Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several retrospective and nonrandomized studies have indicated that lowering atherogenic lipoprotein, in particular low-density lipoprotein cholesterol, may retard the hemodynamic progression of aortic stenosis (AS). This valvular disease shares pathogenic and pathoanatomic similarities with atherosclerosis, at least in their early developments. Two randomized placebo-controlled studies researching the effect of lowering low-density lipoprotein on AS progression and its clinical consequences have been published recently-the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) study and the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Both of these studies had neutral outcomes. The causes for the negative outcome may be that cholesterol lowering does not influence AS development in a clinically significant way or it may be due to traits in the design of the studies or treatments. Therefore, statin treatment for prevention of AS progression cannot be ruled out as a future therapeutic option in AS. The outcome of the ongoing Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) study, which is examining lipid lowering as a treatment for AS, is greatly anticipated.
 ...
PMID:Lipid lowering and aortic valve disease. 1966 82

Dyslipidemia is one of the major causes of atherosclerosis, although in the last few years an increase in cholesterol control rates has been reported. However, results from the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) surveys indicate that approximately 50% of the patients with ischemic heart disease still do not attain LDL-cholesterol goals despite the use of lipid-lowering therapy (including statins). Rosuvastatin is a new and potent statin that produces greater reductions of LDL-cholesterol when compared with other agents in this class. Furthermore, rosuvastatin provides additional benefits in the lipid profile such as increased HDL-cholesterol, and decreased triglycerides, total cholesterol, apolipoprotein B and apolipoprotein B:A-1 ratio. Cardiovascular disease is a continuum: from risk factors to subclinical organ damage and finally to overt clinical cardiovascular disease. Several trials have investigated the effects of rosuvastatin along this cardiovascular continuum. The results provided by the GALAXY program emphasize the importance of the early treatment with rosuvastatin in the cardiovascular continuum to achieve the greatest benefit. In this paper, the efficacy and safety of rosuvastatin along the cardiovascular continuum is reviewed.
 ...
PMID:Rosuvastatin along the cardiovascular continuum: from JUPITER to AURORA. 1990 15

Statins have been shown to reduce cardiovascular events across a broad spectrum of patients at risk, irrespective of baseline LDL-cholesterol levels. In a meta-analysis of 14 statin trials involving more than 90,000 participants, statin therapy reduced the 5-year incidence of cardiovascular events by about 20% for each mmol/L of LDL-cholesterol reduction. The results of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study suggest that the degree of reduction in Japanese subjects may be greater than this for the same degree of LDL-cholesterol reduction. Given the success of statins in preventing cardiovascular events, it is not surprising that they have been tested in a variety of related conditions, three of which are discussed in this article. Heart failure is characterized by inflammation, endothelial dysfunction and neurohumeral activation, conditions that are ameliorated by statin therapy. The Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) showed no significant benefit of rosuvastatin upon the primary endpoint, cardiovascular death, myocardial infarction and stroke. However, subgroups identified by the biomarkers plasma amino-terminal pro-brain natriuretic and C-reactive protein showed a reduction in events. Aortic stenosis and atherosclerosis share common risk factors, including hypertension and hypercholesterolemia. Although non-randomized cohort studies have suggested that statins slow the progression of aortic stenosis, this was not shown in either of the two randomized placebo-controlled trials testing this hypothesis. Similarly, Alzheimer's disease shares many risk factors with atherosclerosis, and several observational studies have reported a lower risk of developing this condition in patients taking statins. However, two recently completed clinical trials indicate that neither atorvastatin nor simvastatin slow the progression of early Alzheimer's disease. In conclusion, although statins are effective, established therapy for the prevention of vascular events in patients at risk, they have as yet not proven to be successful for these newer indications.
 ...
PMID:Exploring new indications for statins beyond atherosclerosis: Successes and setbacks. 2020 67

The inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) has been proposed as a novel instrument to assess cardiovascular risk, to determine the need for statin therapy in specific individual otherwise not deemed to meet current criteria, and to represent a potential target of treatment. CRP is predominantly secreted by the liver and adipose tissues in response to inflammatory stress and is regulated, in great part, by interleukin-6. The issues of CRP as a causal factor (rather than a biomarker) has been addressed by three types of studies: animal models, in which CRP was injected; transgenic mice over-expressing human CRP; and Mendelian randomization studies. All indicate that CRP may not have a direct role in promoting atherosclerosis but, instead, serves as a marker of vascular inflammation and the presence of atherosclerosis. Several clinical studies have shown that individuals reaching both low-density lipoprotein cholesterol (LDL-C) and hsCRP targets (LDL-C less than 2.0 mmol/L and hsCRP less than 2 mg/L) have the lowest event rate, suggesting that hsCRP may become a secondary target of treatment after LDL-C. The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study showed that apparently healthy men and women with elevated hsCRP, but normal LDL-C (less than 3.4 mmol/L), had an overall 44% reduction in the primary end points with rosuvastatin 20 mg/day. The results of this study have now been incorporated in the new Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease.
 ...
PMID:C-reactive protein: risk factor, biomarker and/or therapeutic target? 2038 60

Evidence for the role of inflammation in the pathogenesis of atherosclerosis is compelling and has generated interest in high-sensitivity C-reactive protein (hs-CRP) as a marker of cardiovascular risk. Data regarding hs-CRP and cardiovascular risk, though largely consistent, is of unclear clinical relevance. Most recently, the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial has led to further debate regarding the utility of hs-CRP. This article provides a comprehensive review of the data regarding cardiovascular risk and hs-CRP with an emphasis on the JUPITER trial and concludes with an evidence-based analysis of the current role of hs-CRP in cardiovascular risk assessment.
 ...
PMID:Should we measure C-reactive protein on earth or just on JUPITER? 2039 38

Much evidence supports a pivotal role for inflammation in atherosclerosis. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a cardiovascular risk marker and may also promote atherogenesis. CRP levels are increased in metabolic syndrome and hypertension and confer increased risk of cardiovascular events in patients in these subgroups. Statins have been shown to lower low-density lipoproteins and CRP independently, and reduce cardiovascular events in subjects with and without metabolic syndrome and hypertension. In this review, we focus on the results from the primary prevention statin trial, Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), which showed reductions in LDL, CRP, and cardiovascular events. Post-JUPITER, the new guidelines will now need to consider recommending high-sensitivity CRP testing to intermediate-risk metabolic syndrome patients and those with hypertension and intermediate risk so that we can better identify candidates at greater risk and reduce cardiovascular burden in these subjects with statin therapy.
 ...
PMID:Statin therapy in metabolic syndrome and hypertension post-JUPITER: what is the value of CRP? 3066 99

The major public health concern worldwide is coronary heart disease, with dyslipidemia as a major risk factor. Statin drugs are recommended by several guidelines for both primary and secondary prevention. Rosuvastatin has been widely accepted because of its efficacy, potency, and superior safety profile. Inflammation is involved in all phases of atherosclerosis, with the process beginning in early youth and advancing relentlessly for decades throughout life. C-reactive protein (CRP) is a well-studied, nonspecific marker of inflammation which may reflect general health risk. Considerable evidence suggests CRP is an independent predictor of future cardiovascular events, but direct involvement in atherosclerosis remains controversial. Rosuvastatin is a synthetic, hydrophilic statin with unique stereochemistry. A large proportion of patients achieve evidence-based lipid targets while using the drug, and it slows progression and induces regression of atherosclerotic coronary lesions. Rosuvastatin lowers CRP levels significantly. The Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was designed after the observation that when both low density lipoprotein and CRP were reduced, patients fared better than when only LDL was lowered. Advocates and critics alike acknowledge that the benefits of rosuvastatin in JUPITER were real. After a review, the US Food and Drug Administration extended the indications for rosuvastatin to include asymptomatic JUPITER-eligible individuals with one additional risk factor. The American Heart Association and Centers of Disease Control and Prevention had previously recognized the use of CRP in persons with "intermediate risk" as defined by global risk scores. The Canadian Cardiovascular Society guidelines went further and recommended use of statins in persons with low LDL and high CRP levels at intermediate risk. The JUPITER study focused attention on ostensibly healthy individuals with "normal" lipid profiles and high CRP values who benefited from statin therapy. The backdrop to JUPITER during this period was an increasing awareness of a rising cardiovascular risk burden and imperfect methods of risk evaluation, so that a significant number of individuals were being denied beneficial therapies. Other concerns have been a high level of residual risk in those who are treated, poor patient adherence, a need to follow guidelines more closely, a dual global epidemic of obesity and diabetes, and a progressively deteriorating level of physical activity in the population. Calls for new and more effective means of reducing risk for coronary heart disease are intensifying. In view of compelling evidence supporting earlier and aggressive therapy in people with high risk burdens, JUPITER simply offers another choice for stratification and earlier risk reduction in primary prevention patients. When indicated, and in individuals unwilling or unable to change their diet and lifestyles sufficiently, the benefits of statins greatly exceed the risks. Two side effects of interest are myotoxicity and an increase in the incidence of diabetes.
 ...
PMID:Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease--a perspective. 2126 17

Inflammation plays a pivotal role in all phases of atherosclerosis. High-sensitivity C-reactive protein (hsCRP), the best characterized biomarker of inflammation, is an independent predictor of future cardiovascular (CV) events and can add further insight to risk stratification. Assessment of hsCRP levels in clinical practice is feasible and inexpensive. Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) was a landmark primary prevention trial that enrolled 17,802 apparently healthy men and women with low-density lipoprotein cholesterol levels of less than 130 mg/dL and hsCRP levels of 2 mg/L or higher and randomly assigned them to rosuvastatin, 20 mg daily, or placebo. The trial demonstrated that treatment with statin was associated with significant lowering of hsCRP (37%), with 44% reduction in incident CV and 20% reduction in all-cause mortality. These compelling data from the JUPITER trial should encourage changes in our approach toward primary prevention of CV disease and lipid-lowering therapy, as these data shift the focus toward a link between inflammation, statin therapy, and prevention of atherosclerotic CV diseases.
 ...
PMID:C-Reactive Protein: How Has JUPITER Impacted Clinical Practice? 2160 45

On the basis of large randomized clinical trials, pharmacological antagonists of HMG-CoA reductase (statins) have become increasingly used in clinical practice for the prevention of cardiovascular disease. Rosuvastatin was developed as a potent statin, which appeared to raise levels of HDL-cholesterol, in addition to marked reductions in levels of LDL-cholesterol. These effects on lipids are associated with a beneficial impact of rosuvastatin on progression of various stages of atherosclerosis and cardiovascular outcomes in clinical trials. The clinical experience of rosuvastatin will be reviewed in this article.
 ...
PMID:Clinical experience with rosuvastatin in the management of hyperlipidemia and the reduction of cardiovascular risk. 2205 87

The review summarises data on statins efficacy in primary prophylaxis of cardiovascular complications. Main results of the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial are analysed in detail. Its role in possible changes in current recommendations on prophylaxis and treatment of atherosclerosis is shown. Statins are considered as drugs essential in the strategy of improvement of life quality.
 ...
PMID:[Statins in primary prophylaxis of cardiovascular diseases]. 2214 92


<< Previous 1 2 3 4 5 6 7 Next >>