Current Appointments • Staff Angiologist and Vascular Surgeon, Service of Angiology and Vascular Surgery, Hospital Universitario Getafe, Madrid. (Spain) • Titular Research Investigator, Cardiovascular Research, Hospital Universitario Getafe, Madrid. • Chief of Cardiovascular Research Center, Hospital Universitario Getafe, Madrid • Angiology and Vascular Surgery Fellowship Tutor at Hospital Universitario Getafe, Madrid • Member of Scientific Research Committee, Hospital Universitario Getafe, Madrid • Member of Ethics Committee for Clinical Trials, Hospital Universitario Getafe, Madrid • Staff Vascular Surgeon, Division of Angiology and Vascular Surgery, Hospital La Zarzuela, Madrid. • Staff Vascular Surgeon, Department of Angiology and Vascular Surgery, Hospital Sur, Alcorcon, Madrid. • Professor, Universidad Europea Madrid, Medical School, Cardiovascular Department.
Education and Training • M.D., Ph.D., Valencia University, Valencia, Spain, 2000 • Surgery Rotation at School of Medicine of University of Virginia (Charlottesville, VA), 1998 • Post-doctoral courses in Endovascular Treatment for Vascular Diseases, Hospital Vall d’Hebron, Barcelona, Spain, 2004 • Post-doctoral courses in Laparoscopy in the Treatment for Aorta Disease, Leon University, Spain, 2005 • Fellowship in Cardiovascular Research, Angiogenesis, Gene and Cell Therapy Program, Cardiovascular Research Centre, Caritas St. Elizabeth’s Medical Center, Boston (MA), USA, 2005 • International Vascular Course, Salamanca University, Spain, 2004 • Endovascular Surgery Course in experimental models, Leon University, Spain, 2005 • Postgraduate University Master Degree in "Security of X Ray Facilities, Company Manager", Ilustre Colegio de Medicos de Madrid, Spain, 2008 • Postgraduate University Master Degree in Music Therapy, Vic University (Barcelona), Spain, 2007-2010
Awards and Honors • Best Research Work Award, Spanish Society of Angiology and Vascular Surgery Congress, 2003 • Spanish Society of Angiology and Vascular Surgery Research Award (Professor Martorell Award), 2006 • Best Published Article Award in Angiologia Journal during 2008: Angiologia 2008;60:395-401 • Member of Spanish Society of Angiology and Vascular Surgery • Member of Centro Society of Angiology and Vascular Surgery • Member of Valencian Society of Angiology and Vascular Surgery • Member of European Society of Vascular Surgery • Member of European Atherosclerosis Society • Editorial Board Member of Angiology Journal • Editorial Board Member of World Journal of Methodology • Reviewer of British Medical Journal • Reviewer of British Medical Journal Case Reports • Reviewer of European Journal of Pharmacology • Reviewer of Annals of Vascular Surgery • Reviewer of Vascular Medicine • Reviewer of Diabetes & Vascular Disease Research Journal • Juan Muñoz Tello Grant from Lain Entralgo Biomedic Research Agency (2006) • Research Grant from Spanish Society of Angiology and Vascular Surgery Fundation (2009) • Referee of Biomedical and Therapeutic Research Committee of Scottish Government (UK) • Member of Advisory Committee for Vascular Surgery and Angiology in Ministry of Health of the Community of Madrid. Working Committee "Relationship to other specialties" 2011-2015 • Best Research Study Award, Scientific Sessions of Foundation for Biomedical Research of Getafe University Hospital (2nd edition, 2009) for the study "Long-term pleiotropic effect of statins upon nitric oxide and C-reactive protein levels in patients with peripheral arterial disease" • Spanish Society of Angiology and Vascular Surgery Research Award (Professor Martorell Award), 2010 • Servier Award 2010: Best Paper Published in an International Journal from Spanish Society of Angiology and Vascular Surgery during 2009: Eur J Vasc Endovasc Surg 37: 4; 443-447 • Research Grant from Mutua Madrileña Medical Research Fundation (2010) • Spanish National Award for Medical Research (Ulysses National Award), 2010 for the project "DETERMINATION OF DIFFERENCES OF VEGF GENE HAPLOTYPE AND ITS PROTEINOMICS EXPRESSION WITH DIABETES RETINOPATHY VS PERIPHERAL ARTERY DISEASE IN DIABETES PATIENTS" • Annual Research Award of Foundation for Biomedical Research of Getafe University Hospital (3rd edition, 2010) • Research Grant from Spanish Society of Angiology and Vascular Surgery Fundation (2011) • "Cardiva-Vascutek Award" 2011: Best Paper Published in an International Journal in Vascular Tech field from the Spanish Society of Angiology and Vascular Surgery: J Vasc Surg 51: 4. 857-862 • Best Research Work Award, Spanish Society of Vascular Nursery Congress, 2011 for the study "Safety and Efficacy of Music Therapy in intraoperative anxiety control in Saphenectomy intervention: A Controlled Randomized Clinical Trial" • Peer Referee for the Cochrane Peripheral Vascular Diseases Group • Reviewer in the Cochrane Peripheral Vascular Diseases Group • Cirujanos Vasculares de Habla Hispana Society International Research Award (Beven Award), 2011 in the XIII Biannual Congress, Granada • Best Research Study Award, Scientific Sessions of Foundation for Biomedical Research of Getafe University Hospital (4rd edition, 2011) for the study "Anti-endothelial cell antibodies are associated with peripheral arterial disease and markers of endothelial dysfunction and inflammation" • Member of Scientific Committee for "Foundation for Biomedical Research of Getafe University Hospital" Awards
Research Interest • Arterial Gene Therapy for Therapeutic Angiogenesis in Patients with Peripheral Arterial Disease. • Angiogenic Gene Therapy for Reestenosis. • Aortic Aneurysm: Endovascular Stent-grafts. • Angiogenic Cell Therapy in Patients with Peripheral Arterial Disease • Role of Inflammation in Etiology, Diagnosis and Treatment of Peripheral Arterial Disease. • Role of Endothelial Dysfunction in Etiology, Diagnosis and Treatment of Peripheral Arterial Disease. • Antagonist of Receptors of Endotelin-1 in Atherosclerosis Diseases Therapy. • Role of Auto-Inmunity processes in Etiology, Diagnosis and Treatment of Peripheral Arterial Disease.
Abstract: To determine the potential genotype differences in the vascular endothelial growth factor (VEGF) gene in diabetic patients, which might explain the difference in terms of the development of clinical vascular complications: great vessels atherosclerosis vs. retinopathy.
Abstract: OBJECTIVE: Immunohistochemical techniques have revealed the presence of vascular endothelial growth factor (VEGF) in the epidermis of patients with chronic venous disease (CVD). Our objective was to perform a quantitative analysis of the VEGF gene transcription in tissues that are potential sources of this factor (skin, varicose veins [VV] and great saphenous vein [GSV]) in patients with CVD. METHODS: In all, 212 skin and venous tissue samples were collected from patients diagnosed with CVD and controls. The VEGF gene expression was analysed using quantitative realtime polymerase chain reaction (PCR). RESULTS: The skin VEGF expression was lower in the CVD group than in the control group (P = 0.04). There were no significant differences between the insufficient GSV of the CVD group and the control healthy vein (P = 0.22). There was a greater expression of VEGF in the VV of the CVD group than in the control healthy vein (P = 0.03). Comparison of the VEGF expression between the different tissue types in the CVD group revealed significant differences between the skin and GSV (P = 0.02) and between the skin and the VV (P = 0.004), and between the VV and the GSV (P = 0.02). CONCLUSIONS: The results of the present study show an over-expression of VEGF gene in the VV tissue of patients with CVD. Based on the data in patients with C2 disease, the VVs appear to be the source of increased VEGF expression.
Abstract: Objectives. To perform a quantitative analysis of the vascular endothelial growth factor (VEGF) gene transcription in the skin of ischemic legs and provide information for VEGF in the pathogenesis in critical limb ischemia (CLI). Methods. Skin biopsies were obtained from 40 patients with CLI. Control samples came from 44 patients with chronic venous disease. VEGF gene expression was analysed using quantitative polymerase chain reaction. Results. Patients with CLI had higher skin VEGF expression than control group (RQ: 1.3 ± 0.1 versus 1, P=0.04). Conclusions. We found an association between ischemic skin and an elevated VEGF expression in legs from patients with CLI. These data support that the mechanism for VEGF upregulation in hypoxia conditions is intact and acts appropriately in the ischaemic limbs from patients with CLI.
Abstract: Objectives. To perform a quantitative analysis of the vascular endothelial growth factor (VEGF) gene transcription in the skin of ischemic legs and provide information for VEGF in the pathogenesis in critical limb ischemia (CLI). Methods. Skin biopsies were obtained from 40 patients with CLI. Control samples came from 44 patients with chronic venous disease. VEGF gene expression was analysed using quantitative polymerase chain reaction. Results. Patients with CLI had higher skin VEGF expression than control group (RQ: 1.3 ± 0.1 versus 1, P = 0.04). Conclusions. We found an association between ischemic skin and an elevated VEGF expression in legs from patients with CLI. These data support that the mechanism for VEGF upregulation in hypoxia conditions is intact and acts appropriately in the ischaemic limbs from patients with CLI.
Abstract: OBJECTIVE: C-reactive protein (CRP) is an independent risk factor for arteriosclerosis, but its role in abdominal aortic aneurysm (AAA) expansion remains not completely verified. There are no data about the prognostic significance of rates of variation of the CRP levels in asymptomatic AAAs. This study investigated the association between plasma CRP levels and AAA diameter and assessed the relationship between the gradient of CRP levels and rates of expansion in asymptomatic AAAs. METHODS: Plasma levels of high-sensitive CRP (hs-CRP) were measured using a high-sensitivity technique and AAA size was determined by computed tomography in 435 patients with asymptomatic AAAs followed up in our outpatient department. RESULTS: The median hs-CRP level was 4.23 mg/L. The aorta diameter increased in the four groups of patients determined according to hs-CRP quartiles (35 ± 2, 40 ± 3, 49 ± 4, and 58 ± 5 mm; P = .01). The median rate of CRP level variation per year was 1.4 mg/L. Patients with an elevation >1.4 mg/L had an expansion rate of 4.8 mm vs 3.9 mm in those <1.4 mg/L (P < .01). The multivariate age-adjusted logistic model confirmed initial diameter and variation of CRP level were the only factors associated with expansion, with odds ratios (95% confidence intervals) of 6.3 (3.1-7.5) and 3.4 (2.1-5.6). CONCLUSIONS: These results confirm a statistical association between AAA diameter and hs-CRP plasma levels. This cohort study corroborates this potential causal association and contributes information about the value of the hs-CRP plasma level gradient as a marker of disease progression and rate of expansion.
Abstract: Our aim is to describe the effect of circulating anti-endothelial cell antibodies on the endothelial dysfunction, inflammation and early structural changes of the vascular wall that surround peripheral arterial disease. For this purpose, an observational translational controlled study was carried out. We included 32 patients with symptomatic peripheral arterial disease and 16 healthy control individuals with no previous autoimmune disease. We assessed the flow-mediated arterial dilatation as a marker of endothelial function, the carotid intima-media thickness and the plasma levels of C-reactive protein in all the subjects. Circulating anti-endothelial cell antibodies were detected with indirect immunofluorescence. We found a higher prevalence of these autoantibodies in patients than in controls (40% vs. 6%; P=0.01). Flow-mediated arterial dilatation was lower in subjects with anti-endothelial cell antibodies [3.10% (0-5.05%) vs. 12.54% (6.74-18.40%); P<0.01]. Carotid intima-media thickness [1.04 (0.78-1.17) vs. 0.72 (0.54-1.02) mm; P=0.01] and C-reactive protein level [10.00 (3.50-14.80) vs. 3.00 (3.00-6.95) mg/l; P=0.01] were higher in subjects seropositive for these autoantibodies. We concluded that circulating anti-endothelial cell antibodies could be associated with peripheral arterial disease in individuals with no previous autoimmune disease; however, further prospective studies are required to establish a causal relationship.
Abstract: Objectives Peripheral arterial disease can be regarded as a systemic inflammatory disorder affecting the entire vascular system. In the early clinical stages, it is characterised by the deterioration of endothelial function, which does not progress with the development of the disease. This study analyses the pleiotropic effects upon the plasma nitrite and C-reactive protein (CRP) levels in claudicating patients after 12 months of treatment with statins.
Study design A prospective randomised controlled translational study was made in patients with Fontaine grade II ischaemia, treated with the best medical treatment with or without statins for 12 months from the time of diagnosis for assessing the pleiotropic effects of those statins.
Methods Measurements of plasma high-sensitivity CRP (hsCRP), lipid profile and nitrites were made at baseline and after 1 month and 1 year of treatment with atorvastatin 40 mg/day.
Results A significant reduction in nitrite levels was observed after 1 month of treatment (11.8±7.8 μM vs 5.7±1.8 μM, p=0.0001), but this effect did not persist after 1 year (11.8±7.8 μM vs 9.4±8.9 μM, p=0.27). HsCRP underwent a significant reduction after both 1 month (7 (2.2â12) vs 3.4 (1.6â5.5), p<0.01) and 1 year of treatment with atorvastatin (7 (2.2â12) vs 2.25 (1.67â6.7), p=0.02). Statin treatment reduced hsCRP levels in 9.64 (95% CI (1.60 to 17.68)) after 1 month and in 9.14 (95% CI (0.18 to 18.47)) after 1 year.
Conclusions The long-term biological pleiotropic effects of statins provide information on the role of endothelial function and systemic inflammation in the aetiopathogenesis of peripheral arterial disease. Statins slow endothelial degradation at the start of the disease, with no effects over the long term. These drug substances reduce progressive inflammation throughout the treatment period. This supports the novel hypothesis that endothelial dysfunction is only a disease-triggering phenomenon, while systemic inflammation would be responsible for both the origin and the maintenance of peripheral arterial disease.
Abstract: Flow-mediated dilation of the brachial artery (FMDB) indirectly reflects the action of nitric oxide liberated by the endothelium. In patients with abdominal aortic aneurysms (AAA), the changes in nitric oxide metabolism in close association with inflammation, appear to play a leading role in the aetiopathology of this disease, although it is still not clear. The objective was to study the correlation and behavior of FMDB relative to the aneurysm diameter (AD). To evaluate the relationship between C-reactive protein (CRP) and the FMDB in these patients. To study the correlation and behavior of FMDB relative to the aneurysm diameter (AD). To evaluate the relationship between C-reactive protein (CRP) and the FMDB in these patients.
Abstract: The study tested the feasibility of using a new portable mechanical compression device for the treatment of claudication. The device applies intermittent non-pneumatic mechanical compression (IMC) to the calf. It was hypothesized that it can offer a low-cost convenient option for patients and achieve good compliance and improved clinical outcomes.
Abstract: Endothelial dysfunction and inflammation are understood to contribute to the onset of peripheral arterial disease (PAD), and endothelin (ET) may play an important role in this process. This study investigated the role of ET in PAD, and its relationships with symptoms, endothelial dysfunction and inflammation.
Abstract: A 78-year-old woman with long-standing bilateral knee osteoarthritis underwent a right total knee arthroplasty(TKA). She had previous history of hypertension and breast cancer. There were no complications during the operation and the pedal pulse was present after TKA. On the fifth day after TKA, the examination revealed pain in the right calf that increased when she walked, swelling and oedema in the popliteal fossa, local haematoma and a pulsatile mass. All extremity pulses were palpable.
The duplex showed a 3 cm hypoechoic mass in the popliteal fossa with Doppler flow consistent with a popliteal artery pseudoaneurysm and no signs of arteriovenous fistula. A limb arteriogram (figures 1â4) confirmed a pseudoaneurysm arising from the third portion of the popliteal artery just below the tibial prosthesis.
The pseudoaneurysm was urgently excised, open-surgically repaired with direct suture of the bleeding point and the haematoma drained. Surprisingly, a well-shaped circular hole was identified only on the posterior wall of the artery. Distal pulses were present at the end of the vascular surgery.
The patient had no further complications. The postoperative duplex showed no evidence of residual pseudoaneurysm and after 48 h the patient was walking without difficulty.
This case illustrates an arterial complication after TKA, which is infrequent (incidence ranges from 0.03â0.5%).1
It is very important to perform a prompt diagnosis and treatment to avoid serious complications like limb loss.2
Treatment includes conservative management, open-surgical repair, and embolisation or endovascular stenting. The latter is the less desirable treatment because it is associated with a high rate of early occlusion.3
Abstract: Analyze the influence of the collateral distal vessels on ischemic ulcer healing and limb salvage after successful distal procedures, according to an angiosome model.
Abstract: Buerger disease (thromboangiitis obliterans) is a non-atherosclerotic segmental inflammatory disease strongly associated with tobacco use, and it affects small and medium-sized blood vessels in the upper and lower extremities. The only known treatment for this disease is complete discontinuation of tobacco use. This report describes the case history of a woman with Buerger disease treated with the oral dual endothelin receptor antagonist bosentan. It is believed that this is the first description in the literature of this use for bosentan.
Abstract: To determine whether the increase in plasma levels of C-Reactive Protein (CRP), a non-specific reactant in the acute-phase of systemic inflammation, is associated with clinical severity of peripheral arterial disease (PAD).
Abstract: OBJECTIVES: Inflammatory and other processes mediating impairment of endothelial function, where there are increased levels of C-reactive protein (CRP) and plasma nitrites, have a part to play in the early stages of peripheral arterial disease (PAD). Our objective was to analyse the effect of statins on the plasma nitrite and CRP levels in PAD. MATERIAL AND METHODS: A prospective study of 30 patients with PAD Fontaine stage II, with no prior treatment with statins, determined high sensitivity (hs)-CRP and lipid profile in the patients. Plasma nitrite levels were determined by colorimetric assay based on the Griess reaction, at baseline and after 1 month of treatment with atorvastatin 40 mg day(-1). RESULTS: A significant reduction in plasma nitrite levels was detected after the treatment with statins (11.88+/-7.8 microM vs. 5.7+/-1.8 microM, p=0.0001). There was also a significant reduction in hs-CRP levels (13.58+/-24.00 vs. 3.93+/-3.19, p=0.02). When the patients were stratified according to claudication stage, a significant reduction in nitrite levels was obtained, both in patients with PAD Fontaine stage IIA (9.5+/-3.3 microM vs. 5.3+/-1.7 microM, p=0.0001) and in stage IIB (16.6+/-11.6 microM vs. 6.7+/-1.8 microM, p=0.032). CONCLUSIONS: Treatment with statins lowers plasma nitrite and CRP levels in patients with PAD. Our data support the effects of statins in vivo that have been demonstrated on the endothelium ex vivo, suggesting a beneficial effect by acting on the initial processes that trigger the disease, reducing oxidative stress (increase in the bioavailability of nitric oxide as peroxynitrite levels decrease) and curtailing the inflammatory processes which perpetuate the disease.
Abstract: To analyse the role of nitric oxide (NO) in peripheral arterial disease (PAD) and its association with inflammation and brachial artery flow-mediated dilation (BAFMD) as an estimation of endothelial dysfunction.
Abstract: 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.
Abstract: Buerger disease (thromboangiitis obliterans) is a non-atherosclerotic segmental inflammatory disease strongly associated with tobacco use, and it affects small and medium-sized blood vessels in the upper and lower extremities. The only known treatment for this disease is complete discontinuation of tobacco use. This report describes the case history of a woman with Buerger disease treated with the oral dual endothelin receptor antagonist bosentan. It is believed that this is the first description in the literature of this use for bosentan.
Notes: Novel treatment (new drug/intervention; established drug/procedure in new situation)
Abstract: Both endothelial dysfunction and a proinflammatory state are present during the early stages of atherosclerosis. In this context, increased expression of cyclooxygenase-2 (COX-2) results in higher levels of vasoconstrictive and proinflammatory substances. The aim of this study was to investigate the influence of COX-2 activity on endothelial dysfunction associated with peripheral arterial disease (PAD).
Abstract: Objectives: To determine the relationship between endothelial function by means of brachial artery flow-mediated dilation (BAFMD) and the clinical severity of peripheral arterial disease (PAD).Methods and Results: We examined the brachial artery diameter by ultrasound, before and after ischemia of the arm in 3 groups of participants-group A: healthy individuals under 30 years, without cardiovascular risk factors (n = 30); group B: patients with PAD and ischemic claudication (n = 30); and group C: patients with critical leg ischemia (n = 20). There were no differences between groups B and C, in regard to age, sex, and main cardiovascular risk factor. The BAFMD was 9.9% in group A compared with 5.5% in the pooled patients group (B + C; P<.001). Significant differences were absent between groups B and C (P > .05). Correlation coefficient of ankle-brachial index/BAFMD was r = .1; P = .49.Conclusions: Patients with PAD present endothelial dysfunction, but this does not seem to determine the severity of the disease.
Abstract: OBJECTIVES: To evaluate the relationship between C-Reactive Protein (hsCRP), a serum marker of inflammation, and endothelial dysfunction in patients with intermittent claudication. DESIGN, PATIENTS AND METHODS: Cross-sectional study with stratified sampling on dependent variables of age, genre, hypertension, hyperlipidemia, diabetes, smoking status and ankle-brachial index (ABI) to select 156 patients from a target population of 4,100 patients with claudication. We assessed the flow-mediated arterial dilation (FMAD) as a reporter of endothelial function and plasma levels of hsCRP and fibrinogen. RESULTS: Patients with a FMAD<3% (range for the lowest 5% of healthy subjects) had increased levels of plasma hsCRP (6.3 vs 2.3mg/L; p<0.05) and fibrinogen (351vs 302mg/L; p<0.05) in comparison to those with FMAD>3%. There was a negative correlation between hsCRP and FMAD(r=-0.465; p<0.05). CONCLUSION: 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.
Abstract: We performed a systematic review of the literature on the diagnosis and treatment of secondary aortoenteric fistulas (AEF). A MEDLINE search was performed of articles published in English or Spanish between January 1991 and August 2006. Diagnostic methods, treatment modalities and the results of surgical treatment were analyzed. The most frequent first aortic surgery associated with AEF was repair of abdominal aortic aneurysm (54.31%). The most common form of presentation was gastrointestinal bleeding. Repair through in situ prosthetic replacement had the lowest early mortality rates (8-13.3%) compared with graft excision and extraanatomic revascularization (18.2-44%). AEF is a serious entity and diagnosis requires a high index of suspicion based on clinical findings and indirect data from imaging techniques (computed tomography). The most appropriate therapeutic option continues to be controversial.
