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 transplan-
tation 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 dis-
eases, 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 transplanta-
tion 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 This study was supported by a grant from the Shiraz Medical
Transplant Center (A.M., G.A.R.-J.), Nemazee Hospital, and the University and Namazi Hospital Transplantation Center.
Cardiology Department (M.A.O.), Shiraz University of Medical Address reprint requests to Afsoon Fazelzadeh, PO Box 71455-
Sciences, Shiraz, Iran. 166, Shiraz, Iran. E-mail: fazelzadeh23@yahoo.com

0041-1345/06/$–see front matter © 2006 by Elsevier Inc. All rights reserved.

doi:10.1016/j.transproceed.2006.01.001 360 Park Avenue South, New York, NY 10010-1710

506 Transplantation Proceedings, 38, 506 –508 (2006)

CARDIOVASCULAR RISK FACTORS AND COMPLICATIONS
C ARDIOVASCULAR DISEASE is a leading cause
of death after renal transplantation, with an inci-
dence considerably higher than in the general popula-
tion.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 mea-
sures 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 trans-
plant and the prevalence of cardiovascular risk factors
prior to versus following the procedure.
MATERIALS AND METHODS
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 eval-
uations and posttransplant outcomes of recipients. The variables
included: age, gender, presence/absence of diabetes, hyperten-
sion, 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 de-
scribed 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 cardio-
vascular 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
Before After
Cardiovascular Risk Factors Transplant Transplant P Value
Hypertension (%) 67 86 .01
Diabetes mellitus (%) 7 16 .001
Obesity (BMI ⬎ 25 kg/m2) (%) 26 48 .005
Triglycerides (mg/dL) 235 ⫾ 44 217 ⫾ 122 .04
Total cholesterol (mg/dL) 232 ⫾ 65 273 ⫾ 62 .03
HDL cholesterol (mg/dL) 47 ⫾ 29 56 ⫾ 21 .04
LDL cholesterol (mg/dL) 180 ⫾ 62 189 ⫾ 53 .04
507
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, cardio-
vascular diseases were significantly associated with male gen-
der, 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 diabet-
ics 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 indepen-
dent risk factors.
DISCUSSION
Although cardiovascular disease is a major cause for
death after renal transplantation, risk factors for cardio-
vascular events other than dialysis have not been well
defined.3 Pre- and posttransplant screening of cardiovas-
cular risk factors and also detection of occult cardiovas-
cular diseases can improve the outcome of renal trans-
plant 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 fre-
quent abnormality, which was associated with corticoste-
roid 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 trans-
plantation, although its importance has been greatly under-
estimated.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 new-
onset diabetes after transplantation. Use of these guide-
lines 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
508
Future prospective studies must evaluate the success of
treatment of these risk factors regarding reduction of cardio-
vascular morbidity and mortality in this high-risk population.
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