Atherosclerosis lipids, lowering

The development of CHD is a lifelong process. Except in rare cases of severely elevated serum cholesterol levels, years of poor dietary habits, sedentary lifestyle, and life-habit risk factors (e.g., smoking and obesity) contribute to the development of atherosclerosis.3 Unfortunately, many individuals at risk for CHD do not receive lipid-lowering therapy or are not optimally treated. This chapter will help identify individuals at risk, assess treatment goals based on the level of CHD risk, and implement optimal treatment strategies and monitoring plans. 

Bea F, Blessing E, Shelley MI, Shultz JM, Rosenfeld ME. Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis 2003 167(2) 187-194. 

A common hepatic lipase gene promoter variant determines clinical response to intensive lipid lowering treatment. Atherosclerosis 2000 151 266. 

Figs. 12—16 to 12—22) and prevent the progressive course of Alzheimer s disease. Direct inhibition of gene expression for the biosynthesis of these proteins is not currently possible and is currently not a very feasible therapeutic possibility. Perhaps a more realistic therapeutic possibility would be to inhibit the synthesis of beta amyloid, in much the same way that lipid-lowering agents act to inhibit the biosynthesis of cholesterol in order to prevent atherosclerosis. This could be done by means of enzyme inhibitors, such as protease inhibitors, which are at least a theoretical possibility. 

Giral P, Bruckert E, Jacob N, Chapman MJ, Foglietti MJ, Turpin G. Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia. Atherosclerosis 2001 154(2) 421-7. 

Nissen SE, Tuzcu EM, Schoenhagen R et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis a randomized controlled trial. JAMA 2004 291 1071-1080. 

Leng GC, Price Jp Jepson RG. Lipid-lowering for lower limb atherosclerosis (Cochrane review). In The Cochrane Library. Oxford, England Update Software, 2001. 

Although atherosclerosis exerts its most important effects on the coronary vessels, other vascular beds are frequently affected, such as the carotid arteries, the aorta, and the vessels of the legs. However, the possibility that effective lipid lowering could have beneficial effects on atherosclerotic diseases other than CHD has received relatively little attention. Although there is some evidence that hypercholesterolemia is a risk factor for stroke, especially in younger patients (Prospective Studies Collaboration, 1995), the epidemiologic data are not nearly as extensive or unequivocal as for CHD. The first evidence that HMG-CoA reductase inhibitors could reduce the risk of cerebrovascular effects was provided by 4S, in which there was a significant 28% reduction in the... 

Probucol is a lipid-lowering agent, but the results are not consistent with respect to LDL cholesterol. It lowers HDL cholesterol hence it is not the first drug of choice in therapy. The ability of probucol to correct atherosclerosis has been attributed to its antioxidant properties.77 The usual oral dose is 500 mg twice daily and is administered after food. Many experts use it as adjuvant therapy in familial hypercholesterolemia. The drug is well tolerated but causes GI side effects such as nausea and flatulence, headache, and dizziness. Patients taking probucol must be on a low-fat diet. Probucol should not be used in patients with recent myocardial infarction, and it should not be given to children or pregnant women. 

In secondary prevention the patient has the disease and the objective is to reduce risk factors and to retard progression (e.g. aspirin and lipid-lowering drugs in atherosclerosis and post-myocardial infarction). In breast cancer, the use of tamoxifen, which can itself rarely cause endometrial cancer (which is detectable and treatable), raises complex scientific and socioeconomic issues. 

Several studies have demonstrated that intensive lowering of serum cholesterol or LDL cholesterol may retard progression of coronary atherosclerosis [32]. At present the inhibitors of key enzyme of cholesterol biosynthesis (HMG-CoA-reductase inhibitors) used in the clinical conditions as one of the most effective lipid-lowering drugs [32]. Note should be taken that HMG-CoA-reductase inhibitors may depress not only cholesterol but also ubiquinon Qio biosynthesis so far as biosynthesis of both this substances involved a common precursor [33] (Figure 16). 

Schmitz. G. er al. (1994) Lipid-lowering therapy - implications for the prevention of atherosclerosis. Bask. Res. CardioL,99S.l. 185-198. 

Aside from their effect on lipid-lowering pathways, statins have been reported to affect most of the molecular mechanisms implicated in atherosclerosis (Fig. 3). Global gene expression profiling has been valuable towards elucidating this association. 

G. Crepaldi, P. Avogaro, and G.C. Des-coviCH, et ah. Plasma lipid lowering activity of acipimox in patients with type 11 and type IV hyperlipoproteinaemia a double blind trial, Atherosclerosis, 1988,... 

AECAPS/TexCAPS = Air ForceAexas Coronary Atherosclerosis Prevention Study (Downs et ah, 1998) Helsinki = The Helsinki Heart Study (Frick et al., 1 987) LRC-CPPT = The Lipid Research Clinics Coronary Primary Prevention Trial (insull et al., 1984) Oslo = The Oslo Study (Hjermann et ah, 1988) WOSCOPS = The West of Scotland Coronary Prevention Study (Shepherd et al., 1995) ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial approximately 13-15% of patients had a history of coronary heart disease (CHD) events are CHD events only WHI = Women s Health initiative RRR = relative risk reduction ARR = absolute risk reduction NNT = number needed to treat NA = not available CEE = conjugated equine estrogen MPA = medroxyprogesterone acetate CARDS = Collaborative Atorvastatin Diabetes Study (presented at the 2004 American Diabetes Association meeting). 

Hanefeld, M., Kemmer, C., and Kadner, E. (1983). Relationship between morphological changes and lipid-lowering action of p-chlorphenoxyisobutyric acid (CRIB) on hepatic mitochondria and peroxisomes in man. Atherosclerosis 46, 239—246. 

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