J Korean Soc Transplant.  2011 Dec;25(4):229-238. 10.4285/jkstn.2011.25.4.229.

Cardiovascular Diseases after Solid Organ Transplantation

• Kim JJ

• KMID: 1450970
• DOI: http://doi.org/10.4285/jkstn.2011.25.4.229

Abstract

Despite recent advances in the prolongation of patient and graft survival, transplant patients continue to die prematurely of cardiovascular disease. Cardiovascular disease after solid organ transplantation is a serious complication caused by numerous factors, most shared with the general population and others specific to transplant recipients including immunosuppressive drugs and renal dysfunction. Among traditional risk factors in general population, hypertension, dyslipidemia and diabetes are more common in solid organ transplant recipients. The control of risk factors is more difficult in transplant recipients than in general population. Immunosuppressive drugs are related to hypertension, dyslipidemia and posttransplant DM. Reduction of immunosuppression is helpful to reduce the risk of cardiovascular disease but may increase the risk of rejection and graft loss. mTOR inhibitor has less potential risk to develop cardiovascular disease. Future development of new immunosuppressive drug with less potential risk of CV disease but same efficacy to prevent rejection and graft loss will be a promising goal to prevent CV disease. In conclusion, multidisciplinary approach that emphasizes evidence-based management of traditional risk factors and development of new immunosuppressive drugs are the best approach to reducing the risk of CV disease after solid organ transplantation.

Keyword

Solid organ transplantation; Cardiovascular diseases; Risk factors

MeSH Terms

Cardiovascular Diseases
Dyslipidemias
Graft Survival
Humans
Hypertension
Immunosuppression
Organ Transplantation
Rejection (Psychology)
Risk Factors
Transplants

Reference

References

1). Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998; 32(5 Suppl 3):S112–9.

2). Wheeler DC, Steiger J. Evolution and etiology of cardiovascular disease in renal transplant recipients. Transplantation. 2000; 70(11 Suppl):SS41–5.

3). Aker S, Iven K, Guon Z, Grabensee B, Heering P. Cardiovascular complications after renal transplantation. Transplant Proc. 1998; 30:2039–42.

4). Lindholm A, Albrechtsen D, Frödin L, Tufveson G, Persson NH, Lundgren G. Ischemic heart disease – major cause of death and graft loss after renal transplantation in Scandinavia. Transplantation. 1995; 60:451–7.

5). Rabkin JM, Corless CL, Rosen HR, Olyaei AJ. Immunosuppression impact on longterm cardiovascular complications after liver transplantation. Am J Surg. 2002; 183:595–9.

6). Meier-Kriesche HU, Baliga R, Kaplan B. Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation. 2003; 75:1291–5.

7). Fellström B, Jardine AG, Soveri I, Cole E, Grönhagen-Riska C, Neumayer HH. Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation: experience from the Assessment of Lescol in Renal Transplantation trial. Transplantation. 2005; 79:1160–3.

8). Morales JM, Dominguez-Gil B. Cardiovascular risk profile with the new immunosuppressive combinations after renal transplantation. J Hypertens. 2005; 23:1609–16.

9). Bostom AD, Brown RS Jr, Chavers BM, Coffman TM, Cosio FG, Culver K, et al. Prevention of post-transplant cardiovascular disease – report and recommendations of an ad hoc group. Am J Transplant. 2002; 2:491–500.

10). Fellström B. Risk factors for and management of post-transplantation cardiovascular disease. BioDrugs. 2001; 15:261–78.

11). Campistol JM, Romero R, Paul J, Gutiérrez-Dalmau A. Epidemiology of arterial hypertension in renal transplant patients: changes over the last decade. Nephrol Dial Transplant. 2004; 19(Suppl 3):iii62–6.

12). Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003; 42:1206–52.

13). Haydar AA, Covic A, Jayawardene S, Agharazii M, Smith E, Gordon I, et al. Insights from ambulatory blood pressure monitoring: diagnosis of hypertension and diurnal blood pressure in renal transplant recipients. Transplantation. 2004; 77:849–53.

14). Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw PW, Duprez DA, Fagard RH, et al. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003; 348:2407–15.

15). Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994; 24:793–801.

16). Veenstra DL, Best JH, Hornberger J, Sullivan SD, Hricik DE. Incidence and longterm cost of steroid-related side effects after renal transplantation. Am J Kidney Dis. 1999; 33:829–39.

17). Fryer JP, Granger DK, Leventhal JR, Gillingham K, Najarian JS, Matas AJ. Steroid-related complications in the cyclosporine era. Clin Transplant. 1994; 8(3 Pt 1):224–9.

18). Ahsan N, Hricik D, Matas A, Rose S, Tomlanovich S, Wilkinson A, et al. Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil–a prosperctive randomized study. Steroid Withdrawal Study Group. Transplantation. 1999; 68:1865–74.

19). Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK 506 Kidney Transplant Study Group. Transplantation. 1997; 63:977–83.

20). Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000; 36:646–61.

21). Kidney Disease. Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009; 9(Suppl 3):S1–155.

22). Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004; 43(5 Suppl 1):S1–290.

23). EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. Nephrol Dial Transplant. 2002; 17(Suppl 4):1–67.

24). Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van Veldhuisen P, et al. A prospective, randomized, double blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus longterm, low dose corticosteroid therapy. Ann Surg. 2008; 248:564–77.

25). Sivaraman P, Nussbaumer G, Landsberg D. Lack of longterm benefits of steroid withdrawal in renal transplant recipients. Am J Kidney Dis. 2001; 37:1162–9.

26). Johnson RW, Kreis H, Oberbauer R, Brattström C, Claesson K, Eris J. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation. 2001; 72:777–86.

27). Textor SC, Schwartz L, Wilson DJ, Wiesner R, Romero JC, Augustine J, et al. Systemic and renal effects of nifedipine in cyclosporine-associated hypertension. Hyoper-tension. 1994; 23(1 Suppl):I220–4.

28). Waanders F, Rienstra H, Boer MW, Zandvoort A, Rozing J, Navis G, et al. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats. Am J Physiol Renal Physiol. 2009; 296:F1072–9.

29). Mitterbauer C, Heinze G, Kainz A, Kramar R, Hörl WH, Oberbauer R. ACE-inhibitor or AT2-antagonist therapy of renal transplant recipients is associated with an increase in serum potassium concentrations. Nephrol Dial Transplant. 2008; 23:1742–6.

30). Fernández-Fresnedo G, Rodrigo E, Valero R, Arias M. Traditional cardiovascular risk factors as clinical markers after kidney transplantation. Transplant Rev. 2006; 20:88–94.

31). Kasiske BL, Ballantyne CM. Cardiovascular risk factors associated with immunosuppression in renal transplantation Transplant Rev. 2002; 16:1–21.

32). Wissing KM, Abramowicz D, Broeders N, Vereerstraeten P. Hypercholesterolemia is associated with increased kidney graft loss caused by chronic rejection in male patients with previous acute rejection. Transplantation. 2000; 70:464–72.

33). Varghese Z, Fernando RL, Turakhia G, Psimenou E, Fernando ON, Sweny P, et al. Calcineurin inhbitors enhance low-density lipoprotein oxidation in transplant patients. Kidney Int Suppl. 1999; 71:S137–40.

34). Hoogeveen RC, Ballantyne CM, Pownall HJ, Opekun AR, Hachey DL, Jaffe JS, et al. Effect fo sirolimus on the metabolism of apoB-100 containing lipoproteins in renal transplant patients. Transplantation. 2001; 72:1244–50.

35). Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-low-ering treatment: prospective metaanalysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005; 366:1267–78.

36). Holdaas H, Fellström B, Jardine AG, Holme I, Nyberg G, Fauchald P, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomized, placebo-controlled trial. Lancet. 2003; 361:2024–31.

37). Kasiske B, Cosio FG, Beto J, Bolton K, Chavers BM, Grimm R Jr, et al. Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Am J Transplant. 2004; 4(Suppl 7):13–53.

38). Vesco L, Busson M, Bedrossian J, Bitker MO, Hiesse C, Lang P. Diabetes mellitus after renal transplantation: characteristics, outcome, and risk factors. Transplantation. 1996; 61:1475–8.

39). Miles AM, Sumrani N, Horowitz R, Homel P, Maursky V, Markell MS, et al. Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes? Transplantation. 1998; 65:380–4.

40). Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003; 3:178–85.

41). Weir MR, Fink JC. Risk for posttransplant Diabetes mellitus with current immunosuppressive medications. Am J Kidney Dis. 1999; 34:1–13.

42). Kasiske BL, Chakkera H, Roel J. Explained and unexplained ischemic heart disease risk after renal transplantation. J Am Soc Nephrol. 2000; 11:1735–43.

43). Varagunam M, Finney H, Trevitt R, Sharples E, McCloskey DJ, Sinnott PJ, et al. Pretransplantation levels of C-reactive protein predict all-cause and cardiovascular mortality, but not graft outcome, in kidney transplant recipients. Am J Kidney Dis. 2004; 43:502–7.

44). Ducloux D, Challier B, Saas P, Tiberghien P, Chalopin JM. CD4 cell lymphopenia and atherosclerosis in renal transplant recipients. J Am Soc Nephrol. 2003; 14:767–72.

45). Friedman AN, Rosenberg IH, Selhub J, Levey AS, Bostom AG. Hyperhomocysteinemia in renal transplant recipients. Am J Transplat. 2002; 2:308–13.

46). Bostom AG, Carpenter MA, Kusek JW, Levey AS, Hunsicker L, Pfeffer MA, et al. Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial. Circulation. 2011; 123:1763–70.