Lipid elevated plasma

Which of the following individual drugs or drug combinations can safely be used to produce maximum lowering of her elevated plasma lipids ... 

Oral vitamin E, 300 mg and 600 mg daily for 2 weeks, administered to type II and IV hyperlipoproteinaemia patients increased the serum vitamin E concentration 2- fold and suppressed the normally elevated plasma lipid peroxide... 

Rigas, J.R., Warrell, R.P., Jr., and Young, C.W. 1994. Elevated plasma lipid peroxide content correlates with rapid plasma clearance of all-trans-retinoic acid in patients with advanced cancer. 

Voutilainen S, et al. Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels. Arterioscler Thromb Vase Biol 1999 19(5) 1263-1266. 

Since the time the lipid hypothesis was proposed, a number of other risk factors, that can be modified, for CHD have been reported. Of importance are hypertension, cigarette smoking, obesity and physical inactivity, diabetes mellitus, and elevated plasma levels of Lp(a) and homocysteine (Braunwald, 1997 Schaefer, 2002). 

MahadikSP, MukherjeeS, Scheffer R, CorrentiEE, Mahadik JS. 1998. Elevated plasma lipid peroxides at the onset of nonaffective psychosis. Biol Psychiatry 43 674-679. Malaspina D, Coleman E, Goetz RR, Harkavy-Friedman J, Corcoran C, et al. 2002. Odor identification, eye tracking and deficit syndrome schizophrenia. Biol Psychiatry 51 809-815. 

V5. Voutilainen, S., Morrow, J. D., Roberts, L. J., II, Alfthan, G., Alho, H., Nyyssonen, K., and Salonen, J. T., Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels. Arterioscler. Thromb. Vase. Biol. 19, 1263-1266 (1999). 

Elevated plasma levels of lipoprotein Lp(a) increase the risk of atherosclerosis in humans. Apolipoprotein (a), a constituent of Lp(a), is not found in most species other than primates. Transgenic mice expressing the human apolipoprotein(a) gene, placed on an atherogenic diet, show increased susceptibility to the development of lipid-containing lesions in the aorta (Lawn et al, 1992 Scott, 1992). 

As the knowledge of the pathogenesis of atherosclerosis rapidly increases, it appears that an active vascular endothelium, smooth muscle cells, and blood-borne cells such as monocytes and macrophages all play active roles in the atherosclerotic disease process. Risk factors, such as elevated plasma levels of certain lipids, prooxidants, and cytokines, may contribute to the chronic activation/stimulation as well as to the damage of the endothelium and other vascular tissues (160). There is evidence that supports the hypothesis that it is not only pure cholesterol and saturated fats but rather oxidation products of cholesterol and unsaturated fats (and possibly certain pure unsaturated fats) that are atherogenic, possibly by causing endothelial cell injury/dysfiinction. Lipid-mediated endothelial cell dysfunction may lead to adhesion of monocytes, increased permeability of the endothelium to macromolecules, i.e., a decrease in endothelial barrier function, and disturbances in growth control of the vessel wall. 

The effects of palm oil on serum lipids and lipoproteins recorded in animal studies have similarly been observed in several human studies. In some early human studies (152, 153), it was reported that subjects on a palm oil diet had elevated plasma and low-density lipoprotein cholesterol LDL-C levels compared to a diet containing a polyusaturated fat. However, on a critical reassessment of these and other relevant studies (154), it was found that plasma cholesterol levels after the palm oil period were actually lower than at the point of entry of the experiments when the subjects were on their habitual diets. 

Hyperlipidemia is the most prevalent indicator for.suscep-nbility to atherosclerotic heart disease it is a term u.sed to ilrvribc elevated plasma levels of lipids that are usually in liefonn of lipoproteins. Hyperlipidemia may be caused by... 

The increased fat mass in obese individuals, associated with enhanced lipolysis in insulin-resistant NIDDM, leads to elevated plasma FFA and stimulates lipid oxidation by peripheral tissues. In non-insulin-dependent diabetics, ketone formation, however, is not increased because sufficient insulin is available to restrain hepatic production and stimulate peripheral utilization. 

Patients with diabetes frequently have elevated plasma concentrations of triglycerides and low-density lipoprotein (LDL) cholesterol concentration, together with reduced high-density lipoprotein (HDL) cholesterol concentration. Studies of the effect of sulphonylureas on lipid metabolism in Type-II diabetes, however, are quite controversial and the results have been discussed widely during the last few years. Glibenclamide and metformin were found to have no primary effect on serum triglycerides (Rains et al., 1988). Neither drug altered HDL cholesterol or subfraction cholesterol. Metformin alone, however, reduced LDL cholesterol. 

Mahadik SP, Mukheijee S, Scheffer R, Correnti EE, Mahadik JS. Elevated plasma lipid peroxides at the onset of nonaffective psychosis. Biol Psychiahy 1998 43 674-679... 

Lipid Phenotype Plasma Lipid Levels, mmol/L (mg/dL) Lipoproteins Elevated Phenotype Clinical Signs... 

Schaefer EJ, Lamon-Fava S, Ordovas JM, Cohn SD, Schaefer MM, Castelh WP, Wilson PW. Factors associated with low and elevated plasma high density hpoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study. J Lipid Res 35(1994)... 

The casual association of certain forms of hyperlipidaemia and CHD is clearly the major stimulus for the measurement of plasma lipids and lipoproteins in clinical practice. The most common lipid disorder linked with aiherogenesis and an increased risk of CHD is an elevated plasma LDL cholesterol level, hut increasingly it is being recognized that individuals with low plasma HDL cholesterol and hypertriglycerid-aemia are also at increased risk. 

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