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PubMed2004

[Statins: therapeutic cascade of their effects].

Concept of sequence and time of appearance of various effects of statins is presented. Apart from hypolipidemic action due to inhibition of HMG CoA reductase activity statins exert multiple pleiotropic effects. Combination of these effects makes statins a unique instrument for solution of global tasks of prevention and treatment of atherosclerosis and its consequences (ischemic heart disease etc.). Manifestations of various pleiotropic effects of statins appear after different time intervals and in most cases are not related to suppression of cholesterol synthesis in the body. First 3-4 months (first level of the statin cascade) are characterized mainly by activity of pleiotropic properties aimed at restoration of endothelial function. These properties are responsible for enhanced eNOS expression, antiischemic, antithrombotic and antiatherogenic effects. During same period of time stabilization of unstable atheromas takes place. Manifestations of second level of the cascade of statin action appear after 2 years of treatment. They are represented by retardation of progression and even partial regression of atheromatosis of coronary and peripheral arteries. Third level is signified by achievement of strategic aims of therapy with statins (in 4-5 years) -- lowering of total and cardiac mortality, reduction of number of cardiac complications. Forth level of the cascade is represented by beneficial influences on nonatherogenic cardiological phenomena and comprise hypotensive, antiarrhythmic and cardiotonic effects. And finally some other important properties of statins constitute the fifth level of the therapeutic cascade. These properties are responsible for effects directed at noncardiac pathology (prevention of diabetes, dementia, including dementia associated with Alzheimer's disease, fractures). Immunodepression, ability to reduce saturation of bile with cholesterol belong to this group of effects.

Arteriosclerosis↗
PubMed2004

Recurrent acute pancreatitis possibly induced by atorvastatin and rosuvastatin. Is statin induced pancreatitis a class effect?

CONTEXT: Few data exist about the incidence of drug-induced pancreatitis in the general population. Drugs are related to the etiology of pancreatitis in about 1.4-2% of cases. While statins are generally well tolerated they have been known to be associated with pancreatitis. Acute pancreatitis has been reported in a few cases treated with atorvastatin, fluvastatin, lovastatin, simvastatin and pravastatin. CASE REPORT: We report the case of a 77-year-old patient who developed acute pancreatitis after treatment with rosuvastatin, which resolved on withdrawal of the medication. She had a similar episode of pancreatitis a year ago precipitated by atorvastatin, which resolved on withdrawal. Extensive workup on both occasions failed to reveal any other etiology for the pancreatitis. CONCLUSION: To our knowledge this is the first report of rosuvastatin-induced pancreatitis. The occurrence of pancreatitis with two different statins in our patient argues that statins induced pancreatitis may be a class-effect of statins. With statin prescriptions on the rise clinicians need to be aware of this complication of statin treatment and remember that the newest statin, rosuvastatin is not dissimilar to the other statins in causing pancreatitis.

Acute Disease↗
PubMed2005

Antioxidant effects of statins.

Statins, a group of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used in clinical practice for their efficacy in producing significant reductions in plasma cholesterol and LDL cholesterol and in reducing morbidity and mortality from cardiovascular disease. However, several large clinical trials have suggested that the cholesterol-lowering effects of statins may not completely account for the reduced incidence of cardiovascular disease seen in patients receiving statin therapy. A number of recent reports have shown that statins may also have important antiinflammatory effects, in addition to their effects on plasma lipids. Since inflammation is closely linked to the production of reactive oxygen species (ROS), the molecular basis of the observed antiinflammatory effects of statins may relate to their ability block the production and/or activity of ROS. In this review, we will discuss both the inhibition of ROS generation by statins, through interference with NAD(P)H oxidase expression and activity, and the actions of statins that serve to blunt the damaging effects of these radicals, including effects on antioxidant enzymes, lipid peroxidation, LDL cholesterol oxidation and nitric oxide synthase. These antioxidant effects of statins likely contribute to their clinical efficacy in treating cardiovascular disease as well as other chronic conditions associated with increased oxidative stress in humans.

Antioxidants↗
PubMed2005

The past, present, and future of statin therapy.

Statins are a remarkably safe and efficacious class of medications that have proved to be invaluable in the fight against heart disease. Statins have been prescribed to millions of patients for nearly 20 years; thus there have been hundreds of millions of patient-years of use, with relatively few adverse effects and incalculable benefits. Results from large-scale clinical trials have shown that statins are associated with dramatic decreases in cardiovascular risk. It seems certain that statins will remain a valuable and essential part of the lipid-lowering landscape, but combinations of statins with other lipid-lowering agents are increasingly important. Even with the most potent statins, the desired low-density lipoprotein cholesterol goal might not be attained with statin monotherapy. Furthermore, because of the increasing prevalence of diabetes and the metabolic syndrome, along with their attendant multiple lipid abnormalities, combinations of statins with medications targeted toward multiple lipoprotein particles will emerge.

Cardiovascular Diseases↗
PubMed2005

Impact of routine in-hospital assessment of low-density lipoprotein levels and standardized orders on statin therapy in patients undergoing percutaneous coronary interventions.

BACKGROUND: Previous studies have shown that a significant proportion of patients undergoing percutaneous coronary intervention (PCI) are not receiving guideline-recommended statin therapy upon hospital discharge. We evaluated the impact of the implementation of routine cholesterol profile measurements and standardized orders post-PCI on the number of patients receiving statin therapy. METHODS: We conducted a prospective, observational study on all patients undergoing PCI in an urban teaching hospital from February 2002 to March 2003. Patient baseline characteristics, statin therapy pre- and post-PCI, and fasting lipid profiles were recorded as part of an ongoing PCI database. A similar cohort of patients undergoing PCI in the one-year time period immediately before the intervention was used as a comparison group. RESULTS: A total of 1,748 patients underwent PCI during the study period. Statin therapy was prescribed in 78% of patients pre-PCI and increased to 92% at hospital discharge. In the year before implementation of the standardized post-PCI orders, there was only a 5% absolute increase in statin use after PCI compared to a 14% absolute increase in the study time period (p = < 0.0001). Low-density lipoprotein (LDL) levels were available in 1,268 patients. The median LDL level was 2.08 mmol/L for patients on statin therapy versus 2.40 mmol/L for those not on statins. CONCLUSIONS: Routine assessment of LDL levels and lipid-lowering therapy at the time of PCI resulted in a further increase in statin use. However, approximately one-third of patients still had an LDL level above recommended guidelines for secondary prevention.

Angioplasty, Balloon, Coronary↗
PubMed2005

Myonecrosis after elective percutaneous coronary intervention: effect of clopidogrel-statin interaction.

BACKGROUND: A recent ex vivo study suggests that the metabolic activation of clopidogrel is catalyzed by cytochrom P450 (CYP) 3A4 and is competitively inhibited by atorvastatin, but not pravastatin. OBJECTIVE: To determine whether the incidence of procedure-related myocardial injury, assessed by cardiac troponin T (cTnT) release, is altered when clopidogrel is coadministered with a statin that is predominantly CYP3A4-metabolized. METHODS AND RESULTS: Of the 211 consecutive patients who underwent coronary stenting after pretreatment with clopidogrel, 114 were receiving a CYP3A4-metabolized statin (59 simvastatin and 55 atorvastatin, Group 1), and 37 were receiving a non-CYP3A4-metabolized statin (30 pravastatin and 7 fluvastatin, Group 2) whereas 60 patients were not taking any statins (Control). All were troponin-negative before the procedure. The overall incidence of postprocedural cTnT positivity (> 0.10 ng/ml) was 30.8%. Group 2 patients were less likely to exhibit cTnT rise relative to Group 1 patients (8% versus 41.6%; p = 0.004) and relative to controls (8% versus 32.5%; p < 0.001). Multivariate analysis identified the use of a non-CYP3A4-metabolized statin before coronary stenting as the sole independent predictor for lower incidence of procedure-related cTnT elevation with estimated Odds ratios of 0.16 relative to no statin therapy (95% CI: 0.04-0.59; p = 0.006) and 0.18 relative to CYP3A4-metabolized statin therapy (95 CI: 0.053-0.637; p = 0.008) CONCLUSION: Benefit derived from the preprocedural use of pravastatin and fluvastatin but not atorvastatin and simvastatin suggest that the ex vivo finding of a negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel may be of clinical significance.

Aged↗
PubMed2005

Statin therapy in Canadian patients with hypercholesterolemia: the Canadian Lipid Study -- Observational (CALIPSO).

BACKGROUND: Although statins are widely used to reduce low density lipoprotein cholesterol (LDL-C), there is little information about patient profiles, treatment patterns and goal achievement among statin-treated patients in Canada. OBJECTIVES: To assess the profile of statin-treated patients and to determine whether they are achieving recommended targets for LDL-C. METHODS: The Canadian Lipid Study -- Observational (CALIPSO) was a cross-sectional study involving Canadian physicians who were among the top statin prescribers. Each physician enrolled up to 15 patients who were at least 18 years of age with a diagnosis of hyper-cholesterolemia and who had been using a statin for at least eight weeks. Sociodemographics, coronary artery disease (CAD) risk factors, pretreatment and current lipid levels, and history of lipid-lowering therapy were reported for 3721 patients. RESULTS: Sixty-eight per cent of statin-treated patients were at high CAD risk according to the 2003 Canadian guidelines, 46.4% had established cardiovascular disease, 33.9% had diabetes and 59.5% had hypertension. Average LDL-C reductions of 32% (37% for high-risk patients) were initially required to reach goal. At the study visit, patients had been treated for an average of 4.3 years and 24.2% were using a high statin dose. Despite statin therapy, 27.2% of all patients and 36.4% of those at high CAD risk had not achieved LDL-C targets. For 67.4% of these patients, the current therapy was not modified at the study visit. CONCLUSIONS: Despite effective therapies, many treated patients are not achieving recommended LDL-C targets. Strategies should be implemented to promote achievement of lipid treatment goals for high-risk patients, thereby reducing the risk of cardiovascular events and their associated clinical and economic burdens.

Aged↗
PubMed2005

The intensive statin therapy myth.

Statins play an important role in the treatment and prevention of coronary artery disease and atherosclerosis. Currently, however, despite its important qualities, the use of statin therapy in the treatment of CAD patients ranges only between 30 and 60% in Europe, the United States and Israel. A wide gap still exists between the numerous scientific publications demonstrating the beneficial effects of statins and the low rate of implementing the guidelines in practice. A Medline search up to June 2005 on all prospective, double-blind, randomized clinical trials evaluating the impact of intensive statin therapy (any statin dose >40 mg/daily) on clinical outcomes after a 1 year follow-up revealed only eight trials. In all the eight trials, with a follow-up period of 12-60 months, intensive statin therapy was significantly more effective than and at least as safe as placebo or other standard statin regimens. Thus, based on the current evidence-based medicine, intensive statin therapy enables more patients with CAD to achieve the current National Cholesterol Education Program goal for low density lipoprotein, while ensuring a relatively high safety profile.

Cholesterol, LDL↗
PubMed2006

Benefit of adding pioglitazone to statin therapy in non-diabetic patients with the metabolic syndrome.

Statins frequently do not control all of the lipid abnormalities found in patients with the metabolic sydrome. Pioglitizone (PIO), an insulin sensitizing agent, has been shown to have favorable lipid effects in diabetic patients. Little information is available regarding the effect of combined statin and PIO therapy in non-diabetic patients with the metabolic syndrome. We report our experience of adding PIO to statin therapy in non-diabetic patients with the metabolic syndrome. Pioglitazone was administered to 24 non-diabetic patients in our lipid clinic who were already on a statin yet continued to have significant lipid abnormalities. All patients had characteristic lipid abnormalities and clinical features of the metabolic syndrome. The treatment period was 59+/-29 (range 7-123) weeks. Lipid profiles, fasting glucose, and alanine aminotransferase were assessed before and at least 6 weeks after pioglitazone was added to statin. Triglyceride levels decreased from 307+/-295mg/dL to 173+/-129mg/dL (P=0.003), non-high-density lipoprotein cholesterol (non-HDL) decreased from 151+/-53mg/dL to 130+/-49mg/dL, (P=0.003), and high-density lipoprotein cholesterol (HDL) levels increased from 42+/-11mg/ dL to 45+/-12mg/dL, (P=0.039). The addition of PIO to statin in non-diabetic patients with metabolic sydrome produced significant additional benefits in the lipid profile over statin monotherapy. Favorable effects were seen in triglycerides, HDL, and non-HDL levels. Study limitations include: this is a small non-blinded observational study in which patients served as their own controls. The duration of combination therapy and type of statin employed were variable.

Aged↗
PubMed1991

Isolation and characterization of the rat chromosomal gene for a polypeptide (pS1) antigenically related to statin.

Increasing evidence shows the existence of nonproliferation-specific gene(s) whose expression is mostly present in growth-arrested cells. One member of this gene family has been identified by previous work as a nuclear protein of 57,000 Da, termed statin. Logical extensions of statin research are to identify the genomic and cDNA clones encoding for statin and to study the regulation of statin gene expression. During the search for the statin gene, we have identified a cDNA clone and a genomic clone named S1 and S10, respectively, by screening a rat brain lambda gt11 expression library with the statin antibody and subsequently using S1 cDNA as a probe to screen a rat genomic cosmid library. Here, we report the cloning and sequencing of the S1 cDNA and S10 genomic clones. Primary sequence analyses indicate that the derived amino acid sequence of S1 shares high homology (greater than 92.6%) with human elongation factor 1 alpha (EF-1 alpha), whereas the 5'- and 3'-untranslated regions are less than 20% homologous. Despite the unusually high degree of similarity between S1 and human EF-1 alpha at the amino acid sequence level, their protein products are different and immunologically distinct. The in vitro transcription and translation product of S1 (pS1), a 49,000-Da polypeptide, reacts only with the monoclonal antibody against statin; this antibody exhibits no antigenic reaction to the EF-1 alpha protein. Northern blot analysis shows that the S1 message is most abundant in G0 phase of 3T3 mouse fibroblasts, but becomes significantly reduced in G1 and S phase cells. EF-1 alpha messages do not show such dramatic changes during cell cycle phase transition. These findings suggest that the expression of the identified S1 cDNA clone is specific for nonproliferating cells and that the in vitro translation product of the S1 cDNA is recognized by the statin antibody. Genomic Southern blots indicate that S1 cDNA is encoded by a single copy gene in the rat genome and is a unique member of the EF-1 alpha/S1 supermultigene family. DNA sequence analysis demonstrates that the rat S1 transcription unit is 12 kilobase pairs in length and contains seven introns. The organization of exons is virtually identical between S1 and human EF-1 alpha. In contrast, neither a TATA box nor a CAAT box is located in the proximal 5'-flanking regions from positions -1 to -1359 of the S1 gene, where we could expect to find the regulatory region containing the elements controlling gene expression; no evident sequence homology to the human EF-1 alpha gene is detected in this region.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed2001

Use and monitoring of "statin" lipid-lowering drugs compared with guidelines.

BACKGROUND: In patients with high cholesterol, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (or "statins") have been shown to reduce overall mortality in primary and secondary prevention. The National Cholesterol Education Program expert panel's guidelines (Adult Treatment Panel II) recommend evaluation and treatment of high cholesterol based on stratification of patients according to cardiovascular risk. While evidence suggests that many patients are undertreated, comparatively few data are available regarding overtreatment. OBJECTIVES: To assess the appropriateness of statin therapy compared with national guidelines and to examine the appropriateness of monitoring for adverse effects. METHODS: For all patients at a tertiary medical center, electronic medical records were evaluated for presence or absence of statin use and for presence of established coronary heart disease or cardiac risk factors. Therapy was compared with the recommendations of the National Cholesterol Education Program guidelines. Our primary outcome measures included, for all patients taking statins, prevalence of appropriateness vs overuse, and for all patients with coronary heart disease, prevalence of appropriateness vs underuse. RESULTS: Overuse of statin therapy was found among 69% of patients undergoing primary prevention, and among 47% of patients undergoing secondary prevention. In addition, among patients with coronary heart disease who were not taking statins, 88% were undertreated. Monitoring of liver function varied widely, and did not correlate with the risk of adverse events secondary to statin use. CONCLUSIONS: Overtreatment and undertreatment for hyperlipidemia were frequent. Decision support may help physicians improve their performance compared with guidelines.

Adult↗
PubMed2001

Use of the statins in patients after acute myocardial infarction: does evidence change practice?

OBJECTIVE: To compare the use of lipid-lowering agents in 42 628 elderly patients (aged > or =65 years) after acute myocardial infarction, before and after the publication of the Scandinavian Simvastatin Survival Study (4S), using the Ontario Myocardial Infarction Database. METHODS: Multivariate regression models were created to estimate changes in the rate of statin use over time in monthly cohorts of elderly patients after acute myocardial infarction in Ontario from April 1, 1992, to March 31, 1997. Changes in the rate of statin use over time were estimated using patient and prescriber characteristics. RESULTS: We found a 3.6-fold significant increase in the monthly rate of statin use after the publication of 4S compared with before the publication of 4S (P<.001); specifically, the rate of increase in simvastatin and pravastatin sodium use was higher after the publication of 4S (P<.001 for each). Before the publication of 4S, the rate of increase in statin use in younger patients (aged 65-74 years) was 2.7 times higher than in older patients (aged > or =75 years) (P =.02), while after the publication of 4S, the rate of increase in statin use was only 1.8-fold higher in the younger group (P<.001). After the publication of 4S, there was a 1.6-fold higher rate of increase in statin use in male compared with female patients (P =.006). Also after the publication of 4S, specialists (cardiologists and internists) had a 2-fold higher rate of increased use of the statins than did generalists (P<.001). CONCLUSION: It is possible to shift practice if the evidence of benefit is strong, the intervention is easy to implement, and the intervention is marketed aggressively.

Aged↗
PubMed2004

Impact of concurrent medication use on statin adherence and refill persistence.

BACKGROUND: Effective therapy for chronic illness requires daily medication adherence (DMA) for prolonged periods. Overall medical regimen complexity may represent one barrier to successful adherence. METHODS: To assess the relationship between the number of concurrently prescribed medicines and adherence to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), we analyzed a cohort of 5488 patients in a single health insurance plan who began statin therapy between July 1, 1999, and June 30, 2002. We assessed 2 parameters of statin adherence: (1) DMA ([total number of pills dispensed/total number of days between first and last prescription] x100) and (2) refill persistence (RP) (consecutive months of refills after initial prescription). RESULTS: The cohort was 61.6% male, with a mean +/- SD age of 52.7 +/- 9.3 years. Patients were prescribed a mean +/- SD of 2.9 +/- 2 total medicines (range, 1-13), with a mean +/- SD statin DMA of 82.1% +/- 26.5%. By 12 months, only 68% of patients continued filling statin prescriptions. After controlling for age, income level, and treatment for hypertension or ischemic heart disease, a greater number of concurrently prescribed medicines was significantly associated with better DMA (P = .005) and longer RP (P = .03). CONCLUSIONS: In this cohort, statin DMA was generally adequate, but RP was suboptimal. Patients with more concurrently prescribed medicines had higher DMA and better RP, even after adjusting for demographic factors and cardiovascular comorbidity. Physicians should not be deterred from initiating statin therapy by a patient's medical regimen complexity but should be alert for lack of therapy persistence, particularly in younger and healthier patients.

Adult↗
PubMed2005

Statin use and fracture risk: study of a US veterans population.

BACKGROUND: Whether statins reduce the risk of fractures is still contested. Several studies support a favorable association, whereas post hoc analyses of statin-randomized trials have failed to find a benefit. We sought to assess this possible relationship in a large population of elderly, predominantly male veterans. METHODS: We established the study population using all health care encounters and services from patients who received care in the New England Veterans Affairs health care system between January 1998 and June 2001. According to evidence from the literature, covariates that would affect the risk of fractures were included in the final model, as were medications that were clinically meaningful and significant in univariate models and the Charlson Comorbidity Index as a surrogate for general health. We also conducted a similar analysis among new statin users. We used pooled logistic regression to assess for significant associations. RESULTS: Of the 91 052 patients in the final cohort, 28 063 were prescribed statins and 2195 were prescribed nonstatin lipid-lowering medications. In the adjusted analyses, statin use was associated with a 36% (odds ratio, 0.64; 95% confidence interval, 0.58-0.72) reduction in fracture risk when compared with no lipid-lowering therapy and a 32% (odds ratio, 0.67; 95% confidence interval, 0.50-0.91) reduction when compared with nonstatin lipid-lowering therapy. Similar findings were found for the new statin user group. CONCLUSIONS: We have provided yet another study in a unique population of mostly male veterans that found a significant reduction in fractures among statin users. More studies need to be performed to confirm or refute our findings.

Aged↗
PubMed2001

Use of statins and risk of fractures.

CONTEXT: Previous studies have reported lower fracture risks in patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To investigate risk of fracture among statin users. DESIGN: Case-control study of data from the General Practice Research Database (GPRD). SETTING: A total of 683 general clinical practices in the United Kingdom. PATIENTS: Cases were 81 880 patients aged 50 years or older who had a fracture of the vertebrae, clavicle, humerus, radius/ulna, carpus, hip, ankle, or foot occurring between the enrollment date of their practice into the GPRD and July 1999, paired with 81 880 age-, sex-, and practice-matched controls. MAIN OUTCOME MEASURE: Risk of fracture in current users vs nonusers of statins. Odds ratios were estimated from conditional logistic regression and adjusted for smoking, medications and illnesses associated with fracture risk, and body mass index when known. RESULTS: The adjusted odds ratio (OR) for current use of statins compared with nonuse was 1.01 (95% confidence interval [CI], 0.88-1.16). For forearm, hip, and vertebral fractures, the ORs were 1.01 (95% CI, 0.80-1.27), 0.59 (95% CI, 0.31-1.13), and 1.15 (95% CI, 0.62-2.14), respectively. Relative to nonuse, a statin dosage of less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture of 1.13 (95% CI, 0.96-1.33); this OR was 1.07 (95% CI, 0.82-1.38) at dosages of 20 to 39.9 mg/d and 0.85 (95% CI, 0.47-1.53) at dosages of 40 mg/d or more. The adjusted OR was 0.71 (95% CI, 0.50-1.01) for statin use durations of 0 to 3 months, 1.31 (95% CI, 0.87-1.95) for durations of 3 to 6 months, 1.14 (95% CI, 0.82-1.58) for durations of 6 to 12 months, and 1.17 (95% CI, 0.99-1.40) for durations of more than 12 months. CONCLUSION: In this study, use of statins at dosages prescribed in clinical practice was not associated with a reduction in risk of fracture.

Aged↗
PubMed2004

Assessment of the efficacy of different statins in murine collagen-induced arthritis.

OBJECTIVE: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are widely used lipid-lowering agents. In addition to their well-known effect on cholesterol levels, statins have been reported to display antiinflammatory activities both in vitro and in vivo. In this context, in vivo prophylactic and therapeutic effects of simvastatin were recently demonstrated in mouse collagen-induced arthritis, a well-described experimental model for human rheumatoid arthritis (RA). The aim of this study was to further investigate in vivo effects of 3 different statins, atorvastatin, rosuvastatin, and simvastatin, using the same experimental model. METHODS: Different doses and routes of administration were used for the various statins in an attempt to elicit antiarthritic activity in preventive and curative treatment protocols. RESULTS: Atorvastatin and rosuvastatin had no in vivo efficacy, as indicated by clinical, histologic (synovial hyperplasia, exudate, and cartilage damage), immunologic (anti-type II collagen IgG production), and biochemical (interleukin-6, serum amyloid A, and glucocorticoid production) parameters of inflammation and autoimmunity. The previously described beneficial effects of administration of intraperitoneal simvastatin were reproduced in our experiments, but could be accounted for by very severe side effects of the treatment, leading to increased glucocorticoid levels. CONCLUSION: This work shows that different statins have no effect in a murine model of arthritis, an unexpected observation given the previously described therapeutic effect of statins in immune-mediated inflammatory diseases. It is still unclear whether statins will have benefit in the treatment of RA.

Animals↗
PubMed2001

What do the statin trials tell us?

The results of five large-scale, randomized, placebo-controlled trials, involving nearly 31,000 subjects, attest to the benefits of statins in the prevention of coronary events. Several key observations can be made on the basis of the evidence from these investigations. Of primary importance is the fact that statins reduce coronary event rates in patients with or without coronary heart disease. The percentage reduction in risk increases with each successive year of statin therapy. Moreover, the risk reduction is proportional to the reduction in low-density lipoprotein cholesterol. Subgroup analyses have demonstrated that the efficacy of statins extends to specific subgroups of patients, including women, people with diabetes, and older individuals. These agents also reduce the risk of stroke and transient ischemic attacks in patients with coronary disease. Both the randomized trials and widespread clinical experience have confirmed that statins are safe and do not increase the risk of cancer or mortality. Several markers of atherosclerotic risk are ameliorated by statins, although the clinical significance of this observation remains under investigation. The broad range of the therapeutic effects of statins yields safe, effective management of hypercholesterolemia in current practice while also providing a foundation for additional therapeutic refinements in the future.

Age Factors↗
PubMed1995

Identification of resting cells by dual-parameter flow cytometry of statin expression and DNA content.

Statin, a 57-kDa nuclear protein, has been recognized as a unique marker of quiescent (G0) cells; specific monoclonal antibodies (MoAb) against statin have been produced and used to label resting cells in tissue sections and in cultured cells. We present an improved method for the identification of G0 cells by dual-parameter flow cytometry of statin expression and DNA content. The appropriate technical conditions were set up by using resting and cycling human fibroblasts as a model cell system. Several fixatives proved to be suitable for the immunocytochemical detection of statin; among them, 70% ethanol was selected because this fixation procedure is suitable for DNA staining with intercalating dyes and is routinely used for the immunolabeling of proliferation markers (such as proliferating cell nuclear antigen [PCNA] and Ki-67) and of bromodeoxyuridine (BrdUrd) incorporation. Following cell permeabilization with detergent, exposure to the antistatin antibody (S-44), and indirect fluorescein isothiocyanate immunolabeling, cells were counterstained for DNA with propidium iodide and analyzed by dual-parameter flow cytometry. In cells from several animal sources (rat thymocytes and C6 glioma cells, mouse 3T3 cells, and human MCF-7 cells), under different experimental conditions, the expression of statin was found to correlate inversely with that of PCNA and Ki-67, and with the BrdUrd labeling index. In dual-parameter flow scattergrams, G0 (statin positive) cells can be discriminated from the potentially cycling (statin negative) G1 cells, i.e., within a cell fraction having the same DNA content. This approach can be envisaged as a powerful tool both for monitoring changes in the resting cell fraction and for investigating the process of G0-G1 transition in unperturbed and drug-treated cell populations.

3T3 Cells↗