In clinical practice, biological markers are not available to routinely assess the progression of atherosclerotic disease or the development of restenosis following endarterectomy or catheter based interventions. Endarterectomy procedures provide an opportunity to study mechanisms of restenosis and progression of atherosclerotic disease since atherosclerotic tissue is obtained. Athero-Express is an ongoing prospective study, initiated in 2002, with the objective to investigate the etiological value of plaque characteristics for long term outcome. Patients are included who undergo an endarterectomy of the carotid artery. At baseline blood is withdrawn, patients fill in an extensive questionnaire and diagnostic examinations are performed. Atherosclerotic plaques are freshly harvested, immunohistochemically stained and examined for the presence of macrophages, smooth muscle cells, collagen and fat. Parts of the atherosclerotic plaques are freshly frozen to study protease activity and protein and RNA expressions. Patients undergo a duplex follow up to assess procedural restenosis (primary endpoint) at 3 months, 1 year and 2 years. Secondary endpoints encompass major adverse cardiovascular events. In the future, the creation of this biobank with atherosclerotic specimen will allow the design of cross-sectional and follow up studies with the objective to investigate the expression of newly discovered genes and proteins and their interaction with patients and plaque characteristics in the progression of atherosclerotic disease. Objective is to include 1000-1200 patients in 5 years. In January 2004, 289 patients had been included. It is expected that 250 patients will be included yearly.

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 × 10−10. In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 × 10−5), peripheral arterial disease (OR = 1.14, P = 3.9 × 10−5) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases—that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

Summary Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0.83, 95% CI 0.63–1.09; p=0.18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1.91, 1.06–3.44; p=0.0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0.82; appendix); these events included pulmonary embolism (two patients [<1%] vs four [1%] patients; p=0.41) and sepsis (seven [1%] vs six [1%]; p=0.79). Interpretation In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. Funding National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians’ Services Incorporated.

MOCA is associated with significantly less postoperative pain, faster recovery, and earlier work resumption compared with RFA in the treatment of GSV incompetence. MOCA and RFA are both related to a rapid improvement in quality of life.

This study showed that endovenous MOCA, using polidocanol, is feasible and safe in the treatment of GSV incompetence. Larger studies with a prolonged follow-up are indicated to prove the efficacy of this technique in terms of obliteration rates.

Objective-Rupture of unstable atherosclerotic plaques is the pathological substrate for acute ischemic events. Underlying cellular and molecular characteristics of plaque rupture have been studied extensively. However, the natural course of symptomatic plaque remodeling after ischemic events is relatively unexplored. Methods and Results-Atherosclerotic carotid plaques were obtained from 804 symptomatic (strokeϭ204 and TIAϭ426) and asymptomatic (nϭ174) patients undergoing carotid endarterectomy. See accompanying article on page 3but it has been suggested that progression of atherosclerosis is a summation of sequential repetitive events resulting in plaque stabilization and plaque destabilization. Most research on plaque progression has been focused on the cellular and molecular structure of the plaque that may precede local rupture. 2,4 -6 The alterations in plaque phenotype after a clinical event are relatively unexplored. To identify the natural history of plaque remodeling after a thrombotic event, we examined the structure of carotid endarterectomy specimen at histological and protein level in relation to the time elapsed between the most recent cerebrovascular event and surgery. For this purpose we used plaque samples and medical data from the multi center study "Athero-Express," including symptomatic and asymptomatic patients who had undergone carotid endarterectomy. Besides histological characteristics we assessed mediators that have been associated with the unstable plaque like cytokines, matrix metalloproteinases (MMP) and an apoptosis marker in 804 protein samples. [7][8][9][10] The search for therapeutic options to prevent plaque destabilization is hampered by the lack of surrogate markers of disease progression. Therapeutic and diagnostic molecular targets often require validation of expression levels in human atherosclerotic plaques. In this study we assessed to what extent the outcome of validation studies may be influenced by the time that elapsed between the clinical event and the dissection of the atherosclerotic plaque. We report that after stroke, plaques remodel into a noninflammatory stable phenotype. The outcome of this study supports the concept that plaque stabilization and destabilization are sequential events in the progression of atherosclerotic disease.

No abstract

In contrast with MMP-2, increased carotid MMP-8 and MMP-9 plaque levels are associated with an unstable plaque phenotype. High collagenase MMP-8 levels in the carotid plaque are associated with the occurrence of systemic cardiovascular outcome during follow-up.