Atherosclerosis: Difference between revisions

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 ===Diabetes mellitus===
 With estimated global incidence of 170 million people diabetes mellitus remains a large problem worldwide. Diabetes mellitus increases the risk of acute coronary events by three- to five folds and 80% of diabetic patients will face atherosclerosis-related cardiovascular diseases. Risk for atherosclerosis among diabetes group is considered as high as a group with previous myocardial infarction.
+There are several possible mechanisms executed by diabetes that makes this group particularly vulnerable to atherosclerosis. An example of mechanism is non-enzymatic glycation of lipoproteins, which promotes uptake of cholesterol by scavenger macrophages. Furthermore, pro-thrombotic and anti-fibrinolytic properties of diabetes can also contribute to this vulnerability. The high prevalence of endothelial dysfunction among diabetes group leads to reduced bioavailability of NO and enhanced leukocyte adhesion. The most effective prevention of atherosclerosis among diabetes group is tight regulation of serum glucose levels. This intervention significantly reduces the risk of microvascular complications such as retinopathy and nephropathy. Furthermore, intense anti-diabetic regime also reduced macrovascular outcomes such as myocardial infarction and stroke among a group of diabetes type 1. Additionally managing hypertension and dyslipidemia among diabetic groups also significantly reduces the risk of cardiovascular diseases.
+===Metabolic syndrome===
+The metabolic syndrome entails a clustering of risk factors, such as hypertension, hypertriglyceridemia, reduced HDL, cellular insulin resistance and visceral obesity. Within both groups of diabetes and non-diabetes, this syndrome is associated with a high risk for atherosclerosis. Even before developing diabetes, this syndrome appears to promote atherogensis due to insulin resistance.
+==Biomarkers==
+One out of five cardiovascular events occur in patients without any of the well-established risk factors described in last sections. In order to understand this phenomenon and the pathogenesis of atherosclerosis, studies of the biomarkers of atherosclerosis have recently emerged.
+===Homocysteine===
+Homocyteine is an intermediary amino acid formed by 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 promoting oxidative stress, vascular inflammation, and platelet adhesiveness 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. Despite this observational relationship, there is no data yet that proves reducing high serum level of homocysteine will lead to marked down atherosclerosis or its complications.
+===Lipoprotein (a)===
+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, higher serum level of lipoprotein (a) may attribute to competition with normal plasminogen activity, leading to decrease of lysis of fibrin clots. 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.
+===C-Reactive Protein and other markers of inflammation===
+Since atherosclerosis involves inflammation at every development stage, 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 when cytokines such as IL-6 mobilize to the liver from intima during fatty streak stage.  From these markers, CRP has shown the greatest association with atherosclerosis as a marker of low-grade systemic inflammation. A large randomized trial in the healthy population, showed that higher basal CRP levels are related to increased risk of adverse cardiovascular outcomes, independent of cholesterol level in blood. Several prospective studies suggest that CRP can be an independent predictor for many cardiovascular diseases such as myocardial infarction, stroke, peripheral artery disease, and sudden cardiac death. Also,lrecent studies have shown that CRP also has a role of a mediator of atherogenesis by activating complement to sustain inflammatory state of atherosclerosis.
+===Infection===
+A variety of infectious agents such as Chlamydia 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 infections can cause endothelial injury and inflammation that can lead to initiation or exacerbation of atherosclerosis.
+{| class="wikitable"
+|-
+! Figure 6. Risk factors of atherosclerosis
+|-
+| * Dyslipidemia
+* Tabacco smoking
+* Lack of physical activity / obesity
+* Estrogen status
+* Bio-markers
+** Homocysteine
+** Lipoprotein (a)
+** C-reactive proteins
+** Infectious agents
+** Co-mobidity groups
+** Hypertension
+** Diabetes Mellitus
+|}