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Objective: Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations are considered risk factors for venous thromboembolism. It remains to be characterized whether the presence of these relatively common mutations poses a risk for peripheral arterial disease (PAD). Therefore, we intended to test, by conducting a case-control study, the hypothesis that PAD was associated with an increased prevalence of factor V G1691A, prothrombin G20210A, and MTHFR C677T mutations., Methods: The study comprised 433 patients admitted for inpatient diagnostics and treatment of PAD in patients with chronic limb ischemia. Patients with acute ischemia or malignancy were excluded. A total of 433 control subjects matched to the patients with PAD in a 1:1 design by sex, age (+/-2 years), and diabetes mellitus status were recruited. Factor V G1691A, prothrombin G20210A, and MTHFR C677T genotypes were assessed by polymerase chain reaction., Results: For the factor V G1691A polymorphism, the genotype frequencies in PAD patients were 92.8% GG (normal homozygotes = wild type) and 7.2% GA (mutant heterozygotes), and in control subjects they were 94.0% GG and 6.0% GA (chi 2 test; P = .493). The distribution of the prothrombin G20210A genotypes was 96.3% GG (normal homozygotes = wild type) and 3.7% GA (mutant heterozygotes) in PAD patients and was 97.2% GG and 2.8% GA in control subjects (chi 2 test; P = .442). Genotype frequencies for the MTHFR C677T polymorphism were 47.8% CC (normal homozygotes = wild type), 43.4% CT (mutant heterozygotes), and 8.8% TT (mutant homozygotes) in PAD patients, compared with 47.1% CC, 44.1% CT, and 8.8% TT in control subjects (chi 2 test; P = .977). Accordingly, as determined by logistic regression analysis, no significant odds ratios for heterozygous or homozygous genotypes of the three polymorphisms could be observed., Conclusions: PAD was not associated with an increased prevalence of factor V G1691A, prothrombin G20210A, and MTHFR C677T mutations in the population studied. Thus, there is no indication that of one of these mutations may be a risk factor for chronic limb ischemia. However, the role of these mutations in acute limb ischemia remains to be clarified.

Objective: Circulating 8-iso-prostaglandin F 2alpha (8-iso-PGF 2alpha ) has been proposed as new indicator of oxidative stress, which is involved in the pathophysiologic changes of atherosclerosis. We proposed to test the hypothesis that 8-iso-PGF 2alpha is an independent predictor of symptomatic peripheral arterial disease (PAD)., Methods: A case-control study in 100 patients with symptomatic PAD and 100 control subjects matched for age, sex, and diabetes mellitus was conducted. Smokers and subjects using lipid-lowering drugs were excluded. Serum total 8-iso-PGF 2alpha was quantified with an enzyme immunoassay., Results: Median 8-iso-PGF 2alpha was higher in patients with PAD than in control subjects (63 vs 42 pg/mL; P = .001). Logistic regression with hypertension, body mass index, and creatinine, low-density lipoprotein (LDL) cholesterol, triglyceride, high-sensitivity C-reactive protein (hs-CRP), 8-iso-PGF 2alpha , and total homocysteine concentrations as independent variables and case-control status as dependent variable revealed significant odds ratios (OR) for hypertension (OR, 3.74; 95% confidence interval [CI], 1.85-7.53), low-density lipoprotein cholesterol (OR, 1.16, for an increment of 10 mg/dL; 95% CI, 1.07-1.27), high-sensitivity C-reactive protein (OR, 1.02, for an increment of 1 mg/L; 95% CI, 1.00-1.03), and 8-iso-PGF 2alpha (OR, 1.11, for an increment of 10 pg/mL; 95% CI, 1.03-1.20)., Conclusions: Serum total 8-iso-PGF 2alpha was an independent predictor of PAD in the population studied. This finding supports the hypothesis that 8-iso-PGF 2alpha is a risk marker for PAD. Our results indicate increased systemic oxidative stress in patients with PAD.

A tool to identify vascular patients who receive antiplatelet therapy nd to distinguish between responders and non-responders to antiplatelet therapy could be of clinical importance. The present observational study was designed to investigate whether the PFA-100 device (Dade Behring) is suitable to detect long-term therapy of aspirin (100 mg/d) and/or clopidogrel (75 mg/d) in a cohort of patients with peripheral arterial disease (PAD). A total of 150 consecutive patients with PAD were studied; 34 patients were excluded from the study due to irregular intake of antiplatelet therapy or due to method limitations. Of the remaining 116 patients, 42 had no antiplatelet therapy, 47 had daily aspirin (100 mg) intake, 19 were administered clopidogrel 75 mg daily, and 10 received a medication with 100 mg aspirin plus clopidogrel 75 mg daily, all for at least 10 days. Nonparametric Kruskal-Wallis test with post hoc comparisons showed that collagen plus epinephrine (CEPI) closure times of the patient group receiving aspirin and the group receiving aspirin plus clopidogrel were similar (p>0.05). In contrast, both patient groups exhibited prolonged CEPI values compared to patients without antiplatelet therapy and patients taking clopidogrel (p<0.001). Finally, both patients without antiplatelet therapy and patients with clopidogrel did not show marked differences with respect to their CEPI values (p>0.05). However, Kruskal-Wallis test results revealed that collagen plus adenosine-5'-diphosphate closure times were not significantly different in all four patient groups (p=0.257). In conclusion, the PFA-100 device may be a suitable tool for monitoring aspirin 100 mg therapy, but it is not appropriate for the detection of clopidogrel administration in its current setup. Although it appears plausible that patients with PAD could benefit from monitoring platelet inhibition, clear evidence for this concept is still lacking.

There are currently no data on whether high total serum homocysteine (tHcy) is predictive for cerebrovascular events in patients with symptomatic peripheral arterial disease (PAD). Therefore, the purpose of this study was to determine whether high tHcy levels were related to the evidence of non-fatal stroke in PAD. Evidence of non-fatal atherothrombotic stroke events was verified in 450 consecutive male patients, admitted for inpatient treatment of symptomatic PAD. The extent of carotid stenosis was evaluated by colour duplex Doppler measurement and fasting tHcy was determined by high-performance liquid chromatography. Within the population of 450 PAD patients a documented history of ischaemic stroke was evident in 50 subjects. The median tHcy values were significantly higher in PAD patients with stroke (18.6 micromol/l) than in PAD patients without stroke (15.1 micromol/l, P < 0.001). Logistic regression analysis revealed that tHcy was an independent and significant predictor (P=0.001) with an odds ratio (OR) of 1.37 for an increment of 5 micromol/l. In this multivariate model, diabetes mellitus (OR=2.34, P=0.011) and carotid stenosis > or =50% (OR=2.59, P=0.005) were also independently related to clinical cerebrovascular disease in PAD. In conclusion, the present study demonstrates an association of tHcy and evidence of non-fatal atherothrombotic stroke in patients with symptomatic PAD. This could be important, as a reduction of elevated tHcy concentrations by vitamin supplement might decrease the high frequency of cerebrovascular complications in PAD patients.

Elevated erythrocyte mean corpuscular volume (MCV) may be a risk factor for peripheral arterial disease (PAD). The aim of the present study was to evaluate whether MCV was associated with the severity of atherosclerotic findings in the lower limbs of PAD patients, as measured by an angiographic scoring system based on vessel lumen reduction. One hundred male patients with symptomatic PAD were studied. MCV was significantly correlated with the angiographic score (rs = 0.247, p = 0.013). PAD patients with an angiographic score in the lower third were compared to those with values in the upper third using a logistic regression model with age, smoking, hypertension, MCV, homocysteine, and total cholesterol and triglycerides as independent variables. This model revealed significant odds ratios (OR) for MCV (OR = 2.02 for an increment of 5 fl, 95% CI = 1.08-3.8) and for age (OR = 2.41 for an increment of 10 years, 95% CI = 1.21-4.81) and facilitated classification of 71% of all subjects correctly. In conclusion, MCV may be associated with angiographically determined disease severity in patients with PAD. This finding supports the hypothesis that MCV is a risk factor for PAD, although the mechanism by which MCV may contribute to the presence and severity of the disease is not yet determined.

Background: The aim of the study was to determine predictors of hemodynamically relevant atherosclerosis (HRA) in different segments of lower limb arteries in patients with peripheral arterial disease (PAD)., Methods: In a retrospective case-control study 106 hospitalized consecutive patients with symptomatic PAD and 52 asymptomatic control subjects were studied. All patients underwent distal aortofemoral angiography. The arteries of the lower limbs were divided into three sections: in the aorto-iliac and femoro-popliteal segments HRA was defined as one or more stenosis of over 50%. In the crural segment it was considered if at least two arteries of one lower leg had occlusions/stenoses of over 50%., Results: In 106 patients, there were 132 cases of hemodynamically relevant lesions, and in 26 patients in two segments. We separately compared 23 cases with aorto-iliac, 82 with femoro-popliteal and 27 with crural manifestation to the 52 control subjects. Calculating age- and sex-adjusted odds ratios, we found that current smoking status and plasminogen levels were significantly associated with HRA in the aorto-iliac and femoro-popliteal segments, whereas in diabetes mellitus the association was found to be in the crural and femoro-popliteal segments. However, there was no such association for lipid profiles and fibrinogen., Conclusions: We conclude that the anatomic distribution of HRA in patients with PAD is different according to the risk factor profile. The aorto-iliac and crural segments show specific risk profiles while the femoro-popliteal segment seems to be a transition zone. Smoking and high plasminogen levels may be related to atherosclerosis of proximal segments, diabetes to that of the distal segments.