Cholesterol reduction

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

The scientific interest in cereal /1-glucans arose partly from the problems they cause in brewing and animal-feed industries in the case of barley [318] and partly from the health benefits, such as cholesterol reduction [319-321], regulation of postgrandial seriun glucose levels in humans and animals [319,322], and immunostimulatory activity [323,324]. Some of these activities have been observed with both oat and barley )6-glucans [325]. 

Goldberg Arnold R, Kaniecki D, Tak Piech C, et al. An economic evaluation of HMG-CoA reductase inhibitors for cholesterol reduction in the primary prevention of coronary heart disease. 11th International Conference on Pharmacoepidemiology. Montreal, Quebec, Canada, 1995. 

One of the first pharmacogenomic studies investigating lipid-lowering drags was published by Nestrack et al. in 1987 [29], describing that carriers of at least one apo E4 allele who received probucol showed the greatest cholesterol reduction in comparison to those without an apo E4 allele. These data were confirmed in a second study by Eto et al. [30]. 

It would be very interesting to go back into the other cohorts, in which no difference in cholesterol reduction between the genotypes has been seen and to examine, whether the statin treatment also abolished excess mortality of apo E4 carriers. 

The most common practice in cost-effectiveness analysis involving a drug is to use average wholesale price (AWP) as the measure of cost from a societal perspective. Here is a classic example. The well-regarded Gold et al. (1996) book on methods for cost-effectiveness analysis presents some worked examples of analysis done from a societal perspective. One is the study by Stinnett et al. (1996) on the cost effectiveness of dietary and pharmacologic therapy for cholesterol reduction. The authors stated that they use a societal perspective. 

Stinnett, A. A., et al. 1996. The Cost Effectiveness of Dietary and Pharmacologic Therapy for Cholesterol Reduction in Adults, in Cost Effectiveness in Health and Medicine, ed. by M. Gold, J. E. Siegel, L. B. Russell, and M. C. Weinstein, 349-391. Oxford Oxford... 

Modest cholesterol reductions as monotherapy (15%) primary use in combination with statins to achieve and sustain LDL goals... 

In 1999, the US FDA allowed health claims (on food labels) on the association between soy protein and reduced risk of coronary heart disease for foods containing >6.25 g of soy protein, assuming either four servings, or that a total of 25 g of soy protein are consumed daily. Furthermore, in 2002, the UK Joint Health Claims Initiative approved a health claim on the association between soy protein and cholesterol reduction, the inclusion of at least 25 g of soy protein per day, as part of a diet low in saturated fat, can help reduce blood cholesterol levels and it is important to note that this claim relates to soy protein that has retained its naturally occurring isoflavones. 

This break-out of values is much more informative to the vast majority of patients than the all-patient average. Variable dosing, which occurred as well in the placebo group, though with a somewhat different distribution than in the active group, had no evident effect on the two main endpoints of the LRC-CPPT, cholesterol reduction and coronary risk reduction (Lipid Research Clinics Coronary Primary Prevention Trial, 1984). 

The interaction of diltiazem with simvastatin has been investigated in 135 patients attending a hypertension clinic (39). Cholesterol reduction in the 19 patients taking diltiazem was 33% compared with 25% in the other 116 patients (median difference 8.6% 95% Cl = 1.1, 12). Multivariate analysis showed that concurrent diltiazem therapy, age, and the starting dose of simvastatin were independent predictors of percentage cholesterol response. The authors concluded that patients who take both diltiazem and simvastatin may need lower doses of simvastatin to achieve the recommended reduction in cholesterol. 

Yeo KR, Yeo WW, Wallis EJ, Ramsay LE. Enhanced cholesterol reduction by simvastatin in diltiazem-treated patients. Br J Clin Pharmacol 1999 48(4) 610-5. 

D.E. values for the citrus and tomato pectins were 56 and 40%, respectively. Thus, differences in D.E. levels rather than pectin source could have accounted for the superior effectiveness of citrus pectin. Mokady (80) and Judd et al. (81) confirmed that serum cholesterol reduction is most pronounced with high D.E., high-molecular-weight pectin (Table I). 

Gallaher, C.M., Munion, J., Hesslink, R., Jr., Wise, J., and Gallaher, D.D. 2000. Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J. Nutr. 130, 2753-2759. 

Nagaoka, S., Awano, T., Nagata, N., Masaoka, M., Hori, G., and Hashimoto, K. 1997. Serum cholesterol reduction and cholesterol absorption inhibition in CaCo-2 cells by a soyprotein peptic hydrolyzate. Biosci. Biotechnol. Biochem. 61, 354-356. 

However, the reductase inhibitors clearly induce an increase in high-affinity LDL receptors. This effect increases both the fractional catabolic rate of LDL and the liver s extraction of LDL precursors (VLDL remnants), thus reducing plasma LDL (Figure 35-2). Because of marked first-pass hepatic extraction, the major effect is on liver. Preferential activity in liver of some congeners appears to be attributable to tissue-specific differences in uptake. Limited reduction of LDL levels in patients who lack functional LDL receptors indicates that decreases in de novo cholesterologenesis also contribute to cholesterol reduction. Modest decreases in plasma triglycerides and small increases in HDL also occur. 

Muldoon MF, Manuck SB, Mendelsohn AB, Kaplan JR, Belle S. Cholesterol reduction and non-illness mortality Meta-analysis of randomized clinical trials. BMJ 2001 322 11-15. 

Law MR. Lowering heart disease risk with cholesterol reduction evidence from observational studies and clinical trials. Eur HeartJ Suppl I999 I(suppl S) S3-S8. 

Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995 92 3172-3177. 

Robinson JG, Smith B, Maheshwari N, Schrott H, Pleiotropic effects of statins benefit beyond cholesterol reduction A meta-regression analysis. J Am Coll Cardiol 2005 46 1855-1862. 

Buchwald H, Bourdages HR, Campos CT, et al. Impact of cholesterol reduction on peripheral arterial disease in the Program on the Surgical Control of the Hyperlipidemias (POSCH). Surgery 1996 120 672-679. 

Mohler ER111, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation 2003 108(12) 1481-1486. 

Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP Jr, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. Jama 2004 291 2821-2827. 

Figure 9.22 Coprastanol and cholestanol, products of cholesterol reduction. Dotted lines indicate positions below the plane of the ring (trans with respect to -CH3 on position 10) solid lines indicate positions above the plane of the ring (cis with respect to -CH3 on position 10). Both structures are of the /3 type.

Boudreau, A., Arul, J. 1993. Cholesterol reduction and fat fractionation technologies for milk... 

Entry Reduction in Plasma Cholesterol (%) Reduction in Cholesterol Esters (%) Dose (mg/kg)... 

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