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Showing posts with label atherotrombosis. Show all posts
Showing posts with label atherotrombosis. Show all posts

Sunday, August 30, 2015

microvascular disease


The science of microvascular disease

ESC Congress News 2015 - London


IN THIS MORNING’S William Harvey lecture Axel Pries will challenge basic scientists to explore the ‘black box’ of the microcirculation. ‘To my mind, the coronary microcirculation, the business end of the circulation where oxygen diffuses into cells, represents one of the contemporary frontiers in cardiology research,’ says Pries, from the Charité University of Medicine, Berlin. ‘We still know extraordinarily little about what’s going on here.’
Basic Sciences, Pharmacology, Genomics and Cardiovascular Pathology

Axel Pries will deliver today’s William Harvey lecture  on basic science, describing microcircular networks as ‘the business end of the circulation’.
Axel Pries will deliver today’s William Harvey lecture on basic science, describing microcircular networks as ‘the business end of the circulation’.
Recent studies show that a substantial number of patients with suspected coronary artery disease examined by coronary angiography have apparently normal arteries, suggesting they suffer from microvascular disease. Such pathologies can be attributed to spasm, coagulation, micro-obstruction by leucocytes, adverse microvascular remodelling, and endothelial dysfunction among other potential mechanisms.
Although there has been an increase in clinical papers addressing the coronary microcirculation, says Pries, the amount of basic science research has declined over the past few decades. ‘What’s needed,’ he adds, ‘is a greater understanding before we can move on to develop treatments.’
Since the microcirculation lies beyond the domain of catheter investigation and intravascular imaging, much of Pries’s work has involved mathematical modelling collaborations with the mathematician Timothy Secomb from the University of Tucson. Adequate function of terminal vascular beds, they suggest, depends on exact adjustment of vessel diameters by adaptive processes. Here they believe a ‘feedback’ system operates through the conduction of electrical signals upstream along arterioles within vascular network, preventing generation of functional arterio-veneous shunts. This conduction relies on the adequate function of connexins forming gap junctions between cells in the vessel wall. ‘The system provides the arteriole with information about the capillaries it is serving,’ explains Pries.
Another focus has been the ‘endothelial surface layer’ or ‘glycocalyx’, a gel like layer around 0.5 μm thick influencing flow resistance, inflammation and permeability. Conditions such as inflammation, diabetes mellitus and hypertension, they believe, have a negative effect on this layer.
Since graduating from the University of Cologne in 1980 Pries has exclusively focused on basic science. While he does not deny there are frustrations, the rewards of the scientific life are worthwhile. ‘Scientists need to be really determined with a thick skin because it can take years to achieve breakthroughs,’ he says. ‘But each morning you’re like a pioneer exploring new territory and don’t know where your journey will take you.’
His advice to young colleagues is to ‘cherish’ the time before administration catches up. For Pries such freedom is now gone. In December 2014 he was appointed Dean of the Charité with shared responsibility for an overall budget of €1.5 billion and 13,000 staff.
To relax he spends time with his wife and two daughters and enjoys wood turning bowls. ‘In a matter of hours you create from scratch something that is beautiful and useful. It’s a refreshing antidote to the irritants of the scientific and administrative processes,’ he says.

ESC William Harvey Lecture on Basic Science  30 Aug  9:20-10:00, Regents Park – The Hub.

Saturday, March 16, 2013

Peropheral Arterial Disease

Vorapaxar in Patients with Peripheral Artery Disease: Results from TRA2°P-TIMI 50

  1. David A. Morrow1
+Author Affiliations
  1. 1Brigham and Women's Hospital and Harvard Medical School, Boston, MA
  2. 2Mount Sinai School of Medicine, New York, NY
  3. 3University Hospitals of Geneva, Geneva, Switzerland
  4. 4Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital - Östra, Gothenburg, Sweden
  1. * Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115mbonaca@partners.org

Abstract

Background—Vorapaxar is a novel antagonist of protease-activated receptor (PAR)-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease (PAD) are at risk of systemic atherothrombotic events as well as acute and chronic limb ischemia and need for peripheral revascularization.
Methods and Results—The TRA2°P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar in 26,449 patients with stable atherosclerotic vascular disease (MI, stroke, or PAD). Patients with qualifying PAD (N= 3,787) had a history of claudication and ABI of <0 .85="" 0.39-0.86="" 0.58="" 0.73-0.97="" 0.78-1.14="" 0.84="" 0.94="" 1.21-2.18="" 1.62="" 11.9="" 22.2="" 3.9="" 4.5="" 95="" acute="" and="" artery="" bleeding.="" bleeding="" cardiovascular="" ci="" cohort="" compared="" death="" did="" differ="" efficacy="" endpoint="" for="" frequently="" gusto="" hospitalization="" however="" hr="" in="" ischemia.="" ischemia="" limb="" lower="" mi="" more="" not="" occurred="" of="" or="" p="0.001).</p" pad="" patients="" peripheral="" placebo="" primary="" principal="" prior="" randomized="" rates="" revascularization="" safety="" significantly="" stroke="" the="" to="" vorapaxar.="" vorapaxar="" vs.="" was="" were="" with="">
Conclusions—Vorapaxar did not reduce the risk of cardiovascular death, MI, or stroke in patients with PAD; however, vorapaxar significantly reduced acute limb ischemia and peripheral revascularization. The beneficial effects of PAR-1 antagonism on limb vascular events were accompanied by an increased risk of bleeding.
Clinical Trial Registration Informationhttp://www.clinicaltrials.gov;Identifier: NCT00526474.

Wednesday, July 25, 2007

Atherothrombosis - Wave Goodbye to Combined Anticoagulation and Antiplatelet Therapy?

Atherothrombosis - Wave Goodbye to Combined Anticoagulation and Antiplatelet Therapy? [Editorial]
Mohler, Emile R. III.
From the Department of Medicine, Cardiovascular Division, Section of Vascular Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Atherothrombosis describes the occurrence of both atherosclerosis and thrombosis in an artery, a common feature of peripheral arterial disease. [1] It is estimated that 1 in 16 U.S. residents who were at least 40 years of age in 2000 (approximately 8.5 million persons) had peripheral arterial disease. [2] Although claudication is frequent in and seriously limits the lifestyle of patients with peripheral arterial disease, the most common cause of death in these patients is from coexisting atherothrombosis in the coronary or carotid arteries, resulting in a risk of myocardial infarction or stroke that is three times as high as the risk in patients without peripheral arterial disease. [3] It is estimated that half of patients with peripheral arterial disease have concomitant coronary artery disease. [4] The Reduction of Atherothrombosis for Continued Health (known as REACH) Registry, which follows a cohort of approximately 68,000 patients, showed that the annual rate of myocardial infarction, stroke, or death from cardiovascular causes for patients with peripheral arterial disease was 5%./.../