Document Type : Meta-analysis

Authors

1 Professor, Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

2 School of Medicine AND Menzies Health Institute, Griffith University, Southport, Queensland, Australia

3 Assistant Professor, Nutrition and Food Security Research Center AND Department of Nutrition, School of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Assistant Professor, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

5 Associate Professor, Cardiac Anesthesiology Research Center, Chamran Heart Center Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

6 Assistant Professor, Psychosomatic Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

BACKGROUND: This systematic review and meta-analysis aimed to assess the effect of cardiac rehabilitation (CR) on serum C-reactive protein (CRP) as an indicator of the inflammatory state and predictor of recurrent cardiovascular events.METHODS: PubMed, SCOPUS, Cochrane library, and Google Scholar databases were searched up to January 2014 for original articles which investigated the effect of CR on CRP among adult patients with previous cardiovascular events. The random effects model was used to assess the overall effect of CR on the variation in serum CRP levels.RESULTS: In the present systematic review and meta-analysis, 15 studies were included. The analysis showed that CR might significantly reduce high-sensitivity CRP (hs-CRP) levels [Difference in means (DM) = -1.81 mg/l, 95% confidence interval (CI): -2.65, -0.98; P = 0.004). However, the heterogeneity between studies was significant (Cochran's Q test, P < 0.001, I-squared = 84.9%). To find the source of variation, the studies were categorized based on study design (quality) and duration. The negative effect was higher among studies which followed their participants for 3 weeks or less (DM = -2.75 mg/l, 95% CI: -3.86, -1.64; P < 0.001) compared to studies which investigated the effect of CR for 3-8 weeks (DM = -0.89 mg/l, 95% CI: -1.35, -0.44; P < 0.001) and those which lasted more than 8 weeks (DM = -1.71 mg/l, 95% CI: -2.53, -0.89; P < 0.001). There was no evidence of heterogeneity when the categorization was based on the follow-up period.CONCLUSION: Both short- and long-term CR have resulted in improvement in serum hs-CRP levels. CR can be perceived as a beneficial tool to reduce inflammatory markers among patients with previous cardiac events.

Keywords

  1. Talaei M, Sarrafzadegan N, Sadeghi M, Oveisgharan S, Marshall T, Thomas GN, et al. Incidence of cardiovascular diseases in an Iranian population: The Isfahan Cohort Study. Arch Iran Med 2013; 16(3): 138-44.
  2. Wilensky RL, Hamamdzic D. The molecular basis of vulnerable plaque: Potential therapeutic role for immunomodulation. Curr Opin Cardiol 2007; 22(6): 545-51.
  3. Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 2006; 83(2): 456S-60S.
  4. van de Ree MA, Huisman MV, Princen HM, Meinders AE, Kluft C. Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus. Atherosclerosis 2003; 166(1): 129-35.
  5. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344(26): 1959-65.
  6. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998; 98(9): 839-44.
  7. Wenger NK, Froelicher ES, Smith LK, Ades PA, Berra K, Blumenthal JA, et al. Cardiac rehabilitation as secondary prevention. Agency for Health Care Policy and Research and National Heart, Lung, and Blood Institute. Clin Pract Guidel Quick Ref Guide Clin 1995; (17): 1-23.
  8. Cesari F, Marcucci R, Gori AM, Burgisser C, Francini S, Sofi F, et al. Impact of a cardiac rehabilitation program and inflammatory state on endothelial progenitor cells in acute coronary syndrome patients. Int J Cardiol 2013; 167(5): 1854-9.
  9. Hansen D, Dendale P, Raskin A, Schoonis A, Berger J, Vlassak I, et al. Long-term effect of rehabilitation in coronary artery disease patients: Randomized clinical trial of the impact of exercise volume. Clin Rehabil 2010; 24(4): 319-27.
  10. Sarrafzadegan N, Rabiei K, Kabir A, Sadeghi M, Khosravi A, Asgari S, et al. Gender differences in risk factors and outcomes after cardiac rehabilitation. Acta Cardiol 2008; 63(6): 763-70.
  11. Ghashghaei FE, Sadeghi M, Marandi SM, Ghashghaei SE. Exercise-based cardiac rehabilitation improves hemodynamic responses after coronary artery bypass graft surgery. ARYA Atheroscler 2012; 7(4): 151-6.
  12. Sadeghi M, Garakyaraghi M, Khosravi M, Taghavi M, Sarrafzadegan N, Roohafza H. The impacts of cardiac rehabilitation program on echocardiographic parameters in coronary artery disease patients with left ventricular dysfunction. Cardiol Res Pract 2013; 2013: 201713.
  13. Balen S, Vukelic-Damijani N, Persic V, Ruzic A, Miletic B, Samardiija M, et al. Anti-inflammatory effects of exercise training in the early period after myocardial infarction. Coll Antropol 2008; 32(1): 285-91.
  14. Solov'ev AV, Ermolin GA, Ignashenkova GV, Dikov MM. Fibrinogen and fibrin degradation products in the blood of acute myocardial infarct patients at the hospital rehabilitation stage. Ter Arkh 1987; 59(10): 21-3.
  15. Wosornu D, Allardyce W, Ballantyne D, Tansey P. Influence of power and aerobic exercise training on haemostatic factors after coronary artery surgery. Br Heart J 1992; 68(2): 181-6.
  16. Conraads VM, Beckers P, Bosmans J, De Clerck LS, Stevens WJ, Vrints CJ, et al. Combined endurance/resistance training reduces plasma TNF-alpha receptor levels in patients with chronic heart failure and coronary artery disease. Eur Heart J 2002; 23(23): 1854-60.
  17. Kim YJ, Shin YO, Bae JS, Lee JB, Ham JH, Son YJ, et al. Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients. Pflugers Arch 2008; 455(6): 1081-8.
  18. Shin YO, Bae JS, Lee JB, Kim JK, Kim YJ, Kim C, et al. Effect of cardiac rehabilitation and statin treatment on anti-HSP antibody titers in patients with coronary artery disease after percutaneous coronary intervention. Int Heart J 2006; 47(5): 671-82.
  19. Aminlari A, Jazayeri SM, Bakhshandeh AR. Association of cardiac rehabilitation with improvement in high sensitive C-reactive protein post-myocardial infarction. Iran Red Crescent Med J 2012; 14(1): 49-50.
  20. Lavie CJ, Morshedi-Meibodi A, Milani RV. Impact of cardiac rehabilitation on coronary risk factors, inflammation, and the metabolic syndrome in obese coronary patients. J Cardiometab Syndr 2008; 3(3): 136-40.
  21. Madarame H, Kurano M, Fukumura K, Fukuda T, Nakajima T. Haemostatic and inflammatory responses to blood flow-restricted exercise in patients with ischaemic heart disease: A pilot study. Clin Physiol Funct Imaging 2013; 33(1): 11-7.
  22. Milani RV, Lavie CJ, Mehra MR. Reduction in C-reactive protein through cardiac rehabilitation and exercise training. J Am Coll Cardiol 2004; 43(6): 1056-61.
  23. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107(3): 363-9.
  24. Ferratini M, Ripamonti V, Masson S, Grati P, Racca V, Cuccovillo I, et al. Pentraxin-3 predicts functional recovery and 1-year major adverse cardiovascular events after rehabilitation of cardiac surgery patients. J Cardiopulm Rehabil Prev 2012; 32(1): 17-24.
  25. Fukuda T, Kurano M, Iida H, Takano H, Tanaka T, Yamamoto Y, et al. Cardiac rehabilitation decreases plasma pentraxin 3 in patients with cardiovascular diseases. Eur J Prev Cardiol 2012; 19(6): 1393-400.
  26. Cesari F, Sofi F, Caporale R, Capalbo A, Marcucci R, Macchi C, et al. Relationship between exercise capacity, endothelial progenitor cells and cytochemokines in patients undergoing cardiac rehabilitation. Thromb Haemost 2009; 101(3): 521-6.
  27. Kim C, Kim DY, Moon CJ. Prognostic influences of cardiac rehabilitation in Korean acute myocardial infarction patients. Ann Rehabil Med 2011; 35(3): 375-80.
  28. Rankovic G, Milicic B, Savic T, Dindic B, Mancev Z, Pesic G. Effects of physical exercise on inflammatory parameters and risk for repeated acute coronary syndrome in patients with ischemic heart disease. Vojnosanit Pregl 2009; 66(1): 44-8.
  29. Hansen D, Dendale P, Berger J, Onkelinx S, Reyckers I, Hermans A, et al. Importance of exercise training session duration in the rehabilitation of coronary artery disease patients. Eur J Cardiovasc Prev Rehabil 2008; 15(4): 453-9.
  30. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7(3): 177-88.
  31. Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109): 629-34.
  32. Egger M, Davey-Smith G, Altman D. Systematic reviews in health care: Meta-analysis in context. Hoboken, NJ: John Wiley & Sons; 2001.
  33. Pfutzner A, Forst T. High-sensitivity C-reactive protein as cardiovascular risk marker in patients with diabetes mellitus. Diabetes Technol Ther 2006; 8(1): 28-36.
  34. Libby P, Ridker PM. Inflammation and atherosclerosis: Role of C-reactive protein in risk assessment. Am J Med 2004; 116(Suppl 6A): 9S-16S.
  35. Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J, et al. Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol 2003; 42(5): 861-8.
  36. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: Associations with obesity, insulin resistance, and endothelial dysfunction: A potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19(4): 972-8.