Marker Of Peripheral Arterial Disease Research Articles

Abstract TP189: Is A Low Ankle-brachial Index A Predictive Factor For Poor Recovery From Acute Ischemic Stroke?

Background: The ankle-brachial index (ABI) is widely used as a marker of peripheral arterial disease, and it reflects the severity of systemic atherosclerosis. Lower limb hypoperfusion or ischemia may inhibit recovery from neurological impairment. Whether a low ABI is associated with poor functional outcome after ischemic stroke was examined. Methods: 926 acute ischemic stroke patients (598 males; mean age, 71.1±10.8 years; median age, 72.0 years) who did not undergo t-PA or surgical treatment were enrolled. All provided informed consent and underwent ABI measurement during hospitalization. Baseline characteristics and NIHSS scores at admission were noted, and modified Rankin scale (mRS) scores 3 months after stroke were evaluated. The patients were categorized into normal (≥0.9) and decreased (<0.9) ABI groups, and into fair-outcome (mRS score, 0-2) and poor-outcome (mRS score, 3-6) groups. Results: ABI was decreased in 42 (5.9%) of 713 fair-outcome patients and 31 (14.6%) of 213 poor-outcome patients. The poor-outcome group had a higher average NIHSS score, a higher proportion of patients that were female, underweight, had a stroke history, and aged >75 years, and a lower proportion of patients who had dyslipidemia, a smoking history, and a drinking history. Logistic regression analysis including the above factors showed a relationship with poor outcome. Decreased ABI was negatively related to fair outcome (OR=0.569, 95%CI=0.324-0.999, p=0.050). Comments: Decreased ABI was an independent risk factor correlated with poor outcome 3 months after acute ischemic stroke, suggesting that lower limb and general atherosclerosis may delay or hamper recovery from stroke.

Femoral Intima Media Thickness as a Marker for Peripheral Arterial Disease

Femoral Intima Media Thickness as a Marker for Peripheral Arterial Disease

Fasting apolipoprotein B48 is a marker for peripheral arterial disease in type 2 diabetes

An earlier study showed that fasting and postprandial concentrations of apolipoprotein B48 were raised in patients with type 2 diabetes (DM2) and peripheral arterial disease (PAD) as compared with persons without DM2 or persons with DM2 but not PAD. The aim of this study was to confirm the association of PAD and B48 in a larger group of patients with DM2 and the relation of B48 with the preheparin lipoprotein lipase (LPL) mass. We studied 456 patients with DM2. PAD was defined as an ankle-brachial index (ABI) <0.9. Apolipoprotein B48 was quantified by ELISA. Apo B48 was significantly higher in the group with an ABI <0.9 than the groups with ABI of 0.9-1.3 and >1.3 (10.7 ± 6.28 vs. 9.24 ± 5.5 vs. 9.17 ± 8.8 mg/L, ANOVA test, p < 0.05). B48 was independently associated with an ABI <0.9 (OR 1.053; 95 % CI, 1.013-1.094; p < 0.05), together with smoking and duration of diabetes. The preheparin LPL mass was similar in the patients with and without PAD. In conclusion, we confirmed that fasting B48 is an independent marker of PAD in patients with DM2, unrelated to the preheparin LPL mass, statin therapy or glucose lowering treatment.

Abstract MP087: Relation of Risk Factor Profile at Baseline and 39-Year Follow-up to Peripheral Arterial Disease - - The Chicago Healthy Aging Study (CHAS)

Background: Low burden of CVD risk factors (RF) at younger ages is associated with substantially reduced risk for future clinical CVD events. There is no information available regarding associations of long-term patterns in RF profile, from young adulthood to older age, with prevalence at older age of low ankle brachial index (ABI), a marker for peripheral arterial disease (PAD). Methods: Using data from the Chicago Healthy Aging Study (CHAS), we assessed associations of patterns in RF profile -- from baseline (1967-73) to follow-up (2007-10) -- with prevalence of PAD at follow-up (see Table for definitions of RFs and RF groups). ABI was calculated as the ratio of Doppler recorded systolic pressures in the lower and upper extremities, and categorized as follows: low ABI/PAD (ABI&lt;1.00) vs. normal (1.00 ≤ABI ≤1.40). Participants with an ABI &gt;1.40 (n=24) were excluded from the analysis. Results: The study sample consisted of 1,340 participants (27.8% women, 9.2% African Americans) ages 24-45 years, free of major ECG abnormalities and MI at baseline. After 39 years of follow-up, 15.5 percent of persons with no adverse baseline RF levels remained RF-free at follow-up (Group A). The prevalence of PAD was lowest in this Group A (3.7%) and highest (19.9% -- 5 times higher) in Group E, with ≥2 RFs at both baseline and follow-up (p-value &lt; .001). Likewise, with adjustment for baseline age, sex, ethnicity, education, and minor ECG abnormalities, the odds for PAD in Group A was lowest compared with other groups. Further, decrease in number of RFs from baseline to follow-up (Group C) was associated with lower likelihood for PAD compared to increase in number of RFs over time (Groups B and D) and to presence of ≥2 RFs at both baseline and follow-up (Group E). Conclusion: Long-term absence of risk factors is associated with lowest prevalence of PAD at 39 year follow-up. Greater risk factor burden in young adulthood and development of risk factors over decades were both associated with greater likelihood of PAD later in life.

Índice tornozelo-braquial e hipertrofia ventricular na hipertensão arterial

O Índice Tornozelo-Braquial (ITB) é marcador de doença arterial obstrutiva periférica. Raros relatos correlacionam esse índice com hipertrofia ventricular esquerda (HVE), capacidade funcional (CF) e escore de risco coronariano de Framingham (ERCF). O objetivo do trabalho foi verificar a correlação entre ITB, HVE, CF e ERCF em homens com hipertensão arterial (HA). Estudo prospectivo e transversal de pacientes do sexo masculino (n = 40), com idade média de 57,92 ± 7,61 anos, sem complicações cardiovasculares. Essa população foi submetida às medidas de ITB, ecocardiograma (ECO), teste ergométrico (TE) e exames laboratoriais. O ITB (direito e esquerdo) foi considerado anormal quando a relação entre a maior média das pressões sistólicas dos tornozelos e dos braços foi inferior ou igual a 0,9 ou superior a 1,3 mmHg. A HVE foi identificada pelo ECO transtorácico; e a CF, pelo TE. Amostras sanguíneas periféricas foram colhidas para o cálculo do ERCF. Valores normais de ITB foram encontrados em 33 pacientes (82,5%), os quais foram incluídos no Grupo I; sete pacientes (17,5%) com ITB anormal constituíram o Grupo II. Os índices de massa do índice de massa do ventrículo esquerdo (IMVE) ao ECO foram de 111,18 ± 34,34 g/m² (Grupo I) e de 150,29 ± 34,06 g/m2 (Grupo II) (p = 0,009). A prevalência de HVE foi de 4% (Grupo I) e de 35,3% (Grupo II) (p = 0,01), constatando-se diferenças significativas entre os grupos. Quanto à CF no TE, não se registrou diferença entre os grupos. Em relação ao ERCF, a média do Grupo I foi inferior à média do Grupo II: 13,18 ± 2,11 versus 15,28±1,79 (p = 0,019). Em HA, a presença de HVE definida pelo IMVE esteve mais presente nos casos com ITB anormal, identificando maior risco cardiovascular.

Ischemia-modified albumin in type 2 diabetic patients with and without peripheral arterial disease

OBJECTIVE:To determine whether there is an association between serum ischemia-modified albumin and the risk factor profile in type 2 diabetic patients with peripheral arterial disease and to identify the risk markers for peripheral arterial disease.METHODS:Participants included 290 patients (35.2% women) with type 2 diabetes. The ankle-brachial pressure index was measured using a standard protocol, and peripheral arterial disease was defined as an ankle-brachial index <0.90 or ≥1.3. The basal ischemia-modified albumin levels and clinical parameters were measured and analyzed. The risk factors for peripheral arterial disease were examined by multiple logistic analyses.RESULTS:Age, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, urine albumin, homocysteine, and ischemia-modified albumin were significantly higher in patients with peripheral arterial disease than in disease-free patients (p<0.05), while ankle-brachial index was lower in the former group (p<0.05). Ischemia-modified albumin was positively associated with HbA1c and homocysteine levels (r = 0.220, p = 0.030; r = 0.446, p = 0.044, respectively), while no correlation was found with ankle-brachial index. Multiple logistic analyses indicated that HbA1c, systolic blood pressure, homocysteine and ischemia-modified albumin were independent risk factors for peripheral arterial disease in the diabetic subjects.CONCLUSION:The baseline ischemia-modified albumin levels were significantly higher and positively associated with HbA1c and homocysteine levels in type 2 diabetic patients with peripheral arterial disease. Ischemia-modified albumin was a risk marker for peripheral arterial disease. Taken together, these results might be helpful for monitoring diabetic peripheral arterial disease.

ENOS and ACE genes influence peripheral arterial disease predisposition in smokers

Several biologic mediators and genetic predisposing factors may contribute to the development of peripheral arterial disease (PAD). The eNOS gene, encoding for endothelial nitric oxide synthase, has been proposed as a candidate gene in the predisposition to the disease. In this study, we evaluated the role of eNOS-786T>C, -894G>T and 4a/4b polymorphisms as markers of PAD per se and in the presence of the ACE D allele in patients previously investigated. We analyzed 281 consecutive patients (220 men, 61 women; median age, 72 years) with PAD and 562 healthy controls, comparable for sex and age. eNOS-786C, but not -894T and 4a, allele frequency was significantly higher in PAD patients than in controls (P = .03). An association with the predisposition to PAD was found for the eNOS-786C allele (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.11-2.09; P = .009) and the eNOS -786C/4a haplotype (OR, 1.41; 95% CI, 1.02-1.94, P = .04) at univariate analysis but not after adjustment for traditional risk factors. When smoking habit was considered, we observed that eNOS-786C/4a haplotype, but not the eNOS-786C allele, influenced PAD predisposition after adjustment for traditional risk factors in smokers (OR, 2.71; 95% CI, 1.38-5.30; P = .004). The eNOS-786C and eNOS-786C/4a haplotype did not modify the susceptibility to PAD in patients carrying the ACE D allele. Nevertheless, the presence of the eNOS-786C/4a haplotype increased PAD predisposition in smokers also carrying ACE D allele (OR, 2.71 to 3.79; P > .05 for interaction). This study demonstrated an association between eNOS and ACE genes in increasing PAD susceptibility in smokers, thus providing evidence for a gene-environment interaction in modulating predisposition to the disease.

Ankle brachial index as a predictor for mortality in patients with chronic kidney disease and undergoing haemodialysis

The ankle brachial index (ABI) is a marker for peripheral artery disease and can predict mortality in advanced chronic kidney disease (CKD) and haemodialysis patients, respectively. However, it is seldom studied in Taiwan, an area with high prevalence of CKD and end-stage renal disease. The aim of this study was to investigate the predictors for mortality by using ABI value in patients with CKD and undergoing haemodialysis in Taiwan. One hundred and sixty-nine patients with CKD stage 3-5 and 231 haemodialysis patients were enrolled in one regional hospital. The mean follow-up period was 23.3 + or - 3.3 months. Patients were stratified into three groups according to ABI value (<0.9, > or = 0.9 to < 1.3, and > or = 1.3). The relative mortality risk was analyzed by Cox-regression methods. In multivariate analysis, an ABI of 1.3 or more (hazard ratio, 3.846; P = 0.043) and coronary artery disease (P = 0.012) were positively associated with overall mortality, and serum low-density lipoprotein cholesterol level (P = 0.042) was negatively associated with overall mortality. In addition, an ABI of less than 0.9 (P = 0.049), an ABI of 1.3 or more (P = 0.033), coronary artery disease (P = 0.024) and haemodialysis treatment (P = 0.043) were strong predictors for cardiovascular mortality. Our findings show that an ABI of 1.3 or more predicts for both overall and cardiovascular mortality, and an ABI of less than 0.9 predicts for cardiovascular mortality in CKD and haemodialysis patients. Screening patients with chronic renal failure by means of ABI may help to identify a high-risk group for increased mortality.

Relation of the Ankle Brachial Index to Left Ventricular Ejection Fraction

Low and high ankle brachial index (ABI) values are both a marker of peripheral arterial disease and associated with greater cardiovascular disease event rates. The objective of the present study was to determine whether the ABI is associated with left ventricular (LV) systolic function. We studied 175 patients (age 67 +/- 13 years, 58% men) referred for ABI determination who had had the LV ejection fraction (EF) determined using echocardiography within 14 days. The mean LVEF was 47 +/- 13%, mean ABI for the right leg was 0.93 +/- 0.32, and the mean ABI for the left leg was 0.94 +/- 0.26. Of the 175 patients, 91 (52%) had a low, 69 (39%) had a normal, and 15 (9%) had a high ABI. The mean LVEF increased in a stepwise manner from the low, to normal, to abnormally high ABI groups (43 +/- 13% vs 51 +/- 12% vs 57 +/- 5%, respectively; p <0.01). On ordinal regression analysis, ABI status was independently related to LVEF. For each 1% increase in LVEF, the odds of being in the higher category of ABI increased by 1.08 (95% confidence interval 1.02 to 1.12, p = 0.002). No significant interaction was seen between coronary artery disease and LVEF on the ABI (p = 0.48). In conclusion, the ABI might be influenced by LV systolic function, independent of coronary disease. LVEF should be considered when ABI values are used to evaluate and monitor cardiovascular risk in patients.

Abstract 5755: The Role of Adhesion and Migration of Stimulated Multipotent Stromal Cell With EGF in Vasculogenesis in Type 2 Diabetes

Background: Chronic tissue ischemia due to defective vascular perfusion is a marker of peripheral artery disease for which minimal therapeutic options exist. Thus, type 2 diabetes is characterized with altered stem cells and vasculogenesis. Because of the capability of stem cells to differentiate into vascular cells and the importance of epidermal growth factor (EGF) in angiogenesis, their critical role in the treatment of type 2 diabetic patients with ischemia peripheral artery disease may be as prophylactic agents preventing tissue damage by stimulating vasculogenesis. Therefore we determined if multipotent stromal cells (MSC) tagged with enhanced green fluorescent protein (EGFP) stimulated with or without exogenous EGF would improve vasculogenesis in ischemia hind limb of type 2 diabetic (db−/db−) mice. Methods and Results: Isolated bone marrow from db−/db− mice showed an increase in oxidative stress and reduction in Akt compared to control. Ischemia was induced in the hind limb of db−/db− mice and control for 28 days. EGFP-MSC stimulated with or without exogenous EGF (10 ng/ml) for 24 hr were locally injected in the mice hind limb once a week for 4 weeks. After 4 weeks, blood flow measured with MoorLDI-Laser and angiogenesis assessed with X-ray were completely recovered in control mice compared to db−/db− mice. Interestingly db−/db− mice display a significant improvement of blood flow (60% and 96%) and vasculogenesis (61% and 98%) when treated with MSC or MSC pre-stimulated with exogenous EGF, respectively. Western blot analysis on hind limb muscles revealed an increase in phosphorylated Akt and VEGF receptor in db−/db− mice injected with MSC or MSC+EGF compared to non-treated db−/db− mice. Fluorescent microscopy images indicate that EGFP-MSCs differentiate into new microvessels. In vitro studies showed that adhesion and migration of MSC on cultured microvascular endothelial cells were elevated when MSC were pre-stimulated with EGF compared to non-stimulated MSC. Conclusion: Our novel data provide evidence that in type 2 diabetes, MSC stimulated with EGF are able to significantly improve, better than MSC alone, the formation of microvessels in response to ischemia.

Novel markers of peripheral arterial disease

Peripheral arterial disease (PAD), a relatively common manifestation of atherosclerotic vascular disease, is associated with significant morbidity and mortality. Although conventional risk factors contribute to the onset and progression of PAD, the role of 'novel' biomarkers in pathways of inflammation, thrombosis, lipoprotein metabolism, and oxidative stress in determining susceptibility to PAD is being increasingly recognized. Validation of novel risk factors for PAD may allow earlier detection, an improved understanding of disease etiology and progression, and the development of new therapies. In this review, we discuss available evidence for associations between novel circulating markers and several aspects of PAD including disease susceptibility, progression, functional limitation, and adverse outcomes.

Ankle-brachial index as a predictor for mortality in patients with chronic kidney disease and hemodialysis

Background. Ankle-brachial index (ABI) is a marker for peripheral artery disease and can predict mortality in advanced chronic kidney disease (CKD) and hemodialysis patients, respectively. However, it is seldom studied in Taiwan, an area with high prevalence of CKD and end-stage renal disease. The aim of this study was to investigate the predictors for mortality via using ABI value in patients with CKD and hemodialysis in Taiwan. Methods. We enrolled 169 patients with CKD stage 3–5 and 231 hemodialysis patients in one regional hospital. The mean follow-up period was 23.3 ± 3.3 months. Patients were stratified into three groups according to ABI value (< 0.9, ≥ 0.9 to < 1.3, and ≥ 1.3). The relative mortality risk was analyzed by Cox-regression methods. Results. In multivariate analysis, ABI ≥ 1.3 (hazard ratio, 3.846; P= 0.043), and coronary artery disease (P= 0.012) were positively associated with overall mortality, and serum low-density lipoprotein cholesterol level (P= 0.042) was negatively associated with overall mortality. In addition, ABI < 0.9 (P= 0.049), ABI ≥ 1.3 (P= 0.033), coronary artery disease (P= 0.024) and hemodialysis treatment (P= 0.043) were strong predictors for cardiovascular mortality. Conclusions. Our findings show that ABI ≥ 1.3 predicts for both overall and cardiovascular mortality, and ABI < 0.9 predicts for cardiovascular mortality in CKD and hemodialysis patients. Screening patients with chronic renal failure by means of ABI may help to identify a high risk group for increased mortality.

Associated Risk Factors for Abnormal Ankle-brachial Index in Hemodialysis Patients in a Hospital

Ankle-brachial index (ABI) is a marker for peripheral artery disease and can predict mortality in hemodialysis patients. However, it is seldom studied in southern Taiwan, an area with high prevalence of end-stage renal disease (ESRD). The aim of this study was to investigate the prevalence and associated risk factors for peripheral artery disease in the ESRD population in a hospital. All routine hemodialysis patients in one regional hospital were included except for six patients who refused ABI examinations and four patients with atrial fibrillation. Finally, 225 patients formed our study group. ABI was measured using an ABI-form device (Colin VP1000). The prevalence of ABI < 0.9 and > or = 1.3 was 15.6% and 5.8%, respectively. ABI < 0.9 was independently associated with advanced age (p = 0.027), increased pulse pressure (p = 0.005), increased hematocrit (p = 0.008) and decreased serum albumin level (p = 0.009). In addition, ABI > or = 1.3 was significantly associated with diabetes mellitus (p = 0.019). This study demonstrated the associated risk factors of peripheral artery disease in patients with hemodialysis in a hospital. ESRD patients of advanced age and with increased pulse pressure, increased hematocrit and decreased serum albumin level had a relatively high risk for ABI < 0.9 and patients with diabetes had a relatively high risk for ABI > or = 1.3.

Investigating the complex genetic architecture of ankle-brachial index, a measure of peripheral arterial disease, in non-Hispanic whites

BackgroundAtherosclerotic peripheral arterial disease (PAD) affects 8–10 million people in the United States and is associated with a marked impairment in quality of life and an increased risk of cardiovascular events. Noninvasive assessment of PAD is performed by measuring the ankle-brachial index (ABI). Complex traits, such as ABI, are influenced by a large array of genetic and environmental factors and their interactions. We attempted to characterize the genetic architecture of ABI by examining the main and interactive effects of individual single nucleotide polymorphisms (SNPs) and conventional risk factors.MethodsWe applied linear regression analysis to investigate the association of 435 SNPs in 112 positional and biological candidate genes with ABI and related physiological and biochemical traits in 1046 non-Hispanic white, hypertensive participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. The main effects of each SNP, as well as SNP-covariate and SNP-SNP interactions, were assessed to investigate how they contribute to the inter-individual variation in ABI. Multivariable linear regression models were then used to assess the joint contributions of the top SNP associations and interactions to ABI after adjustment for covariates. We reduced the chance of false positives by 1) correcting for multiple testing using the false discovery rate, 2) internal replication, and 3) four-fold cross-validation.ResultsWhen the results from these three procedures were combined, only two SNP main effects in NOS3, three SNP-covariate interactions (ADRB2 Gly 16 – lipoprotein(a) and SLC4A5 – diabetes interactions), and 25 SNP-SNP interactions (involving SNPs from 29 different genes) were significant, replicated, and cross-validated. Combining the top SNPs, risk factors, and their interactions into a model explained nearly 18% of variation in ABI in the sample. SNPs in six genes (ADD2, ATP6V1B1, PRKAR2B, SLC17A2, SLC22A3, and TGFB3) were also influencing triglycerides, C-reactive protein, homocysteine, and lipoprotein(a) levels.ConclusionWe found that candidate gene SNP main effects, SNP-covariate and SNP-SNP interactions contribute to the inter-individual variation in ABI, a marker of PAD. Our findings underscore the importance of conducting systematic investigations that consider context-dependent frameworks for developing a deeper understanding of the multidimensional genetic and environmental factors that contribute to complex diseases.

LB-PO-858 APOB/APOA-1 IS MORE PREDICTIVE OF AMI IN RHEUMATOID ARTHRITIS THAN LDL-C OR NHDL-C/HDL-C IN THE AMORIS STUDY

The aim of this study was to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), which mediates initiation and progression of atherosclerosis in endothelial cells, could be a novel marker for peripheral artery disease (PAD) in patients with type 2 diabetes.We evaluated relationships of serum sLOX-1 to ankle–brachial index (ABI) and examined the association of serum sLOX-1 with PAD in 410 patients with type 2 diabetes.Serum sLOX-1 was inversely correlated with ABI (r = − 0.197, P < 0.0001). Stepwise regression analysis demonstrated that serum sLOX-1 (β = − 0.168, F = 5.571, P < 0.05) was independently associated with ABI, and multiple logistic regression analysis demonstrated that serum sLOX-1 (16.254 (1.237–213.651), P = 0.0339) was independently associated with PAD.Serum sLOX-1 is associated with ABI and it could be a novel marker for PAD in patients with type 2 diabetes.

Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults

We investigated the association of 14 polymorphisms in the endothelial nitric oxide synthase gene ( NOS3) with ankle brachial index (ABI) in non-Hispanic white hypertensives belonging to hypertensive sibships. Subjects ( n = 659, mean age 61 ± 9 years, 54% women) underwent measurement of ABI using a standard protocol, and the lowest of 4 ABI values was used in the analyses. Non-synonymous SNPs with a minor allele frequency >0.02 and tag SNPs selected based on a measure of linkage disequilibrium ( r 2) were genotyped. We reduced the chance of false positives by testing for replication, randomly selecting 1 hypertensive sib from each sibship to create Subset 1 ( n = 330) and Subset 2 ( n = 329). Multivariable linear regression models were used to assess the associations of single NOS3 polymorphisms and haplotypes with ABI after adjustment for covariates (age, sex, body mass index, smoking, total cholesterol, HDL cholesterol, and diabetes). Two specific SNPs in significant LD with each other (rs891512 and rs1808593) were significantly associated with ABI in both subsets. Based on a sliding window approach with a window size of 2, estimated haplotypes from 2 SNP pairs (rs2070744–rs3918226 and rs1808593–rs7830) were also significantly associated with ABI in both subsets. In conclusion, specific NOS3 SNPs and haplotypes were associated with inter-individual variation in ABI, a non-invasive marker of peripheral arterial disease, in replicate subsets of hypertensive subjects. These findings motivate further investigation of the role of NOS3 variants in determining susceptibility to peripheral arterial disease.

L’index de pression systolique, un puissant marqueur de risque d’AOMI

A MARKER OF PERIPHERAL ARTERIAL DISEASE: The measurement of the ankle/arm index (AAI) is a simple, rapid and inexpensive means for the assessment of distal lower limb perfusion. Its decrease reveals an alteration in the patient's arterial status. Consecutively, AAI is an excellent marker of peripheral arterial disease, well before the onset of functional consequences. A TRIPLE MARKER: Beyond the diagnosis of peripheral arterial disease, AAI provides other interests: it is not only a tool for the functional assessment of lower limb perfusion, but also a marker of local and general atherosclerosis, as well as cardiovascular events.

Pulse Wave Velocity in Lower-Limb Arteries among Diabetic Patients with Peripheral Arterial Disease.

Patients with type 2 diabetes mellitus are at an increased risk of atherosclerosis including peripheral arterial disease (PAD). The purpose of this study was to examine the possible alteration in pulse wave velocity (PWV) in lower-limb arteries among diabetic patients with PAD. We measured brachial-ankle PWV (baPWV) using an automatic device in 101 healthy control subjects and 102 type 2 diabetic patients including those with PAD. Diabetic patients without PAD showed a higher baPWV than the healthy control subjects. There was no significant difference in baPWV between the right and left legs in these groups. In contrast, among diabetic patients with PAD, baPWV was significantly lower in the affected legs than in the non-affected legs, and the reduction in baPWV was greater in those with lower ankle-brachial pressure index (ABI). In the patients with PAD who received percutaneous transluminal angioplasty, both baPWV and ABI were increased following successful vessel dilatation. These results suggest that baPWV is increased in diabetic patients, whereas it is decreased in the affected legs in diabetic patients with PAD. Widening of the right-left difference in baPWV may be a novel marker of PAD.

Soluble Fas is a marker of peripheral arterial occlusive disease in haemodialysis patients.

Peripheral arterial occlusive disease (PAOD) including lower-extremity and cerebrovascular atherosclerosis is a leading cause of morbidity in haemodialysis patients. Recent evidence suggests that the expression of Fas, a molecule implicated in the initiation of apoptosis in various cell types, is increased at sites of atherosclerotic plaques. However, the significance of plasma levels of the soluble form of Fas (sFas) as a marker of peripheral arterial disease has yet to be defined. The present report is based on a cross-sectional analysis of baseline data from an ongoing prospective study designed to evaluate the role of sFas as marker of PAOD in end-stage renal disease (ESRD). We evaluated the association between sFas levels and evidence of PAOD in a cohort of 107 chronic haemodialysis patients. Compared with subjects without evidence of disease (n=56), subjects with PAOD (n=51) had significantly higher plasma levels of sFas (30.0+/-8.9 vs 26.4+/-9.5 ng/ml; P=0.04). Using multiple regression, sFas was found to be associated with PAOD independently of classical risk factors for atherosclerosis (hypercholesterolaemia, diabetes, hypertension, and smoking), markers of inflammation (e.g. C-reactive protein, intercellular cell adhesion molecule type 1), and other risk factors (e.g. age, gender). An increase of one quintile in the plasma concentration of sFas was associated with an odds ratio of PAOD of 1.69 (95% CI: 1.09--2.63, P=0.01). In addition, models that incorporated sFas were significantly better at predicting PAOD than models limited to classical risk factors for atherosclerosis, alone or in combination with CRP levels (P=0.01). Increased plasma levels of sFas are associated with established PAOD. These results suggest that sFas may represent a novel and independent marker of atherosclerosis.

Screening of plasma homocysteine in peripheral arterial disease

BACKGROUND. Homocysteine (HCY) was recently established as an independent risk factor for atherosclerosis. The prevalence of an increased homocysteine plasma concentration was reported to be up to 6-fold higher in patients with different locations of arterial occlusive diseases.AIM. This study evaluated critically whether the total HCY plasma concentration can be used as a screening marker for peripheral arterial disease in the general population. METHODS. Study subjects were 40 patients (51.8 ± 7.5 years) with symptomatic lower limb peripheral arterial disease (PAD) (stage II) and 40 healthy volunteers (45.6 ± 6.8 years, P < 0.05 vs PAD). The percentage of women in both groups was 30%. The plasma HCY concentration was determined by using derivatization techniques and subsequent fluorescence high-performance liquid chromatography.RESULTS. Total plasma HCY concentration was significantly higher in the PAD group than in controls (14.90 ± 5.78 μM vs 11.32 ± 2.95 μM, respectively, P < 0.001). Also, the coefficient of variation of plasma HCY in PAD was significantly higher than that in the control group, 0.38 vs 0.25 (P < 0.001), respectively, reflecting greater interindividual differences. In addition to a PAD-specific effect, the plasma HCY concentration was also dependent on gender and age (both P < 0.05). Sensitivity and specificity of HCY as a marker of PAD were 0.3 and 0.95, respectively. Positive and negative predictive values were 0.85 and 0.42, respectively.CONCLUSIONS. From these data it is concluded that HCY metabolism may have an influence on the development of PAD in one-third of all patients with PAD, and that total plasma HCY concentration may not be suited as a screening test for PAD in the general population but rather serves as a monitoring marker in certain risk groups.