Atherothrombosis is a multifactorial disease and risk factors for atherothrombosis are now estimated to be in the hundreds. In addition to classical risk factors like serum lipids (total cholesterol and triglycerides), lipoproteins, apolipoproteins, and a variety of other factors such as infections with corresponding antibodies, autoimmune constituents with corresponding antibodies, inflammatory molecules such as C-reactive protein (CRP), and hemostatic factors have been also considered for risk. In systematic review and meta-analysis of randomized controlled trials, we compared the efficacy and safety of two major natural therapies, plant sterols/stanols and policosanol, in the treatment of coronary heart disease, as measured by alterations in various plasma lipid levels. We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. A total of 4596 patients were available for analysis from 52 eligible studies (23 for plant sterols/stanols and 29 for policosanol). Reduction of low-density lipoprotein-cholesterol (LDL-C) levels was the primary end-point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end-points. The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p less than 0.0001). Policosanol also affected total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride levels more favorably than plant sterols and stanols. Further, policosanol caused a clinically significant decrease in the LDL-C:HDL-C ratio. The withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (p equal to 0.69), for plant sterols/stanols across 20 studies versus 0.86% and 0.31, respectively (p less than 0.0001), for policosanol across 28 studies. Based on these results, we concluded that plant sterols/stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterol/stanols for LDL-C level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy. Over the past year, we also carried out several collaborative studies. In a pilot clinical trial, we studied the outcomes and risks of granulocyte colony-stimulating factor (G-CSF) administration to patients with severe coronary artery disease. Patients with CAD who experience frequent angina despite attempts at revascularization are encountered with increasing frequency. We hypothesized that G-CSF administration to CAD patients may mobilize progenitor cells from bone marrow, without evidence of platelet or thrombosis activation. On the other hand, significant increases in inflammatory cells and CRP would destabilize plaques and cause adverse outcomes during treatment. Although symptoms improved in many patients following administration of G-CSF, we found no evidence of objective cardiac benefit by this cytokine-based therapeutic approach. In another collaborative study, we studied the possible mechanism(s) of increased cardiovascular risk in young premenopausal women with major depressive disorder (MDD). MDD is one of the most common psychiatric illnesses in the adult population and is often associated with an increased risk of cardiovascular disease. Although at the time of evaluation, our study subjects with MDD were mildly depressed and mostly in clinical remission on antidepressants, they had more abdominal fat and increased serum levels of prothrombotic factors (plasminogen activator inhibitor-1 [PAI-1] concentration and coagulation factor VIII [fVIII] activity) than healthy controls. The observed alterations in body fat distribution (increased abdominal fat) and prothrombotic factors (increased PAI-1 and fVIII) may be in part responsible for the increased risk of cardiovascular disease reported in association with major depression.
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