Diabetes, Heart, Stroke | June 15, 2014 | Author: The Super Pharmacist
High levels of cholesterol is associated with a higher risk of heart disease and other disorders related to the impaired or reduced circulation of the blood. This is a significant source of preventable death worldwide; recent estimates indicate that up to 30% of all deaths may be attributed to cardiovascular illnesses. This is mainly due to the strong link between lipoproteins (molecules that bind to cholesterol and contribute to its accumulation) and cardiovascular disease. Not all lipoproteins are equal, or thought of as culprits in this worldwide epidemic, however.
High-density lipoproteins (HDLs) are associated with a reduced risk of heart disease, which may be due to their efficiency in binding cholesterol and transporting it for storage and breakdown.
Low-density lipoprotein type C (LDL-C) is strongly associated with an increased risk of cardiac events, or of other cardiovascular disorders such as stroke and high blood pressure.
Poor transport of cholesterol is associated with the build-up of this substance on the interior surfaces of blood vessels (arterial plaque), which is known as atherosclerosis.
Cholesterol is a large form of lipid that is the basis for many steroid-type molecules.
The prevention and treatment of heart and cardiovascular disease is often based on the reduction of concentrations of LDL-C. A class of drugs that has been found to have both properties are statins.
The mechanism of action of statins is based on inhibition of an initial step in the conversion of dietary fats (triglycerides) to LDL. Statins block the action of an enzyme called HMG-CoA reductase (HMGCR), which start off this process. This is associated with a reduction in the amount of LDL-C, and a relative increase in its high-density analog, HDL-C2.
These drugs are increasingly linked to worrying reports of adverse effects, such as liver damage, macular degeneration and arthritis. However, there is little evidence to support these links. Conversely, there may be some evidence to support the claim that the drugs are associated with a slightly increased risk of dementia and Parkinson's disease.
This is a progressive breakdown of muscle tissue, which may cause pain and weakness in the areas of the body affected. The research into this side-effect produces wildly different results. One such report indicated that the risk of myopathy was somewhat increased by statin intake, but that rhabdomyolysis (advanced muscle breakdown) occurred only once in 10,000 cases. However, other research indicates that this risk is influenced by interactions with other drugs taken by patients in conjunction with statins.
Chemicals that may increase statin-induced myopathy include niacin (vitamin B3) and certain molecules found in grapefruit juice.
There may be a slightly stronger association between statins and the increased risk of type II diabetes. This condition is an acquired resistance to insulin (the major controller of glucose metabolism) and is also associated with the development of cardiovascular disease. One study found a 2.25% increase in the risk of diabetes associated with prolonged use of statins. However, this probability is relatively low, and is often outweighed by the benefits of these drugs. The probability of type II diabetes onset while taking statins may also be influenced by genetic factors.
There are alternatives to statins for those who may be at higher risk of developing the aforementioned side-effects or are concerned about doing so. Many of the alternatives to statins target the production or accumulation of cholesterol in other ways. These alternatives include novel drugs that are currently under clinical investigation for their potential in reducing risk factors for heart disease.
Upcoming statin alternatives may be directed at the inhibition of other biological molecules involved in the formation of cholesterol.
These include apolipoprotein-B100, microsomal triglyceride transfer protein (MTP), proprotein-convertase subtilisin/kexin type 9 (PCSK9), and cholesteryl ester transport protein (CETP). Others promote 'beneficial' lipoproteins, such as apolipoprotein A1, and their mechanisms of production, e.g. adenosine triphosphate-binding cassette transporter A1 (ABCA1).
Until these are available on the market, there are other options extant that reduce either cholesterol or triglyceride levels. These include fibrates, which are a statin alternative that activates peroxisome proliferator-activated receptors (PPARs). These play a role in controlling lipid and glucose metabolism. Fibrates are associated with a reduction in circulating triglycerides16. They are also associated with a modest increase in HDLs.
Ezetimibe is a drug that reduces dietary cholesterol absorption in the gut. It was found to inhibit the binding of cholesterol to apolipoprotein B, which together form an intermediate of LDL, in a recent trial18. In combination with phenofibrate, it also reduced the concentration of LDL.
Phytosterols (stanols and sterols) are molecules found in many foods; most notably yogurt and margarine brands advertising cholesterol-lowering properties. These have in fact been shown to lower LDL concentrations in independent research settings. A recent study demonstrated the ability of approximately three grams of phytosterols a day to reduce LDL by up to 12%. A recent trial also reported a reduction of up to 9% in circulating triglycerides in response to two grams of phytosterols a day. Therefore, these molecules may also be a reliable alternative to statins.
Some B-vitamins are also associated with the potential to combat atherosclerosis. They are associated with the reduction of homocysteine, another biological molecule implicated in the formation of arterial plaque. These B-vitamins include B6, B12 and folic acid.
Vitamin B3, also known as niacin, is also associated with the reduced risk of cardiovascular disease. It has been used in combination with statins, but may increase the risk of side-effects, as mentioned above.
Niacin was shown to increase HDL-C by 17%, and reduce triglycerides by 13%, in a recent trial. Therefore, it may be a viable standalone alternative to statin therapy.
The negative effects of statins may not be as severe as they may be perceived to be. On the other hand, some individuals may be at higher risk of the more prevalent side-effects, such as type II diabetes, if they are taking statins for cardiovascular disease or high blood pressure. In these cases, considering alternatives to statins may be advisable. These include promising new drugs such as PCSK9 inhibitors and apolipoprotein A1 promoters. More established statin alternatives, such as niacin and ezetimibe, are also currently available. Therefore, prevention and treatment of cardiovascular disease is not dependent on statins alone.
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