High low-density lipoprotein cholesterol level is the independent risk factor of primary patency rate of arteriovenous fistula

Abstract

Objectives

An arteriovenous fistula is the first choice of vascular access in dialysis patients. However, the correlations between patient factors and the arteriovenous fistula patency rate remain unclear. Therefore, we examined the effect of dialysis patient factors on arteriovenous fistula patency rate.

Methods

This study included 101 patients who received maintenance dialysis and used arteriovenous fistula for vascular access at Atami Hospital, International University of Health and Welfare in July 2018. A retrospective review was performed from the time of arteriovenous fistula creation to July 2018, and the primary and secondary arteriovenous fistula patency rates were investigated. The patency rate was calculated using the Kaplan–Meier method, and risk factor analysis was performed using Cox proportional hazards regression analysis.

Results

The primary patency rate of arteriovenous fistula was 71.2% at one year and 43.0% at five years, and the secondary patency rate was 92.7% at one year and 79.8% at five years. In the multivariate analysis, high low-density lipoprotein cholesterol (LDL-C) level and a history of diabetes were considered significant risk factors (HR 1.023, p value <0.01 and HR 2.550, p value <0.01, respectively). A log rank test was conducted on the groups of patients with LDL <90 mg/dl and LDL ≥90 mg/dl, and the <90 mg/dl group resulted in a good primary patency rate (p value 0.0327).

Conclusions

High LDL-C level was considered the independent risk factors of arteriovenous fistula primary patency rate.

Keywords

Arteriovenous fistula vascular access patency rate low-density lipoprotein cholesterol

Introduction

An arteriovenous fistula (AVF) is the first choice for vascular access in dialysis patients because it has a lower infection rate and longer patency rate than an arteriovenous graft or central venous catheter. The National Kidney Foundation Kidney Disease Outcome Initiative recommends the use of AVF, and approximately 90% of vascular access in Japan is AVF. However, systematic reviews have reported that the present one-year patency rate of an AVF is approximately 62–68%, and the two-year patency rate is approximately 36–58%, which is not a high value.¹ It has also been reported that hospitalizations due to difficulty with vascular access account for approximately 20–25% of all hospitalizations of dialysis patients.² Therefore, the improvement of AVF patency rate is extremely important.

To improve the patency rate of vascular access, there have been several studies about the factors related to the patency rate of vascular access. These studies report that a preoperative ultrasound examination,³ better timing of first cannulation,⁴ and sufficient artery and vein diameters⁵ improve the patency rate of vascular access and radial-cephalic AVF (RCAVF) had a high primary failure rate.⁶ Regarding patient factors, a history of diabetes^7,8 and increased age⁹ have been reported as worsening factors. However, the relationship between the vascular access patency rate and complications, such as renal anemia, chronic kidney disease mineral bone disease (CKD-MBD), hypertension and dyslipidemia, has not been studied adequately. The most studied drug has been antiplatelet drugs. However, these studies only report that there may be beneficial short-term effects of ticlopidine and the long-term results are unclear¹⁰ At present, there are no drugs with adequate evidence that contributes to the patency rate of vascular access. Therefore, we planned to examine the effect of various patient factors of dialysis patients on the AVF patency rate.

Material and methods

Patients

There were 108 patients included who received maintenance dialysis at Atami Hospital, International University of Health and Welfare, in July 2018. The exclusion criteria were patients who had vascular access other than AVF, such as an arteriovenous graft, superficialized brachial artery or central venous catheter.

Study design

A retrospective review was performed in July 2018, and the primary and secondary AVF patency rates were investigated. The retrospective observation was started at the time of AVF creation. Primary patency was defined as the interval until the first percutaneous transluminal angioplasty (PTA) or surgical thrombectomy, and secondary patency was defined as the interval until the AVF was surgically revised or abandoned. Patient factors, surgical histories and PTA data were extracted from the electronic medical records of our hospital. As patient factors, we chose the known risk factors like history of diabetes and major complications of dialysis patients that could be treated with medications. We also chose the use of medications which was previously reported to affect AVF patency.^10–13 Patient factors included age, sex, CKD-MBD (Ca, P, Ca × P value, iPTH), circulation dynamics (Hb, systolic blood pressure, diastolic blood pressure), dyslipidemia (total cholesterol, HDL, LDL), history of diabetes, RCAVF and medications (β-blocker, antiplatelet agent, anticoagulant agent, statin, vitamin D and erythropoietin-stimulating agent (ESA) amount used). If the AVF was patent until June 2018, the laboratory data and history of medications reflected what was taken in June 2018; otherwise, they reflected what was taken when primary patency was discontinued. Blood pressure was measured before dialysis. In regard to ESAs, 1 mcg darbepoetin alpha was converted to 200 IU epoetin alpha. The ethics committee of the International University of Health and Welfare approved the study protocol in October 2018 (authorization number 18-A-119), and patient informed consent was waived because of the retrospective nature of the study and lack of intervention.

Statistical analysis

The primary and secondary AVF patency rates were calculated using the Kaplan–Meier method. The analysis of patency rate risk factors was performed using Cox proportional hazards regression analysis. In the univariate and multivariate analyses, a p value <0.05 was considered to indicate a significant difference. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of R commander designed to add statistical functions frequently used in biostatistics.

Results

Of the 108 maintenance dialysis patients in our hospital, 101 patients (93.52%) used an AVF for vascular access, 5 patients (4.63%) used an arteriovenous graft, 2 patients (1.85%) used a superficialized brachial artery and none of the patients used a central venous catheter. The average length of the observation period was 4.14 years in the survey of the primary patency rate and 5.13 years in the survey of the secondary patency rate. The average time from AVF creation until July 2018 was 5.48 years (minimum 23 days, maximum 25 years). The primary patency rate of the 101 patients who used AVF for vascular access was 71.2% at one year, 43.0% at five years. The secondary patency rate was 92.7% at one year, 79.8% at five years (Figures 1 and 2).

Figure 1.

Primary patency survival of arteriovenous fistula.

Figure 2.

Secondary patency survival of arteriovenous fistula.

Patient characteristics are described in Table 1. The average age was 70.4 ± 10.9 years, 37.6% of patients were female, and 45.5% of patients were diabetic. The average LDL cholesterol level was 89.8 ±24.0 mg/dl with a median value of 90 mg/dl. The statin usage rate was 11.8% and the antiplatelet drug use rate was 48.5%.

Table 1.

Baseline characteristics of the study population.

	n = 101
Age (yr)	70.4 ± 10.9
Female, n (%)	38 (37.6%)
RCAVF (%)	93 (92.1%)
DM, n (%)	46 (45.5%)
Ca (mg/dl)	8.6 ± 0.8
P (mg/dl)	5.9 ± 1.4
Ca × P	50.2 ± 12.7
iPTH (mg/dl)	167.3 ± 106.9
Hb (g/dl)	11.2 ± 1.1
sBP (mmHg)	152.8 ± 26.9
dBP (mmHg)	76.1 ± 14.6
TC (mg/dl)	159.1 ± 35.5
HDL (mg/dl)	51.3 ± 17.1
LDL (mg/dl)	89.8 ± 24.0
Antiplatelet, n (%)	49 (48.5%)
Anticoagulant, n (%)	6 (5.9%)
Statin, n (%)	12 (11.8%)
Vitamin D, n (%)	87 (86.1%)
β-blocker, n (%)	15 (14.8%)
ESA (IU/ml/week)	4450.5 ± 3834.4

Note: Data are expressed as the mean ± standard deviation or the count (percentage).

Ca: calcium; dBP: diastolic blood pressure; DM: diabetes; ESA: erythropoietin stimulating hormone; Hb: hemoglobin; HDL: high-density lipoprotein cholesterol; iPTH: intact parathyroid hormone; LDL: low-density lipoprotein cholesterol; P: phosphate; RCAVF: radial-cephalic arteriovenous fistula; sBP: systolic blood pressure; TC: total cholesterol.

In the univariate analysis, the risk factors for primary patency in the Cox proportional hazards model were considered to be a history of diabetes (HR 1.991, p value 0.0088), total cholesterol (TC) level (HR 1.010, p value 0.0043), and LDL cholesterol value (HR 1.020, p value 0.0003) (Table 2). In the multivariate analysis, age, sex, history of diabetes, LDL, Hb and P were used as the explanatory variables. Although TC had a small p value (<0.01), it was not adopted as an explanatory variable because it was considered to have a strong correlation with LDL. In the multivariate analysis, a history of diabetes and LDL cholesterol level were considered to be significant risk factors (HR 2.550, p value 0.0017 and HR 1.023, p value 0.0004, respectively) (Table 3). The median LDL cholesterol level was 90 mg/dl. Therefore, a log rank test was conducted on the groups of patients with LDL <90 mg/dl and LDL ≥90 mg/dl, and the <90 mg/dl group predominantly resulted in a good primary patency rate (p value 0.0327) (Figure 3).

Table 2.

Risk factors influencing AVF primary patency in the univariate Cox proportional hazards model.

	HR (95% CI)	p value
Female	0.938 (0.560–1.573)	0.8091
Age	0.991 (0.966–1.017)	0.4909
RCAVF	1.185 (0.473–2.967)	0.7170
DM	1.991 (1.189–3.332)	0.0088
Ca	0.950 (0.698–1.293)	0.7444
P	1.149 (0.948–1.394)	0.1569
Ca × P	1.012 (0.991–1.032)	0.2616
iPTH	1.001 (0.999–1.003)	0.2552
Hb	1.188 (0.942–1.497)	0.1448
TC	1.010 (1.003–1.016)	0.0043
HDL	0.989 (0.973–1.007)	0.2341
LDL	1.020 (1.009–1.032)	0.0003
sBP	1.001 (0.991–1.010)	0.9076
dBP	1.003 (0.984–1.022)	0.7723
β-blocker	0.701 (0.319–1.543)	0.3776
Antiplatelet	1.258 (0.761–2.082)	0.3707
Anticoagulant	0.799 (0.289–2.205)	0.6650
Statin	1.236 (0.559–2.733)	0.6009
Vitamin D	0.935 (0.421–2.075)	0.8682
ESA	0.999 (0.999–1.000)	0.0691

Table 3.

Risk factors influencing AVF primary patency in the multivariate Cox proportional hazards model.

	HR (95% CI)	p value
Age	1.014 (0.988–1.041)	0.2967
Female	0.869 (0.503–1.504)	0.6179
DM	2.550 (1.417–4.588)	0.0017
LDL	1.023 (1.010–1.035)	0.0004
Hb	0.991 (0.751–1.307)	0.9489
P	1.099 (0.885–1.391)	0.3664

DM: diabetes; Hb: hemoglobin; LDL: low-density lipoprotein cholesterol; P: phosphate.Note: The bold characters mean p value <0.05.

Figure 3.

Primary patency survival of arteriovenous fistula in patients with LDL <90 mg/dl (solid line) and LDL ≥90 mg/dl (dotted line).

Discussion

The purpose of this study was to investigate the factors that affect the AVF patency rate and find the factors that lead to the improvement of AVF patency. In this study, a history of diabetes and high LDL level were considered to be independent risk factors of the AVF primary patency rate.

Generally, in dialysis patients, dyslipidemia is characterized by no rise in LDL cholesterol, an increase in TG, and a decrease in HDL cholesterol.¹⁴ This is because the accumulation of uremia results in the decrease of lipoprotein lipase (LPL) activity and hepatic triacylglycerol lipase (HTGL) activity, and intermediate density lipoprotein (IDL) is not converted to LDL. Indeed, in our study, the average LDL value was 89.8 mg/dl and the median value was 90 mg/dl, which are not high values. The K/DOQI target value for LDL cholesterol in chronic kidney disease is less than 120 mg/dl,¹⁵ and the LDL values in this study were not at the level requiring therapeutic intervention. However, in this study, AVF patency was significantly improved in the LDL <90 mg/dl group.

It has previously been reported that dyslipidemia increases the risk of thrombosis of AVF. A prospective study by De Marchi et al.¹⁶ reported that the total cholesterol level of patients with AVF failure was 244 ±81 mg/dl and that of patients without AVF failure was 179 ± 35 mg/dl and that dyslipidemia carried a risk of AVF failure. In a prospective study by Serati et al.,¹⁷ it was reported that the risk of AVF thrombosis was lower in patients with LDL ≤130 mg/dl. In the current study, the median LDL value was 90 mg/dl and the median TC value was 153 mg/dl, which were lower than the criteria of these past reports.

Although not in the field of vascular access, it has been reported in the field of coronary artery disease that the incidence of ischemic heart disease decreased by 13% as a result of a decrease in LDL 130 mg/dl to 70 mg/dl with the oral administration of atorvastatin.¹⁸ In the 2015 annual summary of the National Lipid Association, the secondary prevention of coronary artery disease was announced as a target LDL-C of 70 mg/dl,¹⁹ and meta-analysis results also showed that the group achieving the lowest LDL had the lowest number of cardiovascular events.²⁰ As well as coronary artery disease, lowering the LDL value as much as possible had the potential to improve the patency rate of AVF.

In this study, statin administration was not a beneficial factor of the AVF patency rate. This was because the LDL value of the no statin group was 90.8 mg/dl, which was not significantly different from that of the statin group (85.5 mg/dl). Some studies had reported that statin oral administration was effective for improving the AVF patency rate.^11,21 However, one meta-analysis had reported that this was invalid.²² In these reports, there was no information about LDL value. That might be the reason for the difference in the effectiveness of statin oral administration. Considering the result of our study, there is the possibility that the AVF patency rate might be improved by the statin administration to lower the LDL value as much as possible.

There were two limitations in this research. First, it was a retrospective, single-center study and various biases might have been applied. For example, the patients of this study were only Japanese people and further studies would be needed to support the results in other ethnic groups. Second, the criteria of PTA for AVF treatment were not clearly defined. Therefore, the primary patency rates could be affected by the physician’s judgements. To clarify the further relationship between AVF patency rate and LDL value, a prospective study and clear criteria of PTA are desired.

Conclusion

In conclusion, high LDL level was considered as the independent risk factor of the AVF primary patency rate and lowering the LDL level might improve the patency rate of AVF patency rate of dialysis patients.

Footnotes

Acknowledgements

We thank for all medical staff in the dialysis center of Atami hospital, International University of Health and Welfare, for helping collecting data.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Tomotaka Yamazaki

References

Al-Jaishi

Oliver

Thomas

, et al. Patency rates of the arteriovenous fistula for hemodialysis: a systematic review and meta-analysis. Am J Kidney Dis 2014; 63: 464–478.

Rayner

Pisoni

Bommer

, et al. Mortality and hospitalization in hemodialysis patients in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2004; 19: 108–120.

Nursal

Oguzkurt

Tercan

, et al. Is routine preoperative ultrasonographic mapping for arteriovenous fistula creation necessary in patients with favorable physical examination findings? (Results of a randomized controlled trial). World J Surg 2006; 30: 1100–1107.

Bhomi

Shrestha

Bhattachan

CL.

Role of systemic anticoagulation in patients undergoing vascular access surgery. Nepal Med Coll J 2008; 10: 222–224.

Glass

Johansson

DiGragio

, et al. A meta-analysis of preoperative duplex ultrasound vessel diameters for successful radiocephalic fistula placement. J Vasc Ultrasound 2009; 33: 65–69.

Rooijens

Tordoir

Stijnen

, et al. Radiocephalic wrist arteriovenous fistula for hemodialysis: meta-analysis indicates a high primary failure rate. Eur J Vasc Endovasc Surg 2004; 28: 583–589.

Sedlacek

Teodorescu

Falk

, et al. Hemodialysis access placement with preoperative noninvasive vascular mapping: comparison between patients with and without diabetes. Am J Kidney Dis 2001; 38: 560–564.

Konner

Hulbert-Shearon

Roys

, et al. Tailoring the initial vascular access for dialysis patients. Kidney Int 2002; 62: 329–338.

Lazarides

Georgiadis

Antoniou

, et al. A meta-analysis of dialysis access outcome in elderly patients. J Vasc Surg 2007; 45: 420–426.

10.

Tanner

da Silva

AF.

Medical adjuvant treatment to improve the patency of arteriovenous fistulae and grafts: a systematic review and meta-analysis. Eur J Vasc Endovasc Surg 2016; 52: 243–252.

11.

Chang

, et al. Statins improve long term patency of arteriovenous fistula for hemodialysis. Sci Rep 2016; 6: 22197.

12.

Rosenberg

Astor

Deluca

, et al. The association of mineral metabolism with vascular access patency. J Vasc Access 2016; 17: 392–396.

13.

Jeong

Kim

, et al. Administration of a high-dose erythropoietin-stimulating agent in hemodialysis patients is associated with late arteriovenous fistula failure. Yonsei Med J 2017; 58: 793–799.

14.

Shoji

Nishizawa

Kawagishi

, et al. Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients. J Am Soc Nephrol 1998; 9: 1277–1284.

15.

Kidney Disease Outcomes Quality Initiative (K/DOQI) Group. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis 2003; 41: S1–91.

16.

De Marchi

Falleti

Giacomello

, et al. Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. J Am Soc Nephrol 1996; 7: 1169–1177.

17.

Serati

Roozbeh

Sagheb

MM.

Serum LDL levels are a major prognostic factor for arteriovenous fistula thrombosis (AVFT) in hemodialysis patients. J Vasc Access 2007; 8: 109–114.

18.

Schwartz

Olsson

Ezekowitz

, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285: 1711–1718.

19.

Bays

Jones

Brown

, et al. National lipid association annual summary of clinical lipidology 2015. J Clin Lipidol 2014; 8: S1–36.

20.

Boekholdt

Hovingh

Mora

, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol 2014; 64: 485–494.

21.

Sanada

Miyasaka

Kanno

, et al. Efficacy of statin on vascular access patency in diabetic hemodialysis patients. J Vasc Access 2017; 18: 295–300.

22.

Wan

Yang

, et al. Impact of statins on arteriovenous fistulas outcomes: a meta-analysis. Ther Apher Dial 2018; 22: 67–72.