Atherosclerosis: Difference between revisions

In the past, hormone replacement therapy has been suggested by several studies due to the findings of potential athero-protective roles of estrogen. However, these findings were not confirmed in the randomized primary prevention studies of Women’s Health Initiative and HERS trial of secondary prevention. These studies showed that hormone replacement therapy (estrogen-progestin replacement) may increase cardiovascular risk in women and have no cardioprotective effect. Thus hormone replacement therapy is currently not recommended for reducing cardiovascular risk, due to its possible harmfulness according to current clinical trials. <br />

Biomarkers can serve to identify patients with subclinical atherosclerotic disease that are at risk of developing cardiovascular events.<br />

Homocysteine is an intermediary amino acid produced during the conversion of methionine to cysteine. A significant positive correlation was found between the serum levels of homocysteine and the incidence of cardiovascular diseases. Although the clear mechanism of this correlation is undetermined, the overall result of the most current evidence suggests that homocysteine can modestly contribute to cardiovascular risk by inducing vascular injury. Homocysteine promotes oxidative stress, intimal thickening, disruption of elastic lamina, hypertrophy of smooth muscle cells, vascular inflammation platelet accumulation and production of occlusive thrombi when elevated in blood. Several conditions can cause hyperhomocystinemia, such as genetic defects in methionine metabolism or insufficient consumption of folic acid, which is involved in the methionine pathway. Such disorders cause premature and severe atherosclerosis. Despite this observational relationship, there is no data yet that proves reducing high serum level of homocysteine will lead to a decrease in atherosclerosis or its complications.<br />

Some studies have concluded that lipoprotein A is an independent risk factor for coronary artery disease. As lipoprotein A contains apo A, which structurally resembles plasminogen, lipoprotein A interferes with fibrinolysis by competing with plasminogen binding with molecules. This leads to impairment of plasminogen activation, plasmin generation and lysis of fibrin clots. In addition, lipoprotein A binds with macrophages through a high-affinity receptor, promoting foam cell production and deposition of cholesterol in atherosclerotic plaques. As with homocysteine, not all studies support this theory of correlation, although increased risk of cardiovascular events appear to correlate with people with highest lipoprotein A serum level.<br />

Since the participation of inflammatory cells and mediators in atherosclerosis is well established, markers of inflammation have received a lot of attention from the researchers. Several markers of inflammation such as C-reactive protein (CRP), fibrinogen and amyloid A are produced by hepatocytes in an acute phase under the influence of cytokines such as IL-6 when they mobilize from intima to the liver during the fatty streak stage. From these markers, CRP has shown the greatest association with atherosclerosis as a marker of low-grade systemic inflammation. A significant association between elevated CRP level in blood and prevalence of atherosclerosis has been shown in more than 30 epidemiologic studies. Different studies showed that higher basal CRP levels (four-fold higher) were found grouping patients with MI as compared to controls. Several studies have proposed that elevated plasma CRP can be an independent predictor for many cardiovascular diseases based on the result that CRP plasma value was able to predict the long-term risk of first MI, ischemic stroke or peripheral vascular disease among the male group. In addition, recent studies have shown that CRP also has a role as a mediator in atherogenesis. By inducing adhesion molecule expression and release of IL-6 and monocyte chemoattractant protein-1 via endothelial cells, CRP sustains inflammatory state of atherosclerosis by recruiting monocytes and lymphocytes.<br />

A variety of infectious agents such as Chlamydia pneumonia, cytomegalovirus and Helicobacter pylori were identified in the lesions of atherosclerosis and this observation raised a suggestion that these infectious agents may contribute to atherogenesis. However, to date the definite proof of this theory is lacking and also there haven’t been any clinical studies that showed significant relationship between the antibiotic treatment against these infectious agents and the risk of cardiac events of the survivors of acute coronary syndromes. Chlamydia is a strong candidate among other infectious agents, since they produce heat shock protein 60 (HSP-60) that activates macrophages and stimulates the production of matrix metalloproteinases. Furthermore, HDP-60 can also stimulate foam cell formation, lipoprotein oxidation, and increased pro-coagulant activity, which are the major attributing components of atherosclerosis. Although there is no evidence to date, some researchers believe that exogenous pathogens can cause endothelial injury and inflammation that can lead to initiation or exacerbation of atherosclerosis.<br />

   

Hypertension is defined as a systolic blood pressure (SBP) ≥ 140mmHg and/or a diastolic blood pressure (DBP) ≥ 90mmHg. Elevated blood pressure is a well established risk factor of atherosclerosis, including mortality from coronary heart disease and stroke. For example, cardiovascular disease doubles with every 20 mmHg increase in SBP or every 10 mmHg increase in DBP.<br />

One of the mechanisms of hypertension in contributing to atherosclerosis is injury of vascular endothelium by elevated hemodynamic stress. Injury of endothelium may increase the permeability of the vessel wall to lipoproteins. Increased blood pressure may also increase the number of scavenger receptors on macrophages, which enhances the development of foam cells. Furthermore, increased cyclic circumferential strain in hypertensive arteries can result into promoting LDL accumulation in the intima and facilitation of their oxidative modification. Finally, hypertension can contribute to atherogenesis due to the presence of Angiotensin II, which not only works as a vasoconstrictor, but also as a pro-inflammatory cytokine. <br />

Antihypertensive therapy can either consist of lifestyle interventions or pharmacotherapy. Lifestyle modifications consist of diet, body weight reduction, increased activity, and cessation of smoking. As for diet, high consumption of fruits, vegetables, dairy products low in fat, fish oils, potassium and reduced consumption of sodium and alcohol are recommended.