| Abstract|| |
This study was performed to assess the cardiovascular disease (CVD) risk factors in the prevalent peritoneal dialysis (PD) and hemodialysis (HD) patients and their association with cardiovascular events (CVEs) in a Saudi end-stage renal disease cohort. This was a prospective, observational, single-center study. A total of 192 patients were screened of which 157 patients were eligible (HD = 121, PD = 36). All patients underwent assessment of cardiovascular risk factors at the time of enrollment including electrocardiogram and echocardiography, lipid profile, homocysteine, and insulin levels. Patients were followed for one year and CVE [acute myocardial infarction, cerebrovascular accident (CVA), and congestive heart failure] and mortality were recorded. SPSS ® Version 16 was used for the analysis. T-test and ANOVA were used for continuous data; categorical data were analyzed using Chi-square and Mann-Whitney tests. The primary end-point of CVE and all-cause mortality was compared in the two groups using Kaplan-Meier survival analysis. HD patients were older and had been longer on dialysis. While PD patients had higher urine output and better Kt/V values, they were more edematous and using more antihypertensive medications. PD patients also had a lower ejection fraction (EF). Age >57 years and the use of more than one antihypertensive medication were associated with higher risk of CVE, while EF >53 was found to be protective. Age >57 years and EF <53 at enrollment were predictive of all-cause mortality. Saudi patients undergoing PD have worse CVD risk profiles compared to HD patients. Age less than 57 years and an EF >53 were cardioprotective.
|How to cite this article:|
Sharabas I, Siddiqi N. Cardiovascular disease risk profiles comparison among dialysis patients. Saudi J Kidney Dis Transpl 2016;27:692-700
|How to cite this URL:|
Sharabas I, Siddiqi N. Cardiovascular disease risk profiles comparison among dialysis patients. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2021 Oct 18];27:692-700. Available from: https://www.sjkdt.org/text.asp?2016/27/4/692/185225
| Introduction|| |
The incidence of end-stage renal disease (ESRD) has been steadily rising in Saudi Arabia.  For patients on renal replacement therapy (RRT), the main cause of mortality is cardiovascular disease (CVD). The rate of CVD mortality among this population is 10-20 times higher than the general population. ,,, The Saudi population has not been well studied in this respect. Compared to the US, where diabetes is the main cause of ESRD, the main cause of ESRD in Saudi Arabia is changing; now only 39% of patients starting dialysis are reported to be diabetics. ,, One can hypothesize that the pattern and risk factors for CVD in Saudi population will be different from other ethnic groups.
Risk factors for CVD in dialysis patients can be divided into traditional risk factors which affect the general population and those associated with the effect of chronic kidney disease (CKD). Among the latter is the effect of the modality of ESRD therapy.
There are very few studies from the Middle East comparing the cardiovascular risk profile of peritoneal dialysis (PD) versus hemodialysis (HD) patients. The goal of this study is to examine the prevalence of CVD risk factors among PD and HD patients and correlate association of CVD events with the two types of dialysis.
| Study design|| |
This was a prospective, observational, and single-center study in Saudi Arabia on stable ESRD patients receiving dialysis therapy over one year. The study cohort consisted of adult patients (age >12 years), of both genders, receiving RRT at our institution for at least three months prior to enrollment.
Patients with a history of malignancy, rheumatic heart disease, congenital heart disease, previous cardiac surgery, or previous transplantation who had been on dialysis for <3 months were excluded from the study. Patients unable to give consent or whose guardian was unable or refused to give consent were also excluded.
A total of 192 patients on both maintenance HD (n = 150) and PD (n = 42) were screened. After applying the exclusion criteria, a total of 157 patients were eligible, 121 were on HD and 36 on PD. The causes of exclusion are shown in [Figure 1].
Patients who had transplantation, shifted to another center, or shifted from one modality to the other during the study were analyzed in the initial group to which they were assigned and were analyzed as intention-to-treat analysis.
Of the subjects included, 132 (105 HD and 27PD) completed the study in the group they were assigned to. One hundred and fifty seven patients were available for final analysis. The data were collected by reviewing the patients' files and the Electronic Medical records system.
All patients underwent a history and physical exam (H&P) at the time of enrollment unless there was a recent H&P within last month. Data were collected on demographics such as age, gender, smoking, duration on dialysis, and cause of renal failure if available. Blood pressure, rhythm, weight, and height were recorded. Past medical history of diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD), congestive heart failure (CHF), cardiovascular events (CVE), chronic liver disease, peripheral vascular disease, malignancy, and collagen disease were extracted. Use of medications such as anti-hypertensives, hypoglycemic agents including insulin was also recorded. Data regarding nonfatal myocardial infarction (MI), fatal coronary disease, coronary bypass surgery or angioplasty, stroke, new onset atrial fibrillation (AF), heart failure, and cause of death were extracted from the medical records. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m 2 ). Electrocardiogram and transthoracic echocardiography (Echo) were done twice for the entire study population, at the beginning of the study and at the end of the follow-up. For HD patients, it was done post-HD as per the recommendations of the American Society of Echo. The left ventricular mass and left ventricular mass indexed (LVMI) to body surface area were calculated by the modified Devereux et al formula. 
Blood for biochemical analysis was collected after overnight fasting from PD and HD patients. For HD patients, a sample was taken from the arterial side prior to the first HD of the week. The following laboratory tests were recorded every three months: hemoglobin, iron, ferritin, transferrin saturation, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), calcium, albumin, phosphorus, intact parathyroid hormone (PTH), high sensitive C-reactive protein (CRP), and for diabetic patients HbA1c. 25-hydroxycholeclciferol was measured using ELISA. Homocysteine levels were measured using Roche ® enzymatic kit on COBAS Integra 800 while insulin levels were measured using Merocodia ® insulin ELISA enzyme immunoassay.
Patients who were maintained on HD were dialyzed three times a week with high-flux polysulfone dialyzer, either 1.9 m 2 or 2.1 m 2 (Fresenius, Germany; Nipro, Japan). All the treatments were of 3-4 h duration with conventional bicarbonate-based dialysate containing 1.25-1.5 mM calcium, 2.0 mM potassium, and 138 mM sodium. Dialysate flow was 500 mL/min.
All PD patients used lactate-buffered, 1.36% to 3.86% glucose-containing solutions (Baxter) along with long daytime dwell of Extraneal ® as prescribed for routine care at our institution. Patients were followed up monthly.
Adequacy of dialysis was measured with Kt/V. Peritoneal membrane transport was recorded by peritoneal equilibration test for PD patients. Residual urine volumes were obtained from a 24 h urine collection at the beginning of the study in all patients.
The primary outcome was CVEs defined as nonfatal MI, fatal coronary disease, coronary bypass surgery or angioplasty, and fatal or nonfatal stroke (both ischemic and hemorrhagic), new onset atrial fibrillation and heart failure. The diagnosis of heart failure was based on an ejection fraction (EF) below 40% or New York Heart Association Criteria Grade 3 or more.  The secondary outcome was all-cause mortality.
Time was measured from the date of initiation of HD or PD to the date of mortality, the censored events, or December 2013. The censored events included transfer to other dialysis centers or other modalities (PD, HD, or kidney transplantation).
| Statistical Analysis|| |
SPSS ® Version 16 was used for the analysis. Continuous and categorical data were expressed respectively as mean ± standard deviation and proportions. Data were compared using t-test and ANOVA for continuous data, while Chi-square and Mann-Whitney tests were used for categorical data.
The primary endpoint of CVEs and all-cause mortality was compared in the two groups using Kaplan-Meier survival analysis.
Repeated measures two-way ANOVA were performed to compare the variables which were measured every three months also for EF, and LVMI which were measured twice. A Cox proportional hazards model was also done with variables that were significantly different between groups with a value equal or less than 0.05. A P <0.05 was inferred as statistically significant.
The study protocol and all relevant data collection forms were approved by the Research and Ethics Committee at King Fahd Armed Forces Hospital.
| Results|| |
There were 157 subjects available for analysis. Patients' characteristics are shown in [Table 1]. The mean age of the patient in the study was 57 years +17.9 (range: 13-90). Nearly, half the subjects were female (52%). There were slightly higher number of females in the PD group compared to males but was not statistically significant (P = 0.257).
Patients on HD were on dialysis for a longer period, 53 ± 38 months, compared to PD patients, 31 ± 26 months (P <0.02) and were older 59.3 ± 17.1 years versus 50.8 ± 19.4 years (P <0.05). Patients on PD had higher residual urine volume 383.66 ± 548.393 (mL) in comparison to HD patients 12.40 ± 96.238 (mL) (P<0.001). Patients on PD had higher Kt/V than HD patients, 1.8781 ± 0.68062 versus 1.4709 ± 0.27539 (P <0.001).
There was a significant difference between the two groups in volume status and percentage of patients using antihypertensive medication, where 25% of PD patients were edematous and 80.5% of them were using antihypertensive medications in comparison to HD patients, 3.3% of whom were edematous, and only 45.4% on antihypertensive medications.
There was no statistically significant difference between the two groups regarding gender, smoking, BMI, HTN, DM, DM medication, and comorbidities such as IHD, cardiomyopathy, collagen diseases, peripheral vascular disease, and endocarditis.
Comparing the metabolic profile at the start of the study, PD patients had higher hemoglobin 11.3 g/L versus 10.8 g/L (P <0.05) and a lower albumin 35.3 g/L versus 40.3 g/L (P <0.001). Both groups had low Vitamin D levels with PD patients having significantly lower levels 25.2 nmol/L versus 51.7 nmol/L (P <0.001). Otherwise, there was no statistically significant differences between the two groups regarding the level of iron, ferritin, transferrin saturation, calcium, phosphate, PTH, CRP, HbA1C, and insulin (181 ± 257.9 pmol/L in HD vs. 102.9±106.3 pmol/L) in PD patients. Homocysteine was high in both groups without significant difference between the two groups. PD patients had higher levels of total cholesterol, LDL, and HDL compared to HD patients. They had lower EF than HD patients [49.4 ± 13.2 vs. 54.0 ± 10.5 (P <0.05)]. No significant difference was found in LVMI or valve calcification as shown in [Table 2].
|Table 2: Profile of biochemical and other tested parameters of the study population.|
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On repeated measure ANOVA for variables measured more than once, PD patients had higher levels of hemoglobin, iron, and cholesterol and lower level of Vitamin D and calcium than HD patients. There was a statistically significant difference within the same group; some variables like hemoglobin which was higher at the start of the study in the PD group 11.3 ± 1.3 g/L compared to 10.6 ± 1.6 g/L at the end of the study (P <0.05). Whereas, LDL was higher in the HD group at the start 2.0 ± 0.92 mmol/L versus 1.89 ± 0.89 mmol/L at 12 months (P<0.05). There were fluctuations in the quarterly values of cholesterol and PO 4 within each group.
Regarding the primary endpoint of CVEs, there were 17 events in the HD group (four patients with new CVA, seven with new-onset AF, two with CHF, two with MI, and one each with cardiac arrest and cardiac surgery) compared to two in the PD group (one each for cardiac surgery and MI). The survival curve since enrollment is shown below in [Figure 2].
In Cox Proportional Hazard model for CVEs, PD showed a trend toward being safer but did not reach statistical significance with the other variables in the equation. Age >57 years and the use of >1 antihypertensive medication were associated with higher risk while EF >53 was found to be cardioprotective as shown in [Table 3].
The secondary end point of all-cause mortality occurred in 12 patients in HD group compared to four patients in PD group, the difference was not statistically significant.
Cox proportional hazards modeling was done for all-cause mortality for all variables which showed a significant difference between the two groups. In the final model, only the age of the participant and EF at enrollment to the study was predictive of all-cause mortality, with a higher EF >53 conferring a survival benefit.
| Discussion|| |
East Asian patients tend to have better survival on PD compared to Caucasians.  Comparative data from Saudi Arabia are lacking. We were unable to show any difference in cardiovascular mortality depending on the modality of treatment. This may be related to the small sample size and short duration of follow-up. Some differences were noted regarding the modality of RRT. Our patients on PD are typically younger than patients on HD, similar to the reports from other countries.  This means we must consider the fact that they may have a lower mortality rate simply because of the age factor.  In general, in Saudi Arabia most patients prefer HD and this is evident in the number of prevalent patients with nearly two-thirds being on HD.  Our experience is similar to the US as more females are on PD compared to males. 
Studies comparing the outcomes with PD and HD patients have shown conflicting results ,, probably due to difference in study populations (incident or prevalent dialysis patients). Dyslipidemia is prevalent in patients on PD with high levels of LDL and Apolipoprotein A and lower levels of HDL.  Our patients had similar biochemical profiles but patients on PD had worse cardiovascular profiles with higher cholesterol, more evidence of edema, and use of antihypertensive medications.
Despite this, the present study did not show a difference in CVEs between the two modalities. This again stresses the point that routine cardiovascular risk factors may not be as important in this population, especially in prevalent dialysis patients. The differences in cardiovascular mortality in the different studies between incident and prevalent patients may be due to the fact that different risk factors may be important at different stages of ESRD.
Among nondiabetic patients, PD may have a survival advantage over HD.  This mostly could be related to the effect of a younger PD population. In our Cox regression model, older age (>57) was associated with higher odds of CVEs. Preservation of residual renal function has been suggested to contribute to the survival advantage of younger patients.  Our patients on PD also had higher residual urine volumes but this was not important in the Cox model.
HTN is associated with higher mortality in both PD and HD patients and treatment with antihypertensive medication reduces the CVD-related mortality.  The most important risk factor in our model was HTN medication use (surrogate for persistent HTN). Also a higher EF was protective and we did not notice a significant change in left ventricular hypertrophy or EF, which may be a function of the short duration and very good anemia control in our population. It would be interesting to look at the change in EF over a defined period of time in a larger cohort as a predictor of cardiovascular outcomes.
Many other potential factors have been suggested to explain the link between CKD and CVD mortality including chronic inflammation,  endothelial dysfunction,  vascular calcification, , hyperhomocysteinemia,  and Vitamin D deficiency.  We found no difference in the prevalence of homocysteine or CRP in the two populations. Despite the CRP being constantly elevated in both groups, it was not significant in the final analysis.
Limitations of our study include being a single-center study with a small sample size which may have precluded us finding a real difference. Second, with a short follow-up time of one year, this probably is not sufficient to elucidate the difference in mortality or CVEs. Finally, we studied patients who were already on these modalities for some time; it would be interesting to compare patients initiating the two modalities and follow them for an appropriate period. This would require a multicenter collaboration to recruit the appropriate number of patients.
| Conclusion|| |
We have shown that Saudi patients undergoing PD have worse cardiovascular risk profiles compared to HD patients. Despite this, there was no difference in CVEs. PD patients tended to be younger, female, with higher residual urine volumes, with significant volume overload and usage of antihypertensive medications. Lastly, age <57 years and a higher EF were cardioprotective. This population needs further study with possibly a larger sample to elucidate any significant differences.
Conflict of interest: None.
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Department of Nephrology, King Fahd Armed Forces Hospital, P. O. Box 9862, Jeddah 21159
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]