Awareness of smoking cessation amongst German vascular surgeons.

Background: Smoking represents the well-known enemy of vascular well-being. Numerous previous studies emphasised the important role of smoking on the development and progression of atherosclerotic cardiovascular disease. The current study aimed to identify hurdles and barriers for an insufficient implementation of secondary prevention in the treatment of lower extremity peripheral arterial disease (PAD). Methods: All members of the German Society for Vascular Surgery and Vascular Medicine (DGG) with valid email addresses were invited to participate in an electronic survey on smoking. Results are descriptively presented. Results: Amongst 2716 invited participants, 327 (12%) submitted complete responses, thereof 33% women and 80% between 30 and 59 years old (87% board certified specialists). 83% were employed by hospitals (56% teaching hospital, 14% university, 13% non-academic) and 16% by outpatient facilities. 6% are active smokers (63% never) while a mean of five medical education activities on smoking cessation were completed during the past five years of practice. Only 27% of the institutions offered smoking cessation programs and 28% of the respondents were aware of local programs while a mean of 46% of their patients were deemed eligible for participation. 63% of the respondents deemed outpatient physicians primarily responsible for smoking cessation, followed by medical insurance (26%). Conclusions: The current nationwide survey of one scientific medical society involved in the care of patients with vascular disease revealed that smoking cessation, although being commonly accepted as important pillar of comprehensive holistic care, is not sufficiently implemented in everyday clinical practice.

Sex disparities in popliteal artery aneurysms.

OBJECTIVE: Only 5% of patients with popliteal artery aneurysms (PAAs) are female. Evidence on PAA treatment and outcomes in women is therefore scarce. The POPART Registry provides one of Europe's largest data collections regarding PAA treatment. Data on clinical presentation, aneurysm morphology, and perioperative outcomes after open surgical PAA repair in women will be presented. METHODS: POPART is a multicenter, noninterventional registry for open and endovascular PAA repair, with 42 participating centers in Germany and Luxembourg. All patients aged >18 years who have been treated for PAA since 2010 are eligible for study inclusion. Data collection is based on an online electronic case report form. RESULTS: Of the 1236 PAAs, 58 (4.8%) were in women. There were no significant differences in age or cardiopulmonary comorbidities. However, female patients had a lower prevalence of contralateral PAAs and abdominal aortic aneurysms (P < .05). PAAs in women were more likely to be symptomatic before surgery (65.5% vs 49.4%; P = .017), with 19% of women presenting with acute limb ischemia (vs 11%; P = .067). Women had smaller aneurysm diameters than men (22.5 mm vs 27 mm; P = .004) and became symptomatic at smaller diameters (20 mm vs 26 mm; P = .002). Only 8.6% of women and 11.6% of men underwent endovascular aneurysm repair (P > .05); therefore, the perioperative outcome analysis focused on open surgical repair. In total, 23.5% of women and 16.9% of men developed perioperative complications (P > .05). There were no differences in major cardiovascular events (P > .05), but women showed a higher incidence of impaired wound healing (15.7% vs 7.2%; P = .05) and major amputation (5.9% vs 1.1%; P = .027). Female sex was significantly associated with the need for nonvascular reinterventions within 30 days after surgery (odds ratio: 2.48, 95% confidence interval: 1.26-4.88), whereas no significant differences in the odds for vascular reinterventions were observed (odds ratio: 1.98, 95% confidence interval: 0.68-5.77). In the multiple logistic regression model, female sex, symptomatic PAAs, poor quality of outflow vessels, and graft material other than vein graft were independently associated with perioperative reinterventions. CONCLUSIONS: Women have smaller PAAs, are more likely to be symptomatic before treatment, and are more often affected by nonvascular reinterventions in the perioperative course. As our understanding of aneurysmatic diseases in women continues to expand, sex-specific treatment strategies and screening options for women in well-selected cohorts with modified screening protocols should be continuously re-evaluated.

Cold Plasma Therapy in Chronic Wounds-A Multicenter, Randomized Controlled Clinical Trial (Plasma on Chronic Wounds for Epidermal Regeneration Study): Preliminary Results.

Chronic wounds (CWs) pose a significant health challenge in clinical practice. Standard wound therapy (SWT) is currently considered the gold standard. However, recent evidence suggests that cold plasma therapy (CPT) holds promise for improving CWs. In light of this, the POWER study was conducted as a multicenter, randomized clinical trial to investigate the effect of large-area plasma application compared with SWT in patients with chronic, non-healing arterial or venous wounds on the lower leg. To analyze the interim results, we employed a comprehensive range of statistical tests, including both parametric and non-parametric methods, as well as GLS model regression and an ordinal mixed model. Our findings clearly demonstrate that CPT therapy significantly accelerates wound closure compared with SWT. In fact, complete wound closure was exclusively observed in the CPT group during the intervention period. Additionally, the CPT group required significantly less antibiotic therapy (4%) compared with the SWT group (23%). Furthermore, CPT led to a significant reduction in wound pain and improved quality of life compared with SWT. In conclusion, the study highlights that the combination of CPT and SWT surpasses monotherapy with SWT alone.

Negative pressure wound therapy compared with standard moist wound care on diabetic foot ulcers in real-life clinical practice: results of the German DiaFu-RCT.

OBJECTIVES: The aim of the DiaFu study was to evaluate effectiveness and safety of negative pressure wound therapy (NPWT) in patients with diabetic foot wounds in clinical practice. DESIGN: In this controlled clinical superiority trial with blinded outcome assessment patients were randomised in a 1:1 ratio stratified by study site and ulcer severity grade using a web-based-tool. SETTING: This German national study was conducted in 40 surgical and internal medicine inpatient and outpatient facilities specialised in diabetes foot care. PARTICIPANTS: 368 patients were randomised and 345 participants were included in the modified intention-to-treat (ITT) population. Adult patients suffering from a diabetic foot ulcer at least for 4 weeks and without contraindication for NPWT were allowed to be included. INTERVENTIONS: NPWT was compared with standard moist wound care (SMWC) according to local standards and guidelines. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was wound closure within 16 weeks. Secondary outcomes were wound-related and treatment-related adverse events (AEs), amputations, time until optimal wound bed preparation, wound size and wound tissue composition, pain and quality of life (QoL) within 16 weeks, and recurrences and wound closure within 6 months. RESULTS: In the ITT population, neither the wound closure rate (difference: n=4 (2.5% (95% CI-4.7% - 9.7%); p=0.53)) nor the time to wound closure (p=0.244) was significantly different between the treatment arms. 191 participants (NPWT 127; SMWC 64) had missing endpoint documentations, premature therapy ends or unauthorised treatment changes. 96 participants in the NPWT arm and 72 participants in the SMWC arm had at least one AE (p=0.007), but only 16 AEs were related to NPWT. CONCLUSIONS: NPWT was not superior to SMWC in diabetic foot wounds in German clinical practice. Overall, wound closure rate was low. Documentation deficits and deviations from treatment guidelines negatively impacted the outcome wound closure. TRIAL REGISTRATION NUMBERS: NCT01480362 and DRKS00003347.

Diagnosis, Treatment and Follow-up in Extracranial Carotid Stenosis.

BACKGROUND: Around 15% of cerebral ischemias are caused by lesions of the extracranial carotid artery. The goal of this guideline is to provide evidence- and consensus-based recommendations for the management of patients with extracranial carotid stenoses throughout Germany and Austria. METHODS: A systematic literature search (1990-2019) and methodical assessment of existing guidelines and systematic reviews; consensus-based answers to 37 key questions with evidence-based recommendations. RESULTS: The prevalence of extracranial carotid artery stenoses is around 4% overall, higher from the age of 65 years. The most important examination modality is duplex sonography. Randomized trials have shown that carotid endarterectomy (CEA) significantly reduces the 5-year risk of stroke in patients with 60-99 % asymptomatic stenoses (absolute risk reduction [ARR] 4.1% over 5 years, number needed to treat [NNT] 24) or 50-99% symptomatic stenoses (50-69%: ARR 4.6 % over 5 years, NNT 22; 70-99%: 15.9 % over 5 years, NNT 6). With the aid of intensive conservative treatment, the carotid artery-associated risk of stroke can be reduced to as little as 1% per year. Critical determination of indications and strict quality criteria are therefore necessary for CEA and carotid artery stenting (CAS). Systematic reviews of controlled trials comparing CEA and CAS show that the procedural risk of stroke is higher for CAS (asymptomatic: 2.6% versus 1.3%; symptomatic: 6.2% versus 3.8%). There are no differences in the long term. CEA is recommended as standard procedure for high-grade asymptomatic and moderate to high-grade symptomatic carotid artery stenoses; CAS may be considered as an alternative. For both procedures, the periprocedural combined rate of stroke or death should not exceed 2% for asymptomatic stenoses or 4% for symptomatic stenoses. CONCLUSION: Future studies should evaluate even better selection criteria for optimal individualized treatment, whether conservative, surgical, or endovascular.

[Anti-Thrombotic Therapy of Peripheral Arterial Disease - A Review of Current Evidence, Practice and Outlook]. / Antithrombotische Therapie der peripheren arteriellen Verschlusskrankheit ­ ein Überblick über aktuelle Evidenz, Praxis und Ausblick.

Peripheral arterial occlusive disease is a frequent and chronic vascular disorder mostly affecting the lower limbs and caused by fibrous plaques in arteries that can result in stenoses and thrombi. Patients suffering from this condition show a high risk for cardiovascular complications of the complete arterial vascular system, especially post-procedural. Thus, there is a need to optimize anti-thrombotic therapy. Data on multiple antiplatelet aggregation therapy including new drug classes are expected in the coming years. In addition, recent studies showed that direct oral anticoagulation provided clinical advantages combined with a reasonable safety profile. Management of risk factors such as overweight and nicotine and correction of metabolic disorders are not to be ignored and the background to further therapy. All treating physicians should be aware of these aspects to guarantee an optimal care and motivation of their patients.

Different perioperative antiplatelet therapies for patients treated with carotid endarterectomy in routine practice.

OBJECTIVE: There is currently no clear consensus regarding the optimal perioperative antiplatelet therapy regimen for carotid surgery. Therefore, associations between different antiplatelet therapies and the risk of stroke or death and perioperative complications after carotid endarterectomy on a national level in Germany were analyzed. METHODS: Overall, 117,973 elective carotid endarterectomies for asymptomatic or symptomatic carotid artery stenosis between 2010 and 2014 were included. Data were extracted from the statutory nationwide quality assurance database. The primary outcome was any in-hospital stroke or death until discharge from the hospital. Secondary outcomes were any major stroke or death, death alone, stroke, myocardial infarction, local bleeding, and any local complications (cranial nerve palsy, severe bleeding, acute occlusion). Descriptive statistics and multilevel multivariable regression analyses were applied. Single-agent therapy with aspirin was used as reference. RESULTS: Patients were predominantly male (68%), with a mean age of 71 years. Carotid stenosis was symptomatic in 40%. Of all patients, 82.8% were treated perioperatively by monotherapy with aspirin alone, 2.7% received other platelet inhibitors, and 4.8% of the patients were operated on under dual antiplatelet therapy. The primary outcome occurred in 1.8% of all patients. Multilevel multivariable regression analysis revealed that the combined stroke and death rate of patients with no perioperative antiplatelet therapy was significantly higher (risk ratio [RR], 1.21; 95% confidence interval [CI], 1.04-1.42) compared with the group of patients receiving monotherapy. The same was true for the major stroke and death rate (RR, 1.23; 95% CI, 1.02-1.48). In contrast, dual antiplatelet therapy was associated with a lower risk of death alone (RR, 0.67; 95% CI, 0.51-0.88) but with a significantly higher rate of secondary bleeding requiring reoperation (RR, 2.16; 95% CI, 1.88-2.50). CONCLUSIONS: This study shows that the risk of stroke or death was significantly higher in patients without any perioperative antiplatelet therapy. In contrast, dual antiplatelet therapy vs aspirin monotherapy was associated with a lower risk only of perioperative death but with a higher risk of neck bleeding until discharge. Perioperative antiplatelet therapy was significantly associated with a decreased in-hospital stroke and death risk. Further studies are needed to evaluate the risk-benefit ratio of single vs dual antiplatelet therapy.

[Indications and contraindications for modern compression therapy]. / Indikationen und Kontraindikationen der modernen Kompressionstherapie.

Compression therapy is a physical therapy with few side effects, which is used especially in patients with edema of the lower extremities. The indication for compression therapy is given here for edema of very different origins such as, for example, venous or lymphatic disease symptoms as well as renal insufficiency, obesity or inflammation. However, different contraindications must be considered in these patients. Of particular importance are the advanced peripheral arterial occlusive disease and the polyneuropathy, which need special attention.Due to the large number of different compression materials and systems available today, in spite of these contraindications, compression therapy can be carried out with a large proportion of patients with edema of the lower extremities. The therapy should be adapted to the comorbidities and individual needs as well as personal abilities in the context of a patient-oriented care.

Treatment of blunt thoracic aortic injury in Germany-Assessment of the TraumaRegister DGU®.

PURPOSE: Using the data delivered by the German Trauma Register DGU® from 2002 till 2013, the value of different therapies of blunt thoracic aortic injury (BTAI) in Germany was analyzed. METHODS: Prospectively collected data of patients suffering from BTAI were retrospectively analyzed with focus on the different treatment modalities for grade I-IV injuries. RESULTS: 821 patients suffering from BTAI were identified: 51.6% (424) grade I injury, 35.4% (291) grade II or III injury and 12.9% (106) grade IV injury (77.5% men [44.94 ± 20.6 years]). The main patterns of injury were high- speed accidents and falls (78.0% [n = 640], 21.8% [n = 171] respectively). Significant differences between grade I and grade II/III as well as IV injuries could be assessed for the incidence of cardiopulmonary resuscitation, a Glasgow Coma Scale score below 8 and a systolic blood pressure below 90 mmHg (p-value: <0.001). In the primary admission subgroup, 44.1% (197/447) of the patients received best medical treatment, 55.9% received surgical intervention (250/447): Thereof 37.2% (93/250) received open surgery and 62.8% (147/250) had been treated by endovascular means. Significantly lower 24-h- and in-hospital-mortality rates were encountered after endovascular treatment for all gradings of BTAI (p-value: <0.001). Yet this subgroup of patients showed the lowest incidence of further severe injuries and cardiac arrest. CONCLUSION: Endovascular therapy became the treatment of choice for BTAI in Germany. Patients who have been treated by surgical means showed the highest survival rate, especially endovascular therapy showed a favorable low mortality rate.

Women and men derive comparable benefits from an ultra-low-profile endograft: 1-year results of the European OVATION registry.

BACKGROUND: Female patients are underrepresented in most stent-graft (EVAR) trials due to a reduced anatomical eligibility for endovascular treatment. The purpose of this analysis was to determine the performance of the Ovation® and Ovation Prime® stent graft in women versus men for elective abdominal aortic aneurysm (AAA) repair. METHODS: From May 2011 to December 2013, 501 patients (86% men, mean age 73 years) from 30 sites were prospectively enrolled in the OVATION Registry and electively treated with endovascular aneurysm repair. Patients returned for clinical and imaging follow-up at 1 month, 6 months, and 1 year. A post-hoc analysis was performed to assess the influence of gender on patient outcomes. RESULTS: Women were older (median 77 vs. 73 years, P<0.01) although men reported a higher frequency of ASA class III/IV (54% vs. 34%), coronary artery disease (43% vs. 29%), diabetes mellitus (19% vs. 7%), and history of tobacco use (50% vs. 33%). Median external iliac diameter was 6.4 mm in women and 7.5 mm in men (P<0.001). Proximal neck diameter was larger in men versus women (24 vs. 22 mm). Technical success was 100% in women and 99.5% in men. Type I endoleak was identified in 5 men (1.5%) and a type III leak was identified in 1 (0.3%) man. No woman presented with type I or III endoleak at 1 year. The rate of AAA enlargement was similar in women (2.5%) and men (2.7%). Freedom from aneurysm-related mortality through 1 year was 100% in women and 99.3% in men (log-rank P=0.49). Freedom from all-cause mortality through 1 year was 94.0% in women and 95.8% in men (log-rank P=0.51). One contained AAA rupture was reported in a male patient. One female patient underwent conversion to open surgery. Freedom from a secondary intervention through 1 year was 88.2% in women and 93.7% in men (log-rank P=0.11). CONCLUSIONS: Women and men derive similarly favorable benefits with the Ovation stent graft through 1-year follow-up. Longer-term follow-up will be required to determine the durability of these outcomes.

Short Time Interval Between Neurologic Event and Carotid Surgery Is Not Associated With an Increased Procedural Risk.

BACKGROUND AND PURPOSE: Guidelines recommend that carotid endarterectomy should be performed within 2 weeks in patients with a symptomatic carotid stenosis. Because a Swedish register study indicated that patients treated within the first days after a stroke or transient ischemic attack might have an increased perioperative stroke and mortality risk, this study aimed to find out whether these findings are also true under everyday conditions in Germany. METHODS: Secondary data analysis including 56 336 elective carotid endarterectomy procedures performed for symptomatic carotid stenosis under everyday conditions between 2009 and 2014. The patient cohort was divided into 4 groups according to time interval between index event and surgery (I: 0-2, II: 3-7, III: 8-14, and IV: 14-180 days). Primary outcome was any in-hospital stroke or death. For risk-adjusted analyses, a multilevel multivariable regression model was used. RESULTS: Mean patients' age was 71.1±9.6 years; 67.5% were men. Overall rate of any stroke or death was 2.5% (n=1434). Risk of any in-hospital stroke or death was 3.0% in group I, 2.5% in group II, 2.6% in group III, and 2.3% in group IV. Multivariable regression analysis revealed that the time interval was not significantly associated with the primary outcome. CONCLUSIONS: The time interval between the index event and carotid endarterectomy was not associated with the risk of any in-hospital stroke or death in patients with symptomatic carotid stenosis in Germany. In clinically stable patients, carotid endarterectomy might, therefore, be performed safely as soon as possible after the neurological index event.

The ovation abdominal stent graft for the treatment of abdominal aortic aneurysms: current evidence and future perspectives.

The Ovation Abdominal Stent Graft System is a trimodular endoprosthesis recently introduced for the endovascular repair of abdominal aortic aneurysm (AAA). It uncouples the stages of stent-graft fixation and sealing with the suprarenal fixation achieved with a long, rigid anchored stent while the sealing onto the neck is accomplished via a pair of polymer-filled inflatable rings that accommodate to each patient's individual anatomy. Moreover, the lack of Nitinol support enables lower profiles of the endograft's delivery system, thus facilitating the navigation through angulated and stenosed iliac vessels. Ovation's novel design expands further the AAA eligibility to endovascular repair. This article discusses the clinical and hemodynamic consequences of the Ovation design and contributes to better understanding of current and future implications.

Negative pressure wound therapy versus standard wound care in chronic diabetic foot wounds: study protocol for a randomized controlled trial.

BACKGROUND: In August 2010, the Federal Joint Committee (G-BA) decided that negative pressure wound therapy (NPWT) would not be reimbursable in German ambulatory care. This decision was based on reports from the Institute for Quality and Efficiency in Health Care (IQWiG), which concluded that there is no convincing evidence in favor of NPWT. The aim of this diabetic foot study (DiaFu study) is to evaluate whether the clinical, safety and economic results of NPWT are superior to the results of standard wound treatment. METHODS/DESIGN: The DiaFu study is designed as a national, multicenter, randomized controlled clinical superiority trial with a special focus on outpatient care in Germany. Competent patients in inpatient and outpatient care suffering from a chronic diabetic foot wound for a minimum of four weeks may be included in the study. The trial evaluates the treatment outcome of the application of a technical medical device which is based on the principle of NPWT (intervention group) in comparison to standard moist wound therapy (control group). All treatment systems used in the intervention group bear the symbol of free trade capacity in the European Union (CE mark) and will be operated within normal conditions of clinical routine and according to manufacturer's instructions. Primary endpoints are the time to complete wound healing and the rate of wound healing achieved in each group within the maximum study treatment time of 16 weeks. Primary endpoints will be confirmed by blinded assessment of wound photographs. DISCUSSION: The DiaFu study will provide solid evidence regarding the efficacy and effectiveness of NPWT until 31 December 2014, the date when G-BA plans to decide on future reimbursement of NPWT in both ambulatory and in-hospital care. The study is designed to comply with all quality requirements of G-BA and IQWiG and will contribute to evidence-based wound care in Germany. The study has been initiated by the statutory health insurance companies in Germany and is co-funded by two manufacturers of NPWT systems. TRIAL REGISTRATION: Clinical Trials.gov registration number: NCT01480362 (date of registration: 23 November 2011).German Clinical Trials Register number: DRKS00003347 (date of registration: 22 November 2011).

Results from the first in man german pilot study of the silver graft, a vascular graft impregnated with metallic silver.

The purpose of this study was to assess the safety of a novel vascular prosthesis in 50 patients who underwent inguinal and infrainguinal vascular reconstructions. The safety data were based on ultrasound Doppler data at 2 and 18 months to quantify the graft-tissue integration in this patient cohort. Between August 9, 2005, and January 25, 2006, 50 patients underwent inguinal or infrainguinal reconstructions with the Silver Graft (SG; B. Braun Melsungen AG, B. Braun Aesculap AG, Tuttlingen, Germany) in six vascular centers. All participating centers received the metallic silver-coated polyester graft (SG) with a diameter of 8 mm and a total length of 60 cm, which was length adjusted to fit the patient's anatomy and the planned vascular reconstruction. The mean patient age was 69.1 +/- 9.0 years, the male inclusion rate was 72.0%, and the Fontaine classifications were stage IV (16%), stage III (14%), stage IIb (66%), and stage IIa (4%), whereas aneurysm repairs amounted to 4%. In-hospital results revealed the presence of minimal perigraft fluid in 14.0% of all cases (7 of 50). At the 2-month follow-up, perigraft fluid was detected in one patient (1 of 50). At 18 months, a single case of minimal perigraft fluid was detected in an asymptomatic patient. Wound healing was accomplished at discharge in 96% of all patients, whereas at the 2-month follow-up, no signs of wound infection or irritation could be detected. The accumulated primary patency rates were 94% at 2 months and 88% at 18 months. The available clinical data on perigraft fluid as a marker for graft-tissue incorporation at 2 and 18 months, patency, and wound healing are comparable to those of other relevant clinical results with polyester grafts and support the safety of the metallic SG in the studied patient population with inguinal and infrainguinal reconstructions. However, it cannot be guaranteed that all graft infections can be avoided with the SGs.

Midterm results of a precuffed expanded polytetrafluoroethylene graft for above knee femoropopliteal bypass in a multicenter study.

INTRODUCTION: Above knee (AK) femoropopliteal bypass remains a sufficient and durable therapy for long occlusions of the superficial femoral artery in the era of endovascular repair. A novel, precuffed expanded polytetrafluoroethylene (ePTFE) graft that was designed for AK femoropopliteal bypass (Dynaflo, Bard Peripheral Vascular Inc, Tempe, Ariz) has been available for clinical use since March 2005, promising better patency rates by optimizing the hemodynamic patterns within the distal anastomosis. METHODS: A prospective, multicenter, nonrandomized study was performed to investigate the clinical results of the Dynaflo graft. Primary end points were patency rates, limb salvage, and complications. RESULTS: Between March 2005 and August 2007, the Dynaflo graft was used in 135 AK bypasses in 134 patients (110 men) with a mean age of 66 years. Indication for revascularization was claudication in 99 (73%) and critical ischemia in 36 (27%). With a mean follow-up of 18 months the 6-, 12- and 24-month primary patency rates were 90%, 83% and 72.5% and the secondary patency rates were 93%, 88.6% and 82.2%, respectively. The cumulative limb salvage rate at 24 months was 95%. Complications were observed in 39 patients (29%), with bypass failure (29 cases) and significant thrombus accumulation at the distal anastomosis (4 cases) being the most severe. CONCLUSION: This study presents the first clinical results of a novel ePTFE graft for supragenicular revascularization. The implantation of the Dynaflo graft seems to be safe and feasible for AK bypass, achieving acceptable medium-term patency rates. Nevertheless, long-term results have to be awaited, and prospective comparative studies are warranted.

Leptin inhibits cell growth of human vascular smooth muscle cells.

Elevated leptin levels are thought to contribute to the individual cardiovascular risk, however, the role of leptin in the pathogenesis of atherosclerosis remains unclear. The aim of our study was to elucidate the effects of leptin on growth of human vascular smooth muscle cells (VSMC) and leptin receptor expression. By establishing a new quantitative real-time PCR for leptin receptor (ObR) isoforms we showed that the short isoforms of ObR were expressed in a 10- to 27-fold excess compared to the long isoform in cultured human VSMCs. Incubation of VSMCs with 100 ng/ml leptin downregulated the short isoforms significantly, whereas the long isoform was not influenced. Increasing leptin concentrations of 50 and 100 ng/ml significantly reduced the cell number of VSMCs compared to untreated controls. Our findings suggest a role for leptin in vascular smooth muscle cell growth, associated to a downregulation of leptin receptor isoforms.