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)

The aim of this review of the landmark HMG-CoA reductase inhibitors (statins) studies is to enable the clinician to draw practical lessons from these trials. The Scandinavian Simvastatin Survival Study (4S) established the importance of treating the hypercholesterolemic patient with established cardiovascular heart disease. The West of Scotland Coronary Prevention Study (WOSCOPS) showed the benefit of treating healthy hypercholesterolemic men who were nevertheless at high risk of developing cardiovascular heart disease in the future. The Cholesterol and Recurrent Events (CARE) study, a secondary prevention trial, proved the benefit of treating patients with myocardial ischemia and cholesterol levels within normal limits. This conclusion was confirmed by the Long-term Intervention With Pravastatin in Ischemic Disease (LIPID) study, another secondary prevention study that enrolled patients with a wide range of cholesterol levels (4-7 mmol/dL), into which the large majority of patients would belong. The importance of treating patients with established ischemic heart disease (IHD), and those at high risk of developing cardiovascular heart disease, regardless of cholesterol level, was being realized. The Air Force/Texas Coronary Artery Prevention Study (AFCAPS/TexCAPS) then showed that treatment can reduce adverse cardiovascular events even in the primary prevention of patients with normal cholesterol levels. The Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) trial showed that hypocholesterolemic therapy is useful in the setting of an acute coronary syndrome, while the Atorvastatin Versus Revascularisation Treatment (AVERT) study showed that aggressive statin therapy is as good as angioplasty in reducing ischemic cardiac events in patients with stable angina pectoris. Finally, the Heart Protection Study (HPS) randomized more than 20,000 patients, and the value of statins in reducing adverse cardiovascular events in the high-risk patient, including the elderly, women, and even in those with low cholesterol levels, is beyond doubt. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not be dependent on the actual cholesterol level of the patient. It is interesting to compare the large amount of data on the value and safety of the statins with the much more limited and less convincing data on antioxidant vitamins.
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PMID:Protecting the heart: a practical review of the statin studies. 1281 99

Allograft coronary artery disease represents a major limitation to long-term survival after cardiac transplantation. Hyperlipidemias have been linked to the development of native coronary atherosclerosis, and hyperlipidemic states have correlated with the severity of allograft coronary artery disease. Heart transplant recipients typically manifest increases in plasma levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months following transplantation. Factors known to promote post-transplant hyperlipidemia include the use of corticosteroids, cyclosporine (interference with clearance and increased oxidizability of LDL), sirolimus (hypertriglyceridemia), and patient-specific causes of hyperlipidemia which contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors are the foundation of antilipid therapy following cardiac transplantation. Pravastatin is effective in lowering plasma cholesterol levels and is associated with a decreased incidence and progression of allograft coronary artery disease. All HMG-CoA reductase inhibitors except pravastatin are metabolized by the hepatic cytochrome P450 system which metabolizes cyclosporine, increasing the risk of myostitis when they are used in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin have been studied in heart transplant recipients. Gemfibrozil has proved effective in transplant recipients when there is isolated marked elevation of plasma triglyceride levels. When hyperlipidemia persists despite therapy, some benefit may result with conversion from cyclosporine to tacrolimus. Although a definitive link between hyperlipidemia and allograft coronary disease has yet to be proven, available evidence points to abnormal lipid metabolism as part of the complex etiologic machinery driving the process of 'chronic rejection'. Consensus exists within the transplant community that a HMG-CoA reductase inhibitor such as pravastatin, should be part of the routine post-transplant drug regimen, and persistent hyperlipidemia should be aggressively treated.
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PMID:Strategies for minimizing hyperlipidemia after cardiac transplantation. 1472 53

Prescription medicines are increasingly being switched to over-the-counter (OTC, nonprescription) status in the developed world, with the support of government policy. These changes may provide greater choice for individuals and offer potential savings in government spending on health while expanding the market for pharmaceutical companies. However, there is concern regarding the safety of these reclassifications. Elderly people are the largest consumers of prescription and OTC medicines and are more vulnerable to drug adverse effects and the risks of multiple or inappropriate medications. Commonly purchased agents such as NSAIDs have recognised adverse effects which have been shown to be more common in the elderly. Furthermore, all sedatives, including antihistamines, have a propensity to cause falls in older people. As many doctors do not ask patients about OTC medicine use, problems related to use of these drugs may go undetected. Furthermore, the increased availability of OTCs may result in a delay in patients consulting medical practitioners for potentially serious conditions, although this has not so far been investigated. In the UK, the recent switch of a low-dose HMG-CoA reductase inhibitor (statin) to OTC status has caused concern. Although there might theoretically be some benefits from improved access to medications used in primary and secondary prevention of heart disease, the actual outcomes of use of this reduced dose of the statin will be difficult or impossible for patients or practitioners to monitor. OTC drug use implies a mutual responsibility for communication between patients and health professionals that in practice is not always achieved. Epidemiological research is needed to investigate patterns of OTC use and evaluate the potential risks of OTC medicines in elderly people. Governments, regulatory bodies, professionals and the drug industry have a responsibility to ensure that robust systems are in place if the increased use of OTC medicines by elderly people is to be safe and effective.
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PMID:Switching of prescription drugs to over-the-counter status: is it a good thing for the elderly? 1590 49

The landmark HMG-CoA reductase inhibitor (statin) studies have practical lessons for clinicans. The 4S trial established the importance of treating the hypercholesterolaemic patient with cardiovascular heart disease. Next, WOSCOPS showed the benefit of treating healthy, high-risk hypercholesterolaemic men. CARE, a secondary prevention trial, showed the benefit of treating patients with cholesterol levels within normal limits. This was confirmed by the LIPID trial, another secondary prevention study, which enrolled patients with cholesterol levels 155-271 mg/dl (4-7 mmol/l). The importance of treating patients with established ischaemic heart disease, and those at high risk of developing heart disease, regardless of cholesterol level, was being realized. In the MIRACL trial, hypocholesterolaemic therapy was useful in the setting of an acute coronary syndrome, while the AVERT study showed that aggressive statin therapy is as good as angioplasty in reducing ischaemic events in patients with stable angina. By showing the value of fluvastatin after percutaneous intervention, LIPS confirmed that benefit is a class action of the statins. The HPS randomized over 20 000 patients, and showed beyond doubt the value of statins in reducing cardiovascular events in the high-risk patient. Although PROSPER showed benefit in treating the elderly patients above 70 years, statin therapy in this trial was associated with an increase in cancer incidence. The comparative statin trials, PROVE-IT, REVERSAL, Phase Z of the A to Z, ALLIANCE and TNT, all showed that high-dose statins will better reduce cardiovascular events in the high-risk patient, although the adverse effects of therapy will also be increased. ALLHAT-LLT, ASCOT-LLA and CARDS showed that for statin therapy to demonstrate a significant benefit, hypertensive or diabetic patients must be at sufficiently high risk of cardiovascular events. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not the lipid level of the patient. No therapy is free of adverse effect. Treatment of those most at risk will bring the most benefit; treatment of those not at high risk of cardiovascular disease may expose patients who would not benefit much from therapy to its adverse effects.
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PMID:The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient. 1600 1

This article is a review of the scientific literature with respect to fine particulate matter (PM), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and coronary artery disease (CAD). The association between air pollution and respiratory diseases has been extensively investigated for decades; however, the role of air pollution in exacerbating heart disease has only recently become a focus of attention. It has been shown that for every 10-microg/m(3) increase in fine PM in the air, there appears to be a 2.1% increase in the number of deaths related to ischemic heart disease. PM has been linked to increased levels of systemic inflammation biomarkers such as C-reactive proteins (CRP). Daily variation of ambient pollution is correlated with rises and falls in CRP levels. Increased CRP levels have been associated with increased morbidity and mortality in individuals with CAD. Seventy-five percent of patients with elevated CRP levels have reportedly experienced a major cardiac event despite low-density lipoproteins (LDL) levels that were below the threshold recommended for pharmacological intervention. HMG CoA reductase inhibitors (statins) have been shown to cause a reduction in coronary events by lowering LDL levels. However, recently it has been shown that statins have the effect of lowering CRP levels. This may explain why individuals with normal lipid levels may benefit from statin therapy. Ambient PM exposure levels and its effects on CRP are risk factors associated with coronary events and should be considered as a target for the treatment of CAD.
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PMID:Ambient particulate matter, C-reactive protein, and coronary artery disease. 1602 37

Diseases of the heart and blood vessels are a major cause of illness and disability worldwide. The relationship between ethanol consumption and cardiovascular disease are both complex and interconnected. Our aim of this study was to explore the effect of leptin on lipid metabolism in ethanol supplemented mice. Male Swiss mice (Mus musculas) weighing 25+/-2 g were administered ethanol (6.32 g kg(-1) body weight) for the first 30 days. Subsequently, ethanol fed mice were given intraperitoneal injections of exogenous mouse recombinant leptin (230 microg kg(-1) body weight) every alternate day for 15 days. Food and water intake and total body weight were measured every day and at the end of the experimental period of 45 days, plasma and cardiac lipids were analyzed. Exogenous leptin injections to ethanol fed mice significantly (P < 0.05) prevented the accumulation of total cholesterol, phospholipids (PL), triglycerides (TG) and free fatty acids (FFA) in the mouse heart and blood as compared to the untreated ethanol fed mice whereas, the plasma concentration of free cholesterol was significantly increased on leptin administration as compared to normal untreated mice. Moreover leptin administration significantly elevated the activities of cardiac lipoprotein lipase (LPL) and plasma lecithin cholesterol acyl transferase (LCAT) and significantly reduced the activities of cardiac HMG CoA reductase and cholesterol ester synthase (CES) on leptin administration to ethanol fed mice. Thus we could postulate that an increase in systemic leptin level prevents the accumulation of lipids in the plasma and heart of ethanol treated mice.
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PMID:Intraperitoneal leptin regulates lipid metabolism in ethanol supplemented Mus musculas heart. 1613 12

It is widely known that elevated cholesterol and triglycerides levels favor the development of heart disease. In this paper we studied the effect of a protein concentrate from Amaranthus cruentus (Ac) on the lipid content in serum and liver tissue of male Wistar rats. The animals were separated into two groups, each group with 16 rats. The control diet had casein as protein source (CD), and the experimental one had Ac protein concentrate (PCAcD). The diets contained 1% cholesterol. Parameters of oxidative stress in liver with CD and PCAcD were also evaluated. No significant differences were observed in serum total cholesterol, whereas LDL decreased and HDL increased (P < 0.001), and the amount of triglycerides decreased in PCAcD as compared to CD. In liver, a decrease of total cholesterol and triglycerides (P < 0.001) was observed in the experimental group in relation to control. Fatty acid synthase (FAS) activity decreased significantly in the experimental group. The mRNA of HMG-CoA reductase did not change, and mRNA of FAS decreased in rat liver fed with PCAcD compared with CD. The excretion of total lipids in feces increased with PCAcD compared to CD (P < 0.001). The activity of reactive substances to thiobarbituric acid in liver showed no significant differences between the control and experimental diets. However, total glutathione and reduced glutathione increased in PCAcD compared to CD (P < 0.001). It can be concluded that PCAcD has a hypotriglyceridemic effect, affects the metabolism of liver lipids, and increases parameters of antioxidant protection in male Wistar rats.
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PMID:Influence of a protein concentrate from Amaranthus cruentus seeds on lipid metabolism. 1638 Jun 44

The early morphogenetic mechanisms involved in heart formation are evolutionarily conserved. A screen for genes that control Drosophila heart development revealed a cardiac defect in which pericardial and cardial cells dissociate, which causes loss of cardiac function and embryonic lethality. This phenotype resulted from mutations in the genes encoding HMG-CoA reductase, downstream enzymes in the mevalonate pathway, and G protein Ggamma1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell-autonomous requirement of Ggamma1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.
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PMID:The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1. 1685 2

Diseases of the heart and vascular systems are the leading cause of death in the United States and worldwide. High-risk patients have been the focus of lipid-lowering trials and treatment guidelines, which recognize that more intensive reduction of low-density lipoprotein cholesterol is appropriate for a redefined, broader high-risk population. Lifestyle modifications and lipid-lowering drug therapy form the foundation of primary- and secondary-prevention programs for patients at moderate to very high risk. Evidence shows that despite the availability of effective agents, such as HMG CoA reductase inhibitors (statins), many patients still do not achieve low-density lipoprotein cholesterol goals. Nurse-centered case management programs that support early and continued adherence with lifestyle and medical therapies have been consistently successful at improving the rates of achieving lipid goals in high-risk patients.
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PMID:Lipid-lowering therapy today: treating the high-risk cardiovascular patient. 1872 14

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


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