Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND: To compare the cholesterol-lowering potency of fluvastatin and lovastatin, a randomized, prospective, open-label parallel study was conducted in patients eligible for drug therapy by National Cholesterol Education Program guidelines. The study was conducted at eight centers in the United States. METHODS AND RESULTS: Patients were required to follow a cholesterol-lowering diet and were withdrawn from all lipid-lowering agents for 4 seeks prior to study entry. Patients were randomized to receive lovastatin 20 mg of fluvastatin 20 mg daily for 6 weeks. The two treatment groups were comparable with respect to demographic and clinical characteristics. Baseline lipid levels in the two groups were comparable. Lovastatin was significantly more effective than fluvastatin in lowering total cholesterol (-;19.5% vs -12.8%, P <.001) and low-density lipoprotein cholesterol (-27.6% vs -18.2%, P <.001). Changes in high-density lipoprotein and triglyceride levels were comparable in the two groups. The differences in cholesterol lowering were similar in the three strata of coronary heart disease risk factor status as defined by the second NCEP Adult Treatment Panel. Both treatments were well tolerated. CONCLUSIONS: Across the three chronic heart disease risk strata, lovastatin appears to be significantly more potent than fluvastatin, on a per milligram basis, in lowering cholesterol levels.
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PMID:A Comparison of the Tolerability and Efficacy of Lovastatin 20 mg and Fluvastatin 20 mg in the Treatment of Primary Hypercholesterolemia. 1068 6

We have previously shown that titers of soluble platelet selectin (s-P-selectin) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients with Chagas' disease at different levels of disease severity. Patients with a mild form of Chagas' disease showed a lower number of CD49d(+) cells, in comparison with those with severe chronic cardiopathy. Decreased levels of CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x) expression was found to be decreased in patients with severe Chagas' disease. Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were significantly increased in the plasma of patients with severe Chagas' disease while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P-Selectin ligands are differentially expressed during the chronic phase of the Trypanosoma cruzi infection. These findings also reinforce a role of the P-selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1, in the pathogenesis of Chagas' disease.
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PMID:alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease: further evidence of persistent immune activation. 1130 61

The developments and trends of antihyperlipidemic drugs and their effects on the mortality of coronary heart disease in Japan were investigated. The developed drugs available for hyperlipidemia were recorded with their approval dates by the Ministry of Health and Welfare (Table 1). 1. Antihyperlipidemic drugs have been developed since the late 1950s. Useful drugs among them include the fibrate series and the statin (HMG-CoA reductase inhibitor) series. Clofibrate, developed in 1965, was the first fibrate drug, and pravastatin sodium (Mevalotin(R) Sankyo Co.), developed in 1989, was the first statin drug. They have sure effectiveness for lowering serum cholesterol and triglyceride. But they induce an unfavorable side-effect, rhabdomyolisis, especially after the continuous or simultaneous use of both. The other drug classes using hyperlipidemia include various different types, e.g., probucol, nicotinates, anion exchange resins, ethyl icosapentate, and dextran sodium sulfate. Despite their mild activities, the low incidence of adverse effects make them suitable for supplementary use with fibrates or statins. 2. "Guideline for Diagnosis and Treatment of Hyperlipidemia in Adult" was presented by the Japan Atherosclersis Society in 1997. The standard criteria of serum cholesterol and triglyceride levels in Japanese adults were proposed. The hypercholesterolemia is the state of more than a 220 mg/dl level of serum cholesterol, and hypertriglyceridemia is of more than a 150 mg/dl level of serum triglyceride. The pharmacotherapy should be applied for a high serum level of cholesterol exceeding 240 mg/dl. But the standard routine formula of drug therapy were not indicated in the present guideline. 3. Epidemiological surveys show that hyperlipidemia induces coronary heart diseases in the United States, European countries, and Japan. The mortality of all heart disease patients in Japan increased rapidly from the late 1960s, but the mortality resulting from coronary heart disease was suppressed from 1968. This suppression continued throughout 1994 when artificial statistical changes occurred. It may be due to the newly developed antihyperlipidemic drugs, e.g., the clofibrate group, the statin series, and others (Fig.2).
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PMID:[A 50-year history of new drugs in Japan: the developments and trends of antihyperlipidemic drugs]. 1196 19

Lovastatin and other statins inhibit HMG-CoA reductase, which carries out an early step in the sterol biosynthesis pathway. Statins lower cholesterol and are widely prescribed to prevent heart disease, but like many drugs, they can interact with nutritionally acquired metabolites. To probe these interactions, we explored the effect of a diverse library of metabolites on statin effectiveness using a Saccharomyces cerevisiae model. In yeast, treatment with lovastatin results in reduced growth. We combined lovastatin with the library of metabolites, and found that copper and zinc ions impaired the ability of the statin to inhibit yeast growth. Using an integrated genomic and metabolomic approach, we found that lovastatin plus metal synergistically upregulated some sterol biosynthesis genes. This altered pattern of gene expression resulted in greater flux through the sterol biosynthesis pathway and an increase in ergosterol levels. Each sterol intermediate level was correlated with expression of the upstream gene. Thus, the ergosterol biosynthetic response induced by statin is enhanced by copper and zinc. In cultured mammalian cells, these metals also rescued statin growth inhibition. Because copper and zinc impair the ability of statin to reduce sterol biosynthesis, dietary intake of these metals could have clinical relevance for statin treatment in humans.
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PMID:Suppression of statin effectiveness by copper and zinc in yeast and human cells. 2108 30