Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and ‘modern’ cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.

Objective-The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and Results-We found profound structural alterations in BM from mice with type 1 diabetes with depletion of the hematopoietic component and fatty degeneration. Blood flow (fluorescent microspheres) and microvascular density (immunohistochemistry) were remarkably reduced. Flow cytometry verified the depletion of MECA-32 ϩ endothelial cells. Cultured endothelial cells from BM of diabetic mice showed higher levels of oxidative stress, increased activity of the senescence marker ␤-galactosidase, reduced migratory and network-formation capacities, and increased permeability and adhesiveness to BM mononuclear cells. Flow cytometry analysis of lineage Ϫ c-Kit ϩ Sca-1 ϩ cell distribution along an in vivo Hoechst-33342 dye perfusion gradient documented that diabetes depletes lineage Ϫ c-Kit ϩ Sca-1 ϩ cells predominantly in the low-perfused part of the marrow. Cell depletion was associated to increased oxidative stress, DNA damage, and activation of apoptosis. Boosting the antioxidative pentose phosphate pathway by benfotiamine supplementation prevented microangiopathy, hypoperfusion, and lineage Ϫ c-Kit ϩ Sca-1 ϩ cell depletion. Conclusion-We provide novel evidence for the presence of microangiopathy impinging on the integrity of diabetic BM.These discoveries offer the framework for mechanistic solutions of BM dysfunction in diabetes. (Arterioscler Thromb Vasc Biol. 2010;30:498-508.)

Over the past two decades, extensive research has focused on arterial remodelling in both physiological and pathological ageing. The concept now describes the growth as well as the rearrangement of cellular components and extracellular matrix, resulting in either reduction or increase in vessel lumen. In diabetes, remodelling extends to capillaries, microvascular beds, and arteries of different calibre. This process is paralleled by accelerated atherosclerosis and accounts for an increased incidence of ischaemic complications. The incapacity of pre-existing and de novo formed collaterals to bypass atherosclerotic occlusions, combined with a decline in tissue capillary density, is responsible for the delayed recovery from ischaemia and ultimately leads to organ failure. The mechanisms of vascular remodelling are incompletely understood, but metabolic and mechanical factors seem to play an important role. Hyperglycaemia represents the main factor responsible for the fast progression of atherosclerosis as well as microangiopathy. However, intensive blood glucose control alone is insufficient to reduce the risk of macrovascular complications. Pharmacological control of oxidative stress and stimulation of nitric oxide release have proved to exert beneficial effects on vascular remodelling in experimental diabetic models. New approaches of regenerative medicine using vascular progenitor cells for the treatment of ischaemic disease have been shown to be safe and are now being tested for efficacy in pre-clinical and clinical trials.