP et al (2009) Prevalence of pulmonary arterial hypertension in an Australian scleroderma population: screening allows for earlier diagnosis. Intern Med J 39:682–691

    Article  CAS  PubMed  Google Scholar 

  93. Sanz J, Kariisa M, Dellegrottaglie S, Prat-Gonzalez S, Garcia MJ, Fuster V, Rajagopalan S (2009) Evaluation of pulmonary artery stiffness in pulmonary hypertension with cardiac magnetic resonance. J Am Coll Cardiol Img 2:286–295

    Article  Google Scholar 

  94. Fisher MR, Mathai SC, Champion HC et al (2006) Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. Arthritis Rheum 54:3043–3050

    Article  PubMed  Google Scholar 

  95. Dimitroulas T, Giannakoulas G, Papadopoulou K et al (2010) Left atrial volume and N-terminal pro-B type natriuretic peptide are associated with elevated pulmonary artery pressure in patients with systemic sclerosis. Clin Rheumatol 29:957–964

    Article  PubMed  Google Scholar 

  96. Tongers J, Schwerdtfeger B, Klein G et al (2007) Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J 153:127–132

    Article  PubMed  Google Scholar 

  97. Mathai SC, Bueso M, Hummers LK et al (2010) Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension. Eur Respir J 35:95–104

    Article  CAS  PubMed  Google Scholar 

  98. Allanore Y, Meune C, Vonk MC et al (2010) Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of systemic sclerosis patients. Ann Rheum Dis 69:218–221

    Article  CAS  PubMed  Google Scholar 

  99. Aversa A, Greco E, Bruzziches R, Pili M, Rosano G, Spera G (2007) Relation-ship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study. Int J Impot Res 19:200–207

    Article  CAS  PubMed  Google Scholar 

  100. Koka S, Das A, Salloum FN, Kukreja RC (2013) Phosphodiesterase-5 inhibitor tadalafil attenuates oxidative stress and protects against myocardial ischemia/reperfusion injury in type 2 diabetic mice. Free Radic Biol Med 60:80–88

    Article  CAS  PubMed  Google Scholar 

  101. Varma A, Das A, Hoke NN, Durrant DE, Salloum FN, Kukreja RC (2012) Anti-inflammatory and cardioprotective effects of tadalafil in diabetic mice. PLoS One7:e45243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Metsios G, Lahart IM (2015) Exercise as medicine in rheumatoid arthritis. Mediterr J Rheumatol 26:54–61

    Google Scholar 

  103. John H, Carroll D, Kitas GD (2011) Cardiovascular education for people with rheumatoid arthritis: what can existing patient education programmes teach us? Rheumatology (Oxford) 50:1751–1759

    Article  Google Scholar 

  104. Domsic RT, Dezfulian C, Shoushtari A, Ivanco D, Kenny E, Kwoh CK et al (2014) Endothelial dysfunction is present only in the microvasculature and microcirculation of early diffuse systemics clerosis patients. Clin Exp Rheumatol 32(6 Suppl 86):S-154-60

  105. Turiel M, Gianturco L, Ricci C, Sarzi-Puttini P, Tomasoni L, Colonna Vde G et al (2013) Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross-sectional study. Arthritis Care Res (Hoboken) 2013(65):274–280

    Article  Google Scholar 

Download references

Authors contributions

Review concept and design: Antonios Psarras, Theodoros Dimitroulas. Drafting of the manuscript: Antonios Psarras, Stergios Soulaidopoulos. Critical revision of the manuscript for important intellectual content: George Kitas, Alexandros Garyfallos, Theodoros Dimitroulas.

Author information

Authors and Affiliations

  1. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK

    Antonios Psarras

  2. Fourth Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Str, 54642, Thessaloniki, Greece

    Stergios Soulaidopoulos, Alexandros Garyfallos & Theodoros Dimitroulas

  3. Arthritis Research UK Epidemiology Unit, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    George Kitas

Authors
  1. Antonios Psarras
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stergios Soulaidopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexandros Garyfallos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George Kitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Theodoros Dimitroulas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Theodoros Dimitroulas.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Psarras, A., Soulaidopoulos, S., Garyfallos, A. et al. A critical view on cardiovascular risk in systemic sclerosis. Rheumatol Int 37, 85–95 (2017). https://doi.org/10.1007/s00296-016-3530-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-016-3530-3

Keywords

Search

Navigation