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)

Recent studies emphasized the non-lipid-lowering effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on endothelial function, inflammation, and platelet activation in patients with stable atherosclerosis. This study sought to evaluate the impact of statin pretreatment in patients with acute myocardial infarction (AMI) on level of systemic inflammation and myocardial perfusion. A total of 253 consecutive patients undergoing primary angioplasty on a native vessel within 12 hours of AMI were divided into a group with statin pretreatment (n = 86) and control patients (n = 167). Angiographic myocardial blush grade (MBG) after revascularization of the infarct-related artery was determined to evaluate myocardial perfusion. Statin pretreatment was associated with a lower frequency of increased C-reactive protein (>or=5 mg/L) on admission compared with the control group (48% vs 64%; p = 0.019). The frequency of normal perfusion (MBG 3) was higher in the statin-pretreatment group than the control group (45% vs 26%, respectively; p <0.001). Statin pretreatment was an independent predictor of normal myocardial perfusion (MBG 3; odds ratio 2.53, 95% confidence interval 1.15 to 9.53, p = 0.022) in addition to age <or=70 years and C-reactive protein <5 mg/L. In conclusion, statin pretreatment in patients with AMI was associated with decreased systemic inflammation and better perfusion after primary angioplasty of the infarct-related artery.
 ...
PMID:Effect of statin therapy before Q-wave myocardial infarction on myocardial perfusion. 1817 95

Statin drugs represent a major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides the tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, fatigability) occur frequently. Many hypotheses were proposed to explain statin myotoxicity. The goal of this review is to highlight some of the most recent findings that can account for interpreting the pathophysiological mechanisms for statin-induced myotoxicity. Statin-induced myotoxicity appears multifactorial. Apart from the deleterious effect due to a reduction in cholesterol biosynthesis, statins have a direct effect on the respiratory chain of the mitochondria. It is proposed that mitochondrial impairment leads to a mitochondrial calcium leak that directly interferes with the regulation of sarcoplasmic reticulum calcium cycling without excluding a direct effect of statin on the sarcoplasmic reticulum. Both mitochondrial and calcium impairments may account for apoptosis process, oxidative stress, and muscle remodeling and degeneration that have been extensively reported to explain statin myotoxicity and functional symptoms described by treated patients.
 ...
PMID:New insights into mechanisms of statin-associated myotoxicity. 1824 52

Despite the scientific evidence that secondary prevention medical therapies reduce mortality in patients with established atherosclerosis, these therapies continue to be underused in patients receiving conventional care. To address this issue, the University of California, Los Angeles, Cardiovascular Hospitalization Atherosclerosis Management Program was implemented in 1994. This hospital-based system focused on initiation of antiplatelet therapy, beta-blocker, angiotensin-converting enzyme inhibitor, and statin therapy (irrespective of baseline low-density lipoprotein cholesterol) in conjunction with diet and exercise counseling in patients hospitalized with coronary artery and other atherosclerotic vascular disease. Preprinted orders, critical pathways, discharge forms, physician and nursing education, pocket cards, patient educational material, and treatment utilization reports facilitated program implementation. Statin use at the time of discharge increased from 6% before initiation of the program to 86% after the Cardiovascular Hospitalization Atherosclerosis Management Program was implemented (P < 0.001). Improved use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors was also observed. Importantly, in-hospital initiation of cardiovascular protective therapies had a dramatic effect on long-term treatment rates and patient compliance. The improved use of cardiovascular protective therapies was associated with a significant reduction in clinical events the first year after discharge: the death and nonfatal myocardial infarction rate decreased from 14.8% to 6.4% (odds ratio, 0.43; 95% confidence interval, 0.27-0.59; P < 0.01). These improved treatment rates have been sustained over an 8-year period. Compared with conventional care, the Cardiovascular Hospitalization Atherosclerosis Management Program has been associated with a significant increase in treatment utilization of evidence-based medications, more patients achieving low-density lipoprotein cholesterol less than 100 mg/dL, and improved clinical outcomes in patients hospitalized for cardiovascular disease. Hospital-based atherosclerosis treatment systems are an important step to help eliminate the cardiovascular treatment gap and dramatically reduce the death and disability caused by atherosclerotic vascular disease.
 ...
PMID:In-hospital initiation of cardiovascular protective therapies to improve treatment rates and clinical outcomes: the University of California-Los Angeles, Cardiovascular Hospitalization Atherosclerosis Management Program. 1834 Mar 22

Statin therapy has reduced cardiovascular morbidity and mortality across the spectrum of atherosclerosis. The administration of statins has been demonstrated to be effective in primary and secondary prevention clinical trials evaluating patients with high and low risk-factor profiles. The presumed mechanism of benefit of hypolipidemic therapy in the prevention of atherosclerotic disease was a reduction in the deposition of atherogenic lipoproteins in vulnerable areas of the coronary vasculature. Subsequent experimental studies with statins demonstrated a variety of potentially beneficial effects that would extend clinical benefit beyond lipid-lowering per se. Statin therapy beneficially alters inflammation, coagulation and fibrinolytic parameters, endothelial function, vasoreactivity, and platelet function. The demonstration of the non-lipid or pleiotropic effects provided the theoretical basis for a possible role as an adjunctive therapy in acute coronary syndromes. Retrospective analysis of a variety of early trials indicated a potential benefit of statins during acute ischemic syndromes. Recent clinical trials have addressed this important clinical question in a prospective controlled manner. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) and the Thrombolysis In Myocardial Infarction (TIMI)-22 studies present strong clinical evidence in favor of the administration of statins as adjunctive therapy in acute ischemic syndromes.
 ...
PMID:Adjunctive interventions in myocardial infarction: the role of statin therapy. 1841 69

Coronary artery disease (CAD) constitutes the most common cause of morbidity and mortality in developed countries. Statins effectively reduce low-density lipoprotein cholesterol, an important risk factor for CAD and related acute coronary syndromes. They are an extensively studied group of drugs with versatile properties. Overall, they are safe and effective drugs but their myotoxic potential cannot be overlooked. In this review we focus on the pathogenesis of statins' myopathic side effects. Statins can interfere with protein modification at multiple levels. They can affect protein prenylation, an important post-translational modification of membrane bound proteins. They can also adversely affect selenoprotein synthesis, or can interfere with the biosynthesis of dolichols, which are involved in the process of protein glycosylation. Statin-induced myopathy may be also associated with mitochondrial dysfunction. Statins remain the spearhead of our armamentarium in treating atherosclerotic disease. Consistent with their versatile properties it is anticipated to see in the future their indications to expand. Better understanding of the molecular mechanisms involved in statin-induced myopathy may help identify patient groups susceptible to statins' side effects, thereby increasing their safety.
Atherosclerosis 2009 Jan
PMID:Molecular basis of statin-associated myopathy. 1858 18

Statin treatment markedly reduces the incidence of acute coronary events in patients with coronary atherosclerosis. Although imaging studies have indirectly shown the beneficial effects of statins on plaque morphology, there has to our knowledge been no reported histologic comparison of the morphology of coronary plaque in statin-treated versus untreated patients who had substantial coronary artery atherosclerosis. We retrospectively studied arterial sections from the native hearts of patients who had experienced end-stage ischemic heart disease and subsequent cardiac transplantation. Of 44 qualified patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not. Pathologic examination of each explanted heart confirmed coronary artery disease and previous myocardial infarction in all patients. Diabetes mellitus was more prevalent in the study group. The groups were similar in levels of total and low-density lipoprotein cholesterol, and in the available number of arterial cross-sections per patient. All patients had plaques. High-grade lesions were found in 66.3% of cross-sections in the control group, and in 34.6% in the study group (P=0.011). Conversely, the degree of inflammation was markedly lower in the study group: low-grade fibrous plaques occurred in 45.7% of cross-sections in the study group, versus 11.3% in the control group (P=0.006). The study group had significantly fewer high-grade plaques and more fibrous plaques than did the control group at the time of transplantation. Our findings show that statin therapy substantially enhances plaque stabilization. We further suggest that reduction of plaque inflammation is an important aspect of this stabilization.
 ...
PMID:Statins improve human coronary atherosclerotic plaque morphology. 1861 39

Atherothrombosis of the coronary and cerebral vessels is understood to be a disorder of inflammation and innate immunity, as well as a disorder of lipid accumulation. From a vascular biology perspective, the processes of cellular adhesion, monocyte and macrophage attachment, and transmigration of immune cells across the endothelium are crucial steps in early atherogenesis and in the later stages of mature plaque rupture, particularly the transition of unstable plaque at the time of acute thrombosis. There is abundant clinical evidence demonstrating that many biomarkers of inflammation are elevated years in advance of first ever myocardial infarction (MI) or thrombotic stroke and that these same biomarkers are highly predictive of recurrent MI, recurrent stroke, diabetes, and cardiovascular death. In daily practice, the inflammatory biomarker in widest use is high-sensitivity C-reactive protein (hsCRP); when interpreted within the context of usual risk factors, levels of hsCRP <1, 1 to 3, and >3 mg/l denote lower, average, and higher relative risk for future vascular events. Risk-prediction models that incorporate hsCRP, such as the Reynolds Risk Score, have been developed that improve risk classification and the accuracy for global risk prediction, particularly for those deemed at "intermediate risk" by usual algorithms, such as the Framingham Risk Score. With regard to cerebral vessels, increased biomarkers of inflammation, including hsCRP, have been associated with increased stroke risk as well as an increased rate of atherosclerosis progression in the carotid vessels. Although the proportion of variation in hsCRP explained by genetic factors may be as large as 20% to 40%, diet, exercise, and smoking cessation remain critical tools for risk reduction and CRP reduction. Statin therapy reduces hsCRP in a largely low-density lipoprotein (LDL)-independent manner, and the "anti-inflammatory" properties of these agents have been suggested as a potential mechanism beyond LDL reduction for the efficacy of these agents. The ongoing multinational Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial of 17,802 initially healthy men and women with low levels of LDL cholesterol but increased levels of hsCRP will help to define whether vascular protection can be achieved with statin therapy, even in the absence of hyperlipidemia. Targeted anti-inflammatory therapies are being developed that may provide a direct method of translating the biology of inflammation into new clinical treatments across multiple vascular beds. This article summarizes data supporting a role for inflammation in cardiovascular disease and offers the possibility that other disorders characterized by inflammation, such as periodontal disease, may have an indirect role by influencing the risk, manifestation, and progression of vascular events.
 ...
PMID:Inflammation, C-reactive protein, and atherothrombosis. 1867 9

Although the hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are widely used in atherosclerosis to reduce serum cholesterol, statins have multiple other effects, including direct effects on cells of the vessel wall. Recently, DNA damage, including telomere shortening, has been identified in vascular smooth muscle cells (VSMCs) in human atherosclerosis. Although statins reduce DNA damage in vitro, the mechanisms by which they might protect DNA integrity in VSMCs are unknown. We show that human atherosclerotic plaque VSMCs exhibit increased levels of double-stranded DNA breaks and basal activation of DNA repair pathways involving ataxia telangiectasia-mutated (ATM) and the histone H2AX in vivo and in vitro. Oxidant stress induced DNA damage and activated DNA repair pathways in VSMCs. Statin treatment did not reduce oxidant stress or DNA damage but markedly accelerated DNA repair. Accelerated DNA repair required both the Nijmegen breakage syndrome (NBS)-1 protein and the human double minute protein Hdm2, accompanied by phosphorylation of Hdm2, dissociation of NBS-1 and Hdm2, inhibition of NBS-1 degradation, and accelerated phosphorylation of ATM. Statin treatment reduced VSMC senescence and telomere attrition in culture, accelerated DNA repair and reduced apoptosis in vivo after irradiation, and reduced ATM/ATR (ATM and Rad3-related) activity in atherosclerosis. We conclude that statins activate a novel mechanism of accelerating DNA repair, dependent on NBS-1 stabilization and Hdm2. Statin treatment may delay cell senescence and promote DNA repair in atherosclerosis.
 ...
PMID:Statins use a novel Nijmegen breakage syndrome-1-dependent pathway to accelerate DNA repair in vascular smooth muscle cells. 1872 44

Atherosclerosis is a disease whose pathogenesis involves inflammatory and immunological mechanisms, including an autoimmune reaction against heat shock proteins (Hsps). The purpose of this study was to analyze whether the antiatherogenic effect of statin therapy was not limited to its lipid lowering effect, but also included anti-inflammatory and immunomodulatory effects, paying special attention to the measurement of circulating concentrations of anti-Hsp70 and anti-Hsp60 antibodies previously related to vascular disease. Two-hundred and seventy-five subjects aged 40-60 years, randomly selected in an epidemiological study on the incidence of vascular risk factors, were studied. Laboratory tests included a complete lipid profile after a 12-h fast and measurements of glucose, C-reactive-protein, anti-Hsp70 and anti-Hsp60 antibodies. Subjects with hypercholesterolemia had significantly higher concentrations of anti-Hsp70 antibodies as compared to subjects with normal cholesterol concentrations. Statin therapy was associated with 11.63 and 15.3% reductions in total and LDL-cholesterol (P = 0.005 and 0.017, respectively) as compared to untreated subjects, and with lower concentrations of circulating anti-Hsp70 (P = 0.016) antibodies. No differences were found in C-reactive-protein values. Since statin therapy not only reduces lipid profile, but also anti-Hsp70 and anti-Hsp60 antibody concentrations, without changing C-reactive-protein values, it is suggested that such an effect could not be accounted for by the anti-inflammatory properties of statins, but by their direct immunomodulatory properties through their effects on lymphocyte function.
 ...
PMID:Reduction of heat shock protein antibody levels by statin therapy. 1903 47

Hypercholesterolemia increases the risk for dementia. Some studies suggest that statins may protect cognition, but findings are conflicting. Unmeasured confounders, including high-density lipoprotein (HDL) cholesterol or subclinical atherosclerosis, may have influenced prior study outcomes. In older adults participating in a population-based cohort study (n=1711, aged 65 to 97 y), we investigated the relationships of total and HDL cholesterol levels, statin use, and carotid intima-media thickness with the prevalence of cognitive impairment. In adjusted models, participants in the highest quartile of non-HDL (total-HDL) cholesterol had an increased odds of cognitive impairment compared with those in the lowest quartile [odds ratio (OR): 2.06, 95% confidence interval (CI): 1.07-3.98]. Statin use was associated with lower odds of cognitive impairment in unadjusted models (OR: 0.57, 95% CI: 0.36-0.89), but this relationship was not significant after adjusting for vascular and lifestyle factors (OR: 0.84, 95% CI: 0.47-1.49). In this analysis of older adults, increased atherogenic lipoproteins were associated with impaired cognition. Statin use was related to many factors that both negatively and positively affect cognition, but was not associated with better cognitive function. These results suggest that confounding by indication may explain the contradictory findings in studies assessing the association of statins with cognition. Randomized-controlled clinical trials and longitudinal studies are necessary to determine if statins protect against cognitive decline.
 ...
PMID:Increased atherogenic lipoproteins are associated with cognitive impairment: effects of statins and subclinical atherosclerosis. 1993 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>