Cholesterol Lowering Atherosclerosis Study

Carlson and Rosenhamer 1988) Cholesterol Lowering Atherosclerosis Study (CLAS) (Blankenhom et al. 1987) Familial Atherosclerosis Treatment Study (FATS) (Brown et al. 1990)... 

These studies suggest the importance of TG-rich lipoprotein reduction and HDL raising for the retardation of atherosclerosis in mild to moderate lesions, and a role for fibric acid derivatives in secondary prevention. Analysis of data from Cholesterol Lowering Atherosclerosis Study (CLAS), the Program on the Surgical Control of Hyperlipidemias (POSCH), and MARS studies also provide evidence for the importance of TG rich lipoprotein in progression of CAD. 

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

Finally, creatine supplements may be useful in the treatment of heart problems. Creatine has improved exercise capacity in patients suffering from congestive heart failure, and lowered blood cholesterol in animal studies. Limited study of creatine s effect on blood cholesterol levels in healthy humans has had mixed results, with one study reporting a positive impact and another reporting no effect at all. Further research is needed to determine if creatine is beneficial in improving blood cholesterol and preventing atherosclerosis. 

Lees, A.M., Mok, H. Y. I., Lees, R.S., McCluskey, M.A., and Grundy, S.M. 1977. Plant sterols as cholesterol-lowering agents Clinical trials in patients with hypercholesterolemia and studies of sterol balance. Atherosclerosis 28, 325-338. 

These transgenic mice are potentially promising models for the study of atherosclerosis and cardiovascular disease, and also for the development and testing of cholesterol-lowering drugs. 

Phytosterols (PS) are plant sterols and stanols widely distributed in plant sources that resemble cholesterol in terms of structure and physiological functions. The cholesterol-lowering capacity of PS is well documented in animal and human studies. However, recent studies suggest that the beneficial effects of PS are not only limited to their hypocholesterolemic capacity as they can also act as immunomodulatory, anti-inflammatory, and antidiabetic agents. Further, there is a growing body of evidence which supports that they play an important role in the prevention of other diseases such as cancer and atherosclerosis. Nevertheless, the mechanisms by which PS exert their beneficial functions, the physiological relevance of PS, and their potential adverse effects are not yet fully understood. Therefore, the main aim of this chapter is to provide a contemporaneous overview of the beneficial properties of PS, their mechanism of action, and safety. 

The cholesterol-lowering properties of phytosterols were first demonstrated in the early 1950s by Peterson (1951), who fed cholesterol and plant sterols to chicks and found that soy sterols inhibited the increase in cholesterol concentration otherwise induced by cholesterol feeding. Shortly afterwards, Poliak (1953) showed the same effect in humans, to whom he administered 5-10 g of crude sitosterol daily for up to 8 months. In similar studies in rabbits, he observed that sitosterol was poorly absorbed and that, if present in excess, it blocked the absorption of cholesterol and prevented atherosclerosis. Poor absorption and lack of any endogenous synthesis of sitosterol in humans were subsequently demonstrated by Salen et al. (1970). 

Despite stmctural similarities, the pharmacological consequences of excesses of these substances are quite different. Due to the interest in the effects of nicotinic acid on atherosclerosis, and in particular its use based on its abiUty to lower semm cholesterol, the toxicity of large doses of nicotinic acid has been evaluated. Eor example, in a study designed to assess its abiUty to lower semm cholesterol, only 28% of the patients remained in the study after receiving a large initial dose of 4 g of nicotinic acid due to intolerance at these large doses (70). 

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