The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease.There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the vasodilatation produced by drugs that are NO donors, such as nitroglycerine, called "endothelium independent". The vasodilatation is quantified by measuring the arterial diameter with high resolution ultrasonography. LaserDoppler techniques are now starting to be used that also consider tissue perfusion.There is so much proof about endothelial dysfunction that it is reasonable to believe that there is diagnostic and prognostic value in its evaluation for the late outcome. There is no doubt that endothelial dysfunction contributes to the initiation and progression of atherosclerotic disease and could be considered an independent vascular risk factor. Although prolonged randomized clinical trials are needed for unequivocal evidence, the data already obtained allows the methods of evaluation of endothelial dysfunction to be considered useful in clinical practice and have overcome the experimental step, being non-invasive increases its value making it use full for follow-up of the progression of the disease and the effects of different treatments.
The CREATE-ECLA Randomized Controlled TrialThe CREATE-ECLA Trial Group Investigators* See also pp 427 and 489.
Cardiovascular (CV) events or their minor syndromes, as various forms of ischemia, are medical emergencies that do not allow enough time for a guiding anamnesis or proper clinical examination, and lead to relying on Treatment Guidelines, but in many situations it is appropriate to deviate from them. Pathological studies have associated 75% of coronary artery events with atherosclerotic plaque rupture; it is now known that rupture alone is not enough for obstruction or occlusion of the vessel lumen. Concomitant conditions are required for the clinical manifestation of cardiovascular disease, including prothrombogenic and dysfunctional endothelium, less fibrinolytic capacity to protect it, increased platelet activation, increased adrenergic tone, microcirculation vasoconstriction, and other countless factors that contribute to thrombus formation, causing ischemia or infarction. But in most cases, repair of plaque rupture and re endothelization of the lesion are asymptomatic and silent. Atherosclerotic process is a chronic and progressive immune inflammation. Most of the therapeutic indications include statins, which cause side effects in 10% of patients, with a range varying between 7 and 21%, according to different authors. Many investigators have proved that statin use contribute to the genesis of diabetes, reports vary between 1 and 46%, where marked elevation of blood glucose fasting levels and glycosylated hemoglobin have been observed, be it by increased tissue resistance to insulin or by reduced β-cell insulin secretion. Physicians should base their indications on the recommendations provided by Guidelines, but they should not forget that every patient is different, and they should not get confused due to lack of time in an emergency nor be influenced by the latest publications or techniques until they have been properly tested.
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