81
edits
Atherosclerosis: Difference between revisions
Jump to navigation
Jump to search
→Complications of atherosclerosis
Secretariat (talk | contribs) |
Secretariat (talk | contribs) |
||
| Line 117: | Line 117: | ||
# Embolization is the transfer of the fragments of disrupted atheroma to distal vascular sites, which results into occlusion of those sites. | # Embolization is the transfer of the fragments of disrupted atheroma to distal vascular sites, which results into occlusion of those sites. | ||
# After a chronic period, fibrous plaque can increase the pressure of the medial layer, which results into atrophy and loss of elastic tissue, forming dilatation and weakness of the artery, causing aneurysm. | # After a chronic period, fibrous plaque can increase the pressure of the medial layer, which results into atrophy and loss of elastic tissue, forming dilatation and weakness of the artery, causing aneurysm. | ||
Depending on where atherosclerotic plaque is located and the type of the plaque, the clinical consequences varies. For example, ‘stable plaque’ can easily result into angina pectoris due to its thick fibrous cap that directly affects occlusion of the relatively small coronary vessels. On the other hand, ‘vulnerable plaque’ is non-stenotic, but can easily cause acute thrombosis and therefore myocardial infarction due to its fragility towards rupture when located at a physically stressed area such as bifurcations. Often with ‘vulnerable plaques’ there are relatively few symptoms, however they are more numerous and dispersed throughout the arteries compared to ‘stable plaque’. In conclusion, you can either have an occlusion due to the growing plaque or due to the embolization of the ruptured fragments of the original plaque. | |||
Due to the difficult detection of ‘vulnerable plaques’ while they are widely dispersed, it is important to understand that tackling the risk factors prior to plaque rupture is highly important. Thus in the following paragraph, we would like to bring attention to the critical risk factors for preventing progressive atherogenesis. | |||
=Risk factors of atherosclerosis= | |||
Recent studies have shown that atherosclerosis is not just the inevitable process of aging, but can be a process with many modifiable attributes. Due to the evidence of strong correlations between specific attributes and atherosclerotic diseases, the concept of risk factors became more essential than ever. Many important studies have established the importance of modifiable risk factors for atherosclerosis, since they account for up to 90% of population-attributable cardiac risk. A variety of non-modifiable risk factors such as advanced age, gender and hereditary coronary heart disease are important to diagnosing and recognizing patients with atherosclerosis. Furthermore, recent researches accentuate the importance of recognizing several biological markers associated with the development of cardiovascular events. | |||
=Common risk factors= | |||
==Dyslipidemia== | |||
One of the major modifiable risk factors for atherosclerosis is hypercholesterolemia. In countries with high consumption of saturated fat and high cholesterol levels (e.g. the United States), observational studies have shown that the mortality rates from coronary disease are higher compared with those in countries with traditionally low consumption of saturated fat and cholesterol levels (e.g. Japan). Several trials have shown that the risk of ischemic heart disease positively correlates with higher total serum cholesterol levels. The impact of hypercholesterolemia can be illustrated by an observational result, which shows that a person with a total cholesterol level of 240 mg/dl has twice the coronary risk a person would have with a cholesterol level of 200 mg/dl. | |||
However, it is a mistake to think that all lipoproteins consisting of cholesterol are harmful. Cholesterol can provide critical functions to all cells that need to form membranes and to synthesize products such as steroid hormones and bile salts. | |||
Incidence of atherosclerosis and coronary artery disease increases with higher levels of LDL particles. As mentioned earlier LDL can accumulate in the intima of the artery in excess proportions, and undergo chemical modifications that activate endothelial cells to contributing atherosclerosis. When people refer to ‘bad cholesterol’, they are referring to LDL particles. On the other hand, high level of high-density lipoprotein (HDL) is ‘good cholesterol’ since it protects against atherosclerosis by reversing the cholesterol transport from peripheral tissues to the liver for disposal and functioning as antioxidant. | |||
There are several causes to persistent elevated level of LDL, such as high-fat consumption or genetic abnormalities (e.g. familial cholesterolemia). Familial hypercholesterolemia is a condition with genetically defected LDL receptors that cannot efficiently dispose LDL from the circulation. There are two types of this disease with different manifestations. Patients with the heterozygote type has only one defective gene for the receptor and he/she suffers from high serum level of LDL and will easily develop atherosclerosis. Homozygotes have complete lack of normal LDL receptors and thus may experience cardiovascular events in the first decade of life. | |||
Although not fully understood, many studies show increased triglyceride-rich lipoproteins such as very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) are positively associated with atherosclerosis. Whether triglyceride-rich lipoproteins directly participate in atherogenesis or simply accompany low HDL levels remains undetermined and seek for more research. | |||
==Lipid-Altering therapy== | |||
Controlling the serum lipid level is a key step to limit the consequences of atherosclerosis. Major clinical trials that form that basis of screening guidelines show that reduction of serum cholesterol by pharmacology and diet can restrict the progression of atherosclerosis significantly. | |||
One of the most important strategies to reduce the complications of atherosclerosis is diet and exercise. Several studies have shown that Mediterranean-styled diet among patients with coronary disease significantly reduced the risk of recurrent cardiac events. Mediterranean-styled diet in this context means replacement of saturated fats with polyunsaturated fats such as omga-3 fatty acid and α-linolenic acid. Polyunsaturated fats are potential anti-atherogenic due to its inhibiting work on cytokine-induced expression of leukocyte adhesion molecules on endothelial cells. Exercise and loss of excessive weight also contributes to improve abnormal lipid levels by reducing triglycerides and increasing HDL. | |||
Pharmacologic agents are the second option when lifestyle modifications fail to achieve targeted lipid profile. There are several groups of lipid-altering medicines such as HMG-CoA reductase inhibitors (statins), niacin, fibric acid derivatives, cholesterol intestinal absorption inhibitors, and bile acid-binding agents. In clinical setting, statins are commonly used as the most cost-effective LDL-lowering drugs. They reduce intracellular cholesterol concentration by inhibiting HMG-CoA reductase, which is an enzyme that synthesizes cholesterol. This results into increased LDL-receptor expression and therefore leads to higher clearance of LDL molecules from blood. They also affect the liver and thereby lower the rate of VLDL synthesis, which results into lower level of serum triglyceride. Statins also raise HDL, but this mechanism is not fully understood yet. | |||
Large studies, which have evaluated the effects of statin therapy, showed that ischemic cardiac events, the occurrence of strokes and mortality rates were significantly reduced by implementing statin therapy. This significant improvement didn’t only apply for people with known preexisting atherosclerotic disease, but also for people within lower ranges of LDL, without preexisting atherosclerotic disease. | |||
Inhibiting HMG-CoA reductase results into several mechanisms that explain the beneficial effect of using statins. One beneficial mechanism is through lowering LDL and raising HDL. This results into less lipid content in atherosclerotic plaques and improve their biologic activity. Furthermore, anti-thrombotic and anti-inflammatory condition is enhanced by other mechanisms such as increased NO synthesis and fibrinolytic antivity, inhibition of smooth muscle proliferation and monocyte recruitment, and reduced production of matrix-degrading enzymes by macrophage. Several studies suggest that other mechanisms also contribute to anti-inflammatory condition. For example, statins reduce endothelial expression of leukocyte adhesion molecules and macrophage tissue factor production by inhibiting the macrophage cytokines or by activating PPAR-α. Another anti-inflammatory working of statins, supported by clinical trials is reducing the serum level of C-reactive protein, which is a marker of inflammation. | |||
Figure 4. Recommendations in relations to dyslipidemia. | |||
General recommendations: | |||
* A varied and balanced diet | |||
* Regular fish intake (n – 3 fatty acids) | |||
* Fruits and vegetables, 3-5 portions per day, cereals and grain products, skimmed dairy products, and low-fat meat | |||
* Restriction of fatty products and products with a high caloric density. | |||
* The total fat intake should not be higher than 30% of calorie intake. The saturated fat intake should not be higher than 30% of total lipids | |||
* The cholesterol intake should be under 300 mg per day | |||
Specific diet recommendations: | |||
* Avoid hard margarines and products of animal origin (meat, dairy products) | |||
* Increase intake of omega-3 fatty acids from fish oils and certain vegetal oils | |||
* Increase intake of polyunsaturated fatty acids, soluble fibres, and phytosterols | |||
* Exercise and body weight reduction within obese group | |||
* Normalization of glycaemia in diabetic patients | |||