Preventing Heart Failure in Inflammatory and Immune Disorders

Heart Failure Prevention (W Tang, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Heart Failure Prevention

Abstract

Patients with chronic inflammatory diseases are at increased risk of heart failure due to ischemic heart disease and other causes including heart failure with preserved ejection fraction. Using rheumatoid arthritis and treated HIV infection as two prototypical examples, we review the epidemiology of heart failure in these populations and potential therapies to prevent it. Particular focus is given to antiinflammatory therapies including statins and biologic disease-modifying drugs. There is also limited evidence for lifestyle changes and blockade of the renin-angiotensin-aldosterone system. We conclude by proposing how a strategy for heart failure prevention, such as the model tested in the Screening To Prevent Heart Failure (STOP-HF) trial, may be adapted to chronic inflammatory disease.

Keywords

Heart failure HIV Rheumatoid arthritis Inflammation 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics – 2013 update: a report from the American Heart Association. Circulation. 2013;127:e6–245.PubMedCrossRefGoogle Scholar
  2. 2.
    Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292:344–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Schocken DD, Benjamin EJ, Fonarow GC, Krumholz HM, Levy D, Mensah GA, et al. Prevention of heart failure: a scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation. 2008;117:2544–65.PubMedCrossRefGoogle Scholar
  4. 4.••
    Ledwidge M, Gallagher J, Conlon C, Tallon E, O'Connell E, Dawkins I, et al. Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. JAMA. 2013;310:66–74. This was a trial of BNP screening, followed by targeted echocardiography, and tailored management of risk factors by an interdisciplinary team. Compared to usual care, this multi-level intervention reduced by 40 – 45% the relative risk of incident LV dysfunction and hospitalization for major CVD events. There was a nonstatistically significant 50 % reduction in clinical heart failure.PubMedCrossRefGoogle Scholar
  5. 5.
    Elster SK, Braunwald E, Wood HF. A study of C-reactive protein in the serum of patients with congestive heart failure. Am Heart J. 1956;51:533–41.PubMedCrossRefGoogle Scholar
  6. 6.
    Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001;103:2055–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323:236–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Nicola PJ, Maradit-Kremers H, Roger VL, Jacobsen SJ, Crowson CS, Ballman KV, et al. The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years. Arthritis Rheum. 2005;52:412–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: a systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2:e000062.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Schoenfeld SR, Kasturi S, Costenbader KH. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum. 2013;43:77–95.PubMedCrossRefGoogle Scholar
  11. 11.
    Butt AA, Chang CC, Kuller L, Goetz MB, Leaf D, Rimland D, et al. Risk of heart failure with human immunodeficiency virus in the absence of prior diagnosis of coronary heart disease. Arch Intern Med. 2011;171:737–43.PubMedCentralPubMedGoogle Scholar
  12. 12.
    O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson Jr SK. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999;340:14–22.PubMedCrossRefGoogle Scholar
  13. 13.
    van Sijl AM, Peters MJ, Knol DK, de Vet HC, Gonzalez-Gay MA, Smulders YM, et al. Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum. 2011;40:389–97.PubMedCrossRefGoogle Scholar
  14. 14.
    Van Sijl AM, Van Den Hurk K, Peters MJ, Van Halm VP, Nijpels G, Stehouwer CD, et al. Different type of carotid arterial wall remodeling in rheumatoid arthritis compared with healthy subjects: a case-control study. J Rheumatol. 2012;39:2261–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Sandoo A, Veldhuijzen van Zanten JJ, Metsios GS, Carroll D, Kitas GD. Vascular function and morphology in rheumatoid arthritis: a systematic review. Rheumatology (Oxford). 2011;50:2125–39.CrossRefGoogle Scholar
  16. 16.
    Corrao S, Messina S, Pistone G, Calvo L, Scaglione R, Licata G. Heart involvement in rheumatoid arthritis: systematic review and meta-analysis. Int J Cardiol. 2013;167:2031–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Myasoedova E, Davis 3rd JM, Crowson CS, Roger VL, Karon BL, Borgeson DD, et al. Brief report: rheumatoid arthritis is associated with left ventricular concentric remodeling: results of a population-based cross-sectional study. Arthritis Rheum. 2013;65:1713–8.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Fine NM, Crowson CS, Lin G, Oh JK, Villarraga HR, Gabriel SE. Evaluation of myocardial function in patients with rheumatoid arthritis using strain imaging by speckle-tracking echocardiography. Ann Rheum Dis. 2013. doi:10.1136/annrheumdis-2013-203314.Google Scholar
  19. 19.
    Liang KP, Myasoedova E, Crowson CS, Davis JM, Roger VL, Karon BL, et al. Increased prevalence of diastolic dysfunction in rheumatoid arthritis. Ann Rheum Dis. 2010;69:1665–70.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.•
    Mavrogeni S, Dimitroulas T, Sfikakis PP, Kitas GD. Heart involvement in rheumatoid arthritis: multimodality imaging and the emerging role of cardiac magnetic resonance. Semin Arthritis Rheum. 2013;43:314–24. This review summarizes the findings of multimodality cardiac imaging studies in patients with rheumatoid arthritis, with a focus on the use of MRI to detect patterns of fibrosis.PubMedCrossRefGoogle Scholar
  21. 21.
    Lebowitz WB. The heart in rheumatoid arthritis (rheumatoid disease). A clinical and pathological study of sixty-two cases. Ann Intern Med. 1963;58:102–23.PubMedCrossRefGoogle Scholar
  22. 22.
    Giles JT, Malayeri AA, Fernandes V, Post W, Blumenthal RS, Bluemke D, et al. Left ventricular structure and function in patients with rheumatoid arthritis, as assessed by cardiac magnetic resonance imaging. Arthritis Rheum. 2010;62:940–51.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Mavrogeni S, Karabela G, Stavropoulos E, Gialafos E, Sfendouraki E, Kyrou L, et al. Imaging patterns of heart failure in rheumatoid arthritis evaluated by cardiovascular magnetic resonance. Int J Cardiol. 2013;168:4333–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Kobayashi Y, Giles JT, Hirano M, Yokoe I, Nakajima Y, Bathon JM, et al. Assessment of myocardial abnormalities in rheumatoid arthritis using a comprehensive cardiac magnetic resonance approach: a pilot study. Arthritis Res Ther. 2010;12:R171.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Davis 3rd JM, Roger VL, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population. Arthritis Rheum. 2008;58:2603–11.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Myasoedova E, Crowson CS, Nicola PJ, Maradit-Kremers H, Davis 3rd JM, Roger VL, et al. The influence of rheumatoid arthritis disease characteristics on heart failure. J Rheumatol. 2011;38:1601–6.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.••
    Freiberg MS, Chang CC, Kuller LH, Skanderson M, Lowy E, Kraemer KL, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173:614–22. In this very large epidemiologic study of over 27,000 HIV+ patients and 55,000 matched uninfected controls in the Veterans Affairs health system, HIV infection was associated with 1.5-fold higher risk of MI after adjustment for a large number of potential confounders.PubMedCrossRefGoogle Scholar
  28. 28.
    Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system. J Acquir Immune Defic Syndr. 2012;60:351–8.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Freiberg M, Chang CC, Oursler KA, Gottdiener J, Gottlieb S, Warner A, et al. The risk of and survival with preserved vs. reduced ejection fraction heart failure by HIV status. Proceedings of the 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, GA, USA; 2013.Google Scholar
  30. 30.
    Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356:1723–35.PubMedCrossRefGoogle Scholar
  31. 31.
    Monforte A, Reiss P, Ryom L, El-Sadr W, Dabis F, De Wit S, et al. Atazanavir is not associated with an increased risk of cardio or cerebrovascular disease events. AIDS. 2013;27:407–15.PubMedCrossRefGoogle Scholar
  32. 32.
    Hsue PY, Deeks SG, Hunt PW. Immunologic basis of cardiovascular disease in HIV-infected adults. J Infect Dis. 2012;205 Suppl 3:S375–82.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Longenecker CT, Hoit BD. Imaging atherosclerosis in HIV: carotid intima-media thickness and beyond. Transl Res. 2012;159:127–39.PubMedCrossRefGoogle Scholar
  34. 34.
    Longenecker CT, Triant VA. Initiation of antiretroviral therapy at high CD4 cell counts: does it reduce the risk of cardiovascular disease? Curr Opin HIV AIDS. 2014;9:54–62.PubMedCrossRefGoogle Scholar
  35. 35.•
    Post WS, Budoff M, Kingsley L, Palella Jr FJ, Witt MD, Li X, et al. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014;160:458–67. HIV-infected patients from the Multicenter AIDS cohort study had higher amounts of noncalcified coronary plaque on CT angiography compared to matched uninfected controls. These noncalcified plaques may explain the higher rates of acute coronary syndromes observed in other observational studies.PubMedCrossRefGoogle Scholar
  36. 36.
    Fitch KV, Srinivasa S, Abbara S, Burdo TH, Williams KC, Eneh P, et al. Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis. 2013;208:1737–46.PubMedCrossRefGoogle Scholar
  37. 37.•
    Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, et al. Arterial inflammation in patients with HIV. JAMA. 2012;308:379–86. Aortic inflammation by FDG PET/CT was increased among 27 HIV+ patients compared to uninfected Framingham risk score-matched controls and similar to uninfected controls with known CAD. The degree of aortic inflammation correlated with soluble CD163, a soluble marker of monocyte activation.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Zanni MV, Abbara S, Lo J, Wai B, Hark D, Marmarelis E, et al. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS. 2013;27:1263–72.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Currie PF, Boon NA. Immunopathogenesis of HIV-related heart muscle disease: current perspectives. AIDS. 2003;17 Suppl 1:S21–8.PubMedCrossRefGoogle Scholar
  40. 40.••
    Holloway CJ, Ntusi N, Suttie J, Mahmod M, Wainwright E, Clutton G, et al. Comprehensive cardiac magnetic resonance imaging and spectroscopy reveal a high burden of myocardial disease in HIV patients. Circulation. 2013;128:814–22. This is the first large study of cardiac MRI in 90 HIV+ subjects compared to 30 matched controls. There were high amounts of cardiac steatosis on MR spectroscopy and cardiac replacement fibrosis by late-gadolinium enhancement. HIV-infected patients also had impaired systolic and diastolic strains.PubMedCrossRefGoogle Scholar
  41. 41.
    Nelson MD, LaBounty T, Szczepaniak L, Szczepaniak E, Smith L, St. John L, et al. Cardiac steatosis and left ventricular dysfunction is associated with exposure to human immunodeficiency virus highly active antiretroviral therapy: a 3-Tesla cardiac magnetic resonance imaging study. Proceedings of the 63rd Annual Scientific Sessions of the American College of Cardiology. Washington, DC, USA; 2014.Google Scholar
  42. 42.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147–239.PubMedCrossRefGoogle Scholar
  43. 43.
    Young DR, Reynolds K, Sidell M, Brar S, Ghai NR, Sternfeld B, et al. Effects of physical activity and sedentary time on the risk of heart failure. Circ Heart Fail. 2014;7:21–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Stavropoulos-Kalinoglou A, Metsios GS, Veldhuijzen van Zanten JJ, Nightingale P, Kitas GD, Koutedakis Y. Individualised aerobic and resistance exercise training improves cardiorespiratory fitness and reduces cardiovascular risk in patients with rheumatoid arthritis. Ann Rheum Dis. 2013;72:1819–25.PubMedCrossRefGoogle Scholar
  45. 45.•
    Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJ, Nightingale P, Sandoo A, Dimitroulas T, et al. Individualised exercise improves endothelial function in patients with rheumatoid arthritis. Ann Rheum Dis. 2014;73:748–51. A tailored 6-month aerobic and resistance exercise intervention improved brachial microvascular and macrovascular function among patients with RA, compared to simply giving information about the importance of exercise.PubMedCrossRefGoogle Scholar
  46. 46.
    Cade WT, Reeds DN, Overton ET, Herrero P, Waggoner AD, Laciny E, et al. Pilot study of pioglitazone and exercise training effects on basal myocardial substrate metabolism and left ventricular function in HIV-positive individuals with metabolic complications. HIV Clin Trials. 2013;14:303–12.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.•
    Pereira MC, Cardoso PR, Da Rocha LF, Rego Jr MJ, Goncalves SM, Santos FA, et al. Simvastatin inhibits cytokines in a dose response in patients with rheumatoid arthritis. Inflamm Res. 2014;63:309–15. Peripheral blood mononuclear cells from 22 patients with RA were exposed to escalating doses of simvastatin in vitro. Simvastatin decreased production of inflammatory cytokines, but those with severe RA disease had a blunted response.PubMedCrossRefGoogle Scholar
  48. 48.
    Lazzerini PE, Lorenzini S, Selvi E, Capecchi PL, Chindamo D, Bisogno S, et al. Simvastatin inhibits cytokine production and nuclear factor-kB activation in interleukin 1beta-stimulated synoviocytes from rheumatoid arthritis patients. Clin Exp Rheumatol. 2007;25:696–700.PubMedGoogle Scholar
  49. 49.•
    Funderburg NT, Jiang Y, Debanne SM, Storer N, Labbato D, Clagett B, et al. Rosuvastatin treatment reduces markers of monocyte activation in HIV infected subjects on antiretroviral therapy. Clin Infect Dis. 2014;58:588–95. In the SATURN-HIV trial, after 24 weeks of rosuvastatin 10 mg daily markers of monocyte activation were reduced.PubMedCrossRefGoogle Scholar
  50. 50.•
    Eckard AR, Jiang Y, Debanne SM, Funderburg NT, McComsey GA. Effect of 24 weeks of statin therapy on systemic and vascular inflammation in HIV-infected subjects on antiretroviral therapy. J Infect Dis. 2014;209:1156–64. In the SATURN-HIV trial, after 24 weeks of rosuvastatin, lipoprotein phospholipase A2 levels were decreased but circulating inflammatory cytokines were not affected.PubMedCrossRefGoogle Scholar
  51. 51.
    Hermann F, Forster A, Chenevard R, Enseleit F, Hurlimann D, Corti R, et al. Simvastatin improves endothelial function in patients with rheumatoid arthritis. J Am Coll Cardiol. 2005;45:461–4.PubMedCrossRefGoogle Scholar
  52. 52.
    Van Doornum S, McColl G, Wicks IP. Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis. Ann Rheum Dis. 2004;63:1571–5.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    He M, Liang X, He L, Wen W, Zhao S, Wen L, et al. Endothelial dysfunction in rheumatoid arthritis: the role of monocyte chemotactic protein-1-induced protein. Arterioscler Thromb Vasc Biol. 2013;33:1384–91.PubMedCrossRefGoogle Scholar
  54. 54.
    Crowson CS, Liao KP, Davis 3rd JM, Solomon DH, Matteson EL, Knutson KL, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166:628.e1.CrossRefGoogle Scholar
  55. 55.
    De Vera MA, Choi H, Abrahamowicz M, Kopec J, Lacaille D. Impact of statin discontinuation on mortality in patients with rheumatoid arthritis: a population-based study. Arthritis Care Res (Hoboken). 2012;64:809–16.CrossRefGoogle Scholar
  56. 56.
    Moore RD, Bartlett JG, Gallant JE. Association between use of HMG CoA reductase inhibitors and mortality in HIV-infected patients. PLoS One. 2011;6:e21843.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Rasmussen LD, Kronborg G, Larsen CS, Pedersen C, Gerstoft J, Obel N. Statin therapy and mortality in HIV-infected individuals; a Danish nationwide population-based cohort study. PLoS One. 2013;8:e52828.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Martin MF, Surrall KE, McKenna F, Dixon JS, Bird HA, Wright V. Captopril: a new treatment for rheumatoid arthritis? Lancet. 1984;1:1325–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Bird HA, Le Gallez P, Dixon JS, Catalano MA, Traficante A, Liauw LA, et al. A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis. J Rheumatol. 1990;17:603–8.PubMedGoogle Scholar
  60. 60.
    Dalbeth N, Edwards J, Fairchild S, Callan M, Hall FC. The non-thiol angiotensin-converting enzyme inhibitor quinapril suppresses inflammatory arthritis. Rheumatology (Oxford). 2005;44:24–31.CrossRefGoogle Scholar
  61. 61.•
    Shi Q, Abusarah J, Baroudi G, Fernandes JC, Fahmi H, Benderdour M. Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis. Arthritis Res Ther. 2012;14:R223. In a rat model of inflammatory arthritis, ramipril attenuated the oxidative stress and profibrotic activity induced by 4-hydroxynonenal infusion.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Flammer AJ, Sudano I, Hermann F, Gay S, Forster A, Neidhart M, et al. Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis. Circulation. 2008;117:2262–9.PubMedCrossRefGoogle Scholar
  63. 63.•
    De Socio GV, Ricci E, Maggi P, Parruti G, Pucci G, Di Biagio A, et al. Prevalence, awareness, treatment, and control rate of hypertension in HIV-infected patients: the HIV-HY study. Am J Hypertens. 2014;27:222–8. Among the HIV+ patients in this Italian clinic, 30 % had hypertension, but one-third were unaware of their diagnosis. Among those who were treated, 75 % were on either monotherapy or combination therapy with ACE inhibitors or angiotensin receptor blockers.PubMedCrossRefGoogle Scholar
  64. 64.
    Nuesch R, Wang Q, Elzi L, Bernasconi E, Weber R, Cavassini M, et al. Risk of cardiovascular events and blood pressure control in hypertensive HIV-infected patients: Swiss HIV Cohort Study (SHCS). J Acquir Immune Defic Syndr. 2013;62:396–404.PubMedCrossRefGoogle Scholar
  65. 65.
    Vecchiet J, Ucciferri C, Falasca K, Mancino P, Di Iorio A, De Caterina R. Antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients. Antivir Ther. 2011;16:639–45.PubMedCrossRefGoogle Scholar
  66. 66.
    Ucciferri C, Falasca K, Mancino P, Di Iorio A, Vecchiet J. Microalbuminuria and hypertension in HIV-infected patients: a preliminary study of telmisartan. Eur Rev Med Pharmacol Sci. 2012;16:491–8.PubMedGoogle Scholar
  67. 67.
    Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation. 2010;121:651–8.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005;352:48–62.PubMedCrossRefGoogle Scholar
  69. 69.
    Lake JE, Tseng CH, Currier JS. A pilot study of telmisartan for visceral adiposity in HIV infection: the metabolic abnormalities, telmisartan, and HIV infection (MATH) trial. PLoS One. 2013;8:e58135.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Baker JV, Huppler Hullsiek K, Prosser R, Duprez D, Grimm R, Tracy RP, et al. Angiotensin converting enzyme inhibitor and HMG-CoA reductase inhibitor as adjunct treatment for persons with HIV infection: a feasibility randomized trial. PLoS One. 2012;7:e46894.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.••
    Wasko MC, Dasgupta A, Hubert H, Fries JF, Ward MM. Propensity-adjusted association of methotrexate with overall survival in rheumatoid arthritis. Arthritis Rheum. 2013;65:334–42. Methotrexate use for more than 1 year was associated with a 70 % reduction in mortality among over 5,000 patients with RA followed for 25 years.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Micha R, Imamura F, Wyler von Ballmoos M, Solomon DH, Hernan MA, Ridker PM, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol. 2011;108:1362–70.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Marks JL, Edwards CJ. Protective effect of methotrexate in patients with rheumatoid arthritis and cardiovascular comorbidity. Ther Adv Musculoskelet Dis. 2012;4:149–57.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Bernatsky S, Hudson M, Suissa S. Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis. Rheumatology (Oxford). 2005;44:677–80.CrossRefGoogle Scholar
  75. 75.
    Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, Zaharris E, et al. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013;166:199–207.e15.PubMedCrossRefGoogle Scholar
  76. 76.
    Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation. 2004;109:1594–602.PubMedCrossRefGoogle Scholar
  77. 77.
    Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133–40.PubMedCrossRefGoogle Scholar
  78. 78.
    Setoguchi S, Schneeweiss S, Avorn J, Katz JN, Weinblatt ME, Levin R, et al. Tumor necrosis factor-alpha antagonist use and heart failure in elderly patients with rheumatoid arthritis. Am Heart J. 2008;156:336–41.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.••
    Solomon DH, Rassen JA, Kuriya B, Chen L, Harrold LR, Graham DJ, et al. Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonist. Ann Rheum Dis. 2013;72:1813–8. This large observational study found no evidence of an association between TNFα blockade and incident heart failure hospitalization among over 11,000 users of TNFα-antagonists compared to over 8,000 users of non-biologic DMARDs.PubMedCrossRefGoogle Scholar
  80. 80.
    Kotyla PJ, Owczarek A, Rakoczy J, Lewicki M, Kucharz EJ, Emery P. Infliximab treatment increases left ventricular ejection fraction in patients with rheumatoid arthritis: assessment of heart function by echocardiography, endothelin 1, interleukin 6, and NT-pro brain natriuretic peptide. J Rheumatol. 2012;39:701–6.PubMedCrossRefGoogle Scholar
  81. 81.•
    Maki-Petaja KM, Elkhawad M, Cheriyan J, Joshi FR, Ostor AJ, Hall FC, et al. Anti-tumor necrosis factor-alpha therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation. 2012;126:2473–80. Anti-TNFα drugs were associated with reduced aortic inflammation on FDG PET/CT and reduced aortic pulse-wave velocity 8 weeks after initiation of the drug (etanercept or adalimumab). Reductions in arterial inflammation were associated with reductions in pulse-wave velocity.PubMedCrossRefGoogle Scholar
  82. 82.•
    McInnes IB, Thompson L, Giles JT, Bathon JM, Salmon JE, Beaulieu AD, et al. Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study. Ann Rheum Dis. 2013. doi:10.1136/annrheumdis-2013-204345. Despite increases in LDL and total cholesterol concentration, serum markers of inflammation and inflammatory lipids such as HDL-associated serum amyloid A content were reduced with tocilizumab + methotrexate versus methotrexate alone. There were no significant differences in aortic stiffness after 24 weeks of therapy.Google Scholar
  83. 83.
    Van Tassell BW, Toldo S, Mezzaroma E, Abbate A. Targeting interleukin-1 in heart disease. Circulation. 2013;128:1910–23.PubMedCrossRefGoogle Scholar
  84. 84.•
    Van Tassell BW, Arena RA, Toldo S, Mezzaroma E, Azam T, Seropian IM, et al. Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure. PLoS One. 2012;7:e33438. Injection of IL-1 into healthy mice resulted in impaired left ventricular function. In a pilot trial in seven patients with systolic heart failure, 2 weeks of anakinra improved aerobic capacity on cardiopulmonary stress testing (+2.8 mL/kg/min).PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.•
    Van Tassell BW, Arena R, Biondi-Zoccai G, McNair Canada J, Oddi C, Abouzaki NA, et al. Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study). Am J Cardiol. 2014;113:321–7. Anakinra for 2 weeks improved exercise capacity (+1.2 mL/kg/min) and reduced inflammation (74 % decrease in CRP) among 12 patients with heart failure with preserved ejection fraction.PubMedCrossRefGoogle Scholar
  86. 86.•
    Abbate A, Van Tassell BW, Biondi-Zoccai G, Kontos MC, Grizzard JD, Spillman DW, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013;111:1394–400. Anakinra reduced the levels of CRP after ST-elevation myocardial infarction, but did not significantly improve LV volumes or ejection fraction. Incidence of HF was significantly reduced (5 % vs. 30 %) compared to placebo.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Ikonomidis I, Lekakis JP, Nikolaou M, Paraskevaidis I, Andreadou I, Kaplanoglou T, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation. 2008;117:2662–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Ikonomidis I, Tzortzis S, Lekakis J, Paraskevaidis I, Andreadou I, Nikolaou M, et al. Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis. Heart. 2009;95:1502–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Ikonomidis I, Tzortzis S, Lekakis J, Paraskevaidis I, Dasou P, Parissis J, et al. Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra. Thromb Haemost. 2011;106:959–67.PubMedCrossRefGoogle Scholar
  90. 90.••
    Ikonomidis I, Tzortzis S, Andreadou I, Paraskevaidis I, Katseli C, Katsimbri P, et al. 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. 2014. doi:10.1161/CIRCIMAGING.113.001193. In this double-blind crossover trial, 60 RA patients with CAD had higher baseline levels of IL-1 and had greater improvements in systolic and diastolic mechanics and decreased circulating markers of apoptosis and oxidative stress after a single-dose of anakinra compared to 20 RA patients without CAD.PubMedGoogle Scholar
  91. 91.
    Abbate A, Canada JM, Van Tassell BW, Wise CM, Dinarello CA. Interleukin-1 blockade in rheumatoid arthritis and heart failure: a missed opportunity? Int J Cardiol. 2014;171:e125–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.University Hospitals Case Medical CenterClevelandUSA
  2. 2.Case Western Reserve University School of MedicineUniversity Hospitals Harrington Heart & Vascular InstituteClevelandUSA

Personalised recommendations