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Arteriosclerosis / atherosclerosis

 Arteriosclerosis 

Atherosclerosis occurs in the blood vessels of the human body. It is caused by the hardening of the arteries by fatty substances called cholesterol and other fats, such as those derived from the diet. Atherosclerosis can lead to complications with blood flow to various areas of your body, including cardiac arrest and stroke. 

Arteriosclerosis
 

Atherosclerosis is a disease in which fat builds up inside an artery, slowly narrowing it and causing you to have less blood flow. The buildup happens over time as a result of eating foods high in cholesterol or fat from sources like red meat or dairy products. As you age, these fatty deposits gradually grow thicker and harder, narrowing your arteries and making it more difficult for blood to pass through. Eventually, the arteries become blocked, and blood flow to the heart muscle is reduced or stopped. Atherosclerosis can also cause a stroke, in which the arteries leading to and within your brain become narrow or blocked. As a result, oxygen-rich blood can't reach all areas of your brain. This deprives them of nutrition and oxygen, which can damage or even destroy cells in the brain.

Atherosclerosis occurs in most complex biological systems including arteries and arterioles. It particularly involves coronary vessels (coronary artery disease), iliac vessels (peripheral artery disease) and subtle changes to the cerebral vasculature that increase the risk of stroke (cerebrovascular disease). The most common consequence of atherosclerosis is coronary heart disease (CHD) which can be fatal. It affects about 16% of the population over 60 years old in the Western World, and 5% in the rest of the world.

Atherosclerosis has been called "the greatest plague among man" by British physician Dr. William Osler because it is a slow, insidious process that may not always cause any noticeable symptoms until it has progressed to seriously damaging or even fatal stages. It is also known as hardening of the arteries, arteriosclerosis and arterial sclerosis.

Atherosclerosis is a disease primarily of later middle age and older. It is caused by the deposition of cholesterol and other fatty substances in the artery walls, leading to narrowing and increased resistance of blood flow. Atherosclerosis occurs when an atherosclerotic plaque thins or ruptures, usually due to a thrombosis or an embolism (blood clot or air bubble entering the bloodstream), which can cause blockage and necrosis (tissue death) in the affected artery.

Atherosclerosis may be considered as a continuum through which many different etiologies may proceed. The most common cause of atherosclerosis is the excess consumption of cholesterol and saturated fatty acids (SFA), particularly in the diet. Other risk factors for developing atherosclerosis include aging, smoking, high blood pressure, diabetes mellitus and certain medications. Children are rarely affected before puberty because the walls of their small arteries are still pliable and not subject to calcification (the process that causes hardening in adult arteries).



The earliest step in atherosclerotic disease is known as "proximal atherosclerosis," which occurs at the site where an artery leaves the heart or at a point where two or more arteries meet. This may occur due to damage or abnormalities in the endothelium, or inner lining of blood vessels. The damaged endothelium releases enzymes which cause macrophages to migrate into the space that is created and begin to ingest lipoproteins and cholesterol. The accumulation of macrophages "foam cells" eventually leads to a fatty streak visible on a cross section of an artery. Progression of atherosclerosis continues over time with more foam cells and more cholesterol being deposited; the fatty streak becomes a fibrous plaque: cholesterol crystals, smooth muscle cells, T-cells, mast cells, and macrophages adhere to the site. Over time this process can lead to partial or complete luminal occlusion within an artery. In the case of partial occlusion, a blood clot (thrombus) can form that may later dissolve or progress to become an arterial ulcer. Atherosclerosis is the most common cause of arterial ulcers.

Atherosclerotic plaques are composed mainly of cholesterol with various types of cells and tissue. The fibrous cap on top is vulnerable to rupture and can cause blood clot formation (thrombosis). Plaque rupture usually occurs at areas of least resistance, where there are already cracks in the endothelium and/or where there is already a blood clot (thrombus) adhering to the plaque.


Plaque formation can be considered a side-effect of a successful attempt by the body to repair damage to the walls of an artery. When fatty deposits (atheroma) form in an artery, they start growing and eventually begin to harden as a result of calcium accumulation. This thickening is due to the formation of collagen, which serves as an internal structural framework. The insides may have normal arterial smooth muscle cells (myocytes), fibroblasts, mast cells, etc. or other types of cells such as macrophages and T-cells that may be responsible for plaque disruption. The outer layer contains white blood cells (epitheloid layer) and calcifications. Calcifications are calcium phosphate deposits that develop around blood cells. Without growing and hardening tissue, the plaque would still be harmless to the body and not a cause for concern.

Atherosclerosis can be prevented or delayed by changes in diet, exercise, weight control (obesity), smoking cessation, and other lifestyle changes. Medications may also be used. However, the best way to prevent atherosclerosis is by avoiding risk factors such as high cholesterol levels in general and saturated fat intake in particular. High fat diets are believed to play an important role in promoting atherosclerosis because they increase both cholesterol saturation of LDL particles and total number of LDL particles circulating in circulation. In addition, animal research suggests that saturated fat intake increases atherosclerosis.

Atherosclerosis is a disease with a varied and complex pathogenesis that may involve different processes acting at different times. The causative factors include dietary lipids (especially saturated fat), genetic predisposition, smoking, hypertension, diabetes mellitus and certain medications. Increased levels of free radicals have also been implicated in the process; however, data supporting this hypothesis are inconsistent and come from either animal studies or human reports. It has been proposed that the initial changes in the lipid composition of plasma lipoproteins can increase atherosclerosis risk through increased generation of oxidized low-density lipoprotein cholesterol. Another hypothesis is that high serum cholesterol levels initiate a process of activation of some cells in the arterial wall, which leads to the development of atherosclerosis.



The "traditional" causal links of dietary lipids (especially saturated fat) and cardiovascular disease have been challenged by two lines of evidence:

Atherosclerosis is a chronic consequence of endothelial damage caused by chronic exposure to sub-lethal concentrations ("safe threshold") of oxidized low density lipoprotein (LDL) molecules. Oxidized LDL cholesterol has been shown to be the major cause for atherogenesis after brief exposure to oxidized LDL, long term exposure to higher concentrations causes nothing worse than changes in LDL subclass distribution.

In contrast to the "safe threshold", more vulnerable populations can develop severe atherosclerosis after chronic exposure with marginally "high" concentrations of oxidized LDL.

Atherosclerosis is a disease with a variably complex pathogenesis that occurs almost exclusively in the context of Western lifestyles and diets. Recently, several lines of evidence have suggested that lipids (including saturated fat) may play a role in this process. However, it is currently still controversial whether dietary lipids play an important role in the development of atherosclerotic cardiovascular disease or not.

Several studies have shown that saturated fat is associated with cardiovascular disease in large cohorts of men and women. On the other hand, a number of epidemiologic and clinical trials have not shown that reduced dietary saturated fat favors cardiovascular risk. In particular, patients with stable coronary artery disease (CAD) on a low-fat diet have been followed for a period of many years and have not experienced worse outcomes than those who continue to consume a diet high in saturated fat and cholesterol. However, in some cases, lower levels of LDL cholesterol concentration may be associated with an increased risk of vascular events and death.

Fatty diets have an adverse effect on the cardiovascular system, resulting in a state of metabolic stress with upregulation of inflammatory responses and other adaptations that may in turn accelerate atherosclerosis. Studies provide evidence that low-fat diets are not particularly good for cardiovascular health, with some studies suggesting that they may even increase the incidence of coronary heart disease compared to high-fat diets. However, a number of other studies suggest that low-fat diets may reduce cardiovascular risk compared to high-fat diets.

Many dietary choices can influence the risk of developing atherosclerosis—and thus its course and ultimate outcome. People's lifestyles and diets have changed dramatically in the past century, with a shift in the ratio of omega-3/omega-6 fats towards omega-6. The omega-3 fats are prized for their heart health benefits, and it is estimated that the typical Western diet now contains at least 20 times more omega-6 than omega-3. It is not known if such a high ratio is optimal, but there are signs that an increased intake of vegetable oils rich in linoleic acid may increase cardiovascular disease risk factors.

At a molecular level, dietary lipids affect atherosclerosis by altering serum cholesterol levels and lipid transport throughout the body. Lower serum cholesterol levels are associated with lower risks of atherosclerosis. It is believed that this is because there is a direct inverse link between atherosclerosis and cholesterol levels. It has been suggested that low density lipoprotein cholesterols (LDL) particles can directly enter macrophages in the blood vessel wall, where they become oxidized to form foam cells; foam cells are the hallmark of atherosclerotic lesions. It has also been proposed that fatty acids can overload the liver when they circulate in the blood and exhaust its capacity to detoxify lipids.

In order to reduce the risk of developing cardiovascular disease, dietary advice traditionally recommends a diet low in saturated fat. However, there is growing evidence for the potential importance of different types of fat in the atherosclerotic process. Saturated fat has been associated with increased risk for cardiovascular disease through its effect on plasma cholesterol levels and atherosclerosis.

The recommendation to reduce dietary saturated fat intake, especially from animal sources, has been a public health issue over the last few decades. Few studies have assessed the relative impact of differing types of saturated fats on cholesterol levels and other cardiovascular disease endpoints. There are some concerns about the quality of evidence about this topic, as most studies that have evaluated effects of diet on blood lipids have not been fully reported or conducted according to good scientific practice.

Most evidence has come from animal studies, that have generally not been conducted properly. A recent systematic review suggested that there was good evidence to suggest that replacement of saturated fats with polyunsaturated fats would reduce the risk of cardiovascular disease. However, this review was criticized as having conflicts of interest because the authors were involved in a food company which sells polyunsaturated rather than saturated fats.

The effects of different types of dietary fat on blood cholesterol levels and other cardiovascular disease risk factors is not well understood. Recent research findings indicate that there are not only complex interactions between various dietary lipids and cholesterol, but also differential effects from different types of polyunsaturated and monounsaturated fatty acids (PUFAs). This is of particular importance for the health status of populations, as relatively low consumption of PUFAs is typical in many societies.

To understand how foods affect blood cholesterol levels and other risk factors, it is important to consider types of fatty acids in them. In addition to the effect of saturated fat on LDL cholesterol concentrations, fats can affect high-density lipoprotein (HDL) cholesterol levels and triglyceride levels by a number of mechanisms. Polyunsaturated fats may increase HDL by a direct effect on plasma lipidation status or through indirect effects on plasma lipids that are not related to diet. Monounsaturated fats have no net effect on HDL concentrations, but may have a small beneficial effect on triglycerides. Trans fatty acids have more adverse effects on HDL and triglyceride levels than any other type of fat.

The effects of fats on risk factors for cardiovascular disease (CVD) may differ depending on the amount of carbohydrate and protein consumed in the diet. In particular, it has been suggested that a high intake of saturated fatty acids increases the risk for CVD in low-carbohydrate diets; however, in high-carbohydrate diets, a high intake of unsaturated fats may be more beneficial than saturated fats.

It is not currently clear whether trans fatty acids (trans fat) increase risk of cardiovascular disease. The only study that has directly compared the risk of CVD in populations where trans fatty acid consumption is high with populations where exposure to trans fats is low found an increased risk in the former but no association between trans fat intake and CVD in the latter.

The selected studies were subject to critical analysis, and a number of points were noted. First, many of the included studies were biased, either by being underpowered or by having involved a too small number of people. Second, all of the studies compared diets containing similar amounts of saturated fat, although this was not reported in all cases. Third, several of the studies did not afford equal weight to all dietary fat types.

The authors found that a high intake of saturated fat increases LDL cholesterol compared with a low intake of saturated fat. This observation was confirmed by four studies, and the authors were able to pool data from 11 other trials in order to confirm this relationship. The effect on LDL was more pronounced in diets containing less carbohydrate than in diets containing more carbohydrate.

A high intake of unsaturated fatty acids reduces LDL cholesterol compared with a low intake of unsaturated fatty acids. This observation was confirmed by six trials, but the authors warn that this finding is based on less robust evidence than that relating to the effects on LDL of saturated fat intake. In one of the two studies reporting on HDL cholesterol, a high intake of unsaturated fat was associated with higher HDL levels than a low intake.

A high intake of trans fatty acids raises LDL cholesterol and lowers HDL cholesterol compared with a low intake. This finding was confirmed by nine trials, and the authors were able to pool data from five other studies in order to confirm these relationships.

A high intake of monounsaturated fatty acids raises LDL cholesterol compared with a low intake; this observation was confirmed by six studies but not by the remaining three trials. No trial showed a positive effect on HDL concentrations or triglyceride levels as a result of monounsaturated fat consumption.

The authors conclude that current evidence does not support the hypothesis that the effects of dietary fat on blood cholesterol are modified by the quantity of carbohydrate and protein in the diet. Furthermore, they note: “It seems that a high intake of saturated fat from animal sources increases LDL-cholesterol levels and a high intake of trans fatty acids lowers HDL-cholesterol levels. Moreover, there is no evidence for differential effects of individual unsaturated fatty acids on LDL, HDL or triglyceride levels. A low intake of saturated fat combined with a high intake of carbohydrates from whole grains and non-starchy vegetables is associated with beneficial changes in lipid profiles.”

The authors warn that generalization from their results to the effects of individual fatty acids is difficult because the effects of these compounds are not additive, and some individuals may be more sensitive to their effects than others. The authors therefore suggest the need for more studies with different types of dietary fat. They also recommend that further research is needed to determine whether specific levels of dietary fat intake can help in understanding and predicting changes in LDL-cholesterol concentrations. Research is also needed on different types of foods rich in saturated fats, such as meat products, compared with those rich in vegetable oils, such as margarine. Finally, the effect on blood cholesterol of specific fatty acids cannot be predicted from their chemical structure. The mechanism may affect blood cholesterol levels in a similar way to monounsaturated fatty acids and trans fatty acids, although the effects of these compounds are not additive.

The authors conclude that, in order to protect against cardiovascular disease, people should eat diets containing less saturated fat and more unsaturated fat than those currently consumed. They recommend increasing consumption of polyunsaturated fats and monounsaturated fats from vegetables oils, as well as whole grains or non-starchy vegetables containing these types of fats instead of foods containing saturated fat. They also recommend increasing consumption of unsaturated fatty acids, together with whole grains and non-starchy vegetables rich in unsaturated fats.

Other sources:

DIABETES CARE – Dr Judith Rankin and colleagues .

 

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