Incidence

Incidence of Cardiovascular Risk Factors and Complications Before and After Kidney Transplantation A. Fazelzadeh, A. Mehdizadeh, M.A. Ostovan, and G.A. Raiss-Jalali ABSTRACT Background. Cardiovascular disease is a leading cause of death after renal transplantation with an incidence considerably higher than that in the general population. The aim of this study was to evaluate the association of atherosclerotic cardiovascular complications and the prevalence of cardiovascular risk factors prior to and following transplantation. Patients and methods. Atherosclerotic cardiovascular diseases including coronary artery disease, as well as cerebral and peripheral vascular disease, and cardiovascular risk factors pre- and posttransplantation were analyzed in 500 renal transplant recipients between 1988 and 1992. The mean recipient age at transplantation was 45 ⫾ 12 years, with 58% men and 7% diabetics. Results. Following transplantation 11.7% developed atherosclerotic cardiovascular diseases, the majority being coronary artery disease (9.8%). Comparison of the risk factors before and after transplantation showed the increased prevalence of systemic hypertension to be 67% to 86%, of diabetes mellitus, 7% to 16%, and obesity, with a body mass index ⬎ 25 kg/m2 from 26% to 48%, whereas the number of smokers was halved to 20%. The triglycerides decreased significantly (from 235 ⫾ 144 mg/dL to 217 ⫾ 122 mg/dL) but the total and high-density lipoprotein (HDL) cholesterol rose significantly (from 232 ⫾ 65 mg/dL to 273 ⫾ 62 mg/dL and from 47 ⫾ 29 mg/dL to 56 ⫾ 21 mg/dL, respectively). The low-density lipoprotein (LDL) cholesterol increase was insignificant (from 180 ⫾ 62 mg/dL to 189 ⫾ 53 mg/dL). Upon univariate analysis, cardiovascular diseases were significantly associated with male gender; age over 50 years; diabetes mellitus (DM); smoking; total cholesterol ⬎ 200 mg/dL; LDL cholesterol ⬎ 180 mg/dL; HDL cholesterol ⬍ 55 mg/dL; fibrinogen ⬎ 350 mg/dL; body mass index ⬎ 25 kg/m2; and more than two antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3; age ⬎ 50 years (RR ⫽ 2.7); body mass index ⬎ 25 kg/m2 (RR ⫽ 2.6); smoking (RR ⫽ 2.5); and LDL cholesterol ⬎ 180 mg/dL (RR ⫽ 2.3) as independent risk factors. Conclusions. The high incidence of cardiovascular disease following renal transplantation is mainly due to a high prevalence and accumulation of classical risk factors before and following transplantation. The treatment of risk factors must be introduced early in the course of renal failure and continued following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high-risk population.

From the Shiraz Transplant Research Center (A.F.), Shiraz Transplant Center (A.M., G.A.R.-J.), Nemazee Hospital, and the Cardiology Department (M.A.O.), Shiraz University of Medical Sciences, Shiraz, Iran.

0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.01.001 506

This study was supported by a grant from the Shiraz Medical University and Namazi Hospital Transplantation Center. Address reprint requests to Afsoon Fazelzadeh, PO Box 71455166, Shiraz, Iran. E-mail: [email protected]

© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 38, 506 –508 (2006)

CARDIOVASCULAR RISK FACTORS AND COMPLICATIONS

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C

ARDIOVASCULAR DISEASE is a leading cause of death after renal transplantation, with an incidence considerably higher than in the general population.1 The grossly increased cardiovascular risk in renal transplant patients is related to a combination of partly related risk factors. Most of the causative factors may be influenced, but to be fully effective, the necessary measures must be started early in the natural history of this process, which means not only before transplant but indeed in most cases well before the start of dialysis.2 The aim of this study was to evaluate the association of atherosclerotic cardiovascular complications after transplant and the prevalence of cardiovascular risk factors prior to versus following the procedure.

rose significantly (from 232 ⫾ 65 mg/dL to 273 ⫾ 62 mg/dL and from 47 ⫾ 29 mg/dL to 56 ⫾ 21 mg/dL, respectively). The LDL cholesterol increase was insignificant (from 180 ⫾ 62 mg/dL to 189 ⫾ 53 mg/dL). In the univariate analysis, cardiovascular diseases were significantly associated with male gender, age over 50 years, diabetes mellitus, smoking, total cholesterol ⬎ 200 mg/dL, LDL cholesterol ⬎ 180 mg/dL, HDL cholesterol ⬍ 55 mg/dL, fibrinogen ⬎ 350 mg/dL, BMI ⬎ 25 kg/m2, and more than two antihypertensive agents per day. The Cox proportional hazards model revealed diabetics to show a relative risk (RR) of 4.3; age ⬎ 50 years (RR ⫽ 2.7); BMI ⬎ 25 kg/m2 (RR ⫽ 2.6); smoking (RR ⫽ 2.5); and LDL cholesterol ⬎ 180 mg/dL (RR ⫽ 2.3) as independent risk factors.

MATERIALS AND METHODS

DISCUSSION

We retrospectively analyzed the outcomes of 500 recipients of renal transplant from 1988 to 1992. We reviewed all inpatient and outpatient records, abstracting data on pretransplant evaluations and posttransplant outcomes of recipients. The variables included: age, gender, presence/absence of diabetes, hypertension, body mass index (BMI) at the time of transplant, lipid profile (total cholesterol, triglycerides, high-density lipoprotein [HDL], low-density lipoprotein [LDL]), fibrinogen level, and smoking status transplant records. We recorded atherosclerotic cardiovascular diseases involving coronary arteries or cerebral and peripheral vessels during this period. Outcomes are described using event-free Kaplan-Meier survival curves. Cox proportional hazards regression was used for both univariate and multivariate analyses.

RESULTS

Of the 500 patients who received transplants between 1988 and 1992, 11.7% developed atherosclerotic cardiovascular disease, the majority being coronary artery disease (9.8%). The mean age at transplantation was 45 ⫾ 12 years, and 58% of patients were men. Comparison of risk factors before and after transplantation showed an increased prevalence of systemic hypertension to be from 67% to 86%; diabetes mellitus, from 7% to 16%, and obesity with a BMI ⬎ 25 kg/m2, from 26% to 48%, whereas the number of smokers halved to 20% (Table 1). The triglycerides decreased significantly (from 235 ⫾ 144 mg/dL to 217 ⫾ 122 mg/dL). The total and HDL cholesterol Table 1. Humoral Parameters (Mean ⴞ SD) and Percentage of Clinical Findings in Patients Before and After Renal Transplantation Cardiovascular Risk Factors

Before Transplant

After Transplant

P Value

Hypertension (%) Diabetes mellitus (%) Obesity (BMI ⬎ 25 kg/m2) (%) Triglycerides (mg/dL) Total cholesterol (mg/dL) HDL cholesterol (mg/dL) LDL cholesterol (mg/dL)

67 7 26 235 ⫾ 44 232 ⫾ 65 47 ⫾ 29 180 ⫾ 62

86 16 48 217 ⫾ 122 273 ⫾ 62 56 ⫾ 21 189 ⫾ 53

.01 .001 .005 .04 .03 .04 .04

Although cardiovascular disease is a major cause for death after renal transplantation, risk factors for cardiovascular events other than dialysis have not been well defined.3 Pre- and posttransplant screening of cardiovascular risk factors and also detection of occult cardiovascular diseases can improve the outcome of renal transplant patients. Smoking is the most important adverse factor. An analysis of 434 transplant patients in one center showed that smokers had a greater than twofold increased risk of cardiovascular death when compared with nonsmokers, namely, a hazard ratio of 2.2 (P ⬍ .001).4 Our data also showed that smoking was associated with development of cardiovascular disease. Short-term studies have demonstrated that hypercholesterolemia with raised LDL cholesterol represented the most frequent abnormality, which was associated with corticosteroid and cyclosporine treatment in a dose-dependent manner.5 Our results supported these findings. As we know statins have been found to improve the lipid profile in transplant recipients without undue side effects and with a decreased risk of cardiovascular mortality.5 So, we have used lipid-lowering diets and drugs to lower the risk of cardiovascular diseases. For many years new-onset diabetes after transplantation has been recognized as a complication of solid-organ transplantation, although its importance has been greatly underestimated.6 Our results showed that an increased incidence of diabetes predisposed patients to the development of cardiovascular disease. It is clear that efforts should be made to reduce the risk of diabetes and treat this condition appropriately. Management of transplant recipients with new-onset diabetes after transplantation has been assisted by the recent publication of International Consensus Guidelines. The guidelines were developed to establish a standard definition and describe risk factors for newonset diabetes after transplantation. Use of these guidelines will help to prospectively identify patients at risk of developing new-onset diabetes after transplantation so that therapeutic strategies can be individualized early in the treatment regimen.6

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Future prospective studies must evaluate the success of treatment of these risk factors regarding reduction of cardiovascular morbidity and mortality in this high-risk population. REFERENCES 1. Raine AEG, Margreiter R, Brunner FP, et al: Report on management of renal failure in Europe, XXII 1991. Nephrol Dial Transplant 7(suppl 2):7, 1992 2. Parfrey PS, Foley RN, Rigatto C: Risk issues in renal transplantation: cardiac aspects. Transplant Proc 31:291, 1999

FAZELZADEH, MEHDIZADEH, OSTOVAN ET AL 3. McGregor E, Stewart G, Rodger RSC, et al: Early echocardiographic changes and survival following renal transplantation. Nephrol Dial Transplant 15:93, 2000 4. Wilson PW, D’Agostino RB, Levy D, et al: Prediction of coronary heart disease using risk factor categories. Circulation 97:1837, 1998 5. Ligten berg G, Hene RJ, Blankestijn PJ, et al: Cardiovascular risk factors in renal transplant patients: cyclosporin A versus tacrolimus. J Am Soc Nephrol 12:368, 2001 6. Piero Marchetti MD: New-onset diabetes after transplantation. J Heart Lung Transplant 23(suppl 1):S194, 2004