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Toward a New Definition of Atherosclerosis Including

Toward a New Definition of Atherosclerosis Including

Journal of Human (2002) 16 (Suppl 1), S23–S25  2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh Toward a new definition of including hypertension: a proposal

I Soltero-Pe´rez Escuela de Medicina “Jose´ Marı´a Vargas” San Jose´, Caracas, Universidad Central de Venezuela, Caracas, Venezuela

Atherosclerosis is a very complex and while high pressure are ignored. Here we present a pro- research about its aetiology and development posal for a redefinition of atherosclerosis and look for- advances, it is more difficult to understand its pathol- ward to having a better understanding about the why ogy. Because of this atherosclerosis is not easy to and how of this lethal disease. define. Old and even new definitions are incomplete. Journal of Human Hypertension (2002) 16 (Suppl 1), S23– Most of them do not take into consideration the endo- S25. DOI: 10.1038/sj/jhh/1001336 thelium on both sides, and some risk factors such as

Keywords: atherosclerosis; definition;

Introduction , , , and race are other compo- nents of the atherosclerotic mosaic, besides genetic Atherosclerosis is a very complex disease. More and and polygenetic conditions which make individuals more information is collected every day about the more or less susceptible to the disease.5,6 possible causes and factors related to the athero- In summary, atherosclerosis is a true multifac- sclerosis process. Starting with an intact vascular torial disease with a very rich natural history. Its bed, the disease progresses because several agents development obeys the conjugation of several fac- interact to produce in the first place endothelial tors and conditioners. damage, and thereafter inflammation which will It is our point of view that this disease needs to lead eventually to the . be redefined, because both older and more current The arterial wall is made up of several layers. The definitions are no longer suitable to express entirely first , at least visible, is in the form of yellow what the morbus actually is. Indeed, many parts of streaks. Atherosclerosis continues accumulating and the atherosclerotic equation are left out, some of an is the consequence, lead- which are of crucial importance. The endothelium ing to endothelial denudation and unpaired nitric 1 and NO, for example, are key participants in that oxide (NO) synthesis. Some other ‘actors’ present equation.7 in the blood, such as , make their contri- bution to the proliferation of the cells beneath the intima where at the same time an extraordinary meeting of different agents participate Atherosclerosis: some definitions together in the inflammatory intimal process: ox-low The following definitions of atherosclerosis have density , , , cyto- been taken from specialists, dictionaries, textbooks, kines, proteoglucans, leucocytes, smooth muscle 2 and other sources. The idea is to make a critical cells, , etc. This process is thought to be dif- review of them and to see how complete they are. fused at the atherosclerosis wall.1,3,4 In addition, high (HBP) and shear stress play a An characterised by the deposition of very important role in this situation, because mech- fatty substances in, and fibrosis of the inner layer of the anical forces act in several ways on the endothelial . and subendothelial areas.5 On the other hand, and their carriers are The components are of Greek origin: ‘athere’, meaning also of great importance, mostly as esters porridge or mush and refers to the soft fatty material in and crystal as conditioners for the inflammation. the core of a plaque; ‘skleros’, meaning hard and refers to the hard scar-like tissue formation involved in the devel- opment of a plaque; ‘osis’ is a Greek suffix that means a 8 Correspondence: Professor Iva´n Soltero Pe´rez, MD, Escuela de diseased condition. Medicina “Jose´ Marı´a Vargas” San Jose´, Caracas, Universidad Central de Venezuela, Caracas, Venezuela A common form of arteriosclerosis in which deposits of E-mail: [email protected] yellowish plaques containing cholesterol, sub- A new definition of atherosclerosis I Soltero-Pe´rez S24 stances, and lipophages are formed within large and vessels, primarily develops as a generalised endo- medium sized arteries.9 thelial dysfunction and intima thickening; secondly, diffuses as atheromatosis but with preferential dis- A disease of the arteries in which fatty material is tribution to certain arteries and zones. Sclerosis, deposited in the vessel wall, resulting in narrowing and which is associated a posteriori, develops mainly eventual impairment of blood flow.10 due to the presence of tissue and ectopic deposition, and is part of the response to the Atherosclerosis comes from the Greek words athero inflammatory process as an expression of protective (meaning gruel or paste) and sclerosis (hardness). It biological and curative action, producing the fiber- involves deposits of fatty substances, cholesterol, cellular atheromatosa plaque. waste products, calcium and other substances in the inner lining of an . This build-up is called plaque.11 I am sure that many discrepancies are going to arise with this proposal. That is the idea. The defi- Atherosclerosis is not a simple disease. Atherosclerosis nition is open for discussion. take different shapes depending on the anatomic side, age, genetic and physiological status of recipients, also including the so-called risk factors. Molecular biology has revealed that each lesion has significant elements of three cellular phenomena: muscular smooth cells, lipid References accumulation and a large amount of , 12 1 Kern MJ. Focus for the new millennium: diffuse coron- collagen and elastic fibre. ary artery disease and physiologic measurements of severity. ACC Curr J Rev 2000; 9:13–19. Atherosclerosis is a special pathological process of 2 Bayes-Genis A, Conover Ch A, Schwartz RS. The insu- thickening with sclerosis of large and medium arteries lin-like growth factor axis. A review of atherosclerosis which lead to a vast majority of attacks and coronary and . Circ Res 2000; 86: 125–130. heart disease. Many pathogenic factors take part in this 3 Gould KL. Focus for the new millennium—diffuse cor- disease with different anatomic, biochemical, and physio- onary artery disease and new paradigms in cardio- logical manifestations.13 vascular medicine. ACC Curr J Rev 2000; 9:10–21. 4 Osende J, Zaman A, Fuster V, Badimo´n JJ. Enfermedad aterosclero´ticas coronaria. Evidencias etiopatolo´gicas Atherosclerosis is the formation of plaques called ather- y prevencio´n. In: Soltero I (ed). Aterosclerosis al Dı´a omas inside the arteries. The atheroma is formed by: lip- IV. ProCrev C.A.: Caracas, 2000, pp 23–51. ids, mostly cholesterol, muscular smooth cell, blood cells, 5Marı´n Vela´squez A, Marı´n Polanco JM, Marı´n Polanco 14 collagen and elastic fibre, and occasionally calcium. E. Stress Arterial y Aterosclerosis. In: Cardona R, Sol- tero I (eds). Aterosclerosis al Dı´a III. Ediciones Asocia- It may be observed that none of the definitions cio´n Venezolana de Atherosclerosis: Caracas, 1996, pp mentions the endothelium or that atherosclerosis is 172–193. 6 Badimo´nJJet al. Ruptura de la placa aterosclero´tica, an inflammatory condition. Also none of them takes trombosis y la enfermedad coronaria. In: Cardona R, into consideration the different areas where the Soltero I (eds). Aterosclerosis al Dı´a III. Asociacio´n can develop, or if the disease is diffuse or Venezolana de Aterosclerosis: Caracas, 1996, pp 17– local. On the other hand, collagen and elastic fibre 40. and calcium are mentioned only as a part of the final 7 Anderson TJ. Assessment and treatment of endothelial lesion of the atheroma, but they are not mentioned dysfunction in humans. J Am Coll Cardiol 1999; 34: as a final product.15 631–638. In summary, I believe that a new and more com- 8 Cardiac Prevention and Rehabilitation Research Center plete definition is probably needed. A definition http://admnweb.ucis.dat.cap/cprrc/med—defi.htlm which takes into consideration: the endothelium in (Acceso el 12/10/00) 9 Academic Press Dictionary of Science and Technology both its faces (one to the blood stream and the other http://harcourt.com/dictionary/def/8/6/0/4/860400.html intimal), the inflammatory and oxidative processes, (Acceso el 12/10/00) and the final reaction which causes the atheroma 10 WebMED. http://health.yahoo.com/health/Diseases— with all its components. and—Conditions/Disease—Feed—Data/Atherosclerosis/ In an attempt to put all the parts together, we pro- (Acceso el 12/10/00) pose the following definition: 11 American Heart Association http://www. americanheart.org/Heart-and-Stroke-A-Z-Guide/athero. Atherosclerosis is a consequence of inflammatory, htlm (Acceso el 12/10/00) oxidative and mechanical processes due to multiple 12 Russell R. Atherosclerotic coronary heart disease. Fac- internal and external agents, particularly lipids and tors influencing atherogenesis. In: JW Hurst (ed). The Heart. Seventh edition. McGrawHill: New York, 1990, their carriers and HBP, which act chronically on the pp 877–892. endothelium, on its haematic and intimal surfaces 13 Wissler R. Patogenia de la Aterosclerosis. In: Braun- and in the intima of the arteries. This process which wald E (ed). Tratado de Cardiologı´a, Vol 2 Cap. 33. can take place all over the arterial tree to a greater Nueva Editorial Interamericana: Me´xico, DF, 1984, pp or lesser degree, excepting and 1357–1383.

Journal of Human Hypertension A new definition of atherosclerosis I Soltero-Pe´rez S25 14 Asociacio´n Venezolana de Atherosclerosis http:// of first unheralded acute myocardial by elec- geocities.com/HotSprings/Falls/2467 (Acceso el tron-beam computed tomography. Circulation 2000; 12/10/00) 101: 850–855. 15 Raggi P et al. Identification of patients at increased risk

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