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

There is now conclusive evidence that lowering cholesterol reduces heart disease. This article describes the use of current lipid lowering drugs and the new HMG CoA reductase inhibitors and fibrates.
 ...
PMID:Treatment of hyperlipidaemias. Current avenues and new horizons. 259 74

To evaluate the effectiveness, tolerance and safety of simvastatin (MK 733), a new HMG-CoA reductase inhibitor, a 28-week, single blind study with placebo was carried out on 10 patients suffering from primary hypercholesterolaemia. All patients followed the AHA Phase 1 or Phase 2 diet and underwent active treatment for 24 weeks with increasing doses of simvastatin from 10 to 40 mg in a single evening administration. A reduction in plasma levels of total cholesterol (-29%, p less than 0.001 and -41%, p less than 0.001), LDL cholesterol (-35%, p less than 0.001 and -49%, p less than 0.001), VLDL cholesterol (-9%, ns and -38%, ns), Apo-B (-27%, p less than 0.005 and -37%, p less than 0.001), Apo-A2 (-3%, ns and -3%, ns), and triglycerides (+2%, ns and -10%, ns), was obtained in the VIth and XXIVth week. There was also an increase in HDL cholesterol (+4%, ns and +17%, p less than 0.05), HDL2 subfractions (+9%, p less than 0.05 and +36%, p less than 0.05), HDL3 (+3%, ns and +11%, ns) and Apo-A1 (+7%, ns and +4%, ns). In all patients, simvastatin was generally tolerated and there were no clinical, laboratory or ophthalmological side-effects related to the drug. If long-term studies confirm its safety, simvastatin will offer excellent prospects for the prevention of ischaemic cardiopathy.
 ...
PMID:[Effects of simvastatin on plasma levels of lipids, lipoproteins and apolipoproteins in primary hypercholesterolemia]. 269 57

The aggressive lipid-lowering goals recommended by the second Adult Treatment Panel (ATP II) have created an increasing demand for treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Fluvastatin is the first completely synthetic agent in this class and offers a considerable price advantage over the other HMG-CoA therapies. In May 1994, the Buffalo Veterans Affairs Medical Center Lipid Clinic adopted a fluvastatin-preferred program in which all patients who were recommended for an HMG-CoA reductase inhibitor would be treated with fluvastatin as a first-line agent. Fluvastatin was started at 20 mg daily and titrated to goal. Patients who were stable with other HMG-CoA reductase inhibitors were converted to fluvastatin as just described. Preliminary analysis shows that, for new patients, 20 mg of fluvastatin daily at bedtime reduced low density lipoprotein cholesterol (LDL-C) by an average of 22% (range, 5-32%). Preliminary results for patients converted from another HMG-CoA reductase inhibitor showed that fluvastatin produced an additional LDL-C reduction of 18% (range, 5-30%). With a daily dose of 20 mg fluvastatin, patients with no heart disease (primary prevention) achieved ATP II goals in 60% of cases. For patients with established heart disease (secondary prevention), the goals of ATP II are lower but, despite this, 30% of patients taking fluvastatin at 20 mg daily achieved these goals. The patients in both groups who failed to achieve ATP II goals were titrated to a 40 mg daily dose, but the results of this titration are not yet available. Pharmacoeconomic outcomes were favorable.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Outcome monitoring of fluvastatin in a Department of Veterans Affairs lipid clinic. 760 1

The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position -93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.
 ...
PMID:The promoter of the rat 3-hydroxy-3-methylglutaryl coenzyme A reductase gene contains a tissue-specific estrogen-responsive region. 1044 99

Cardiomyopathic hamsters develop heart disease early in life, which leads to congestive heart failure and death as these hamsters age. Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to reduce ubiquinone concentrations and to deteriorate myocardial function in humans and in experimental animals. HMG-CoA reductase inhibitors differ regarding their ability to penetrate extrahepatic tissues. As a consequence, lovastatin inhibits cholesterol biosynthesis at least 100-fold more effectively than pravastatin in extrahepatic cells. We examined the effect of lovastatin and pravastatin (approximately 10 mg per kilogram of body weight and per day mixed in the diet) compared with controls on the lifespan of cardiomyopathic hamsters (BIO 8262 strain) in the heart-failure period. In male hamsters, neither lovastatin nor pravastatin significantly affected survival. In female hamsters, lovastatin reduced median survival time from 89 days (control animals) to 30 days (P <.05); pravastatin (median survival, 115 days) had no statistically significant effect. We conclude that lovastatin, but not pravastatin, at a daily dose of 10 mg per kilogram of body weight significantly increases the mortality of cardiomyopathic hamsters. This effect may be the result of inhibition of myocardial ubiquinone supply.
 ...
PMID:Effects of lovastatin and pravastatin on the survival of hamsters with inherited cardiomyopathy. 1115 Mar 97

The metabolic syndrome consists of a cluster of metabolic disorders, many of which promote the development of atherosclerosis and increase the risk to develop cardiovascular disease. The metabolic syndrome is characterized by atherogenic dyslipidemia (elevated triglycerides, increased small dense low-density lipoproteins, and decreased high-density lipoproteins), hypertension, insulin resistance and obesity. To decrease the risk of cardiovascular disease events decreasing body weight by ingesting a healthy diet, increasing physical activity, cessation of smoking and managing dyslipidemia are recommended. Pharmacological treatment of dyslipidemia is based on different drug classes. For LDL-cholesterol-lowering mainly statins and for triglyceride-lowering mainly fibrates are used. In primary and secondary prevention trials of heart disease they have shown to reduce the incidence of coronary artery disease or coronary events by 25-60 percent. Statins reduce mainly LDL-cholesterol levels by competitive inhibition of HMG-CoA reductase but have also shown to reduce fasting and postprandial triglyceride levels. Fibrates effectively reduce fasting and postprandial lipemia, shift the distribution of LDL particles towards less dense particles and increase HDL-cholesterol. Thus fibrates particularly address components of the metabolic syndrome and features of diabetic dyslipidemia. However studies still are needed showing definite evidence on differential therapy in lipid lowering based on prospective controlled trials with endpoints of macro- and microangiopathy in diabetic patients.
 ...
PMID:Treatment of dyslipoproteinemia in the metabolic syndrome. 1145 42

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).
 ...
PMID:[A 50-year history of new drugs in Japan: the developments and trends of antihyperlipidemic drugs]. 1196 19

Hyperlipidemia is a well-known risk factor for atherosclerosis and statins are widely used to treat patients with elevated levels of lipids in their plasma. Notwithstanding the proven benefits of statin drugs on both primary and secondary prevention of heart disease, the high cost of statin treatment, in addition to possible side effects such as liver function abnormalities, may limit their widespread use. We conducted a study on a natural product as an alternative to statin treatment. Cholestin, a dietary supplement, is prepared from rice fermented with red yeast (Monascus purpureus), which has been shown to significantly decrease total cholesterol levels in hyperlipidemic subjects. Our objective was to determine the cellular effect of Cholestin on cholesterol synthesis in human hepatic cells (HepG2) and the mechanism by which it caused a change in lipid metabolism. Cholestin had a direct inhibitory effect on HMG-CoA reductase activity (78-69% of control). Cholesterol levels in HepG2 cells treated with Cholestin (25-100 microg/mL) were significantly reduced in a dose-dependent manner (81-45% of control, respectively). This reduction was associated with decreased synthesis and secretion of both unesterified cholesterol (54-31 and 33-14% of control, respectively) and cholesteryl ester (18-6 and 37-19% of control, respectively). These results indicate that one of the anti-hyperlipidemic actions of Cholestin is a consequence of an inhibitory effect on cholesterol biosynthesis in hepatic cells and provide the first documentation of a biomolecular action of red yeast rice.
 ...
PMID:Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2). 1208 70

The cholesterol-lowering drug simvastatin (SIMV, Zocor reduced heart attacks by 42% in patients who had high cholesterol levels and suffered from heart disease. Upon oral administration, SIMV is quickly hydrolyzed to its beta-hydroxyacid and other acid metabolites, which are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. A Tecan-based enzyme inhibition assay has been developed to improve the existing Zymark-based assay for the determination of both active and total concentrations of HMG-CoA reductase inhibitors in human plasma. A Tecan Genesis 200 robotic workstation equipped with eight probes and customized hardware was utilized to achieve higher sample throughput and improve assay reproducibility and mechanical stability. The developed enzyme inhibition assay was validated over two concentration ranges of 0.4-20 ng equivalent/mL, and 2-50 ng equivalent/mL. Intra- and interday precision data (coefficient of variation (CV)) for both concentration ranges were less than 9%, with an accuracy of 93-107%. The interday precision for the determination of quality control (QC) samples was less than 2% and 8%, respectively. The respective interday QC accuracy values were 93-103% and 97-104%. Good linearity across the two concentration ranges was observed, with acceptable reproducibility. This improved enzyme inhibition assay has been utilized to analyze human plasma samples from several clinical studies.
 ...
PMID:Robotic inhibition assay for determination of HMG-CoA reductase inhibitors in human plasma. 1235 48

Recent advances in the prevention and pharmacotherapy of cerebrovascular disease have provided more favorable clinical outcomes. For the treatment of an acute ischemic stroke, the early use of thrombolytic agents can reduce the degree of brain damage while improving functional outcomes. However, trials evaluating various classes of other neuroprotective agents have not shown benefit to date. For the prevention of second stroke, the use of antiplatelet drugs, HMG-CoA reductase inhibitors, and angiotensin-converting enzyme inhibitors with a diuretic have shown benefit in reducing new events. In patients with underlying heart disease or atrial fibrillation, warfarin appears to be the drug of choice in preventing stroke. Early treatment of hemorrhagic stroke with calcium channel blockers can improve the functional outcome. Innovative therapies are now available for the treatment of migraine and vascular dementia. Primary prevention of stroke remains the optimal therapeutic strategy and includes treatment of systemic hypertension and hypercholesterolemia.
 ...
PMID:Drug therapy of neurovascular disease. 1270 43


1 2 3 Next >>