1 Centro di Fisiologia Clinica del CNR e Divisione di Nefrologia, Reggio Calabria, 2 Istituto di Medicina Interna L. Condorelli, Università di Catania, and 3 Servizio di Cardiologia Ospedale E. Morelli, Reggio Calabria, Italy
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Abstract |
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Methods. To examine this problem we compared a group of 51 CAPD patients, with a group of 201 HD patients. The evaluation included the measurement of atrial natriuretic peptide (atrial natriuretic factor (ANF)), taken as indicator of volume status, and echocardiographic measurements.
Results. CAPD patients were older, had been treated for a shorter time, and had lower serum albumin and phosphate than HD patients. Plasma ANF was higher (P<0.01) in CAPD (median 33.8 pmol/l (interquartile range 18.263.0)) than in HD patients (22.7 pmol/l (14.938.7)). Similarly, the left atrial volume was substantially higher (P<0.0001) in CAPD patients (49±22 ml) than in HD patients (37±17 ml), while the left ventricular end-diastolic diameter was similar in the two groups (CAPD 51±7 mm; HD 50±7 mm). Furthermore, left ventricular hypertrophy was more severe (P<0.0001) in CAPD (157±37 g/m2) than in HD patients (133±39 g/m2). The proportion of CAPD patients requiring antihypertensive drugs was markedly higher than that of HD patients (65 vs 38% P<0.001). Multivariate modelling showed that volume expansion and pressure load as well as serum albumin were independent predictors of left ventricular mass.
Conclusions. Left ventricular hypertrophy is more severe in long-term CAPD patients than in HD patients. This finding is associated with evidence of more pronounced volume expansion, hypertension, and hypoalbuminaemia. Volume and pressure load along with factors associated with hypoalbuminaemia may aggravate LVH in uraemic patients on CAPD.
Keywords: albumin; ANF; CAPD; haemodialysis; hypertension; left ventricular hypertrophy
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Introduction |
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We addressed the problem of arterial blood pressure control and left ventricular hypertrophy (LVH) in CAPD and HD patients in the baseline assessment of patients who participated in the CREED study (Cardiovascular Risk Extended Evaluation in Dialysis Patients), an ongoing observational study. In this paper, we present a cross-sectional analysis of blood pressure control and LVH according to the modality of treatment at the time of patient enrolment. As a marker of extracellular volume status, we measured the concentration of atrial natriuretic peptide (ANF) [10].
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Subjects and methods |
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Study population
Patients were enrolled between 1997 and 1998. The criteria for enrolment were no inter-current acute illness, being on dialysis for more than 6 months, and the absence of clinical evidence of heart failure. Heart failure was defined as dyspnoea in addition to two of the following conditions: raised jugular pressure, bi-basilar crackles, pulmonary venous hypertension, or interstitial oedema on chest X-ray requiring hospitalization or extra ultrafiltration [11], and ejection fraction <35%. Two hundred and fifty-two patients (143 males and 109 females, 201 on HD and 51 on CAPD) with end-stage renal disease and on regular dialysis treatment met these criteria and were enrolled for the study. These patients represented about the 70% of the whole dialysis population of four dialysis units. The remaining 30% of patients were excluded because of the presence of heart failure or major infections (20%) or because they were hospitalized for intercurrent illnesses or for logistic reasons, or unwillingness to participate in the study (10%).
The cause of chronic renal disease and the main characteristics of study patients, including previous cardiovascular events, are shown in Table 1.
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Blood pressure measurements
In haemodialysis patients pre- and post-dialysis blood pressures were calculated as the average value of all recordings (12 measurements (three per week)) taken during the month preceding the study. In CAPD patients the blood pressure values were obtained by averaging home blood pressure measurements (1020 measurements per month).
Laboratory measurements
Atrial natriuretic peptide (atrial natriuretic factor, ANF) was measured by a commercially available kit (RIK 8798, Peninsula, S. Juan Capistrano, CA) (intra-assay CV 6%, inter-assay<10%). Blood sampling in CAPD patients was performed with an empty abdomen. Kt/V in HD patients was measured with standard Gotch equations [12], and in CAPD patients Kt/V was calculated from the total loss of urea nitrogen in the spent dialysate and in a simultaneous 24-h urine collection using the Watson equation [13]. Serum albumin concentration was measured by the bromocresol green method.
Echocardiography
Each patient underwent an echocardiographic study and all echocardiographic measurements were performed according to the recommendations of the American Society of Echocardiography [14]. This study was performed during the dialysis interval in haemodialysis patients and with an empty abdomen in CAPD patients. Left ventricular mass was calculated according to the Devereux formula [15] indexed for body surface area (LVMI). Relative wall thickness (RWT) was calculated by the standard formula RWT= 2*posterior wall thickness (PWT)/left ventricular end-diastolic diameter (LVEDD). Left ventricular hypertrophy was diagnosed according to the Framingham criteria (males, LVMI>131 g/m2; females, LVMI>100 g/m2) [16] as well to those proposed by Koren et al. (LVMI>125 g/m2) [17]. According to Koren LVH is classified as concentric when RWT is 0.45, eccentric when RWT is <0.45. A RWT
0.45 with a LVMI of less than 125 g/m2 is considered remodelling. Patients with LVMI less than 125 g/m2 and RWT<0.45 were considered to have a normal ventricular geometry. Left ventricular dilatation was diagnosed when the LVEDD was equal or exceeded 57 mm [18]. Left atrial volume was estimated by the arealength method from the two- or four-chamber apical examination [19].
Statistical analysis
Data are reported as means±SD or as median and interquartile range, and comparisons between groups were made by t-test or by MannWhitney test as appropriate. Differences in proportions were analysed by the Chi-square test with correction for continuity. Multifactorial hypothesis was tested by stepwise multiple regression analysis. A set of independent variables were identified with age, sex, duration of dialysis treatment, diabetes, systolic pressure, plasma ANF, serum albumin, serum calcium and phosphate and their product, haemoglobin, and modality of treatment. The significant independent variables were ordered according to their standardized effect, defined as regression coefficient/ standard error of the regression (ß). All calculations were done using a standard statistical package (SPSS for Windows, version 9.0.1).
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Results |
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Arterial pressure in CAPD patients did not differ from pre-dialysis arterial pressure in HD patients but was significantly higher (P<0.0001) than post-dialysis pressure (Table 2). The proportion of CAPD patients requiring antihypertensive drugs was markedly higher than that of HD patients (65 vs 38%) (Table 2
). On average left atrial volume was 12 ml higher in CAPD patients than in HD patients. Similarly, plasma ANF was higher in CAPD than in HD patients (Table 2
). The left ventricular end-diastolic diameter was similar in the two groups while the interventricular septum and the posterior wall were significantly thicker in CAPD patients. Consequently, the left ventricular mass index was on the average 24 g/m2 higher in CAPD patients (Table 2
). The proportion of CAPD patients displaying left ventricular hypertrophy was much higher (P<0.01) than that of HD patients both by the Koren and by the Framingham criteria (Table 2
and Figure 1a
). The prevalence of the concentric and eccentric form of LVH was similar in the two dialytic modalities (Figure 1b
). The prevalence of concentric remodelling was also similar (CAPD 54%, HD 41%, NS). There was no difference in the prevalence of left ventricular dilatation (CAPD 21%, HD 16%, NS).
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Discussion |
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Optimal dry weight is difficult to estimate in both HD and CAPD patients, and it is perhaps even more difficult to compare the body fluid volume status in patients treated by these two substitutive treatments. To estimate the body fluid volume status we resorted to the measurement of plasma ANF and of left atrial volume. These two measurements were coherently higher in CAPD patients, suggesting that extracellular volume was more expanded in CAPD patients. In theory, differences in ANF clearance or in heart function might have contributed to the higher ANF levels of CAPD patients. However, it was shown that the clearance of this peptide is identical in HD and CAPD patients [20]. On the other hand, the ejection fraction was on average only modestly lower in CAPD than in HD patients (-3%) (Table 2), which makes it unlikely that the higher ANF in CAPD patients is the expression of a more pronounced systolic dysfunction rather than of extracellular volume expansion. Furthermore, the higher left atrial volume in CAPD patients in the presence of virtually identical left ventricular end-diastolic diameters constitutes an important support to the contention that CAPD patients are more volume expanded than HD patients. Consistent with the hypothesis of volume expansion is the observation that a larger proportion of CAPD patients required antihypertensive drug treatment to achieve a blood pressure level comparable to that of pre-dialysis blood pressure in HD patients.
Our findings contrast with early studies suggesting that CAPD allows better extracellular volume and blood pressure control [46]. These early studies dealt with CAPD patients treated for rather short periods. In our study the vast majority of patients were not in the honeymoon CAPD period: 52% of them had been on CAPD for more than 2 years and their residual diuresis and glomerular filtration rate was negligible in all but eight cases. Our observations are in agreement with more recent studies. Faller and Lameire [21] in a cohort of long-term CAPD patients, found that, after the first 2 years of treatment, the number of antihypertensive drugs had to be progressively increased to maintain blood pressure control. In a cross-over study Velasquez et al. [7] found that control of hypertension was better in the HD period than during CAPD period. A recent cross-sectional study found a 88% prevalence of hypertension in a population of 504 patients on long-term CAPD (average duration of treatment 32 months) [9].
Our study again confirms that left ventricular hypertrophy is very prevalent among dialysis patients [2225] and shows that this complication is more severe and more frequent in CAPD patients. This finding is in line with observations by Takeda et al. [8], who, like us, studied CAPD patients treated for a long time.
The observational (rather than interventional) nature is an inherent limitation of our study. In the present study, age and treatment duration were both potential confounders, while the finding that serum albumin was lower in CAPD than in HD patients confirmed previous observations suggesting that hypoalbuminaemia in CAPD patients is, at least in part, treatment dependent [26]. To partly circumvent the limitation introduced by confounding factors we resorted to multivariate analysis. Multivariate modelling showed that the markers of volume (ANF) and pressure load (systolic blood pressure) as well as serum albumin were independent predictors of left ventricular mass. Interestingly, treatment modality (HD vs CAPD) became an independent and highly significant correlate of left ventricular mass when serum albumin was omitted from the model. This observation is in keeping with previous studies showing that low serum albumin is a strong risk factor for LVH [25] and suggests that hypoalbuminaemia is involved in the treatment-dependent (CAPD vs HD) differences in heart mass in dialysis patients. However, it remains unclear whether the link between hypoalbuminaemia and LVH in dialysis patients is causal or non-causal.
In conclusion, our study shows that long-term CAPD patients are more volume expanded than are HD patients, and that their blood pressure is more difficult to control. Volume and pressure load along with factors associated with hypoalbuminaemia may aggravate LVH in uraemic patients on CAPD. Ideally the issue of whether haemodialysis affords a better cardiac protection than CAPD should be examined in prospective studies with random allocation to haemodialysis and CAPD. Such studies, however, have major feasibility problems. Perhaps an intervention study aimed at reducing volume overload is a reasonable possibility to directly prove that a more pronounced degree of volume expansion is the cause of the greater prevalence of LVH in CAPD patients.
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Acknowledgments |
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Notes |
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* *Carmela Marino, Technician1, Rocco Tripepi, Technician1, Francesco Rapisarda MD5, Pasquale Fatuzzo MD4, Grazia Bonanno MD4, Giuseppe Seminara MD5, Benedetta Stancanelli MD5, Vincenzo Candela MD3, Carlo Labate MD3, O. Marzolla MD3, Filippo Tassone MD2.
1Centro di Fisiologia Clinica del CNR e Divisione di Nefrologia, Reggio Calabria; 2Servizio di Cardiologia Ospedale E. Morelli, Reggio Calabria; 3Servizio Dialisi Melito Porto Salvo, Reggio Calabria; 4Divisione Clinicizzata di Nefrologia Chirurgica, Università di Catania; 5Istituto di Medicina Interna e Geriatria, Università di Catania, Italy.
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References |
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