ORIGINAL ARTICLE

JNEPHROL 2011; 24 ( 05 ) : 636-646

DOI:10.5301/JN.2010.6259

Aspirin resistance in patients with chronic renal failure

Azra Meryem Tanrikulu 1, Beste Ozben 1, Mehmet Koc 2, Nurdan Papila-Topal 1, Tomris Ozben 3, Oguz Caymaz 1
Department of Cardiology, Marmara University Faculty of Medicine, Istanbul - Turkey 2 Division of Nephrology, Department of Internal Medicine, Marmara University Faculty of Medicine, Istanbul - Turkey 3 Department of Biochemistry, Akdeniz University Faculty of Medicine, Antalya - Turkey
1
1 1 1

Department of Cardiology, Marmara University Faculty of Medicine, Istanbul - Turkey Department of Cardiology, Marmara University Faculty of Medicine, Istanbul - Turkey Department of Cardiology, Marmara University Faculty of Medicine, Istanbul - Turkey

AbstrAct
Background: Chronic renal failure (CRF) is associated with increased risk of cardiovascular morbidity and mortality. Aspirin resistance worsens clinical prognosis. The aim of this study was to explore the prevalence of aspirin resistance in CRF. Methods: Two hundred and forty-five CRF patients (115 patients undergoing chronic hemodialysis and 130 patients with stage 3-4 chronic kidney disease [CKD]) and 130 patients with normal renal functions (control group) were consecutively recruited. All subjects were taking aspirin regularly. Aspirin responsiveness was determined by Ultegra Rapid Platelet Function Assay-ASA (VerifyNow Aspirin). Aspirin resistance was defined as aspirin reaction unit (ARU) 550. Results: Aspirin resistance was detected in 53 patients undergoing hemodialysis, 32 patients with stage 3-4 CKD and 22 controls. The frequency of aspirin resistance was significantly higher in the CRF group compared with controls (34.7% vs. 16.9%, p<0.001) and in hemodialysis patients (46.1%) compared with stage 3-4 CKD patients (24.6%, p<0.001) and controls (16.9%, p<0.001). Multivariate analysis revealed female sex (odds ratio [OR] = 2.201; 95% confidence interval [95% CI], 1.173-4.129; p=0.014), hemodialysis (OR=3.636; 95%CI, 1.313-10.066; p=0.013) and HDL cholesterol (OR=0.974; 95% CI, 0.950-0.999; p=0.043) as independent predictors of aspirin resistance in this cohort of patients. Conclusion: Patients with CRF have higher frequency of aspirin resistance. This might further increase the risk of cardiovascular morbidity and mortality in these patients. Key words: Aspirin, Aspirin resistance, Chronic kidney

IntroductIon
Aspirin is an effective antiplatelet agent, exhibiting its action by irreversibly inhibiting platelet cyclooxygenase-1 enzyme, thus preventing the production of thromboxane A2 (TXA2). It has been used in the primary and secondary prevention of thromboembolic vascular events (1-3). Yet, some patients have recurrent vascular events despite long-term aspirin therapy, raising the possibility that they are resistant to aspirin. The term resistance has been used to describe the inability of aspirin to produce a measurable response on ex vivo tests of platelet function, to inhibit TXA2 biosynthesis in vivo or to protect individual patients from recurrent thrombotic complications (4). Estimates of the prevalence of aspirin resistance vary widely (5.5% to 60%), reflecting the diversity of various laboratory assays and confounding from the broad range of disease states investigated (5-8). Possible causes of aspirin resistance include poor compliance or inadequate dose (9, 10), reduced bioavailability (11), increased platelet turnover, up-regulation of non-platelet pathways of thromboxane production (12, 13), drug interactions (14, 15) and genetic variability (16-20). Despite ongoing research, there is currently no standardized approach to the diagnosis and no proven effective treatment for aspirin resistance. Chronic renal failure (CRF) is associated with high cardiovascular morbidity and mortality (21). In patients with end-stage chronic kidney disease (CKD) and undergoing hemodialysis, coronary artery disease (CAD) incidence is nearly 40%, and half of the mortality in these patients is associated with cardiovascular diseases (22). Thus aspirin use is important in these patients. Although aspirin resistance has been well demonstrated in cardiovascular disorders including CAD (12, 23), heart failure (24), cerebrovascular disease (25, 26), metabolic syndrome (27) and

disease, Chronic renal failure, Hemodialysis

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diabetes (28-30), little is known about aspirin response and its prognostic value in patients with CRF. The aim of this study was to assess the prevalence of aspirin resistance in patients with CRF.

subjects And methods

The investigation complies with the principles outlined in the Declaration of Helsinki. The study was approved by the local ethics committee, and all participants gave written informed consent before participating. One hundred and fifteen patients undergoing chronic hemodialysis and 130 patients with stage 3-4 CKD were consecutively included into the study as the CRF group. All stage 3-4 CKD patients had stage 3 or 4 CKD with or without underlying morphological renal disease such as diabetic nephropathy, hypertensive nephropathy, chronic glomerulonephritis or polycystic kidney disease, and had an estimated glomerular filtration rate (GFR) between 15 and 60 ml/min per 1.73 m2 for at least 6 months on 2 different measurements. Estimated GFR was calculated using the Modification of Diet in Renal Disease Study formula (31). The patients undergoing chronic hemodialysis had creatinine clearance below 10 ml/min per 1.73 m2 and had been on chronic hemodialysis treatment for more than 6 months. They were dialyzed 3 times a week with polysulfone low-flux dialyzers (Fresenius Medical Care, Lexington, MA, USA). All hemodialysis patients underwent hemodialysis for 4 hours by cannulation of the arteriovenous fistula, and using sterile bicarbonate concentrate, heparin and reverse osmosis water. Dialysate and blood flow rates were 500 and 350 ml/min. Anticoagulation was performed with heparin given as an intravenous bolus of 2,000 IU just before hemodialysis followed by a continuous infusion at a rate of 1,000 IU/hour. The control group included 130 consecutive patients with normal renal functions, estimated GFR 90 ml/min per 1.73 m2 and no underlying morphological renal disease. All study subjects were taking aspirin 100 to 300 mg/ day regularly for at least 1 week. Compliance with aspirin treatment was ascertained by a personal interview at the time of inclusion to the study. A questionnaire on smoking habits, clinical history of CAD, diabetes, hyperlipidemia, hypertension and renal failure was carried out. Weight and height were measured to determine body mass index (BMI). Fasting blood samples were obtained to determine blood glucose, creatinine, blood urea nitrogen, triglycerides, high-density lipoprotein (HDL) cholesterol, lowdensity lipoprotein (LDL) cholesterol, C-reactive protein, hematocrit and platelet counts.

Exclusion criteria included ingestion of ticlopidine, clopidogrel, cilostazol, dipyridamole, abciximab, tirofiban or antiinflammatory drugs for the last 10 days. Patients with stage 2 CKD (patients with underlying morphological renal disease and GFR between 60 and 89 ml/min per 1.73 m2) or a history of major cardiovascular event within the past 3 months were also excluded.

Assessment of aspirin resistance with Ultegra Rapid Platelet Function Assay

From every patient 2-mL blood samples were drawn into tubes containing 3.2% citrate 1 to 4 hours after aspirin intake. Blood samples of the hemodialysis patients were obtained on the second hemodialysis session of the week before the hemodialysis session began. Aspirin-induced platelet inhibition was measured using a commercially available point-of-care assay, the Ultegra Rapid Platelet Function Assay-ASA (VerifyNow System; Accumetrics, San Diego, CA, USA). This is a whole blood optical detection system that measures agonist-induced platelet aggregation using cationic propyl gallate to activate platelets. Platelet function measurement is based on the ability of activated platelets to bind fibrinogen. The instrument measures the change in optical signal caused by aggregation. If aspirin has produced the expected antiplatelet effect, fibrinogencoated beads will not agglutinate, and light transmission will not increase. The results are reported as aspirin reaction units (ARUs). The cutoff point is set as 550 ARU according to the manufacturers clinical studies using optical aggregometry as the comparison standard. An ARU 550 indicates absence of aspirin-induced platelet dysfunction and is defined as aspirin-resistant. An ARU <550 indicates platelet dysfunction consistent with aspirin has been detected and is defined as aspirin-sensitive (32).

Statistical analysis
All statistical tests were performed with a commercially available statistical analysis program (SPSS 11.0 for Windows). Continuous variables were expressed as means standard deviation, while categorical variables were expressed as ratios. Students t-test and the Mann-Whitney U-test were used for comparison of parametric and nonparametric variables between 2 groups, while ANOVA and Kruskal-Wallis tests were used for comparison of parametric and nonparametric variables among 3 groups. Categorical variables were compared using the chi-square test. Pearsons correlation was used for univariate analysis. A logistic regression analysis was modeled to determine the independent predictors of
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aspirin resistance in this cohort of patients. A p value <0.05 was interpreted as statistically significant.

the median aspirin doses were similar between the CRF group and controls.

results
Patient characteristics
All patients were included in the study consecutively among patients taking regular aspirin. The CRF group consisted of 115 patients undergoing chronic hemodialysis and 130 patients with stage 3-4 CKD. The mean Kt/V (urea kinetics, postdialysis volume) and urea reduction ratio (URR) values of the hemodialysis patients were 1.30 0.43 and 69% 7%, respectively. The mean GFR of the stage 3-4 CKD patients was 38 14 ml/min per 1.73 m2. The control group consisted of 130 patients with mean GFR of 98 6 ml/min per 1.73 m2. The general characteristics and laboratory parameters of the CRF group and controls are listed in Table I. There were no significant differences in sex and age distribution between the whole CRF group and controls, although sex and age distributions differed when the CRF group was subgrouped as hemodialysis and stage 3-4 CKD groups. There were statistically significant differences in the frequency of hypertension, BMI and levels of creatinine, LDL cholesterol, HDL cholesterol, triglycerides, hematocrit and platelet counts between the CRF group and controls.

Characteristics of aspirin-resistant and aspirinsensitive patients

The general characteristics and laboratory parameters of aspirin-resistant and aspirin-sensitive patients are shown in Table III. The frequencies of female sex, CRF and hemodialysis were significantly higher in the aspirin-resistant patients. Daily aspirin doses and duration of aspirin therapy were similar between the aspirin-resistant and aspirin-sensitive patients. Among the laboratory parameters, blood urea nitrogen and creatinine levels were significantly higher, while hematocrit levels and platelet counts were significantly lower in the aspirin-resistant patients.

Relations between aspirin resistance and different variables

Aspirin reaction units were correlating positively with serum creatinine levels (p<0.001, r=0.324) and negatively with estimated GFR (p<0.001, r=0.337). An increase of 1 mg/dL in creatinine levels showed a 10% increase in the odds of having aspirin resistance (p=0.001; 95% CI, 4.1%-16.3%) while an increase of 1 ml/min per 1.73 m2 in GFR showed a 1.1% decrease in the odds of having aspirin resistance (p=0.001; 95% CI, 0.5%-1.7%). There was a significant relation between aspirin resistance and sex of patient. Among the aspirin-resistant patients, the percentage of women was 53.3%, while only 40.7% of aspirin-sensitive patients were women (p=0.027; OR=1.663; 95% CI, 1.059-2.611). There were no significant associations between aspirin resistance and age, hypertension, diabetes, hyperlipidemia, CAD or smoking. No significant correlation was found between aspirin reaction units and aspirin daily doses, duration of aspirin therapy, BMI, systolic or diastolic blood pressure, blood glucose, LDL cholesterol or triglyceride levels. However, aspirin reaction units were significantly correlating with HDL cholesterol (p<0.001, r=0.212), hematocrit (p<0.001, r=0.271) and platelet levels (p<0.001, r=0.237). We modeled a logistic regression analysis to determine the independent predictors of aspirin resistance in this cohort of patients. Multivariate analysis for predictors of aspirin resistance is presented in Table IV. Multivariate analysis revealed that female sex (OR=2.201; 95% CI, 1.173-4.129; p=0.014), hemodialysis (OR=3.636; 95% CI, 1.313-10.066; p=0.013) and HDL cholesterol (OR=0.974;

Aspirin resistance in CRF patients and controls

Aspirin resistance was detected in 85 CRF patients (in 53 patients undergoing chronic hemodialysis and in 32 patients with stage 3-4 CKD) and 22 control patients (Tab. II). The frequency of aspirin resistance was significantly higher in the CRF group compared with the control group (34.7% vs. 16.9%; p<0.001; odds ratio [OR] = 2.608; 95% confidence interval [95% CI], 1.537-4.424) and in patients undergoing chronic hemodialysis compared with stage 3-4 CKD patients (46.1% vs. 24.6%; p<0.001; OR=2.618; 95% CI, 1.523-4.501) and controls (46.1% vs. 16.9%; p<0.001; OR=4.196; 95% CI, 2.333-7.548). The frequency of aspirin resistance was higher in stage 3-4 CKD patients compared with controls, but the difference was not significant (24.6% vs. 16.9%; p=0.126; OR=1.603; 95% CI, 0.873-2.944). The CRF group had significantly higher aspirin reaction units than the control group (511 76 ARU vs. 479 72 ARU, p<0.001). The duration of aspirin therapy and
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TABLE I GENERAL CHARACTERISTICS AND LABORATORY PARAMETERS OF CHRONIC RENAL FAILURE GROUP AND CONTROLS

Chronic renal failure group (n=245)

Control group (n=130)

p Value*

Hemodialysis (n=115) Stage 3-4 CKD (n=130)

Age (years)

64.4 14.1 58.3 14.0 105/140 60/55 79.2 67.8 43.3 27.8 33.9 29.6 36.2 20.9 31.8 27.0 26.3 5.4 25.0 5.9 131 24 127 23 76 14 76 12 82 16 83 16 120 54 119 55 79 58 122 55 41 21 120 52 80 16 77 16 135 24 27.3 4.9 36.2 50.0 37.7 56.9 89.2 45/85 69.7 11.8

64.7 12.4

NS <0.001a,b,c NS 0.017d,e 0.032 <0.001a,f NS <0.001a,g,e NS NS NS <0.001a,c NS NS 0.037 <0.001a,b NS 0.011d NS NS NS 0.024g NS NS <0.001 <0.001a,b,f
to be continued 639

Sex, female/male

61/69

Hypertension (%)

69.2

Hyperlipidemia (%)

41.5

Diabetes mellitus (%)

32.3

Coronary artery disease (%)

31.5

Smoking (%)

40.0

Body mass index (calculated as kg/m2)

27.5 4.6

Systolic blood pressure (mm Hg)

129 20

Diastolic blood pressure (mm Hg)

76 12

Heart beat (/min)

78 15

Glucose (mg/dL)

122 45

Blood urea nitrogen (mg/dL)

19 7

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TABLE I CONTINUED Chronic renal failure group (n=245)

Control group (n=130)

p Value*

Hemodialysis (n=115) Stage 3-4 CKD (n=130) 5.4 4.9 Creatinine (mg/dL) 9.2 4.7 C-reactive protein (mg/L) 16.0 22.9 HDL cholesterol (mg/dL) 39 12 35 10 102 41 95 31 158 104 172 105 35.9 8.9 33.0 4.6 223 101 184 61 258 116 38.5 10.8 145 101 108 47 43 12 18.8 31.5 22.7 40.6 44 15 1.9 0.9 22.6 48.7 0.8 0.2 <0.001a,b,c NS NS 0.001 <0.001a,b 0.009 0.001h,i 0.006 0.002i <0.001 <0.001a,b <0.001 <0.001a,b <0.001

LDL cholesterol (mg/dL)

113 35

Triglycerides (mg/dL)

128 67

Hematocrit (%)

40.4 4.7

Platelets (103/mm3)

261 71

CKD = chronic kidney disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NS = not significant. *p values in the upper cell in each row show comparison of all 245 chronic renal failure patients with controls, while p values in the lower cell in each row show ANOVA, Kruskal-Wallis or chi-square test comparing hemodialysis patients, stage 3-4 CKD patients and controls. Post hoc analysis: ap<0.001, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients. bp<0.001, patients undergoing chronic hemodialysis vs. controls. cp<0.01, stage 3-4 CKD patients vs. controls. dp<0.01, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.
e f

p<0.05, stage 3-4 CKD patients vs. controls. p<0.05, patients undergoing chronic hemodialysis vs. controls.

p<0.001, stage 3-4 CKD patients vs. controls. p<0.05, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.

g h i

p<0.01, patients undergoing chronic hemodialysis vs. controls.

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95% CI, 0.950-0.999; p=0.043) were independent predictors of aspirin resistance in this cohort of patients.

dIscussIon
Aspirin resistance has been considered a multifactorial phenomenon underlying factors ranging from nonadherence of patients to antiplatelet therapy to demographic characteristics, acute coronary syndromes as well as genetic polymorphisms involving platelet glycoproteins and cytochrome P450 isoenzymes (33). Although a recent study (34) suggested that aspirin therapy might improve renal outcome after acute renal failure, renal failure itself may play a role in the development of resistance to aspirin therapy, and aspirin resistance, in turn, may worsen the prognosis of patients with CKD. Actually, renal failure was included as a comorbidity associated with aspirin resis-

tance in a review (33). However, Gum et al (35) reported that the presence of renal disease caused no difference in aspirin sensitivity in patients with cardiovascular disease. A recent meta-analysis has reported that aspirin resistance might be higher in patients with previous renal impairment, and recommended future studies exploring the relation of aspirin resistance with renal failure (36). However, no study to date has been designed to evaluate the incidence of aspirin resistance in patients with CKD. In our study, we assessed aspirin resistance in 245 patients with CRF and found that 85 patients (53 patients undergoing hemodialysis and 32 patients with stage 3-4 CKD) had aspirin resistance. The frequency of aspirin resistance was significantly higher in CRF patients compared with the controls, especially in patients undergoing chronic hemodialysis. Multivariate analysis of our data further confirmed hemodialysis as an independent predictor

TABLE II FREQUENCY OF ASPIRIN RESISTANCE IN PATIENTS WITH CHRONIC RENAL FAILURE AND CONTROLS Chronic renal failure group (n=245) Hemodialysis (n=115) Stage 3-4 CKD (n=130)

Control group (n=130)

p Value*

Aspirin resistance, no. (%) 53 (46.1) Aspirin reaction unit, ARU

85 (34.7) 32 (24.6) 511 76 549 60 100 100 100 27 42 18 29 35 50 478 74

22 (16.9)

<0.001 <0.001a,b <0.001 <0.001a,b NS NS

479 72

Median aspirin dose, mg/day

100

Aspirin duration, months

36 67

NS 0.009c,d

CKD = chronic kidney disease; NS = not significant. *p values in the upper cell in each row show comparison of all 245 chronic renal failure patients with controls, while p values in the lower cell in each row show ANOVA test or chi-square test comparing hemodialysis patients, stage 3-4 CKD patients and controls. Post hoc analysis: a p<0.001, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients. b p<0.001, patients undergoing chronic hemodialysis vs. controls. c p<0.05, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.
d

p<0.05, patients undergoing chronic hemodialysis vs. controls.

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of aspirin resistance in our study. Although the stage 3-4 CKD patients had an increased risk of aspirin resistance compared with the controls, the difference did not reach

clinical significance. These findings suggest the possibility of an association between aspirin resistance and renal functions. We found that an increase of 1 mg/dL in creati-

TABLE III CHARACTERISTICS AND LABORATORY PARAMETERS OF ASPIRIN-RESISTANT AND ASPIRIN-SENSITIVE PATIENTS Aspirin-resistant patients (n=107) Age (years) Sex (female/male) Chronic renal failure (%) Hemodialysis (%) Hypertension (%) Hyperlipidemia (%) Diabetes (%) Coronary artery disease (%) Smoking (%) Body mass index (calculated as kg/m2) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart beat (/min) Mean aspirin dose (mg/day) Aspirin duration (months) Glucose (mg/dL) Blood urea nitrogen (mg/dL) Creatinine (mg/dL) C-reactive protein (mg/L) Total cholesterol (mg/dL) LDL cholesterol (mg/dL) Triglycerides (mg/dL) Hematocrit (%) Platelets (103/mm3) 63.9 13.2 57/50 79.4 49.5 74.8 39.3 38.3 33.6 33.6 26.5 5.0 130 24 76 12 81 16 151.9 86.9 27 47 121 56 79 63 5.1 4.2 20.1 30.9 171 50 103 42 147 91 35.8 6.5 214 75 Aspirin-sensitive patients (n=268) 64.7 13.6 109/159 59.7 23.1 76.1 44.0 31.3 34.7 35.1 26.8 5.2 131 22 76 14 80 16 160.6 91.5 31 54 120 49 50 48 3.3 4.5 19.8 40.2 179 46 107 38 148 95 38.1 8.4 245 99 p Value NS 0.027 <0.001 <0.001 NS NS NS NS NS NS NS NS NS NS NS NS <0.001 <0.001 NS NS NS NS 0.012 0.004

HDL = high-density lipoprotein; LDL = low-density lipoprotein; NS = not significant. 642

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nine levels showed a 10% increase in the odds of having aspirin resistance, while an increase of 1 ml/min per 1.73 m2 in GFR showed a 1.1% decrease in the odds of having aspirin resistance. Similarly, Acikel et al (37) detected aspirin resistance in 27.5% of renal transplant recipients and found that the incidence of aspirin resistance was higher among patients with GFR <60 ml/min compared with those with a GFR 60 ml/min. Aspirin resistance may be associated with increased inflammation and oxidative stress (38, 39). Arachidonic acid derivative isoprostanes exhibit potent vasoconstrictor and proaggregatory effects similar to that of TXA2. Increased oxidative stress may increase plasma isoprostane levels, and increased cyclooxygenase-independent isoprostane formation in platelets might contribute to aspirin resistance (40). There is evidence of increased oxidative stress and acute-phase inflammation in patients with CRF compared with healthy subjects (41). Inflammation-induced activation of cyclooxygenase-2 leading to TXA2 synthesis and oxidative stress leading to production of thromboxane A2 through pathways

not blocked by aspirin might contribute to the development of aspirin resistance in patients with CRF. Oxidative stress and disturbances in antioxidant enzymes occur at the early stages of chronic uremia and are exacerbated by hemodialysis (42). A few studies indicated an inverse correlation of oxidative stress biomarkers with estimated GFR (43). This may explain the higher incidence of aspirin resistance in patients undergoing hemodialysis. In our study, C-reactive protein levels were similar between the aspirin-resistant and aspirin-sensitive patients, which raised doubts about the possible role of inflammation in aspirin resistance. This finding might be explained by the small size of the study groups and also by the multifactorial nature of aspirin resistance. We did not study oxidative stress markers or plasma isoprostane levels obviously another study limitation which might be useful in understanding the mechanism of aspirin resistance in patients with CKD. In our study, the percentage of women was significantly higher in aspirin-resistant patients. Multivariate analysis also revealed female sex as an independent predictor

TABLE IV MULTIVARIATE ANALYSIS FOR PREDICTORS OF ASPIRIN RESISTANCE Variable Age Female sex Chronic Renal failure Hemodialysis Hypertension Diabetes Hyperlipidemia Coronary artery disease Smoking Glucose Creatinine Triglycerides HDL cholesterol Hematocrit Platelets
HDL = high-density lipoprotein.
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Odds ratio 1.010 2.201 2.512 3.636 1.113 1.772 0.957 1.255 1.980 1.000 1.009 0.997 0.974 0.983 1.000

95% Confidence interval 0.987-1.034 1.173-4.129 0.937-6.737 1.313-10.066 0.561-2.210 0.894-3.510 0.487-1.882 0.663-2.376 0.985-3.752 0.994-1.007 0.997-1.022 0.994-1.001 0.950-0.999 0.938-1.031 0.998-1.003

p Value 0.395 0.014 0.067 0.013 0.759 0.101 0.899 0.485 0.052 0.901 0.144 0.136 0.043 0.486 0.263

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of aspirin resistance in our study. This is in accordance with other studies showing higher incidence of aspirin resistance in females (32, 35, 44-46). Although we did not find any significant association between aspirin resistance and hyperlipidemia, aspirin reaction units significantly correlated with HDL cholesterol, and multivariate analysis revealed HDL cholesterol as an independent predictor of aspirin resistance. Watala et al (47) found that the reduced response of platelets to aspirin in diabetic subjects was associated with lower concentration of HDL cholesterol. They suggested that HDL cholesterol might be regarded a factorial component of a cluster of lipid variables related to platelet reactivity, and their sensitivity to antiplatelet agents and the prophylactic HDL action might be deduced from its antiatherogenic properties.

Since aspirin resistance is multifactorial in nature, further studies are necessary to elucidate the exact mechanisms underlying aspirin resistance, the relation between aspirin resistance and CRF, and the clinical role of aspirin resistance in CRF patients.
The study was presented at the ESC Congress 2010, Stockholm, Sweden (accepted as poster presentation).

Financial support: This study is supported by both Marmara University and Akdeniz University research funds (no grant number is applicable). Conflict of interest statement: None declared.

conclusIon
We found increased aspirin resistance in patients with CRF, especially in patients undergoing chronic hemodialysis. Aspirin resistance might increase the cardiovascular morbidity and mortality in CRF patients, who are already at increased risk for cardiovascular complications.

Address for Correspondence: Beste Ozben Yildiz Caddesi Konak Apartmani No. 43/24 Besiktas 34353 Istanbul, Turkey bestes@doctor.com, besteozben@yahoo.com

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Accepted: October 25, 2010

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