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1.  Comparing Survival between Peritoneal Dialysis and Hemodialysis Patients with Subclinical Peripheral Artery Disease: a 6-Year Follow-Up 
Peripheral artery disease (PAD) is known to be an increased mortality risk in patients with end-stage renal disease (ESRD). The aim of this study was to compare patient survival between patients with subclinical PAD undergoing peritoneal dialysis (PD) and hemodialysis (HD). Subclinical peripheral artery was defined as an ankle-brachial index of less than 0.9. This study was conducted from April 2005, and the observation period ended on 30 June 2011. At the end of the follow-up, the status of all patients was assessed and data on mortality were obtained for the entire cohort. A total of 91 patients (61 HD and 30 PD) were included for analyses in this study. Mortality rate was 60.0% (18/30) for PD and 52.5% (32/61) for HD. Kaplan-Meier estimate demonstrate that PD patients had a higher mortality rate than those underwent HD (log-rank p = 0.0039). Cox regression model demonstrated that PD was an independent predictor for further mortality in ESRD patients with subclinical peripheral artery disease.(p = 0.012, HR: 1.776, 95% CI: 1.136-2.775). In multivariate analysis, the HD group still had a greater survival than PD group (p = 0.005, HR:1.916, 95% CI: 1.218-3.015). In patients with subclinical peripheral artery disease, the patient survival is better in HD patients as compared with PD patients.
doi:10.7150/ijms.5091
PMCID: PMC3590604  PMID: 23471522
Survival; hemodialysis; peritoneal dialysis; peripheral artery disease.
2.  Prevalence and risk factors associated with peripheral artery disease in elderly patients undergoing peritoneal dialysis 
Background
Rapid growth of the elderly peritoneal dialysis (PD) population is posing a special challenge for renal teams. Peripheral artery disease (PAD) has been reported to be an independent predictor of cardiovascular and all-cause mortality in hemodialysis patients. However, the prevalence and associated risk factors for PAD in elderly PD patients have not yet been fully investigated.
Methods
A total of 69 elderly PD patients were included in the present study. PAD was defined as either an ankle-brachial index < 0.9 or a history of intermittent claudication, lower-limb amputation, foot ulcers, or gangrene. On enrollment, clinical and biochemical characteristics were collected.
Results
The overall prevalence of PAD was 31.9%. Compared with non-PAD patients, PAD patients were significantly older and more likely to be female and have longer PD duration and lower diastolic blood pressure (P < 0.001, = 0.002, 0.018, and 0.007, respectively). Serum albumin level (P < 0.001) and residual renal Kt/V value (P < 0.001) were significantly lower, but the serum C-reactive protein level (P = 0.005) was significantly higher, in PAD patients compared with non-PAD patients. Logistic regression analysis showed that serum albumin level (odds ratio = 1.485, P = 0.040) and residual renal Kt/V value (odds ratio = 1.725, P = 0.016) were independently associated with PAD.
Conclusion
A high prevalence of PAD appeared among elderly PD patients in Macao. Serum albumin level and residual renal Kt/V value were independently related to PAD.
doi:10.2147/VHRM.S37008
PMCID: PMC3480278  PMID: 23112578
ankle-brachial index; atherosclerosis; elderly; peripheral artery disease; peritoneal dialysis
3.  Presence of Peripheral Arterial Disease Predicts Loss of Residual Renal Function in Incident CAPD Patients 
♦ Background: Accelerated cardiovascular disease (CVD), including peripheral arterial disease (PAD), is very common in patients with end-stage renal disease. Residual renal function (RRF) is a strong predictor of patient survival that is suggested to be linked to the degree of CVD. However, the relationship between PAD and decline in RRF has not previously been measured.
♦ Methods: We studied incident continuous ambulatory peritoneal dialysis patients from Peking University Third Hospital. An ankle brachial index of less than 0.9 was used to diagnose PAD. Residual renal function (RRF) was determined as the mean of 24-hour urea and creatinine clearances (glomerular filtration rate). The Cox proportional hazards model was used to identify factors predicting loss of RRF.
♦ Results: The study included 86 patients (age: 61 ± 14 years; men: 51%), 23 of whom had PAD at baseline. Mean follow-up was 19 months (median: 18 months; range: 6 – 30 months). In univariate analysis, baseline PAD, peritonitis during follow-up, inflammation (C-reactive protein), serum uric acid, Ca×P, and serum phosphate were all significantly associated with a greater-than-50% decrease in RRF during follow-up. In multivariate analysis, only baseline PAD, Ca×P, and peritonitis were independently associated with a decline in RRF.
♦ Conclusions: Our study suggests that PAD may be a clinically important marker of CVD predicting the loss of RRF. It remains to be determined whether interventions aimed at decreasing PAD may also improve renal vascular status and thus slow the rate of RRF decline.
doi:10.3747/pdi.2010.00109
PMCID: PMC3525373  PMID: 21532004
Ankle brachial index; end-stage renal disease; cardiovascular disease; inflammation; nutrition; atherosclerosis
4.  Plasma S100A12 Levels and Peripheral Arterial Disease in End-Stage Renal Disease 
Nephron Extra  2011;1(1):242-250.
Background
S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients.
Methods
We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants.
Results
HD patients with PAD (n = 26; 21.9 [13.6–33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5–17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29–25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40–0.74; p < 0.001).
Conclusion
These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.
doi:10.1159/000335198
PMCID: PMC3290833  PMID: 22470398
S100A12; Peripheral arterial disease; Chronic kidney disease; Receptor for advanced glycation end products
5.  The Prevalence of Peripheral Arterial Disease in Korean Patients with Type 2 Diabetes Mellitus Attending a University Hospital 
Diabetes & Metabolism Journal  2011;35(5):543-550.
Background
Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. Diabetes is known to increase the risk of PAD two- to four-fold. The prevalence of PAD in Korean diabetic patients has not been established. In this study, we investigated the prevalence of PAD in Korean patients with type 2 diabetes attending a large university hospital and analyzed the factors associated with PAD.
Methods
A total of 2,002 patients with type 2 diabetes who underwent ankle-brachial index (ABI) measurement in an outpatient clinic were enrolled. PAD was defined as an ABI ≤0.9. Clinical characteristics of 64 patients with PAD were compared with those of 192 age- and sex-matched control patients without PAD.
Results
Of the 2,002 type 2 diabetic patients, 64 (3.2%) were diagnosed as having PAD. PAD was associated with higher prevalences of retinopathy, nephropathy, neuropathy, cerebrovascular and coronary artery disease. Patients with PAD had higher systolic blood pressure and serum triglyceride level and reported higher pack-years of smoking. Multivariate analysis showed that the presence of micro- and macrovascular complications and high systolic blood pressure are factors independently associated with PAD.
Conclusion
The prevalence of PAD in diabetic patients was 3.2%, suggesting that the prevalence in Korean diabetic patients is lower than that of patients in Western countries.
doi:10.4093/dmj.2011.35.5.543
PMCID: PMC3221031  PMID: 22111047
Diabetes mellitus, type 2; Peripheral arterial disease; Prevalence; Risk factors
6.  Fetuin-A Levels Are Increased in Patients With Type 2 Diabetes and Peripheral Arterial Disease 
Diabetes Care  2010;34(1):156-161.
OBJECTIVE
Low levels of fetuin-A, a systemic calcification inhibitor, are linked to mortality in patients on dialysis. In contrast, elevated fetuin-A is associated with cardiovascular events in non-renal patients. We investigated fetuin-A in patients with type 2 diabetes and peripheral arterial disease (PAD).
RESEARCH DESIGN AND METHODS
We studied fetuin-A in 76 patients with PAD and normal glucose metabolism (NGM-PAD) and in 129 patients with PAD and type 2 diabetes (type 2 diabetes–PAD). Additionally, 40 patients with diabetes without any complications (type 2 diabetes–non-PAD) were examined.
RESULTS
Type 2 diabetes–PAD subjects (399 ± 155 μg/ml) had significantly higher fetuin-A levels than type 2 diabetes–non-PAD subjects (247 ± 42; P < 0.001). In NGM-PAD subjects (376 ± 144), fetuin-A was significantly higher than in type 2 diabetes–non-PAD subjects (P < 0.001). Type 2 diabetes–PAD patients with mediasclerosis had lower fetuin-A than subjects without (P < 0.03). Regression analysis in type 2 diabetes–PAD subjects revealed that glycated A1C (P < 0.001) and mediasclerosis (P = 0.004) were the strongest predictors of fetuin-A. Multivariate regression revealed that a 1-SD increase in fetuin-A was associated with an odds ratio (OR) of 2.1 (95% CI 1.1–3.3; P < 0.001) for the prevalence of PAD and an OR of 1.4 (1.0–1.7, P = 0.039) for the prevalence of myocardial infarction.
CONCLUSIONS
In contrast to previous findings, fetuin-A was higher in type 2 diabetes–PAD patients than in type 2 diabetes–non-PAD patients. In NGM-PAD patients, fetuin-A was also higher than in type 2 diabetes–non-PAD patients. In type 2 diabetes–PAD patients, fetuin-A was inversely associated with mediasclerosis—the calcification process pathognomonic for diabetic PAD. This association persisted in multivariate regression, which is in line with the calcification inhibition in coronary heart or renal disease.
doi:10.2337/dc10-0788
PMCID: PMC3005446  PMID: 20929991
7.  Correlation between peripheral arterial disease and coronary artery disease using ankle brachial index-a study in Indian population 
Indian Heart Journal  2012;64(1):2-6.
Objective
To study the prevalence of peripheral arterial disease (PAD) of the lower limbs in a high-risk population and its correlation with coronary artery disease (CAD), using the ankle brachial index (ABI).
Methods
The present study was conducted in randomly selected indoor patients >45 years of age with one or more risk factors for PAD admitted in the cardiology and medicine wards in a tertiary care institute.
Results
Based on ABI <0.9, PAD was diagnosed in 32 of the 182 (18%) patients. Coronary artery disease was present in 15 cases of PAD which was statistically significant.
Conclusion
There is a definite and strong correlation between PAD and CAD. Correct diagnosis and supervision of patients with PAD is important for preventing the local progression of the disease and effective secondary prevention of future coronary and cerebrovascular events.
doi:10.1016/S0019-4832(12)60002-9
PMCID: PMC3860717  PMID: 22572416
Ankle brachial index; Coronary artery disease; Peripheral arterial disease
8.  Substance P and intensity of pruritus in hemodialysis and peritoneal dialysis patients 
Background
Uremic pruritus is a common complication in patients undergoing dialysis. The pathophysiological mechanisms of pruritus in patients with end-stage renal disease remain unknown. Neuropeptides, including substance P, are postulated to play an important role in the pathogenesis of pruritus. The aim of this study was to evaluate the role of substance P in uremic pruritus in patients on hemodialysis and peritoneal dialysis.
Material/Methods
We included 197 patients with end-stage renal disease: 54 on continuous ambulatory peritoneal dialysis and 143 on hemodialysis. Substance P, calcium, phosphorus, iron, ferritin, CRP, albumin, hemoglobin, Ca × P product, and iPTH level were determined in all participants. The correlation between these parameters and self-reported itching was evaluated in patients on hemodialysis in comparison with peritoneal dialysis patients.
Results
The incidence of itching was similar in hemodialysis and peritoneal dialysis patients. No differences in substance P level between the 2 groups were found. There was no correlation between substance P level and the incidence or intensity of pruritus in dialyzed patients.
Conclusions
This study demonstrates that substance P does not play any important role in pruritus in hemodialysed and peritoneal dialyzed patients. However, further studies are necessary to assess the exact role of neuropeptides in uremic pruritus.
doi:10.12659/MSM.889349
PMCID: PMC3767586  PMID: 23995243
substance P; uremic pruritus; end-stage renal disease; hemodialysis; peritoneal dialysis
9.  To screen or not to screen for peripheral arterial disease in subjects aged 80 and over in primary health care: a cross-sectional analysis from the BELFRAIL study 
BMC Family Practice  2011;12:39.
Background
Peripheral arterial disease (PAD) is common in older people. An ankle-brachial index (ABI) < 0.9 can be used as an indicator of PAD. Patients with low ABI have increased mortality and a higher risk of serious cardiovascular morbidity. However, because 80% of the patients are asymptomatic, PAD remains unrecognised in a large group of patients. The aims of this study were 1) to examine the prevalence of reduced ABI in subjects aged 80 and over, 2) to determine the diagnostic accuracy of the medical history and clinical examination for reduced ABI and 3) to investigate the difference in functioning and physical activity between patients with and without reduced ABI.
Methods
A cross-sectional study embedded within the BELFRAIL study. A general practitioner (GP) centre, located in Hoeilaart, Belgium, recruited 239 patients aged 80 or older. Only three criteria for exclusion were used: urgent medical need, palliative situation and known serious dementia. The GP recorded the medical history and performed a clinical examination. The clinical research assistant performed an extensive examination including Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Activities of Daily Living (ADL), Tinetti test and the LASA Physical Activity Questionnaire (LAPAQ). ABI was measured using an automatic oscillometric appliance.
Results
In 40% of patients, a reduced ABI was found. Cardiovascular risk factors were unable to identify patients with low ABI. A negative correlation was found between the number of cardiovascular morbidities and ABI. Cardiovascular morbidity had a sensitivity of 65.7% (95% CI 53.4-76.7) and a specificity of 48.6% (95% CI 38.7-58.5). Palpation of the peripheral arteries showed the highest negative predictive value (77.7% (95% CI 71.8-82.9)). The LAPAQ score was significantly lower in the group with reduced ABI.
Conclusion
The prevalence of PAD is very high in patients aged 80 and over in general practice. The clinical examination, cardiovascular risk factors and the presence of cardiovascular morbidity were not able to identify patients with a low ABI. A screening strategy for PAD by determining ABI could be considered if effective interventions for those aged 80 and over with a low ABI become available through future research.
doi:10.1186/1471-2296-12-39
PMCID: PMC3121584  PMID: 21605447
10.  Carotid intima-media thickness in children with end-stage renal disease on dialysis 
Indian Journal of Nephrology  2010;20(1):29-33.
Cardiovascular morbidity and mortality are common in end stage renal disease (ESRD) patients. There is scarce data on carotid and bulb intima-media thickness (IMT-C and IMT-B) as an early marker of atherosclerosis and related factors in children on hemodialysis (HD) and peritoneal dialysis (PD). Since we did not have enough information about our patients, this study was carried on all ESRD children (hemodialysis and peritoneal dialysis) in a referral center. Data was collected from 16 ESRD children under 18 years with seven patients on PD and nine on HD. Lab tests and biochemical parameters including serum von Willebrand factor (vWF), homocystein, apo lipoprotein A, apo lipoprotein B and quantitative CRP were measured in fasting patients just before initiating dialysis. IMT-C and IMT-B were measured by gray scale ultrasound using 7.5 MHZ probe. The mean of age was 12.76±4.5 years. The mean duration of dialysis in HD and PD patients were not significantly different; 11.88±3.25 months and 10.14±2.4 months respectively. Mean of systolic blood pressure in HD group was significantly higher than PD group, 135.55±25.54 mmHg versus 121.42±12.14 mmHg, P<0.05. Significant differences among all following parameters in ESRD patients, with normal laboratory values, were clarified: cholesterol, triglycerides, apo A, apo B, quantitative CRP, VWF, homocystein and IMT-C. However, we could not demonstrate any difference between IMT-B in case and control group. After adjusting for age, partial correlation showed significant correlation between IMT-C and following factors: N-PTH and serum alkaline phosphatase. Longitudinal studies with large size samples are needed to clarify the contributing factors with intima-media thickness in ESRD children.
doi:10.4103/0971-4065.62095
PMCID: PMC2878408  PMID: 20535268
Carotid intima-media thickness; children; end stage renal disease
11.  The Associations of Fetuin-A with Subclinical Cardiovascular Disease in Community-Dwelling Persons: the Rancho Bernardo Study 
Objective
To determine the association of fetuin-A with subclinical CVD in community-living individuals.
Background
Fetuin-A is a hepatic secretory protein that inhibits arterial calcium deposition in vitro. Lower fetuin-A levels are associated with arterial calcification and death in end-stage renal disease populations. The association of fetuin-A with subclinical cardiovascular disease (CVD) in the general population is unknown.
Methods
Among 1,375 community-living individuals without prevalent clinical CVD, we measured plasma fetuin-A concentrations measured by ELISA. Peripheral arterial disease (PAD) was defined by ankle brachial index (ABI) < 0.90, coronary artery calcification (CAC) was measured by computed tomography, and common and internal intima media thickness (cIMT) were measured by carotid ultrasound. PAD was measured concurrent with fetuin-A, and CAC and cIMT was measured 4.6 years (mean) later.
Results
Mean age was 70 ± 11 years and 64% were female. Fetuin-A levels were inversely associated with CAC severity. When evaluated as CAC categories (0, 1–100, 101–300, > 300) using ordinal logistic regression, each standard deviation higher fetuin-A was associated with a 31% lower odds of CAC severity (proportional odds ratio [POR] 0.69; 95% confidence interval [CI] 0.46, 0.92; p=0.008) in models adjusted for demographics, lifestyle factors, traditional CVD risk factors and kidney function. In contrast, no association of fetuin-A was observed with PAD or high common or internal cIMT in adjusted models.
Conclusions
Lower fetuin-A levels are independently associated with greater CAC severity, but not PAD or cIMT. If confirmed, fetuin-A may mark calcium deposition within the vasculature, but not atherosclerosis per se.
doi:10.1016/j.jacc.2011.08.035
PMCID: PMC3224791  PMID: 22115642
Fetuin-A; Cardiovascular Disease; Coronary Artery Calcification
12.  The association of very-low-density lipoprotein with ankle-brachial index in peritoneal dialysis patients with controlled serum low-density lipoprotein cholesterol level 
BMC Nephrology  2013;14:212.
Background
Peripheral artery disease (PAD) represents atherosclerotic disease and is a risk factor for death in peritoneal dialysis (PD) patients, who tend to show an atherogenic lipid profile. In this study, we investigated the relationship between lipid profile and ankle-brachial index (ABI) as an index of atherosclerosis in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level.
Methods
Thirty-five PD patients, whose serum LDL cholesterol level was controlled at less than 120mg/dl, were enrolled in this cross-sectional study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions and the mean size of lipoprotein particles were measured using an improved method, namely, high-performance gel permeation chromatography. Multivariate linear regression analysis was adjusted for diabetes mellitus and cardiovascular and/or cerebrovascular diseases.
Results
The mean (standard deviation) age was 61.6 (10.5) years; PD vintage, 38.5 (28.1) months; ABI, 1.07 (0.22). A low ABI (0.9 or lower) was observed in 7 patients (low-ABI group). The low-ABI group showed significantly higher cholesterol proportions in the chylomicron fraction and large very-low-density lipoproteins (VLDLs) (Fractions 3–5) than the high-ABI group (ABI>0.9). Adjusted multivariate linear regression analysis showed that ABI was negatively associated with serum VLDL cholesterol level (parameter estimate=-0.00566, p=0.0074); the cholesterol proportions in large VLDLs (Fraction 4, parameter estimate=-3.82, p=0.038; Fraction 5, parameter estimate=-3.62, p=0.0039) and medium VLDL (Fraction 6, parameter estimate=-3.25, p=0.014); and the size of VLDL particles (parameter estimate=-0.0352, p=0.032).
Conclusions
This study showed that the characteristics of VLDL particles were associated with ABI among PD patients. Lowering serum VLDL level may be an effective therapy against atherosclerosis in PD patients after the control of serum LDL cholesterol level.
doi:10.1186/1471-2369-14-212
PMCID: PMC3853217  PMID: 24093487
Peritoneal dialysis; Ankle-brachial index; Very low density lipoprotein; Atherosclerosis; Peripheral artery disease; Chromatography
13.  Family History of Peripheral Artery Disease is associated with Prevalence and Severity of Peripheral Artery Disease: The San Diego Population Study (SDPS) 
Objective
To determine the association of family history of peripheral artery disease (PAD) with PAD prevalence and severity.
Background
PAD is a significant public health problem. Shared genetic and environmental factors may play an important role in the development of PAD. However, family history of PAD has not been adequately investigated.
Methods
The San Diego Population Study (SDPS) enrolled 2404 ethnically diverse men and women aged 29–91 who attended a baseline visit from 1994–98 to assess PAD and venous disease. Ankle brachial index (ABI) measurement was performed at the baseline clinic examination and family history of PAD was obtained via questionnaire. Family history of PAD was primarily defined as having any 1st degree relative with PAD. Prevalent PAD was defined as ABI ≤ 0.90 and severe prevalent PAD as ABI ≤ 0.70, with both definitions also including any previous leg revascularization. Logistic regression was used to evaluate the association of family history of PAD with prevalent PAD.
Results
The mean (SD) age was 59 (11) years, 66% were women, and 58% were Caucasian with 42% comprising other racial/ethnic groups. Prevalence of PAD was 3.6%, and severe prevalent PAD was 1.9%. In fully adjusted models, family history of PAD was associated with a 1.83-fold higher odds of PAD (95% CI (1.03, 3.26), p=0.04), an association which was stronger for severe prevalent PAD (OR 2.42, 95% CI (1.13, 5.23), p=0.02).
Conclusions
Family history of PAD is independently strongly associated with PAD prevalence and severity. This indicates a role for genetic factors and/or other shared environmental factors contributing to PAD.
doi:10.1016/j.jacc.2011.06.023
PMCID: PMC3215334  PMID: 21920269
family history; peripheral artery disease; ankle brachial index
14.  Ankle Brachial Index Values, Leg Symptoms, and Functional Performance Among Community‐Dwelling Older Men and Women in the Lifestyle Interventions and Independence for Elders Study 
Background
The prevalence and significance of low normal and abnormal ankle brachial index (ABI) values in a community‐dwelling population of sedentary, older individuals is unknown. We describe the prevalence of categories of definite peripheral artery disease (PAD), borderline ABI, low normal ABI, and no PAD and their association with lower‐extremity functional performance in the LIFE Study population.
Methods and Results
Participants age 70 to 89 in the LIFE Study underwent baseline measurement of the ABI, 400‐m walk, and 4‐m walking velocity. Participants were classified as follows: definite PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), low normal ABI (ABI 1.00 to 1.09), and no PAD (ABI 1.10 to 1.40). Of 1566 participants, 220 (14%) had definite PAD, 250 (16%) had borderline PAD, 509 (33%) had low normal ABI, and 587 (37%) had no PAD. Among those with definite PAD, 65% were asymptomatic. Adjusting for age, sex, race, body mass index, smoking, and comorbidities, lower ABI was associated with longer mean 400‐m walk time: (definite PAD=533 seconds; borderline PAD=514 seconds; low normal ABI=503 seconds; and no PAD=498 seconds [P<0.001]). Among asymptomatic participants with and without PAD, lower ABI values were also associated with longer 400‐m walk time (P<0.001) and slower walking velocity (P=0.042).
Conclusion
Among older community‐dwelling men and women, 14% had PAD and 49% had borderline or low normal ABI values. Lower ABI values were associated with greater functional impairment, suggesting that lower extremity atherosclerosis may be a common preventable cause of functional limitations in older people.
Clinical Trial Registration
URL: http://clinicaltrials.gov/ Unique identifier: NCT01072500.
doi:10.1161/JAHA.113.000257
PMCID: PMC3886743  PMID: 24222666
aging; exercise; peripheral vascular disease
15.  Genomic Damage in Endstage Renal Disease—Contribution of Uremic Toxins 
Toxins  2010;2(10):2340-2358.
Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-α. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation.
doi:10.3390/toxins2102340
PMCID: PMC3153169  PMID: 22069557
dialysis; genotoxicity; uremic toxins
16.  Abdominal Obesity is Associated with Peripheral Artery Disease in Hemodialysis Patients 
PLoS ONE  2013;8(6):e67555.
Background
Peripheral arterial disease (PAD) is a leading cause of morbidity in hemodialysis (HD) patients. Recent evidence suggests that abdominal obesity (AO) may play a role in PAD. However, the association between AO and PAD has not been thoroughly studied in HD patients.
Methods
The present cross-sectional study aimed to examine the relationship between AO and PAD in a cohort of 204 chronic HD patients. The ankle brachial index (ABI) was used as an estimate of the presence of PAD. Plasma adiponectin levels, interleukin-6 (IL-6) levels, high sensitivity C-reactive protein (hs-CRP) levels, asymmetric dimethylarginine (ADMA) levels, and lipid profiles were measured. Logistic regression was used to estimate the association between the presence of PAD and AO as well as other potential risk factors.
Results
The metabolic risk factors and all individual traits, including elevated ln-transformed hs-CRP, were found to be significant (P<0.05) more frequently in HD patients with AO than that in control subjects. Patients with AO had a higher prevalence of PAD than the control individuals, with a mean ABI of 0.96±0.23 and 1.08±0.16 (P<0.0001) and PAD prevalence of 26.9% and 10.8% (P = 0.003), respectively. By multivariate analysis, AO (odds ratio [OR], 4.532; 95% CI, 1.765–11.639; P = 0.002), elevated serum ln-transformed ADMA (OR, 5.535; 95% CI, 1.323–23.155; P = 0.019), and ln-transformed IL-6 (OR, 1.567; 95% CI, 1.033–2.378; P = 0.035) were independent predictors of the presence of PAD.
Conclusions
HD patients with AO exhibited a cluster of metabolic risk factors and lower ABI. AO, elevated serum ln-transformed ADMA, and ln-transformed IL-6 were independent predictors of the presence of PAD.
doi:10.1371/journal.pone.0067555
PMCID: PMC3695898  PMID: 23840739
17.  Elevated osteoprotegerin is associated with abnormal ankle brachial indices in patients infected with HIV: a cross-sectional study 
Background
Patients infected with HIV have an increased risk for accelerated atherosclerosis. Elevated levels of osteoprotegerin, an inflammatory cytokine receptor, have been associated with a high incidence of cardiovascular disease (including peripheral arterial disease, or PAD), acute coronary syndrome, and cardiovascular mortality. The objective of this study was to determine whether PAD is prevalent in an HIV-infected population, and to identify an association with HIV-specific and traditional cardiovascular risk factors, as well as levels of osteoprotegerin.
Methods
One hundred and two patients infected with HIV were recruited in a cross-sectional study. To identify the prevalence of PAD, ankle-brachial indices (ABIs) were measured. Four standard ABI categories were utilized: ≤ 0.90 (definite PAD); 0.91-0.99 (borderline); 1.00-1.30 (normal); and >1.30 (high). Medical history and laboratory measurements were obtained to determine possible risk factors associated with PAD in HIV-infected patients.
Results
The prevalence of PAD (ABI ≤ 0.90) in a young HIV-infected population (mean age: 48 years) was 11%. Traditional cardiovascular risk factors, including advanced age and previous cardiovascular history, as well as elevated C-reactive protein levels, were associated with PAD. Compared with patients with normal ABIs, patients with high ABIs had significantly elevated levels of osteoprotegerin [1428.9 (713.1) pg/ml vs. 3088.6 (3565.9) pg/ml, respectively, p = 0.03].
Conclusions
There is a high prevalence of PAD in young HIV-infected patients. A number of traditional cardiovascular risk factors and increased osteoprotegerin concentrations are associated with abnormal ABIs. Thus, early screening and aggressive medical management for PAD may be warranted in HIV-infected patients.
doi:10.1186/1758-2652-13-12
PMCID: PMC2859852  PMID: 20307322
18.  Risk Factors Related to Low Ankle-Brachial Index Measured by Traditional and Modified Definition in Hypertensive Elderly Patients 
Peripheral arterial disease (PAD) increases with age and ankle-brachial index (ABI) ≤ 0.9 is a noninvasive marker of PAD. The purpose of this study was to identify risk factors related to a low ABI in the elderly using two different methods of ABI calculation (traditional and modified definition using lower instead of higher ankle pressure). A cross-sectional study was carried out with 65 hypertensive patients aged 65 years or older. PAD was present in 18% of individuals by current ABI definition and in 32% by modified method. Diabetes, cardiovascular diseases, metabolic syndrome, higher levels of systolic blood pressure and pulse pressure, elevated risk by Framingham Risk Score (FRS), and a higher number of total and antihypertensive drugs in use were associated with low ABI by both definitions. Smoking and LDL-cholesterol were associated with low ABI only by the modified definition. Low ABI by the modified definition detected 9 new cases of PAD but cardiovascular risk had not been considered high in 3 patients when calculated by FRS. In conclusion, given that a simple modification of ABI calculation would be able to identify more patients at high risk, it should be considered for cardiovascular risk prediction in all elderly hypertensive outpatients.
doi:10.1155/2012/163807
PMCID: PMC3376503  PMID: 22720134
19.  Prevalence of peripheral arterial disease in patients at non-high cardiovascular risk. Rationale and design of the PANDORA study 
Background
Lower extremity peripheral arterial disease (PAD) is a marker of widespread atherosclerosis. Individuals with PAD, most of whom do not show typical PAD symptoms ('asymptomatic' patients), are at increased risk of cardiovascular ischaemic events. American College of Cardiology/American Heart Association guidelines recommend that individuals with asymptomatic lower extremity PAD should be identified by measurement of ankle-brachial index (ABI). However, despite its associated risk, PAD remains under-recognised by clinicians and the general population and office-based ABI detection is still poorly-known and under-used in clinical practice. The Prevalence of peripheral Arterial disease in patients with a non-high cardiovascular disease risk, with No overt vascular Diseases nOR diAbetes mellitus (PANDORA) study has a primary aim of assessing the prevalence of lower extremity PAD through ABI measurement, in patients at non-high cardiovascular risk, with no overt cardiovascular diseases (including symptomatic PAD), or diabetes mellitus. Secondary objectives include documenting the prevalence and treatment of cardiovascular risk factors and the characteristics of both patients and physicians as possible determinants for PAD under-diagnosis.
Methods/Design
PANDORA is a non-interventional, cross-sectional, pan-European study. It includes approximately 1,000 primary care participating sites, across six European countries (Belgium, France, Greece, Italy, The Netherlands, Switzerland). Investigator and patient questionnaires will be used to collect both right and left ABI values at rest, presence of cardiovascular disease risk factors, current pharmacological treatment, and determinants for PAD under-diagnosis.
Discussion
The PANDORA study will provide important data to estimate the prevalence of asymptomatic PAD in a population otherwise classified at low or intermediate risk on the basis of current risk scores in a primary care setting.
Trial registration number
Clinical Trials.gov Identifier: NCT00689377.
doi:10.1186/1471-2261-10-35
PMCID: PMC2927475  PMID: 20687927
20.  A Study of Association of Ankle Brachial Index (ABI) and the Highly Sensitive C - Reactive Protein (hsCRP) in Type 2 Diabetic Patients and in Normal Subjects 
Background: The Ankle-Brachial Index (ABI) objectively assesses the lower extremity arterial perfusion. A low ABI suggests atherosclerosis and Peripheral Arterial Disease (PAD). PAD is more common in individuals with type2 Diabetes mellitus (Type2 DM). Inflammatory markers are found to be associated with Type2 DM. But the association of the inflammatory markers with the atherosclerotic burden remains poorly defined.
Aims: To compare the ABI and the hsCRP in the Type 2 DM patients with those in the normal subjects and to study the association of serum hsCRP with ABI in the Type 2 DM patients and in normal subjects.
Methods: The subjects were 40 Type2 DM and 40 age, sex and BMI matched normal subjects who were aged between 45-60 yrs. The subjects were assigned to two different groups, Group1- the Type2 DM patients and Group2- the healthy controls. The serum hsCRP levels were determined by the turbidimetry method (BIOSYSTEMS) and the ABI values were determined by using the traditional continuous wave (CW) Doppler of NICOLET VERSALAB.
Statistical Analysis: The data was analyzed by using the Student’s t test (two tailed; independent) to find the significance of the study parameters between the two groups. Pearson’s Correlation was used to find the correlation of serum hsCRP with the ABI in the two groups.
Results: The ABI showed a significantly low value (P=0.035*) and the serum hsCRP showed a trend towards a significant increase (p = 0.069+) in the type2diabetics as compared to those in the normals. There was a significant negative correlation between ABI and hsCRP in the Type 2 DM patients (r=-0.560, p<0.001**). However, such correlation was not observed in the normal subjects.
Conclusion: As serum hsCRP is associated with ABI in the type2 DM patients, inflammation may play a role in the pathogenesis of atherosclerosis.
doi:10.7860/JCDR/2012/4854.2667
PMCID: PMC3576748  PMID: 23450165
Type 2 Diabetes Mellitus; Ankle-brachial Index (ABI); Highly sensitive C - reactive protein (hsCRP); Peripheral arterial disease; Atherosclerosis
21.  Impact of Peripheral Arterial Disease on Functional Limitation in Congestive Heart Failure: Results from the National Health and Nutrition Examination Survey (1999–2004) 
Background. Peripheral arterial disease (PAD) often coexists with congestive heart failure (CHF) and can be masked by symptoms of CHF such as functional limitation (FL), a common manifestation for both. Therefore, we sought to estimate the prevalence of PAD and its independent association with FL in CHF. Methods. We conducted a cross-sectional study on National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 to quantify weighted prevalence of CHF and PAD. Study cohort consisted of 7513, with ankle brachial index (ABI) measurements at baseline. Independent association of PAD (ABI ≤ 0.9) with FL in CHF was determined with multivariate logistic regression (MVLR). Results. Overall weighted PAD prevalence was 5.2%. CHF was present in 305 participants, and the weighted prevalence of PAD in this subgroup was 19.2%. When compared, participants with CHF and PAD were more likely to be older (P < 0.001), hypertensive (P = 0.005) and hypercholesterolemic (P = 0.013) than participants with CHF alone. MVLR showed that PAD (adjusted OR = 5.15; 95% CI: 2.2, 12.05: P < 0.05) and arthritis (adjusted OR = 2.36; 95% CI: 1.10, 5.06: P < 0.05) were independently associated with FL in CHF. Conclusion. Independent association of PAD with FL suggests the need for reinforced screening for PAD in individuals with CHF.
doi:10.1155/2012/306852
PMCID: PMC3533604  PMID: 23346456
22.  Exercise-Ankle Brachial Pressure Index with One-Minute Treadmill Walking in Patients on Maintenance Hemodialysis 
Annals of Vascular Diseases  2012;6(1):52-56.
Background: The ankle-brachial pressure index (ABI) is widely used as a standard screening method for arterial occlusive lesion above the knee. However, the sensitivity of ABI is low in hemodialysis (HD) patients. Exercise stress (Ex-ABI) may reduce the false negative results.
Patients and Methods: After measuring resting ABI and toe-brachial pressure index (TBI), ankle pressure and ABI immediately after walking (Post-AP, Post-ABI) were measured using one-minute treadmill walking in 52 lower limbs of 26 HD patients. The definition of peripheral arterial occlusive disease (PAD) required an ABI value of less than 0.90, TBI value of less than 0.60, and decrease of more than 15% of the Post-ABI value and 20 mmHg of Post-AP in Ex-ABI. Computed tomographic angiography (CTA) was performed in 32 lower limbs of 16 HD patients. PAD is defined as presence of stenosis of more than 75% in the case of lesions from an iliac artery to knee on CTA.
Results: The accuracy of Ex-ABI (Sensitivity, 85.7%; Specificity, 77.7%) was higher than those of ABI (Sensitivity, 42.9%; Specificity, 83.3%) or TBI (Sensitivity, 78.6%; Specificity, 61.1%).
Conclusion: Ex-ABI with one-minute treadmill walking is the most useful tool for the screening of arterial occlusive lesions above the knee in maintenance HD patients.
doi:10.3400/avd.oa.12.00070
PMCID: PMC3635000  PMID: 23641284
peripheral arterial disease; exercise; diagnosis; screening; hemodialysis
23.  Prevalence of peripheral arterial disease in high-risk patients using ankle-brachial index in general practice: a cross-sectional study 
Aims:
The deleterious nature of peripheral arterial disease (PAD) is compounded by a status of underdiagnosed and undertreated disease. We evaluated the prevalence and predictive factors of PAD in high-risk patients using the ankle-brachial index (ABI).
Methods:
The ABI was measured by general practitioners in France (May 2005–February 2006) in 5679 adults aged 55 years or older and considered at high risk. The primary outcome was prevalence of PAD (ABI strictly below 0.90).
Results:
In all, 21.3% patients had signs or symptoms suggestive of PAD, 42.1% had previous history of atherothrombotic disease and 36.6% had two or more cardiovascular risk factors. Prevalence of PAD was 27.8% overall, ranging from 10.4% in patients with cardiovascular risk factors only to approximately 38% in each other subgroup. Prevalence differed depending on the localization of atherothrombotic events: it was 57.1–75.0% in patients with past history of symptomatic PAD; 24.6–31.1% in those who had experienced cerebrovascular and/or coronary events. Regarding the classical cardiovascular risk factors, PAD was more frequent when smoking and hypercholesterolemia history were reported. PAD prevalence was also higher in patients with history of abdominal aortic aneurysm, renal hypertension or atherothrombotic event. Intermittent claudication, lack of one pulse in the lower limbs, smoking, diabetes and renovascular hypertension were the main factors predictive of low ABI.
Conclusions:
Given the elevated prevalence of PAD in high-risk patients and easiness of diagnosis using ABI in primary care, undoubtedly better awareness would help preserve individual cardiovascular health and achieve public health goals.
doi:10.1111/j.1742-1241.2008.01953.x
PMCID: PMC2705819  PMID: 19125994
24.  A Modified Method in Laparoscopic Peritoneal Catheter Implantation: The Combination of Preperitoneal Tunneling and Pelvic Fixation 
ISRN Surgery  2013;2013:248126.
Introduction. Continuous ambulatory peritoneal dialysis (CAPD) is widely accepted for the management of end-stage renal disease (ESRD). Although not as widely used as hemodialysis, CAPD has clear advantages, especially those related to patient satisfaction and simplicity. Peritoneal dialysis (PD) catheter insertion can be accomplished by several different techniques. In this study, we aimed to evaluate our results obtained with peritoneal dialysis catheter placement by combination of pelvic fixation plus preperitoneal tunneling. Material and Methods. Laparoscopic peritoneal catheter implantation by combining preperitoneal tunneling and pelvic fixation methods was performed in 82 consecutive patients with end-stage renal disease. Sex, age, primary disease etiology, complications, mean duration of surgery, mean duration of hospital stay, morbidity, mortality, and catheter survival rates and surgical technique used were assessed. Analysis of catheter survival was performed using the Kaplan-Meier method. Results. Mean follow-up period was 28.35 ± 14.5 months (range of 13–44 months). Mean operative time was 28 ± 6 minutes, and mean duration of hospital stay was 3 ± 1 days. There were no conversions from laparoscopy to other insertion methods. None of the patients developed serious complications during surgery or the postoperative period. No infections of the exit site or subcutaneous tunnel, hemorrhagic complications, abdominal wall hernias, or extrusion of the superficial catheter cuff was detected. No mortality occurred in this series of patients. Catheter survival was found to be 92% at 3 years followup. Conclusions. During one-year followup, we had seven patients of migrated catheters due to separation of pelvic fixation suture from peritoneal surface, but they were reimplanted and fixated again laparoscopically with success. Over a three-year followup period, catheter survival was found to be 92%. In the literature, similar catheter survival rates without combination of the two techniques are reported. As a conclusion, although laparoscopic placement of PD catheters avoids many perioperative and early complications, as well as increasing catheter free survival period and quality of life, our results comparing to other studies in the literature indicate that different laparoscopic placement methods are still in debate, and further studies are necessary to make a more accurate decision.
doi:10.1155/2013/248126
PMCID: PMC3671265  PMID: 23762625
25.  The prevalence and correlation of carotid artery calcification on panoramic radiographs and peripheral arterial disease in a population from the Republic of Korea: the Dong-gu study 
Dentomaxillofacial Radiology  2013;42(3):29725099.
Objectives:
The aim of this study was to determine the prevalence of carotid artery calcification (CAC) detected on panoramic radiographs and peripheral arterial disease (PAD), and to evaluate the difference in the prevalence of PAD between patients with CAC and patients without CAC detectable by panoramic radiograph.
Methods:
The surveyed population consisted of 4078 subjects aged 50 years and older (1410 males and 2668 females) who underwent medical and dental examination in Gwangju city, South Korea. Two oral and maxillofacial radiologists interpreted the panoramic radiographs for the presence of carotid artery calcification. A trained research technician measured the ankle–brachial index (ABI). An ABI <0.9 in either leg was considered evidence of PAD.
Results:
The prevalence of CAC on panoramic radiographs was 6.2% and that of PAD was 2.6%. Subjects with CAC had a significantly higher prevalence of PAD than those without CAC (5.5% vs 2.4%, respectively). The presence of CAC on panoramic radiographs was associated with PAD (odds ratio 1.84; 95% confidence interval 1.01–3.36) after adjusting for potential confounders.
Conclusion:
CACs detected on panoramic radiographs were positively associated with PAD in middle-aged and older Korean adults.
doi:10.1259/dmfr/29725099
PMCID: PMC3667535  PMID: 22752323
carotid artery; panoramic radiography; peripheral arterial disease; ankle–brachial index

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