Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Statins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed2007

Lupus erythematosus and other autoimmune diseases related to statin therapy: a systematic review.

BACKGROUND: Statins have been increasingly associated with drug-induced autoimmune reactions, including lupus erythematosus. OBJECTIVE: To identify and determine the clinical and biological characteristics of statin-induced autoimmune reactions. MATERIAL AND METHODS: The MEDLINE database (1966 to September 2005) was used to identify all reported cases of statin-induced autoimmune diseases. The keywords used were statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, adverse effects, autoimmune disease, lupus erythematosus, dermatomyositis and polymyositis. RESULTS: Twenty-eight cases of statin-induced autoimmune diseases have been published so far. Systemic lupus erythematosus was reported in 10 cases, subacute cutaneous lupus erythematosus in three cases, dermatomyositis and polymyositis in 14 cases and lichen planus pemphigoides in one case. Autoimmune hepatitis was observed in two patients with systemic lupus erythematosus. The mean time of exposure before disease onset was 12.8+/-18 months; range 1 month-6 years. Systemic immunosuppressive therapy was required in the majority of cases. In many patients, antinuclear antibodies were still positive many months after clinical recovery. A lethal outcome has been recorded in two patients despite aggressive immunosuppressive therapy. CONCLUSION: Long-term exposure to statins may be associated with drug-induced lupus erythematosus and other autoimmune disorders. Fatal cases have been reported despite early drug discontinuation and aggressive systemic immunosuppressive therapy.

Humans↗
PubMed2005

The role of statins in preventing stroke.

Epidemiological studies have not demonstrated a clear relationship between stroke risk and hypercholesterolemia. Clinical trials using statins have demonstrated a reduction in stroke, in particular, in patients with established coronary artery disease. The disparity between epidemiological and clinical studies suggests hypercholesterolemia is a true risk factor for stroke that evaded detection in epidemiological studies, or that statins possess other properties that render them useful in stroke prevention. These effects have been loosely termed "pleiotropic" in the lipid literature and revolve around putative effects of statins on endothelial function, inflammation, thrombosis, plaque stability, and immune regulation. Questions remain as to the mechanisms of benefit of statin therapy in stroke prevention, the role of statins in the primary prevention of stroke, and the role of statins in modulating the immune system in the brain.

Endothelium, Vascular↗
PubMed2007

Optimal treatment of dyslipidemia in high-risk patients: intensive statin treatment or combination therapy?

A recent update to the National Cholesterol Education Program's Adult Treatment Panel III guidelines suggests low-density lipoprotein cholesterol (LDL-C) goals of <70 mg/dL in very-high-risk patients and <100 mg/dL in high-risk patients. Currently available 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are not equal in their ability to lower LDL-C, and it is unlikely that the substantial LDL-C reductions that are often needed in high-risk persons can be achieved with starting doses of some of the older statins. Possible alternatives in such cases include the use of high-dose statin therapy, a more efficacious statin, or combination therapy. Recent clinical data have demonstrated a greater likelihood of coronary heart disease event reduction with aggressive statin therapy that lowers LDL-C in a robust fashion (>30%-40%) than with moderate therapy. Until data from ongoing trials of combination therapy are available, however, monotherapy with a potent statin should be initiated to lower LDL-C. Nonetheless, for residual elevation in triglycerides and/or reduced high-density lipoprotein cholesterol, adding a second agent (eg, fenofibrate, niacin) is a reasonable option.

Algorithms↗
PubMed2006

Fibrates in combination with statins in the management of dyslipidemia.

While elevated low-density lipoprotein cholesterol is the primary target of hypercholesterolemia treatment, high triglycerides and low high-density lipoprotein cholesterol are also important targets for therapy. Correcting these lipid abnormalities should be an integral part of therapy in hypertensive individuals. Medications such as the fibrates are effective and well tolerated for reducing triglycerides and increasing high-density lipoprotein cholesterol, and their use has resulted in a reduction in cardiovascular events. Fibrates are also recommended as adjunct therapy for patients receiving statins whose low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol is not reduced to goal levels. The combination of a statin and a fibrate may, however, raise the risk of myopathy and rhabdomyolysis. Gemfibrozil, one of the fibrates, but not fenofibrate, interferes with statin glucuronidation, which may increase the risk of myopathy due to elevations in statin serum levels. This may at least partially explain the lower incidence of myopathy with fenofibrate compared with gemfibrozil when combined with statins. Combination therapy with a fibrate and a statin is a potentially useful therapy for patients with atherogenic lipid profiles, for which fenofibrate appears to be a more appropriate choice due to less myopathic potential.

Clofibric Acid↗
PubMed2006

Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer's disease.

This paper reviews epidemiological and clinical trials data about whether statin use reduces the risk of Alzheimer's disease (AD). The available information has come in three waves. The initial, mostly cross-sectional observational reports suggested that statins might prevent dementia. Next, two large clinical trials with cognitive add-on studies showed no benefit and neither did the third wave, again with observational studies. The latter were mostly longitudinal, and were critical of the first studies for not adequately addressing confounding by indication (i.e. that patients with dementia would be denied statins). Most recently, new data from the Canadian Study of Health and Aging have produced a mixed result. While methodological considerations are clearly important in understanding why the reports are so variable, there might also be merit in differentiating between statins, based on their presumed - and variable - mechanisms of action in dementia prevention, before concluding that the initial reports are entirely artefactual. Still, the first reports appear to have overestimated the extent of protection, so that unless there are important effects achievable with specific statins, a more than a modest role for statins in preventing AD seems unlikely.

Alzheimer Disease↗
PubMed2001

Comparison of endothelial pleiotropic actions of angiotensin converting enzyme inhibitors and statins.

Two in vitro and one in vivo assay were performed to study the endothelial pleiotropic actions of "tissue type" angiotensin converting enzyme inhibitors (ACE-Is) such as perindopril and quinapril, their active forms, that is, quinaprilat and peridoprilat, or of statins belonging to natural (lovastatin), semisynthetic (simvastatin), and synthetic enantiomeric (atorvastatin, cerivastatin) classes. Cytoplasmic [Ca2+]i levels in cultured bovine aortic endothelial cells and endothelium-dependent nitric oxide-mediated coronary vasodilatation in the Langendorff preparation of guinea pig heart constituted our in vitro assays. The in vivo assay consisted of study of PGI2-mediated thrombolytic response in arterial blood of rats after intravenous administration of drugs. In this last assay, perindopril and quinapril proved to be, by two orders of magnitude, more potent PGI2-dependent thrombolytics than the most potent statin (atorvastatin). However, in both in vitro assays we found a higher endothelial efficacy of statins as compared to ACE-Is. In particular, those statins that contain the lactone ring in their molecules (lovastatin, simvastatin) were the most potent coronary vasodilators. In summary, the in vivo profile of action of ACE-Is and statins contrasted with their reversed order of potency in vitro. We hypothesize that the endocrine-like function of the pulmonary circulation [28-31] may be responsible for the in vivo bradykinin-triggered, PGI2-mediated thrombolysis by ACE-Is, whereas the pleiotropic action of statins, possibly involving inhibition of prenylation [14-19], is diffused throughout many vascular beds.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

The role of Rho-associated kinase in differential regulation by statins of interleukin-1beta- and lipopolysaccharide-mediated nuclear factor kappaB activation and inducible nitric-oxide synthase gene expression in vascular smooth muscle cells.

An optimal level of NO has protective effects in atherosclerosis, whereas large amounts contribute to septic shock. To study how statins, the potent inhibitors of cholesterol synthesis, regulate NO in the vascular wall, we determined their effects on interleukin-1beta (IL-1beta)- and lipopolysaccharide (LPS)-induced NO production in aortic vascular smooth muscle cells (VSMCs). Compared with the large amounts of NO and inducible NO synthase (iNOS) protein expression induced by LPS, the responses of IL-1beta were modest. Various statins were found to inhibit LPS-induced iNOS expression and NO production, although they potentiated IL-1beta responses. In addition, fluvastatin increased IL-1beta-induced p65 nuclear translocation and nuclear factor kappaB (NF-kappaB) activity, although it inhibited those induced by LPS. To address the role of small G proteins in statin's actions, farnesyl transferase inhibitors [alpha-hydroxyfarne-sylphosphonic acid and (2S)-2-[[(2S)-2-[(2S,3S)-2-[(2R)-2-amino-3-mercaptopropyl]amino]-3-methylpentyl]oxy]-1-oxo-3-phenylpropyl]amino]-4-(methylsulfonyl)-butanoic acid 1-methylethyl ester (L-744382)], Rac inhibitor (NSC23766), and Rho-associated kinase (ROCK) inhibitor [N-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide dihydrochloride (Y-27632)] were used. We found that Y-27632 potentiated IL-1beta-induced iNOS expression, p65 nuclear translocation, IkappaB kinase (IKK), and NF-kappaB activation, whereas it had minimal effects on LPS-induced responses. In contrast, farnesyl transferase inhibitors blocked iNOS protein expression induced by LPS and IL-1beta, whereas NSC23766 had no effect. Further studies showed that LPS down-regulated Rho and ROCK activity, whereas IL-1beta increased them, suggesting a negative role of Rho and ROCK signaling, which is regulated in contrary manners by IL-1beta and LPS, in IKK/NF-kappaB activation. Through abrogating this negative signaling, statins differentially regulate iNOS expression induced by LPS and IL-1beta in VSMCs. These differential actions of statins on iNOS gene regulation might provide an additional explanation for the pleiotropic beneficial effects of statins.

Amides↗
PubMed2005

Effect of statins on the mortality of patients with ischaemic heart disease: population based cohort study with nested case-control analysis.

OBJECTIVE: To measure the effect of statins on mortality for community based patients with ischaemic heart disease and determine whether the likely benefits are similar for women, the elderly, and patients with diabetes. DESIGN: Open prospective cohort study with nested case-control analysis. SETTING: 1.18 million patients registered with 89 practices spread across 23 strategic health authority areas within the UK. All practices had a minimum of eight years of longitudinal data and were contributing to the UK QRESEARCH database. SUBJECTS: All patients with a first diagnosis of ischaemic heart disease between January 1996 and December 2003. OUTCOMES: Adjusted hazard ratio with 95% confidence intervals (CIs) for all cause mortality (cohort analysis) and odds ratio (OR) with 95% CI (case-control analysis) for current use of statins. Adjustments were made for current use of aspirin, beta blockers, and angiotensin converting enzyme inhibitors, co-morbidity (myocardial infarction, diabetes, hypertension, congestive cardiac failure), smoking, body mass index, and quintile of deprivation. RESULTS: 13,029 patients had a first diagnosis of ischaemic heart disease in the study period giving an incidence rate of 3.38/1000 person years. 2266 patients with ischaemic heart disease died during the 43,460 person years of observation giving an overall mortality rate of 52.1/1000 person years (95% CI 50.0 to 54.3). In the case-control analysis, patients taking statins had a 39% lower risk of death than did patients not taking statins (adjusted OR 0.61, 95% CI 0.52 to 0.72) after use of other medication, co-morbidity, smoking, body mass index, and deprivation were taken into account. The benefits found in this study compared favourably with those found in the randomised controlled trials, although the current study population is at higher overall risk. The benefits extend to women, patients with diabetes, and the elderly and can be seen within two years of treatment. Longer duration of usage was associated with lower OR for risk of death with a 19% reduction in risk of death with each additional year of treatment (adjusted OR 0.81, 95% CI 0.77 to 0.86 per year). Mortality was similarly reduced among patients prescribed atorvastatin (adjusted OR 0.62, 95% CI 0.48 to 0.79) and simvastatin (adjusted OR 0.62, 95% CI 0.50 to 0.76). CONCLUSIONS: The benefits of statins found in randomised controlled trials extend to unselected community based patients. The benefits can be seen within the first two years of treatment and continue to accrue over time. Since patients in the community are likely to be at higher risk than those in trials, the potential benefits from statins are likely to be greater than expected.

Adolescent↗
PubMed2005

Cost effectiveness of statins in coronary heart disease.

INTRODUCTION: Statin therapy reduces the rate of coronary heart disease, but high costs in combination with a large population eligible for treatment ask for priority setting. Although trials agree on the size of the benefit, economic analyses of statins report contradictory results. This article reviewed cost effectiveness analyses of statins and sought to synthesise cost effectiveness ratios for categories of risk of coronary heart disease and age. METHODS: The review searched for studies comparing statins with no treatment for the prevention of either cardiovascular or coronary heart disease in men and presenting cost per years of life saved as outcome. Estimates were extracted, standardised for calendar year and currency, and stratified by categories of risk, age, and funding source RESULTS: 24 studies were included (from 50 retrieved), yielding 216 cost effectiveness ratios. Estimated ratios increase with decreasing risk. After stratification by risk, heterogeneity of ratios is large varying from savings to $59 000 per life year saved in the highest risk category and from 6500 dollars to 490,000 dollars in the lowest category. The pooled estimates show values of 21571 dollars per life year saved for a 10 year coronary heart disease risk of 20% and 16862 dollars per life year saved for 10 year risk of 30%. CONCLUSION: Statin therapy is cost effective for high levels of risk, but inconsistencies exist at lower levels. Although the cost effectiveness of statins depends mainly on absolute risk, important heterogeneity remains after adjusting for absolute risk. Economic analyses need to increase their transparency to reduce their vulnerability to bias and increase their reproducibility.

Adult↗
PubMed2004

Statin therapy for cardiac hypertrophy and heart failure.

Cardiac hypertrophy leading to heart failure is a major cause of morbidity and mortality worldwide. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been shown to inhibit cardiac hypertrophy and improve symptoms of heart failure by cholesterol-independent mechanisms. Statins block the isoprenylation and function of members of the Rho guanosine triphosphatase family, such as Rac1 and RhoA. Because Rac1 is a requisite component of reduced nicotinamide adenine dinucleotide phosphate oxidase, which is a major source of reactive oxygen species in cardiovascular cells, the ability of statins to inhibit Rac1-mediated oxidative stress contributes importantly to their inhibitory effects on cardiac hypertrophy. Furthermore, inhibition of RhoA by statins leads to the activation of protein kinase B/Akt and up-regulation of endothelial nitric oxide synthase in the endothelium and the heart. This results in increased angiogenesis and myocardial perfusion, decreased myocardial apoptosis, and improvement in endothelial and cardiac function. Because these effects of statins occur independently of cholesterol lowering, statins may have therapeutic benefits in nonhyperlipidemic patients with cardiac hypertrophy and heart failure.

Cardiomegaly↗
PubMed2003

Effects of statins on myocardial and coronary artery response to ischemia-reperfusion.

This study tested the hypotheses that (i) lipophilic statins (atorvastatin and simvastatin) impair ventricular recovery from myocardial ischemia-reperfusion, owing to their greater myocyte permeability, compared with a hydrophilic statin (pravastatin), and (ii) statins enhance endothelium-dependent vasodilation of isolated coronary arteries from the ischemic region. Farm pigs consumed chow supplemented with atorvastatin (2.5 mg.kg(-1).d(-1); n=6), pravastatin (10 (n=3) or 20 (n=2) mg.kg(-1).d(-1)), simvastatin (5 mg.kg(-1).d(-1); n=6), or no statin (control; n=6) for 3 weeks. Animals were anesthetized and instrumented to measure regional (% segment shortening) and global (dP/dt max) left ventricular (LV) function during coronary artery occlusion (10 min) and reperfusion (30 min). Coronary resistance (i.d. = 119 +/- 3 microm) and conductance (i.d. = 487 +/- 11 microm) arteries were isolated from the ischemic region to measure receptor-dependent (acetylcholine (ACh)) and -independent (KCl) vasoconstriction, and endothelium-dependent (bradykinin (BK)) and -independent (sodium nitroprusside (SNP)) vasodilation. At 30 min reperfusion, neither percent recovery of regional ventricular function (atorvastatin, 24% +/- 15%; pravastatin, 36% +/- 13%; simvastatin, 29% +/- 13%; control, 36% +/- 13%) nor percent recovery of global LV cardiac function differed among groups. However, BK-induced vasorelaxation of coronary conductance vessels was greater (P<0.05) in statins versus controls, and ACh-induced vasoconstriction was less in simvastatin-treated animals, suggesting the potential for enhanced coronary arterial blood flow to the jeopardized region. In conclusion, our data suggest that ischemia-induced myocardial stunning is similar among pigs treated for 3 weeks with atorvastatin, pravastatin, or simvastatin, even though statin treatment appears to augment endothelium-dependent vasodilation of conductance, but not resistance, vessels subjected to ischemia-reperfusion.

Animals↗
PubMed2005

Pleiotropic effects of statins.

Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or "pleiotropic" effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

Animals↗
PubMedDate not supplied

Association between statin use and Alzheimer's disease.

CONTEXT: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been associated with a decreased risk for Alzheimer's disease (AD). OBJECTIVE: To evaluate the association between statin use and AD adjusted for comorbid medical conditions. DESIGN: A nested case-control study. PATIENTS: Patients at the Veterans Affairs Medical Center in Birmingham, Ala., USA with a new diagnosis of AD (cases) between 1997 and 2001 (n = 309) and age-matched non-AD controls (n = 3,088). MAIN OUTCOME MEASURE: Odds ratio for association between AD and statin use. RESULTS: Statin users had a 39% lower risk of AD relative to nonstatin users (odds ratio 0.61, 95% confidence interval 0.42-0.87). This association appeared to be modified by the presence of certain chronic medical conditions (i.e., hypertension, ischemic heart disease and cerebrovascular disease) in that the reduced risk was observed among those with these diseases, whereas no association was observed among those without any of these conditions. CONCLUSIONS: In this study, following adjustment for confounding factors, a statistically significant inverse association between statin use and AD was observed. The results lend support to looking at AD outcomes in trials of statins to further evaluate their possible beneficial effects.

Aged↗
PubMed2003

Platelet hyperactivity after statin treatment discontinuation.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.

Adult↗
PubMed2002

Statin therapy in acute coronary syndromes: mechanistic insight into clinical benefit.

Randomized trials have established that statin treatment reduces coronary events in primary prevention and in patients with stable coronary artery disease. In unstable coronary artery disease, however, the pathophysiological background is distinct, and the potential benefits of statin therapy have not been evaluated until recently. Data from animal models and clinical studies indicate that statin treatment can influence a spectrum of molecular and cellular mechanisms that are intimately related to the pathogenesis of acute coronary syndromes; these include the reduction of circulating levels of atherogenic lipoproteins (very low density lipoprotein, very low density lipoprotein remnants, intermediate density lipoprotein, and low density lipoprotein) and thus of arterial lipid deposition and the attenuation of inflammation, modulation of thrombogenesis and thrombolysis, improvement of endothelial dysfunction, and reduction of ischemia/reperfusion injury. Indeed, findings from prospective and observational studies have demonstrated that statin treatment significantly improves clinical outcome after acute coronary syndromes. Therefore, early initiation of statin therapy after an acute coronary event not only enhances adherence to treatment but also preempts the occurrence of new events. In this review, we discuss recent important developments in our knowledge of the clinical evidence of the beneficial effects of early statin therapy in acute coronary syndromes and the biological mechanisms that underlie them.

Acute Disease↗
PubMed2003

Endothelium-dependent effects of statins.

The vascular endothelium is a dynamic endocrine organ that regulates contractile, secretory, and mitogenic activities in the vessel wall and hemostatic processes within the vascular lumen. Risk factors for cardiovascular disease, such as cigarette smoking, hypertension, and elevated serum lipid levels, impair endothelial function and lead to the development of atherosclerotic vessels. Recent studies suggest that statins reduce cardiovascular events in part by improving endothelial function. Statins reduce plasma cholesterol levels, thereby decreasing the uptake of modified lipoproteins by vascular wall cells. There is increasing evidence, however, that statins may also exert effects beyond cholesterol lowering. Indeed, many of these cholesterol-independent or "pleiotropic" vascular effects of statins appear to involve restoring or improving endothelial function through increasing the bioavailability of nitric oxide, promoting re-endothelialization, reducing oxidative stress, and inhibiting inflammatory responses. Thus, the endothelium-dependent effects of statins are thought to contribute to many of the beneficial effects of statin therapy in cardiovascular disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells.

BACKGROUND: Primary and secondary prevention trials suggest that statins possess favorable effects independent of cholesterol reduction. We investigated whether statin therapy may also accelerate reendothelialization after carotid balloon injury. METHODS AND RESULTS: Simvastatin treatment in 34 male Sprague-Dawley rats accelerated reendothelialization of the balloon-injured arterial segments (reendothelialized area at 2 weeks, 12.3+/-1.8 versus 5.4+/-1.1 mm2, P< 0.01) and resulted in a dose-dependent (0.2 or 1 mg/kg IP) significant reduction in neointimal thickening at 2, 3, and 4 weeks compared with saline-injected controls (n=18). To elucidate the mechanism, we investigated the contribution of bone marrow-derived endothelial progenitor cells (EPCs) by bone marrow transplantation from Tie2/lacZ mice to background mice or nude rats. X-gal staining of mouse carotid artery specimens revealed a 2.9-fold increase in the number of beta-gal-positive cells per square millimeter appearing on the carotid artery luminal surface at 2 weeks, and double-fluorescence immunohistochemistry disclosed a significant 5-fold increase in the number of double-positive cells (beta-gal, isolectin B4) on the luminal surface in carotid arteries of statin-treated nude rats (20+/-3 versus 4+/-1 cells/mm surface length, P<0.005). Statins increased circulating rat EPCs (2.4-fold at 2 weeks and 2.5-fold at 4 weeks, P<0.001) and induced adhesiveness of cultured human EPCs by upregulation of the integrin subunits alpha5, beta1, alpha(v), and beta5 of human EPCs as shown by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting. CONCLUSIONS: These findings establish additional mechanisms by which statins may specifically preempt disordered vascular wall pathology and constitute physiological evidence that EPC mobilization represents a functionally relevant consequence of statin therapy.

Angioplasty, Balloon↗
PubMed2003

Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease.

BACKGROUND: We determined whether statin use (versus nonuse) is associated with superior lower-extremity functioning independently of cholesterol levels and other confounders in patients with and without peripheral arterial disease. METHODS AND RESULTS: Participants included 392 men and women with an ankle brachial index (ABI) <0.90 and 249 with ABI 0.90 to 1.50. Functional outcomes included 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ABI, comorbidities, education level, medical insurance status, cholesterol, and other confounders, participants taking statins had better 6-minute walk performance (1276 versus 1218 feet, P=0.045), faster walking velocity (0.93 versus 0.89 m/s, P=0.006), and a higher summary performance score (10.2 versus 9.4, P<0.001) than participants not taking statins. Positive associations were attenuated slightly after additional adjustment for C-reactive protein level but remained statistically significant for walking velocity and the summary performance score. We did not find significant associations between lower-extremity functioning and aspirin, ACE inhibitors, vasodilators, or beta-blockers. CONCLUSIONS: Statin use is associated with superior leg functioning compared with no statin use, independent of cholesterol levels and other potential confounders. These data suggest that non-cholesterol-lowering properties of statins may favorably influence functioning in persons with and without peripheral arterial disease.

Adrenergic beta-Antagonists↗