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New Cardiovascular Risk Factors Atherosclerosis

L ' atherosclerosis (ATS) is still the main cause of deaths from cardiovascular causes in Western countries. Prof. Paolo Puddu , former Professor of Internal Medicine and Lecturer of Biochemistry and Pathology, Department of Internal Medicine and Cardioangiology, University of Bologna, shows an interesting study which highlights the role of other factors, alongside those classics in the genesis of the ATS.

The problem of cardiovascular risk is complex: in fact the most common forms of atherosclerosis have a genesis multifattoriale e possono associrsi alla malattia fattori con una forte componente genetica.

In molti soggetti lo sviluppo della malattia correlata all’aterosclerosi è determinata dall’intreccio di fattori ambientali , metabolici e genetici . In alcuni casi la malattia può essere spiegata da un singolo gene maggiore, mentre in altri variazioni di diversi geni minori possono contribuire allo sviluppo dell’ATS.

I classici fattori di rischio dell’aterosclerosi sono il sovrappeso corporeo e l’ obesità , l’ ipertensione arteriosa , l’ smoking, diabetes mellitus, the and plurimetabolica syndrome (insulin resistance syndrome or syndrome X), which often leads to type 2 diabetes. The following is added lipid abnormalities: hypercholesterolemia (total cholesterol> 200 mg / dL, LDL cholesterol> 135 mg / dL, HDL cholesterol \u0026lt;35 mg / dL in males or \u0026lt;40 mg / dL in women , total cholesterol / HDL cholesterol> 5), hypertriglyceridemia (150-400 mg / dL), lipoprotein Lp (a) > 30 mg / dL.

Estimating traditional factors is not entirely sufficient for the assessment of global risk.

Many studies have shown that several patients with coronary artery disease do not exhibit traditional risk factors and while it was observed that about one-fifth of those taking cholesterol-lowering therapy has gone still be subject to clinical cardiovascular events.

In this context, new factors have been examined .

Hyperhomocysteinemia

Among the new emerging one of the most important factors being considered hyperhomocysteinemia. L ' Homocysteine \u200b\u200bis an amino acid that is formed during metabolism an essential amino acid, methionine the .

seems that when the plasma levels of homocysteine \u200b\u200bthan 12 mg / dL increases the risk of thrombosis.

genetic factors are involved in the etiology of hyperhomocysteinemia, the age, sex, renal dysfunction, nutritional factors, acute lymphoblastic leukemia, lupus erythematosus, psoriasis, liver failure. Some medications, including diuretics tiqzidici, methotrexate, isoniazid, contraceptives, and some AEDs can induce increased levels of circulating homocysteine.

is possinile prevent the risk associated with the states of hyperhomocysteinemia lasomministrazione quotidiana di acido folico, vitamina B12 e di vitamina B6.

Nuovi parametri lipidici

Fra i parametri lipidici emergenti proposti per individuare precocemente i soggetti con ATS subclinica è stata presa in considerazione la lipoproteina (a) (Lp(a)) che è una forma modificata di LDL.

Il rapporto tra colesterolo totale e colesterolo HDL è l’unico forte predittore di rischio e la combinazione con la Lp(a) non aumenta il valore predittivo. Questo risultato negativo non impedisce peraltro che lo screening per la Lp(a) venga eseguito nei soggetti ad alto rischio, come quelli con cardiopatia ischemica precoce, con storia familiare di malattia coronarica oppure nei pazienti senza fattori di rischio tradizionali apparenti. Ciò vale anche per l’omocisteina.

Fattori protrombotici

Le ischemie rappresentano la manifestazione clinica di un evento trombotico dovuto ad una placca instabile, ricca di lipidi, i quali occupano fino al 50-60% del suo volume e che presenta una capsula fibrosa sottile. Questa particolare placca è caratterizzata da una cospicua presenza di cellule infiammatorie (linfociti, macrofagi e mastcellule) che circondano il core lipidico. Nel centro della placca sono presenti anche cellule necrotiche.

La capsula fibrosa va incontro a fissurazioni e a rotture, esponendo il core lipidico altamente trombogeno. La placca è in grado di attivare la coagulazione . Anche le piastrine giocano un ruolo importante. Si forma il trombo piastrinico, composta da una matrice di piastrine e fibrinogeno adeso alla superficie vasale. Il trombo può evolvere fino ad ostruire più o meno completamente il lume, provocando l’infarto miocardico o l’angina instabile.

È emerso un’associazione tra malattia vascolare e fibrinogeno. Un aumento del fibrinogeno è associato a un aumento del rischio di infarto e di ictus.

Il fibrinogeno è in parte modulato da fattori genetici e può aumentare nella menopausa, nel diabete e nei fumatori.

Sindrome metabolica

Also called metabolic syndrome X, is a clinical entity whose main features are: abdominal obesity, dyslipidemia (elevated triglycerides and small LDL particles, low HDL cholesterol), increased blood pressure, insulin resistance, with or without glucose intolerance. These situations present a significant increase in cardiovascular risk.

Infectious agents

There are biological and epidemiological indications that some infectious agents may be involved in the pathogenesis of atherosclerosis.

have been implicated in Helicobacter pilory, the Chlamydia pneumoniae and various viruses, including cytomegalovirus.

is likely that they interact with various risk factors in producing a vascular disease, as un'endotelite, for example, can detrminare proaterosclerotiche alterations in the cells.

markers of inflammation

The finding that inflammation is intimately involved with the development of atherosclerosis has long suggested a potential role of inflammatory markers in predicting the risk of early coronary atherosclerosis.

These have become important predictor of acute phase proteins, such as interleukins, adhesion molecules, vascular il fibrinogeno, la proteina C reattiva.

Una recente valutazione ha dimostrato che il rapporto colesterolo totale/colesterolo HDL e la proteina C reattiva sono i più forti predittori di sviluppo della malattia ed anche il terzo componente del complemento (C3).

Sia la PCR che il C3, che sono proteine della fase acuta, possono comunque essere marcatori di infiammazione presenti in qualunque processo infiammatorio in corso. Sulla base di vari studi epidemiologici è comunque possibile concludere che parametri infiammatori come i livelli di PCR o di altre proteine infiammatorie, come il C3, possano essere utili per determinare quali pazienti, anche se clinicamente stabili, siano a rischio di eventi cardiaci futuri.

Conclusions

has been given importance in atherogenic dyslipidemia, hypertension, diabetes mellitus, obesity, smoking and family history of cardiovascular disease.

The same can be said for the sedentary lifestyle, as it is known that regular exercise can significantly reduce the risk of coronary heart disease through its beneficial effects on endothelial dysfunction, coronary perfusion, balance of the fibrinolytic system with the reduction of ischemic events.

The current strategies for primary and secondary prevention of coronary heart disease have focused mainly on traditional risk factors, with particular emphasis on reducing LDL cholesterol.

The ATS is a multifactorial disease with a strong hereditary component. There is, therefore, the possibility that many genes are involved in atherogenesis.

'm still not completely known genes that determine an increased risk of coronary heart disease.

is significant that at present the cause of coronary heart disease is only 50% of cases attributable to traditional risk factors.

were then evaluated new emerging risk factors, such as' hyperhomocysteinemia, lipid parameters details (Lp (a), apo AI, apo B-100), the prothrombotic factors, the metabolic syndrome , some infectious agents and markers of inflammation .

Prof. Puddu highlights but the scores of each of these factors requires a review of epidemiological evidence, an examination of the mechanism by which the factor might participate all'aterotrombosi, and evaluating the merits of screening. In fact, in some cases there is still some evidence that a selective modification of these new risk factors is associated with a definite clinical benefit.

However, it is possible to say that the rational to implement preventive action to fix even the new risk factors is sufficiently justified.

Although the need for further and more extensive research to determine with certainty the importance of pathogenetic factors emerging need to recognize that any demonstration of this role will certainly be the opportunity to have other useful items to help reduce cardiovascular risk.