Abstract
Background: Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is common among dialysis patients. Cardiovascular disease (CVD) accounts for the leading cause of mortality in dialysis patients, and PAD has been found as a predictor for cardiovascular as well as overall mortality in general population. However, the study on the role of PAD in the prognosis of peritoneal dialysis patients is rather limited. Methods: Prevalent continuous ambulatory peritoneal dialysis patients over 60 years old were recruited in this study and were followed-up regularly to death or the end of the study. The diagnosis of PAD was based on ankle-brachial pressure index (ABI) < 0.9 or intermittent claudication. Univariate and multivariate Cox proportional hazard models were used to identify the risk factors for cardiovascular and overall mortality. Survival curves were estimated by the Kaplan–Meier method followed by log-rank test to compare the mortality rate between PAD and non-PAD patients. Results: One hundred and seventy-one patients were included and 62 (36%) had PAD complication. In the follow-up of 24.4 (median 34.6) months, 36 deaths were recorded: 19 from PAD group and 17 from non-PAD group. Twenty-one patients died due to CVD: 13 from PAD group and 8 from non-PAD group. The presence of PAD and serum albumin was found independently associated with cardiovascular and overall mortality using Cox proportional hazards model. Conclusion: PAD is very common in aged peritoneal dialysis patients and independently associated with both cardiovascular and overall mortality.
INTRODUCTION
End-stage renal disease (ESRD) is a powerful determinant of atherosclerotic vascular disease and is associated with a remarkably high incidence of cardiovascular morbidity and overall mortality.Citation1–3 Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is common among ESRD patients.Citation3–6 Epidemiological and clinical studies of the general population have clearly shown that PAD is a strong predictor for subsequent cardiovascular and overall mortality.Citation7,8 Limited available data also suggest that PAD is prevalent in hemodialysis patientsCitation4,9–12 and is associated with poor outcomes.Citation4,6,13 However, the studies on the role of PAD in predicting mortality in peritoneal dialysis patients are even less.Citation14–16 Liu et al.Citation17 recently reported that the prevalence of PAD is high and is associated with total mortality in 153 Taiwan Peritoneal Dialysis (PD) patients; however, the patients with PAD were much older than non-PAD peers (64.3 years vs. 52.1 years, p < 0.001). Moreover, the prevalence of ESRD is much higher in aged population, so we conducted this study to investigate the role of PAD in prediction of overall and cardiovascular mortality in PD patients more than 60 years old.
METHODS
Patient Selection
Elderly patients (more than 60 years old) on continuous ambulatory peritoneal dialysis (CAPD) between January 2006 and April 2009 at the outpatient clinic in the Division of Nephrology of Peking University Third Hospital were eligible to be recruited. Patients included had to be clinically stable for 3 months before entry, without infectious, or other active diseases. Patients were censored if died, loss of follow-up, transfer to hemodialysis or transplant, and survival to 31 October 2009. This study was approved by the ethical committee of Peking University and written informed consent was obtained from all patients.
Ankle-Brachial Pressure Index Measurement
PAD was defined as either the development of intermittent claudication or ankle-brachial pressure index (ABI) value lower than 0.9. ABI was measured as described by Feigelson et al.Citation18 An ABI was calculated for each leg and the lowest value was used to group patients according to the presence (ABI < 0.9) or absence (ABI ≥ 0.9) of PAD.
Demographic and Clinical Data Collection
Demographic data were collected when ABI measurement was done. Results of laboratory tests were collected within 1 month of ABI measurement or at the fourth month of dialysis if the dialysis vintage was less than 3 months when ABI measurement was performed. All the patients were followed up regularly every 3 months till death or 31 October 2009. Cardiovascular mortality included death caused by cardiac disease, heart failure, and cerebral vascular disease and sudden death.
Diagnosed coronary artery disease (previous myocardial infarction, ischemia detected by cardiogram abnormality, history of coronary artery bypass grafting, or coronary stent implantation) or a previous ischemic or bleeding of cerebral vascular event was classified as cardiovascular or cerebral vascular disease and grouped as cardiovascular disease (CVD). A history of smoking (current or former) was defined as a 1 pack-year or more of tobacco use based on patient interview or chart documentation. Patients taking aspirin or other antiplatelet agents for more than 6 months were treated as aspirin users.Citation19
Statistical Analysis
Statistical analysis was carried out using SPSS (version 13.0: SPSS, Chicago, IL, USA). Continuous variables used were presented as mean ± SD, and categorical variables as percentages. Serum C-reactive protein (CRP) level was transformed to natural logarithm as it was not normally distributed. Student’s t-test was used to find significant difference between PAD and non-PAD patients for continuous variables while Chi-squared test for categorical variables. A two-tailed p-value < 0.05 was regarded as statistically significant. Variables with statistical significance were included in the univariate regression and the significant ones (p < 0.05) for cardiovascular or all-cause mortality were selected into each multivariate model. In addition, factors reported to be associated with survival in literature such as serum albumin, body mass index, and dialysis vintage were also included in the univariate analysis. Variables with statistical difference were selected for univariate and multivariate analyses using Cox proportional hazards model. Survival curves were estimated by the Kaplan–Meier method followed by log-rank test to compare the mortality rate between PAD and non-PAD groups.
RESULTS
One hundred and seventy-one patients were included in the study, of which 62 (36%) were PAD patients. During a mean follow-up time of 24.4 months (median: 34.6 months, range from 5 to 45 months), five patients were lost to follow-up. Four patients were transferred to hemodialysis, whereas six patients were transferred to kidney transplantation. Three patients were transferred to hemodialysis because of peritonitis whereas the other patient was transferred because of inguinal hernia. Thirty-six deaths were recorded: 19 from PAD group and 17 from non-PAD group. Twenty-one patients died due to CVD: 13 from PAD group and 8 from non-PAD group. The primary diseases for causes of renal failure were shown in . The description of clinical characteristics at baseline was presented in . In brief, the percentage of diabetes mellitus and CVD history was higher in PAD patients than in non-PAD patients (p < 0.05). Diastolic blood pressure was lower in PAD group, whereas serum CRP level was higher in PAD group compared to non-PAD group. Other variables were comparable between groups. shows univariate Cox regression results of various parameters contributing to all-cause mortality as well as cardiovascular mortality. PAD and serum albumin levels were found independently predicting both all-cause mortality and the cardiovascular mortality (). PAD patients has a significantly higher overall () and cardiovascular () mortality compared to non-PAD patients by K–M survival curve (both p<0.05).
Figure 1. Overall mortality between PAD and non-PAD patients by K–M analysis.
Figure 2. Cardiovascular mortality between PAD and non-PAD patients by K–M analysis.
Table 1. Causes of death in all patients.
Table 2. Baseline characteristics between PAD and non-PAD groups.
Table 3. Univariate analysis of variables associated with overall and cardiovascular mortality.
Table 4. Multivariate analysis of variables associated with overall and cardiovascular mortality.
DISCUSSION
PAD is very common in ESRD patients and its prevalence in aged patients is even higher.Citation20 In this study, 62 (36%) patients were diagnosed as PAD, although most of them showed no classic symptom. It is interesting to note only 10 of 62 PAD patients was clinically recognized as having PAD before the ABI measurement, reflecting the neglect of PAD in clinic.Citation21 This study showed that PAD patients suffered a much higher CVD as well as all-cause mortality compared to non-PAD patients. The result was consistent with a recent report by Liu et al.Citation17; however, the PAD patients were much older than non-PAD peers (64.3 years vs. 52.1 years, p < 0.001), which may bring some bias. In this study, only aged patients were recruited, which made the two groups more comparable.
PAD is an important manifestation of systemic vascular disease. In this study, 21 (58%) patients died of CVD. Moreover, CVD accounted for 68% of death in PAD group. The predictive role of PAD to CVD and all-cause mortality in aged CAPD patients may in part be highlighted by the systemic atherosclerosis of PAD patients.Citation22
Other mechanisms may also account for the high mortality in PAD patients. Inflammation (by CRP) has been found associated with mortality in various populations including ESRD patients.Citation23 Although point CRP level may not be a good marker to reflect the inflammatory status during the follow-up, we still found that CRP associated with CVD mortality in univariate analysis. Note that PAD is also an atherosclerosis process characterized by inflammation; the impact of PAD on survival may partly lie in the inflammatory status of these patients.
In this study, PAD patients had a much higher percentage of diabetic complication, indicating a contributory role of diabetes to PAD.Citation24,25 However, diabetic complication was associated with neither CVD nor all-cause mortality. It was not strange that the patients had a different diabetic vintage and different glucose management; moreover, the fast blood glucose level but diabetic complication was found associated with cardiovascular as well as all-cause mortality in the univariate analysis (), indicating that a good control of diabetes may result in better survival.Citation20
In consistent with previous studies,Citation6,20 serum albumin is also found as an independent predictor of mortality in this study. Decreased serum albumin is a manifestation of both malnutrition and inflammation,Citation26 which are very common in CAPD patients. In this study, PAD patients showed lower albumin as well as higher CRP levels than non-PAD patients, which is a manifestation of MIA (malnutrition–inflammation–atherosclerosis) syndrome. The increased mortality rate in PAD patients may be due to the combined cardiovascular and diabetic complications and also may be due to the atherosclerotic and inflammatory status manifested by PAD itself.
In conclusion, our study showed that PAD is an independent predictor of overall and cardiovascular mortality in aged CAPD patients. As ABI is a sensitive, noninvasive, and inexpensive measurement tool for PAD detection, we suggest that ESRD patients should undertake an ABI measurement for early recognition and better secondary prevention of PAD.
Potential limitations of our study include the relatively short duration of follow-up and the inclusion of both prevalent and incident CAPD patients. Other limitations in this study are that we did not differentiate medial artery calcification, which is a common complication in ESRD patientsCitation27 from atherosclerotic PAD.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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