UMLS:C0007222 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0007222 (cardiovascular disease)
65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial hypercholesterolemia provides an excellent model for demonstrating how disease prevention can be facilitated by molecular characterization of a genetic disease. To achieve the most efficient yield in terms of patient identification and coronary heart disease prevention, family information should be obtained in the primary care setting. In the majority of cases, measurement of cholesterol levels in a patient's relatives is sufficient to determine presence or absence of familial hypercholesterolemia, and DNA testing may be used in those cases in which cholesterol level is not diagnostic. DNA testing has enabled a more refined assessment of the absolute cardiovascular risks associated with familial hypercholesterolemia, which is currently estimated to have a 50% mortality rate by age 60. Recent investigations using DNA testing have suggested that familial hypercholesterolemia is implicated in one of 12 cases of cardiovascular disease in individuals aged <65 years. Only the most potent lipid-modifying therapies should be used in those found to be affected by this disorder. In this regard, it is noteworthy that the new statin rosuvastatin (Crestor; AstraZeneca) was recently shown to produce significantly greater low-density lipoprotein (LDL) cholesterol reductions and high-density lipoprotein (HDL) cholesterol increases than atorvastatin in a large study in patients with familial hypercholesterolemia, while bringing more of these patients to LDL cholesterol goals. Familial hypercholesterolemia should serve as a paradigm of molecular medicine: we understand the genetic defect, we have the tools to identify the individuals who are at high risk of disease because they have the defect, and we have therapies that can prevent clinical disease. It nevertheless requires effort on the part of clinicians to ensure that optimal risk assessment is performed and optimal treatment provided.
...
PMID:High risk/high priority: familial hypercholesterolemia--a paradigm for molecular medicine. 1197 74

Cardiovascular disease (CVD) remains a major cause of death in industrialised societies, and elevated serum lipids are a significant, highly prevalent and undertreated risk factor for this condition. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have revolutionised the treatment of hyperlipidaemia, and results from large-scale, long-term clinical trials have shown that the substantial reductions in low-density lipoprotein cholesterol (LDL-C) achieved with these drugs are associated with dramatic decreases in cardiovascular risk. Results from recent comparative clinical trials that have included a new drug in this class, rosuvastatin (Crestor), have demonstrated that it is significantly superior to atorvastatin, pravastatin and simvastatin in reducing total cholesterol, LDL-C and apolipoprotein B (Apo B). It is also significantly more effective than atorvastatin in increasing high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I). Rosuvastatin was also superior to all these agents in helping patients meet European Atherosclerosis Society (EAS) and National Cholesterol Education Programme (NCEP) goals for LDL-C. The results of an increasing number of studies indicate that statins have a wide range of pleiotropic properties that almost certainly contribute to their ability to decrease cardiovascular risk and may also make them valuable for treatment of other diseases. These actions include plaque stabilisation, improvement of endothelial function, inhibition of smooth muscle cell proliferation and migration, reduction of expression of adhesion molecules, prevention of cholesterol esterification and accumulation, reduction of secretion of matrix metalloproteinases by macrophages, reduction of platelet activity, reduction of formation of thrombogenic factors, chemoprotection and induction of bone morphogenic protein-2 (BMP-2). Further exploration of these actions will provide key information about class effects and properties of specific members of this highly useful group of drugs.
...
PMID:Statin therapy: rationale for a new agent, rosuvastatin. 1213 48

Familial hypercholesterolaemia (FH) is a hereditary metabolic disorder characterised by defects in the low-density lipoprotein (LDL) receptor, elevated LDL cholesterol (LDL-C) levels and an extremely high risk for premature cardiovascular disease. Heterozygous FH occurs in about one of every 500 individuals in the United States and Europe. The high prevalence of FH and associated morbidity and mortality strongly support aggressive screening and treatment. There are two major barriers to effective management of FH: 1) the failure to screen for this disease in people who may be at increased risk for it; and 2) the inability of most available therapies to enable achievement of LDL-C goals. More aggressive screening, coupled with new genetic screening techniques, and more powerful 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to overcome these limitations. Automated genetic assays are now available for detection of common LDL receptor mutations in individuals at risk for FH, and they have been used effectively to identify patients with this condition. Recent clinical trial results with the new synthetic statin rosuvastatin (Crestor; AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK; licensed from Shionogi & Co, Ltd, Osaka, Japan) in patients with heterozygous FH have shown that it decreased LDL-C by 58% and increased high-density lipoprotein cholesterol (HDL-C) by 12%. Rosuvastatin was significantly superior to high-dose atorvastatin in improving these lipid parameters as well as total cholesterol, apolipoprotein (apo) B, apo A-I, and the LDL-C/HDL-C ratio. Thus, new screening tools and medical therapies have the potential to significantly improve management and reduce cardiovascular disease risk for patients with FH.
...
PMID:Familial hypercholesterolaemia: optimum treatment strategies. 1229 5

Carotid artery intima-media thickness (IMT) measured by ultrasound has been shown to be correlated with existing cardiovascular disease (CVD) and predictive of CVD in individuals without clinically evident disease. Carotid IMT is now widely used as a surrogate marker for atherosclerotic disease. A number of studies have shown that lipid-lowering therapy with a statin can reduce or reverse carotid IMT progression. The METEOR trial (Measuring Effects on Intima-Media Thickness: an Evaluation Of Rosuvastatin) will examine the effects of aggressive lipid-lowering treatment with rosuvastatin on IMT in mildly hypercholesterolemic low-risk subjects with relatively high IMT values. The results will provide important information on the ability to achieve regression of abnormal IMT with robust reductions in low-density lipoprotein (LDL) cholesterol levels to below current target levels. Another study will examine the effects of potent LDL cholesterol reduction with rosuvastatin in young patients with heterozygous familial hypercholesterolemia (FH). Patients with FH are at increased risk of premature coronary heart disease in association with marked LDL cholesterol elevations, exhibiting a rate of progression of IMT 5x greater than that of low-risk controls without the disorder and early intervention may be the optimal approach to modifying atherosclerosis progression in these patients.
...
PMID:Surrogate markers of atherosclerosis: impact of statins. 1271 35

Inflammation is a major factor in atherothrombotic disease. Levels of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Recent findings in 27,939 healthy women in the Women's Health Study indicate that hs-CRP (1) is a stronger predictor of risk than low-density lipoprotein (LDL) cholesterol, (2) predicts elevated risk in subjects without overt hyperlipidemia, and (3) adds prognostic information to risk scoring and LDL cholesterol categories. Other data from this cohort show that hs-CRP level adds prognostic information to the diagnosis of the metabolic syndrome. Taken together with other data in men on the association of hs-CRP with vascular risk, a strong argument is provided for screening in the primary prevention population. With regard to potential treatment, statins have been found to reduce hs-CRP levels, and data from statin treatment trials raise the possibility that subjects with elevated hs-CRP levels may derive greater benefit from treatment than do patients without elevated hs-CRP. The Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial is planned to examine the effects of rosuvastatin treatment in preventing cardiovascular events in 15,000 healthy subjects with elevated hs-CRP levels in the absence of overt hyperlipidemia.
...
PMID:High-sensitivity C-reactive protein and cardiovascular risk: rationale for screening and primary prevention. 1294 72

Statins are central to the government's National Service Framework (NSF) for coronary heart disease (CHD). NHS spending on statins is currently about pounds sterling 500 million per annum and rising at an annual rate of 30%. Although generally considered to be a cost-effective treatment for hyperlipidaemia and cardiovascular disease, given the high and rising expenditure on statins in the UK, there is a pressing need to ensure that the choice between available statins reflects cost-effectiveness considerations. A decision model was developed to establish the cost-effectiveness of treating new hypercholesterolaemic patients to UK and European target levels of blood total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), using rosuvastatin, atorvastatin, simvastatin, pravastatin or fluvastatin. The model was used to estimate the proportion of patients reaching target and the associated costs over a one-year period from the perspective of the NHS. The effectiveness of the alternative statins were modelled using data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. Monte Carlo simulation was used to reflect uncertainty in the parameter estimates applied in the model. Rosuvastatin is demonstrated to dominate (i.e. lower costs and a higher number of patients treated to target) atorvastatin, simvastatin and pravastatin. Compared with fluvastatin, the incremental cost per additional patient to target (PTT) for rosuvastatin was pounds sterling 24 using LDL-C and pounds sterling 83 using TC. The probability that rosuvastatin is cost-effective exceeds 95%, provided the NHS is prepared to pay at least pounds sterling 35 per PTT to achieve target LDL-C cholesterol levels (pounds sterling 160 for TC). The analysis demonstrates rosuvastatin is more cost-effective than the other statins in achieving UK and European cholesterol targets.
...
PMID:The cost-effectiveness of a new statin (rosuvastatin) in the UK NHS. 1468 71

Epidemiological studies identified several risk factors as cardiovascular disease correlates, including smoking, obesity, hypertension, diabetes, and increased plasma lipids. High blood cholesterol, and in particular LDL cholesterol levels, represents a major determinant of coronary artery disease, in particular when included in the context of a comprehensive risk profile. The more recent guidelines (especially NCEP ATP III in the United States, and the European Joint Task Force) have suggested the opportunity to favor treatment of those subjects with higher global cardiovascular risk, first of all of those individuals with coronary artery disease or another cardiovascular manifestation or diabetes, then of subjects with clustered risk factors or with markedly raised levels of single risk factors, eventually of other subjects. In this perspective the treatment also of slight dyslipidemias has been shown capable of reducing cardiovascular event incidence and mortality. Recent investigations, aiming at evaluating the impact of these "clinical recommendations" in the treatment of dyslipidemias or other cardiovascular risk factors within a framework of high global cardiovascular risk (EURO-ASPIRE II, L-TAP, etc.), showed inadequate attention of community-based medicine, disclosed by the insufficient number of subjects investigated and by the large number of untreated or undertreated patients. Rosuvastatin, a recently marketed inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, is an effective drug which may normalize high plasma cholesterol among high-risk subjects more often than other similar molecules, thus permitting to reach stringent guideline lipid targets. It is hoped that coronary risk charts based on Italian data will be implemented, with the purpose of better finding and treating those subjects who may benefit, at a suitable level of cardiovascular risk.
...
PMID:[Dyslipidemia and global cardiovascular risk: treatment guidelines]. 1498 42

Inflammation participates critically in atherosclerosis. Circulating levels of several inflammatory markers rise in individuals at risk for atherosclerotic events. In particular, elevation of plasma C-reactive protein (CRP), a nonspecific acute-phase reactant that is easily and reliably measured, has strong predictive power for cardiovascular events. Indeed, measurements of high-sensitivity CRP (hs-CRP) plasma levels add to both the prognostic information gleaned from assay of plasma lipid risk factors and the risk levels estimated by means of Framingham study-based criteria. Retrospective data suggest the hypothesis that hs-CRP plasma levels may be useful for guiding use of lipid-lowering therapy in individuals who appear to be at low risk according to traditional risk assessment. A large-scale, randomized clinical trial-Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)-will test whether rosuvastatin therapy will reduce incident cardiovascular disease in subjects with elevated plasma hs-CRP concentrations who do not meet current criteria for initiation of lipid-lowering drug therapy. Such clinical trial data may provide an evidence base for the use of plasma CRP assay as an adjuvant guide to therapy to complement the established traditional risk factors such as plasma lipid levels. Thus, medical practitioners are ushering in an era in which the biology of inflammation in atherosclerosis will find its way into clinical application.
...
PMID:Inflammation and atherosclerosis: role of C-reactive protein in risk assessment. 1505 Jan 87

Although large-scale statin trials have demonstrated significant reductions in cardiovascular risk, there are many patients who have a cardiovascular event despite receiving statin therapy. There is increasing evidence that larger reductions in low-density lipoprotein cholesterol (LDL-C) are associated with greater improvements in cardiovascular morbidity and mortality, which highlights the need for more efficacious statins. This article will review the lipid-altering effects of two new statins, rosuvastatin and pitavastatin. Rosuvastatin represents an advance in the pharmacological and clinical properties of other available agents. The large LDL-C reductions observed with rosuvastatin, even at the start dose of 10 mg and in patients switched from other statins to rosuvastatin 10 mg, should help to improve goal attainment, while reducing the need for dose titration. The ability of rosuvastatin to improve other elements of the lipid profile, such as high-density lipoprotein cholesterol (HDL-C), triglycerides and non-HDL-C, may be of utility in patients with diabetes and the metabolic syndrome. Increases in HDL-C, along with the greater efficacy of rosuvastatin for reducing LDL-C and non-HDL-C, may obviate the need for combination therapy. Results of a number of outcome studies with rosuvastatin are expected over the next 5 years, which will contribute to the evidence base for statin therapy and cardiovascular disease prevention.
...
PMID:Statins: can the new generation make an impression? 1557 84

A low level of high-density lipoprotein cholesterol (HDL-C) is a key feature of the metabolic syndrome and type 2 diabetes. HDL particles exert an anti-atherogenic effect, and low HDL-C levels are associated with increased cardiovascular disease risk. The profile of lipoprotein sub-classes may also be abnormal in patients with the metabolic syndrome or type 2 diabetes, with an excess of atherogenic small low-density lipoprotein (LDL) particles. Statins are first-line lipid-modifying drugs that, in addition to varying in their effects on LDL-C, differ in their effects on HDL-C. Rosuvastatin has been shown to be at least as effective at increasing HDL-C compared with atorvastatin, pravastatin or simvastatin. Selecting an agent that will increase HDL-C levels, as well as lowering LDL-C levels, may be particularly beneficial in the treatment of patients with the metabolic syndrome and type 2 diabetes.
...
PMID:HDL-C and the diabetic patient: target for therapeutic intervention? 1595 6

1 2 3 4 5 6 Next >>