Abstract
Background: Left ventricular hypertrophy is common in renal transplant patients but the factors influencing its development remain to be determined. The present investigation was conducted to study the effect of blood pressure load on the left ventricular mass of recently transplanted patients using 24-h ambulatory blood pressure monitoring (ABPM). Methods: We studied 30 renal transplant (RT) patients (36.1 ± 13.7 years old, 11 males, 26 Whites, 4 diabetics, 15 under antihypertensive medication, 21 recipients of cadaver donors, and all treated with steroids, cyclosporin and azathioprine and with adequate (serum creatinine< 1.8 mg/100 ml) renal function). The median duration of dialysis treatment before transplant was 37 months, and the studies were performed during the first 40 days post-transplantation. Blood pressure was measured after a 15-min rest (casual blood pressure) and during a 24-h period with a SpaceLabs™ apparatus. Echocardiograms were obtained from all patients. Results: Mean left ventricular mass index (LVMI) was 153 ± 44 g/m2; casual systolic and diastolic BP (mmHg) was 152 ± 25 and 92 ± 13, whereas systolic and diastolic 24-h BP was 133 ± 12 and 85 ± 8, respectively. The systolic sleeping BP/awake systolic BP (SSBP/ASBP) ratio was 0.94 ± 0.07, and 73% of the patients did not show a significant (>10%) fall of systolic blood pressure during sleep. Multivariate analysis showed that awake systolic blood pressure was the only variable that independently influenced LVMI after adjusting for confounding factors (regression coefficient = 0.49, p = 0.01). Casual systolic and diastolic BP, sleeping systolic and diastolic blood pressure, 24-h heart rate, age, race, gender, smoking, body mass index, duration of dialysis, diabetes, antihypertensive and immunosuppressive drugs and levels of hematocrit, creatinine and serum lipids did not correlate with LVMI. Conclusion: The data indicate that left ventricular hypertrophy during the early post-transplant period is mainly influenced by awake blood pressure load. They also suggest that ABPM may be more useful in the diagnosis and management of post-transplant hypertension than casual BP. The findings emphasize the importance of rigid blood pressure control in renal transplant recipients.
INTRODUCTION
It is now well established that ambulatory blood pressure monitoring (ABPM) is the best method available to characterize the relationship between blood pressure levels and the development of target organ damage, especially the heart Citation[[1]], Citation[[2]]. Hypertension is frequent in renal transplant patients and is associated with decreased allograft and patient survival Citation[[3]]. However, few studies were conducted to define the impact of 24 h blood pressure load on ventricular mass in this population. In the present investigation we address this topic by studying patients during the early phases of the post-transplant period, at the time when chronic rejection and the effects of prolonged exposure to cyclosporin and of other drugs affecting blood pressure control have not completely developed.
METHODS
Patients ()
We studied 30 Brazilian renal transplant patients (11 males, 19 females) aged 36.1 ± 13.7 years (range: 17–63). Twenty-one patients received kidneys from cadaver and nine from living donors. Studies were performed 20 to 40 days after the transplant. The mean time of dialysis treatment prior to transplantation was 46.4 ± 35.3 (median, 37) months. All patients were receiving triple immunosuppressive therapy consisting of cyclosporin (3–5 mg/kg) azatiophrine (1.5–2.0 mg/kg) and prednisone (12.5–40 mg/day). Fifteen (50%) patients were receiving antihypertensive medication consisting of long-acting calcium blockers, ACE inhibitors, diuretics and sympatholytics, alone or in combination. Nine patients (28%) were taking one and six (25%) were taking two or more antihypertensive drugs. Mean serum creatinine was in the normal range, while serum cholesterol was slightly increased and hematocrit reduced. The scientific committee of the institution approved the protocol, and all individuals gave their informed consent to participate in the study.
Table 1. Characteristics of the Study Population (n = 30)
Casual Blood Pressure: All patients underwent clinical evaluation. Blood pressure was measured after a 15-min rest in the seated position. Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were measured with a mercury sphygmomanometer using the Riva-Rocci method. Cuff size was adapted to arm circumference.
Ambulatory Blood Pressure: ABPM was performed during a 24 h period while the individuals were engaged in their routine daily activities, using a SpaceLabs 90207 monitor (SpaceLabs Inc., Redmond, Washington, USA). The monitoring unit was programmed to record blood pressure readings at set intervals of 10 min, except for the period between 11 PM and 6 AM, when measurements were made every 20 min. Patients were instructed to record their activities on a note pad during the test. The readings recorded during the awake period and those recorded during sleep were analyzed together and also separately. Mean awake and sleeping blood pressures were calculated. Dipping was defined as a drop in sleeping systolic blood pressure greater than 10% in comparison with the average awake systolic blood pressure. Upper normal values for 24-h systolic and diastolic blood pressures were defined as 130 and 80 mmHg, respectively.
Echocardiography: All patients underwent uni- and bi-dimensional echo-cardiography according to the recommendations of the American Society of Cardiology using an Apogee 800 Plus apparatus (Advanced Technological Laboratories Inc., Bothel, Washington) equipped with 2 and 4 MHz transducers. Two observers unaware of the study hypothesis read the tracings. In our service, the intra- and inter-observer coefficient of variation is less than 5%. The following formula was used to calculate left ventricular mass (LVM):
Statistics
Data are expressed as means ± S.D. Univariate analysis was performed using the chi-square test, Student's t test and Pearson's correlation coefficient, as appropriate, to determine the variables correlated with left ventricular mass index. Multiple regression analysis was applied to the variables significantly correlated with left ventricular mass index. Two-tailed probabilities (p) for a separate variance estimate are given. Probabilities were considered significant if less than 0.05. All computations were done using the SAS statistical package.
RESULTS
shows the results of the casual and ambulatory 24-h blood pressure and of left ventricular mass index determinations. Casual and 24-h systolic and diastolic blood pressures were slightly above normal limits. The mean fall in systolic blood pressure during sleep was only 6% for the entire group, and 73% of the patients were classified as nondippers. Left ventricle mass index was increased for the whole group. Left ventricular hypertrophy was observed in 73% of the patients by echocardiography (defined as LVMI (g/m2)>134 for men and >110 for women). Univariate analysis () showed that left ventricular mass index was significantly and positively correlated with systolic (p<0.05) and diastolic (p<0.01) 24-h blood pressures, systolic (p<0.01) and diastolic (p<0.005) awake blood pressures, and with the presence of vascular dialysis access (p<0.05), and was negatively associated with the sleeping/awake SBP ratio (p<0.05). Multivariate regression analysis showed that the variable better correlated with left ventricular mass was awake SBP (regression coefficient = 0.49, p = 0.01). Left ventricular mass index was not influenced by age, sex, race, smoking, body mass index, duration of dialysis treatment, diabetes, use of antihypertensive and immunosuppressive drugs, hematocrit or biochemical variables.
Table 2. Casual and 24-h Ambulatory Blood Pressure and Left Ventricular Mass Index During the Early Post-transplant Period
Table 3. Influence of Blood Pressure and Vascular Dialysis Access on Left Ventricular Mass Index During the Early Post-transplant Period (Univariate Analysis)
DISCUSSION
The main finding of our study was that left ventricle mass index, during the early post-transplant period, was mainly influenced by blood pressure as determined by the ABPM, but not by casual blood pressure. Left ventricular hypertrophy is common in renal transplant patients, yet its risk factors have not been well established in this particular group of individuals. It is clear that ventricular hypertrophy is already present in the majority of patients when they are submitted to transplant Citation[[3]]. However, the factors influencing its development after the operation remain to be determined. We were particularly interested in analyzing the possible influence of blood pressure, since this variable is known to be related to ventricular mass in normal individuals Citation[[4]] and in hemodialysis patients Citation[[5]] and because most chronic renal failure patients remain hypertensive even after successful renal transplantation. We tried to mitigate the impact of other factors that could interfere with ventricular mass by studying patients with adequate renal function and short exposure to drugs that increase blood pressure, like cyclosporin and steroids. Significant associations between 24-h ambulatory blood pressure in kidney transplant recipients were reported by other authors Citation[[6]], Citation[[7]] but only in pediatric groups. Our results emphasize the importance of strict control of blood pressure after renal transplant even for individuals with mild hypertension. The fact that awake systolic blood pressure instead of casual blood pressure was significantly related to left ventricle mass index suggests that 24-h ABPM may be useful in the diagnosis and management of patients needing a more stringent control of blood pressure.
Lack of a significant nocturnal fall in blood pressure was not associated with left ventricular mass on multivariate analysis. This may have been due to the reduced number of dippers in our sample and to the modest change (6%) in blood pressure for the whole group during sleep. Abnormal 24-h blood pressure patterns were documented after kidney Citation[[8]], Citation[[9]] and kidney-pancreas Citation[[10]] transplant in adults and children with a prevalence close to that reported here.
In conclusion, our data indicate that left ventricle hypertrophy during the early post-transplant period is mainly influenced by awake blood pressure load, as established by ABPM, even in patients with modest elevations of blood pressure. They also suggest that 24-h ABPM may be more useful in the diagnosis and management of post-transplant hypertension than casual blood pressure and emphasize the importance of rigid blood pressure control after renal transplantation.
ACKNOWLEDGMENT
We are indebted to Mrs. Creuza Dal Bo for the statistical analysis and to Mrs. Elettra Greene for editorial assistance. The study was supported by the EJ Zerbini Foundation, São Paulo, Brazil. Dr. Marcondes was a recipient of grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil.
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