Raising Low HDL Techniques - Essay Example

Raising Low HDL: What is the Best Treatment Fibrates, Niacin, and Fish oil: A Discussion Introduction: It is now well known that oxidation of low-density lipoprotein (LDL) is injurious to the endothelial cells of the arteries, and it is this LDL induced cytotoxicity that plays a central role in atherogenesis, the culprit pathologic lesion of atherosclerotic cardiovascular disease. This lipid peroxidation hypothesis has evolved to focus on specific proinflammatory oxidized phospholipids that essentially result from the oxidation of LDL phospholipids. Fortunately, it has also been demonstrated that high-density lipoproteins (HDL) inhibits this LDL-oxidation induced inflammatory reaction in the vascular endothelium. The pathological picture in an atherosclerotic lesion suggests accumulation of LDL and its oxidation in the vascular subendothelial space, where monocytes from the circulation enter to initiate an inflammatory reaction that would lead eventually to atheroma formation. Research has also demonstrated that monocyte entry occurs at the sites of LDL peroxidation, suggesting that oxidation is the cause of monocytes entry. Research has also shown that HDL apoA-I and apoA-I mimetic peptides have been shown to prevent LDL oxidation. Moreover, HDL apoA-I and apoA-I mimetic peptides have been shown to decrease atherosclerotic lesions and improve vascular reactivity in humans. Regarding its mechanism of action in producing beneficial effects against atherogenesis, studies have suggested that HDL enhances the reverse cholesterol transport. Over the top of it, apoA-I is also capable of scavenging the seeding molecules from LDL, thus preventing the LDL-derived phospholipid oxidation and the inflammatory response out of the byproducts. Thus, clinical managements directed towards improving the HDL cholesterols in the body could result in a therapeutic option of prophylactic potential in persons who are prone to atherosclerosis due to lifestyle reasons of high cholesterol and high triglycerides (Navab, M et al., 2004). Consequently, there are many therapeutic options available to enhance the HDL in human beings, and they are Fibrates, Niacin, and recently Fish oils containing omega-3 fatty acids. All of them are recommended; however, given the volume of evidence, it is very difficult to create a guideline for the patients. This work intends to critically review contemporary literature to compare the findings so a single agent can be chosen based on evidence in order to raise the HDL levels in blood. Fibrates: While statins are regarded as therapeutic cornerstones in dyslipidemia, they are ineffective because they have proven efficacy in reducing the plasma levels of LDL-C. However, they are incompetent is reducing the elevated concentrations of triglyceride rich lipoproteins, VLDL and VLDL remnants, and they have minimal actions in increasing the low levels of HDL-C that are protective. Fibrates have been observed to "reduce plasma levels of triglycerides by 30-50% and typically increase levels of HDL-C by 5-15%, depending on lipid phenotype and baseline concentration. Fibrates may also reduce LDL-C potentially by up to 15-20% although the effect is variable, depending on the underlying lipid abnormality and baseline lipid phenotype "(Chapman, MJ., 2006). This indicates individuals treated with Fibrates, levels of LDL would decrease when their plasma concentrations are elevated and HDL-C levels will increase when baseline plasma concentrations are low. Moreover, it efficiently reduces apoIII-C containing lipid particles which are acknowledged to be markers of increased risks for atherogenesis. The increased HDL levels following Fibrates are generally reflected by increased plasma levels of apoA-I and apoA-II. The Fibrates act via activation of a nuclear transcription factor PPAR in vascular tissues that actively metabolize lipids. This can be used for both primary prevention and secondary prevention of atherosclerotic cardiovascular disease with demonstrably significant decrease in the rates of mortality and myocardial infarction. Moreover, it is highly active in patients with diabetes type 2 and metabolic syndromes where reasons other than primary dyslipidemia predispose to abnormal lipid profile and high incidence of atherosclerotic vascular accidents. This class of drugs is well tolerated and has low incidence of adverse effects. Apart from bezafibrate, none of the Fibrates are indicated in renal failure. Most important adverse effects could be potentiation of Coumadin anticoagulants, so it is contraindicated as a concomitant treatment (Chapman, MJ., 2006). Niacin: Niacin in the form of nicotinic acid when taken in quantities as large as 2 grams three times a day has proved successful in rigorous clinical trials in lowering cholesterol levels in the blood and slowing the development of atherosclerosis. When niacin is taken in these quantities, which are far beyond the established upper limit of intake, it should be treated as a drug and nr taken only under the supervision of a physician. While epidemiologic studies suggest that a 1 mg/dL increase in HDL-C is associated with a 2-4% reduction in coronary heart disease adverse outcomes, it has been pertinent to include low HDL-C of less than 40 mg/dL as an established coronary risk factor. Niacin is the most effective therapy available for treatment of low HDL-C, where with a modest drug dosage of 1 g per day, there is a nonlinear dose-related increase in HDL-C to the extent of 20%. Clinical trial on niacin monotherapy to treat low HDL-C, although sprase, supports its use, and a recent study indicates its role in secondary prevention of atherosclerosis in patients with known CHD already being treated with statin monotherapy. "This study is the first demonstration of an incremental independent effect of combination therapy with statin and niacin compared with statin monotherapy to retard the progression of atherosclerosis"(Taylor, AJ., Sullenberger, LE., Lee, HJ., Lee, JK., and Grace, KA., 2004). However, such a dose is prone to produce side effects, such as flushing, pruritus, gastric irritation. These are minor side effects that can be countered with taking the drug after meals and with an aspirin 30 minutes before the intake. With stepwise increase of dose, this would lead to potential side effects like hyperuricemia, hyperglycemia, and liver function abnormalities. However when the dose first approaches 1 g per day, it reduces hepatic LDL and VLDL synthesis due to 20 to 30% reduction in total cholesterol and triglycerides with demonstrably sharp increase in circulating HDL II fraction as a result of 20 to 30% increase in HDL cholesterol. In this study, the compliance, tolerability, lipid, and carotid intima-media thickness as an indicator of reduction of atherosclerotic burden, has been studied with extended release niacin at 1000 mg/day. Flushing was the only significant side effect that can be avoided by bedtime dosing with concurrent aspirin administration (Taylor, AJ., Sullenberger, LE., Lee, HJ., Lee, JK., and Grace, KA., 2004). Fish Oils: Fish oils contain predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These are of particular interest in cardiovascular care in prevention of cardiovascular disease. They contain omega-3 fatty acids which lower blood cholesterol by an independent action, but it has also been observed that they have favorable modifying effects on various risk factors of cardiovascular disease. It has been postulated that abnormal postprandial dyslipidemia is associated with coronary artery disease. Therefore, reduction of postprandial triglycerides (TG) may prove to be cardioprotective in the long run. Park and Harris in their research article, "Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance" have drawn evidence from literature that chronic omega-3 fatty acid supplementation decreases the postprandial TG irrespective of the fat consumed in the diet. This mechanism has been proved by this research to be accelerated chylomicron clearance. This study conclusively establishes that fish oil supplementation lowers both fasting and postprandial TG concentrations. They are also known to reduce fasting TG concentrations by inhibiting hepatic VLDL-TG production. Fish oil has been known to slow hepatic VLDL production rate and reduce apoB-100 secretions from HepG2 cells. It has been hypothesized that omega-3 fatty acids in fish oil may also reduce TG secretion from the intestines into the blood. There are sufficient proof that this works in the fed state by activation of the lipoprotein lipase, and thus their actions on HDL reduction is more indirect (Park, Y. and Harris, WS., 2003). Comparison: While comparing these findings it can be stated that niacin extended release is the most potent agent that acts against low HDL, and the therapeutic effects are seen at a larger dose of more than 1 g. There are demonstrable benefits at the cost of side effects that can be prevented by an extended release preparation and adjusting the time of intake to bedtime with premedication with aspirin. Otherwise this is well tolerated. However, along with statins, its effects on low HDL is more pronounced, and hence that combination would be more preferred for both primary and secondary preventions of atherosclerotic cardiovascular disease by raising HDL-C levels. Similarly as an adjunct to statin therapy, the fish oil and contained omega-3 PUFA has been shown to provide a demonstrable lipid lowering effect. Particularly, it is different from both Fibrates and Niacin that it does have no direct action in elevating HDL; rather it reduces the levels of TG in the range of 10 to 30% in a dose dependent fashion. This reduced LDL and indirectly elevates low HDL. As an adjunct to statin therapy, it is a good and acceptable agent. However, it is considered less potent than Fibrates. It has been shown that omega-3 fatty acids are less effective than gemfibrozil at lowering the TG. Despite that, it can still be a monotherapy in patients who cannot tolerate statins and Fibrates, and in combination, it can always potentiate the actions of other lipid-lowering treatment that increases HDL. Of these three agents, niacin is the most potent since it effectively decreases total plasma levels of cholesterol, triglycerides (TGs), and LDL cholesterol (LDL-C) and increases HDL cholesterol (HDL-C). It also reduces plasma levels of lipoprotein (a). Thus it works on all parameters of the lipid profile of an individual with cardiovascular risk. When compared to Fibrates, the protective LP-AI particles are reduced by niacin, but not by Fibrates. Studies also indicate that Fibrates are weaker lipid modifying agents than niacin in all comparable parameters, especially while increasing the levels of low HDL is concerned. Although weaker, due to specific actions in diabetic individuals, Fibrates can be the therapy of choice as an effective and well-tolerated therapeutic approach to the long term management of atherogenic dyslipidemia in type 2 diabetes and metabolic syndromes. Reference List Chapman, MJ., (2006). Review: Fibrates: therapeutic review. The British Journal of Diabetes & Vascular Disease; 6: 11 - 19. Navab, M et al., (2004) Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J. Lipid Res; 45: 993 - 1007. Taylor, AJ., Sullenberger, LE., Lee, HJ., Lee, JK., and Grace, KA., (2004). Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: A Double-Blind, Placebo-Controlled Study of Extended-Release Niacin on Atherosclerosis Progression in Secondary Prevention Patients Treated With Statins. Circulation; 110: 3512 - 3517. Park, Y. and Harris, WS., (2003). Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance. J. Lipid Res.; 44: 455. Read More