We aim to determine the efficacy and safety of gene and cell angiogenic therapies in the treatment of peripheral arterial disease (PAD) and evaluate them for the first time by a meta-analysis. We include in the formal meta-analysis only the randomized placebo-controlled phase 2 studies with any angiogenic gene or cell therapy modality to treat patients with PAD (intermittent claudication, ulcer or critical ischemia) identified by electronic search in MEDLINE and EMBASE databases (1980 to date). Altogether, 543 patients are analyzed from six randomized, controlled trials that are comparable with regard to patient selection, study design, and endpoints. We perform the meta-analysis regarding clinical improvement (improvement of peak walk time, relief in rest pain, ulcer healing or limb salvage) and rate of adverse events. At the end of treatment, therapeutic angiogenesis shows a significantly clinical improvement as compared to placebo in patients with PAD (odds ratio [OR] = 1.437; 95% confidence interval [CI] = 1.03-2.00; P = 0.033). The response rate (improvement of peak walk time) of the pooled groups according to clinical severity does not significantly differ for gene therapy as compared with placebo in the treatment of claudicating patients (OR = 1.304; 95% CI = 0.90-1.89; P = 0.16). Otherwise, we find significant efficacy of the treatment in critical ischemia (OR = 2.20; 95% CI = 1.01-4.79; P = 0.046). The adverse events rates show a slightly significantly higher risk of potential nonserious adverse events (edema, hypotension, proteinuria) in the treated group (OR = 1.81; 95% CI = 1.01-3.38; P = 0.045). We find no differences in mortality from any cause, malignancy, or retinopathy. The patients with PAD, and particularly those with critical ischemia, improve their symptoms when treated with angiogenic gene and cell therapy with acceptable tolerability.

Impaired endothelial dysfunction is association with increased plasma concentrations of inflammatory markers, and both may have a role in the aetiopathogenesis of peripheral arterial disease.

Objective: To determine whether the increase in plasma levels of C-Reactive Protein (CRP), a non-specifi c reactant in the acute-phase of systemic infl ammation, is associated with clinical severity of peripheral arterial disease (PAD). Methods and Results:This is a cross-sectional study at a referral hospital center of institutional practice in Madrid, Spain. A stratifi ed random sampling was done over a population of 3370 patients with symptomatic PAD from the outpatient vascular laboratory database in 2007 in the order of their clinical severity: the fi rst group of patients with mild chronological clinical severity who did not require surgical revascularization, the second group consisted of patients with moderate clinical severity who had only undergone only one surgical revascularization procedure and the third group consisted of patients who were severely affected and had undergone two or more surgical revascularization procedures of the lower extremities in different areas or needed late re-interventions. The Neyman affi xation was used to calculate the sample size with a fi xed relative error of 0.1. A homogeneity analysis between groups and a unifactorial analysis of comparison of medians for CRP was done. The groups were homogeneous for age, smoking status, Arterial Hypertension HTA, diabetes mellitus, dyslipemia, homocysteinemia and specifi c markers of infl ammation. In the unifactorial analysis of multiple comparisons of medians according to Scheffé, it was observed that the median values of CRP plasma levels were increased in association with higher clinical severity of PAD (3.81 mg/L [2.14-5.48] vs. 8. 33 [4.38-9.19] vs. 12.83 [9.5-14.16]; p Ͻ 0.05) as a unique factor of tested ones. Conclusion:Plasma levels of CRP are associated with not only the presence of atherosclerosis but also with its chronological clinical severity.

Antiphospholipid syndrome is accepted as one of the most important causes of hypercoagulable states. Thrombotic events in patients with antiphospholipid syndrome, predominantly women, occur at a younger age than in those suffering from atherosclerotic disease. The majority of the thrombotic events affect the deep venous system of the lower limbs and arterial thrombosis predominates in the cerebral territory. The use of anticoagulant therapy prevents recurrent thrombosis but the duration and intensity of treatment remain controversial. Aortic disease is an anecdotal fact in the literature. A case of infrarenal aortic occlusion involving both iliac arteries associated with primary antiphospholipid syndrome is presented.

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