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PubMed2006

Statins and hepatic steatosis: perspectives from the Dallas Heart Study.

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease are independently associated. Due to the efficacy of 3-hydroxy 3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the prevention of cardiovascular disease, increasing interest has been shown in establishing the safety of these drugs in NAFLD. In this study, the relationship between statin use, hepatic triglyceride content (HTGC), and serum alanine aminotransferase (ALT) levels was examined in 2,264 Dallas Heart Study participants who were using no lipid-lowering agent (n = 2,124) or using only a statin for lipid management (n = 140). Statin use was not associated with a greater frequency of hepatic steatosis (38% vs. 34%) or elevated serum ALT (15% vs. 13%) by a pair-matched analysis. Statin use was also not associated with a greater prevalence of elevated serum ALT among subjects with hepatic steatosis (n = 638). This finding persisted when controlling for possible sample bias as a result of current prescribing practices for statins. Among subjects with serum lipid abnormalities who were not using a statin, hepatic steatosis was present in 60% of those with mixed hyperlipidemia and 83% of those with both mixed hyperlipidemia and an elevated serum ALT. In conclusion, statin use was not associated with a higher frequency of hepatic steatosis or serum ALT abnormalities, even among those with hepatic steatosis. Individuals meeting criteria for statin therapy are likely to have coexistent hepatic steatosis.

Alanine Transaminase↗
PubMed2005

Statin therapy is associated with fewer deaths in patients with bacteraemia.

OBJECTIVE: Beneficial effects with statin use are increasingly reported in a variety of patient groups. There is in vitro and clinical evidence for its antiinflammatory and immunomodulatory therapeutic roles. We aimed to assess the association between statin administration and mortality in bacteraemic patients. DESIGN: A retrospective cohort analysis. SETTING: A 300-bed acute general hospital. PATIENTS AND PARTICIPANTS: All patients (n=438) requiring hospital care for an episode of bacteraemia during the years 2000-2003 were included. Statin use, patient outcome, and clinical and laboratory variables were collected. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: There was a significant reduction in all-cause hospital mortality (10.6% vs. 23.1%, p=0.022) and death attributable to bacteraemia (6.1% vs. 18.3%, p=0.014) in patients who were receiving statin therapy at the time of bacteraemia (n=66). The reduction in all-cause hospital mortality (1.8% vs. 23.1%, p=0.0002) and death attributable to bacteraemia (1.8% vs. 18.3%, p=0.0018) was more pronounced in the patients who continued to receive statin therapy after the diagnosis of bacteraemia (n=56). The apparent mortality benefit persisted after controlling for differences between the groups. Statin use prior to admission was associated with a reduced adjusted hospital mortality rate (odds ratio 0.39; CI 95% 0.17, 0.91; p=0.029), and continuing statin use after bacteraemia increased this effect (odds ratio 0.06; CI 95% 0.01, 0.44; p=0.0056). CONCLUSION: This retrospective study demonstrates a significant survival benefit associated with continuing statin therapy in bacteraemic patients. The potential for statins as an adjuvant therapy in sepsis warrants further investigation.

Adult↗
PubMed2005

Being well-informed about statin is associated with continuous adherence and reaching targets.

BACKGROUND: Statins are life saving drugs in cardiovascular practice. However, they still are underprescribed in many situations despite their well-established benefits. Adherence may be improved by increased comprehension of the patients. METHODS: Patients enrolled into a previous survey were randomized into two groups as those, who were informed comprehensively (Group 1) and those not (Group 2). 202 patients, all of whom were on secondary prevention, were contacted after median 15 months of follow up and evaluated whether they continued the statins, and reached targets. RESULTS: 102 out of 202 patients were those enrolled into Group 1, and 100 of them were those enrolled into Group 2. In Group 1, 62.7% of patients were on continuous statin therapy during period between initial and secondary contact, whereas, only 46% of patients in Group 2 were on continuous statin therapy (p = 0.017). Being well-informed about statin increased the likelihood of being on continuous statin therapy after median of 15 months by 1.977 folds. Concerning targets, 64.7% of those in Group 1 reached the targets, whereas, 43% of those in Group 2 reached the targets (p = 0.002). Being well-informed about statin increased the likelihood of having suggested targets by ATP III after median of 15 months by 2.430 folds. CONCLUSION: Providing patients with comprehensive knowledge about statins, even in patients, who were already on statin therapy, seems not only to improve adherence but also increase the percentage of those reaching targets.

Cardiovascular Diseases↗
PubMed2000

Pleiotropic effects of statins.

The advent of statin therapy has revolutionized the ability of the clinician to manage patients at risk for the development of an ischemic event due to dyslipidemia. Large-scale clinical trials involving thousands of patients in both primary and secondary prevention have clearly demonstrated that statin therapy will reduce cardiovascular mortality across a broad spectrum of patient subgroups. Additionally, in adequately powered trials, total mortality has been successfully decreased by the use of statin therapy. However, the precise mechanism underlying the benefit of statin therapy has been controversial due to the multiplicity of potential benefits that statins have demonstrated in addition to pure lipid lowering. The causal theory of pharmacologic benefit reiterates the lipid hypothesis, which states that dyslipidemia is central to the process of atherosclerosis and the clinical benefit which accrues from statin therapy is a function of the degree of lipid lowering. The noncausal theory supports the premise that clinical benefits are related primarily to pleiotropic effects of statins (endothelial function, inflammation, coagulation and plaque vulnerability) as being the major modulators of clinical benefit. This review will focus on the potential beneficial effects of statin therapy on a number of the pleiotropic effects of statins and the potential role that these activities play in the reduction of risk for ischemic events.

Cardiovascular Physiological Phenomena↗
PubMed1989

A rat liver 57-kDa protein is identified to share antigenic determinants with statin, a marker for nonproliferating cells.

The nuclear protein statin, found uniquely in nonproliferating cells, has been previously identified by mouse monoclonal antibodies designated as S-30 and S-44. We report here the screening of various rat tissues for proteins cross-reacting with these antibodies. As revealed by immunoblotting, two polypeptides (mol wt 80 and 57 kDa) and a group of lower-molecular-weight proteins migrating between 34 and 38 kDa were found to react with the anti-statin antibodies. The most prominent immunoreactivity was observed with a 57-kDa protein present in rat liver. Upon further fractionation of the liver protein extract with ammonium sulfate [(NH4)2SO4] the 57-kDa protein, designated as rat liver protein 57 or RLp57, was detected independently with both anti-statin antibodies in the 30 to 60% (NH4)2SO4 fraction. In order to determine whether rat liver protein 57 is indeed specifically recognized by anti-statin antibody S-44, we used RLp57 transferred onto nitrocellulose paper as a specific substrate for the adsorption of the S-44 antibody from ascites fluid. As shown by indirect immunofluorescence microscopy the solution remaining after adsorption failed to stain human fibroblasts. The adsorbed immunoglobulin, however, upon elution revealed statin-specific nuclear staining activity on senescent fibroblasts. These findings suggest that rat liver protein 57 and the human fibroblast statin share similar antigenic determinants recognized by the statin-specific S-44 antibody. Our results indicate furthermore that the statin previously identified in fibroblasts may represent one member of a group of several antigenically related proteins detectable with specific anti-statin antibodies.

Animals↗
PubMed1995

Increased levels of statin, a marker of cell cycle arrest, in response to hippocampal neuronal injury.

Injured neurons in the CNS are known to synthesize high levels of proliferation related oncogene products and heat shock proteins without dividing. Statin is a cell cycle regulated nuclear phosphoprotein, selectively associated with the non-proliferative state in a wide variety of cell types. In the present study, neuronal statin was examined following lethal or sublethal neuronal injuries in the hippocampus of Alzheimer's disease patients, in rats receiving kainate lesions to the dorsal hippocampus and in entorhinal cortex lesioned rats. Immunolabelling of nuclear statin showed that statin immunoreactivity increased preferentially in CA1 pyramidal neurons of the hippocampus in Alzheimer's disease. In kainate lesioned rats, statin immunoreactivity was markedly induced in the CA3 hippocampal region in association with neuronal loss. Entorhinal cortex lesioned rats showed a transient induction of statin between 2 and 6 days post lesion in CA1 neurons. However, cell counts in entorhinal cortex lesioned rats remained unaltered in the CA1 and granule cell layers during the entire 30 day time course, indicating that increased statin levels are not secondary to neuronal degeneration and are not necessarily accompanied by irreversible neuronal death. It is concluded that, in addition to proliferation related gene products, neuronal injury induces an increase in levels of statin, a nuclear marker of cell cycle arrest. Furthermore, statin may be a potentially useful marker of injurious neuronal stress, even under conditions that do not necessarily lead to irreversible cell death.

Alzheimer Disease↗
PubMed2006

Statins are associated with lower risk of gastrointestinal bleeding in patients with unstable coronary syndromes: analysis of the Orbofiban in Patients with Unstable coronary Syndromes-Thrombolysis In Myocardial Infarction 16 (OPUS-TIMI 16) trial.

BACKGROUND: It has recently been shown that statins increase the myocardial content of prostaglandin (PG) I2 (prostacyclin) and PGE2. A systemic increase of PG production may protect the gastric mucosa and prevent gastrointestinal (GI) bleeding. We hypothesized that statins would lower the risk of GI bleeding associated with antiplatelet therapy in patients with acute coronary syndromes (ACS). METHODS: We retrospectively analyzed data on 10288 patients with ACS included in the OPUS-TIMI 16 trial and received aspirin and either the oral IIb/IIIa inhibitor orbofiban or placebo. RESULTS: Inhospital GI bleeding rate was significantly lower in patients who were receiving lipid-lowering drugs before admission compared with those who were not (0.2% vs 0.6%, P = .031). Throughout 10 months of follow-up, GI bleeding occurred in 1.8% of non-statin users compared with 1.0% of statin users (P = .001). Statin use was associated with less overall bleeding in both the orbofiban (1.4% vs 2.4%, P = .006) and the placebo groups (0.2% vs 0.8%, P = .047). Severe and major bleeding occurred less frequently with statin use (0.8% vs 1.5%, P = .001) in both the orbofiban (1.1% vs 2.0%, P = .006) and the placebo groups (0.1% vs 0.5%, P = .119). Logistic regression analysis showed that age > 65 years, orbofiban treatment, Killip class > 1, history of cerebrovascular disease, and calcium-channel blocker use were associated with higher risk of GI bleeding, whereas statin therapy was associated with a lower risk (odds ratio 0.68, 95% CI 0.45-1.04, P = .079). CONCLUSIONS: Statins may exert protective effect against GI bleeding in patients with ACS. Additional studies are warranted to explore this additional potential benefit of statins.

Acute Disease↗
PubMed2026

Association Between Statin Use and Dry Eye Disease: A Systematic Review and Meta-Analysis.

TOPIC: This systematic review and meta-analysis evaluated the literature-pooled association between statins and dry eye disease (DED). CLINICAL RELEVANCE: Statins, a common treatment modality for dyslipidemia, have been proposed as a potential contributor to DED via their activity in meibomian gland epithelial cells. However, single studies show mixed evidence, and there remains an unmet clinical need to clarify whether statin exposure is associated with DED. METHODS: This review was reported in accordance with the Preferred Reporting Items for Systematic Reviews of Interventions (PRISMA) 2020 statement and was registered a priori on PROSPERO (CRD420251238004). Ovid MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and the reference lists of relevant reviews were searched from inception to November 2025 for studies reporting the association between statin use and DED. Random-effects meta-analysis using inverse-variance weighting was conducted to pool effect estimates as odds ratios with 95% confidence intervals (CIs). Study risk of bias was appraised using the ROBINS-E tool, and the certainty of the evidence was reported using the GRADE framework. RESULTS: Six observational studies were included in the meta-analysis (n = 560,821; 356,012/559,141 [63.7%] statin users). The pooled analysis revealed a significant positive association between statins and DED (odds ratio 1.09, 95% CI 1.05-1.13, P < .001), with an absolute risk difference of 10.2 more DED cases per 1000 (95% CI 5.5 more to 15.2 more). This result was derived from very low-certainty evidence given limitations in study design and serious inconsistency. Subgroup and sensitivity analyses for risk of bias (P = .123), method of outcome ascertainment (P = .737), type of effect estimate (P = .496), and leave-one-out analyses showed no evidence of effect modification and demonstrated consistent direction of association across studies. CONCLUSION: Statin use was associated with a small but statistically significant increase in DED, limited by very low-certainty evidence. Physicians should monitor for and educate patients on ocular surface symptoms in patients using statins with pre-existing DED risk factors. Future studies should use standardized DED diagnostic criteria to investigate the impact of statin dose, type, and duration to better characterize this potential association.

Humans↗
PubMed2004

Consumer behavior in the setting of over-the-counter statin availability: lessons from the consumer use study of OTC Mevacor.

Despite the proven benefits of statins, large numbers of patients meeting guideline criteria for therapy are not receiving these drugs. It has been suggested that over-the-counter (OTC) availability of statins would allow more consumers to use statins and achieve cardiovascular risk reduction. However, concerns have been raised as to the consumers' ability to self-manage hyperlipidemia and use statins safely. The Consumer Use Study of OTC Mevacor (CUSTOM) was designed to define consumer behaviors in the setting of OTC statin availability. The study was conducted in a simulated OTC setting and allowed consumers to purchase once-daily lovastatin 20 mg. The CUSTOM dataset includes >3,300 consumers who evaluated OTC lovastatin for potential purchase at study sites and follow-up information on purchasers for up to 6 months of self-managed therapy. These data have been analyzed to address consumers' knowledge of their cholesterol concentrations as well as their ability to make OTC use decisions based on their cardiovascular risk, avoid drug-drug interactions, self-manage their cholesterol treatment after deciding to use the OTC product, and maintain interactions with physicians while using lovastatin OTC. The results showed that most study participants appropriately self-selected OTC statin therapy and managed their treatment. Use of OTC statins by consumers needing more intensive statin therapy or facing the risk of potential drug-drug interactions remains an area of concern but occurred infrequently in CUSTOM. These data are important for making an informed risk-benefit decision concerning OTC statin availability.

Anticholesteremic Agents↗
PubMed2006

Effects of statins on renal function.

This report reviews data on the development of proteinuria in patients with chronic kidney disease who are treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) for dyslipidemia. Although subgroup analyses of statin trials have shown cardiovascular benefits in subjects with chronic kidney disease, concern about statin-induced proteinuria remains high. Experimental studies have suggested that the proteinuria seen with statin treatment results from the inhibition of receptor-mediated endocytosis, the likely mechanism of protein uptake in proximal tubular cells. Transient proteinuria may signify little more than the effective inhibition of cholesterol synthesis at this site. The blockade of protein trafficking in tubular cells is thought to reduce inflammation, slow fibrosis, and diminish proteinuria in the long term. Post hoc analyses of large clinical trials in subjects without overt renal disease have generally supported this notion, showing that statins most benefit patients with the greatest baseline renal deficits. Statins have also been shown to preserve glomerular filtration rate and reduce proteinuria in subjects with nondiabetic renal disease. In conclusion, in the absence of prospective, randomized trials in renally impaired patients, the collective evidence indicates that statin therapy may slow the decrease in renal function that generally attends atherosclerotic disease. The incidence of proteinuria with potent statins is only 1% to 2% when these drugs are given in recommended doses. Several large trials are currently under way to examine the safety and efficacy of statins in renally compromised patients at high risk for cardiovascular disease.

Animals↗
PubMed2006

Effects of colesevelam hydrochloride on low-density lipoprotein cholesterol and high-sensitivity C-reactive protein when added to statins in patients with hypercholesterolemia.

Elevated high-sensitivity C-reactive protein (hs-CRP) levels are associated with an increased risk of atherosclerotic coronary heart disease (CHD). The addition of the bile acid sequestrants, such as colesevelam hydrochloride (HCl), to statins further reduces low-density lipoprotein (LDL) cholesterol levels. However, the effects of approved cholesterol-lowering bile acid sequestrants on hs-CRP have not previously been reported. Three randomized, double-blind, placebo-controlled, parallel, 6-week clinical trials of similar design investigated the efficacy of adding colesevelam HCl to stable simvastatin, atorvastatin, or pravastatin treatment in 204 patients with primary hypercholesterolemia. The primary end point was the mean percent change in the LDL cholesterol levels. Secondary end points included the effects on other lipid parameters and hs-CRP levels. A pooled analysis showed that adding colesevelam HCl to statin therapy significantly lowered LDL cholesterol levels (21 mg/dl or 16% mean reduction from baseline, p = 0.0013, and 11 mg/dl or 9% mean reduction compared with placebo, p = 0.0003). Four times as many patients receiving colesevelam HCl plus a statin achieved a LDL cholesterol target of <100 mg/dl compared with patients receiving a statin plus placebo (39% vs 10%, respectively, p <0.0001). The incidence of mild gastrointestinal adverse effects was slightly higher in the colesevelam HCl plus statin group than in the placebo plus statin group. Finally, the differences in the change in hs-CRP levels with colesevelam HCl plus statin therapy were significant compared with the changes with placebo plus statin (median change -23%, p = 0.0069). In conclusion, this is the first report suggesting that an approved cholesterol-lowering bile acid sequestrant, specifically colesevelam HCl, decreases hs-CRP levels when added to statin therapy.

Allylamine↗
PubMed2006

Incidence of new stroke or new myocardial infarction or death in patients with severe carotid arterial disease treated with and without statins.

We investigated in 449 patients with severe carotid arterial disease, who did not undergo revascularization, the incidence of new stroke or new myocardial infarction (MI) or death in patients treated with statins (66%) and in patients not treated with lipid-lowering therapy (34%). Hypercholesterolemia was present in all of the 298 patients (100%) treated with statins and in 145 of 151 patients (96%) not treated with statins (p = 0.001). Follow-up was 26 +/- 18 months in patients treated with statins and 21 +/- 17 months in patients not treated with statins (p <0.0001). New stroke or new MI or death occurred in 45 of 298 patients (15%) treated with statins and in 102 of 151 patients (68%) not treated with statins (p <0.0001). Stepwise Cox regression analysis showed that significant independent prognostic factors for time to development of new stroke or new MI or death were use of statins (risk ratio 0.13, p <0.0001), smoking (risk ratio 1.45, p = 0.0329), systemic hypertension (risk ratio 1.81, p = 0.0011), diabetes mellitus (risk ratio 2.87, p <0.0001), previous stroke (risk ratio 3.18, p <0.0001), and previous MI (risk ratio 2.15, p <0.0001). In conclusion, statins decrease the incidence of new stroke or MI or death in patients with severe carotid arterial disease who do not undergo revascularization.

Aged↗
PubMed2005

Statin therapy reduces contrast-induced nephropathy: an analysis of contemporary percutaneous interventions.

PURPOSE: We sought to examine whether statin therapy before percutaneous coronary intervention results in reduction in contrast-induced nephropathy (CIN). Intravascular administration of contrast media can have nephrotoxic effects, particularly in patients with baseline renal insufficiency. Along with lowering serum cholesterol, statins have pleiotropic effects in the vasculature. The effect of statin use on CIN is unknown. SUBJECTS AND METHODS: We studied 29409 patients who had both baseline preprocedure and peak postprocedure serum creatinine measured at the time of their percutaneous coronary intervention (PCI). Baseline demographics and creatinine profile before and after the procedure were compared between patients who received preprocedure statins and those who did not. CIN was defined as an increase in serum creatinine of < or =0.5 mg/dL. RESULTS: Baseline serum creatinine was similar between the two groups. When compared with patients who did not receive preprocedure statins, patients on preprocedure statins had a lower incidence of CIN (4.37 vs 5.93, P <0.0001) and nephropathy requiring dialysis (0.32 vs 0.49, P = 0.03). After adjustments for comorbidities, preprocedure statin use was associated with a significant reduction in CIN (odds ration [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, P = 0.03). CONCLUSIONS: Preprocedure statin use is associated with significant reduction in CIN after contemporary PCI. This reinforces the need to initiate statin therapy before percutaneous coronary interventions.

Angioplasty, Balloon, Coronary↗
PubMed2006

Impact of statin therapy at discharge on 1-year mortality in patients with ST-segment elevation myocardial infarction treated with primary angioplasty.

BACKGROUND: Statin therapy can reduce long-term mortality in several subgroups of patients with coronary artery disease, but the benefits after primary angioplasty for ST-segment elevation myocardial infarction (STEMI) have yet to be established. The aim of the current study was to determine whether statin therapy is associated with a reduction in mortality in patients with STEMI treated with primary angioplasty. METHODS: Our population is represented by a total of 1513 consecutive in-hospital survivors treated with primary angioplasty for STEMI between April 1997 and October 2001. Patients were divided in two groups according to statin therapy (statin group, n=893; control group, n=620) at discharge. Clinical follow-up was performed at 1 year. A propensity score, built on the basis of variables independently associated with statin prescription, was used to investigate the benefits from statin therapy in subgroups of patients that were homogeneous in terms of baseline clinical and angiographic characteristics. RESULTS: At 1-year follow-up statin therapy was associated with a significantly lower mortality (1.2% versus 7.1%, R(2) [95% CI]=0.16 [0.09-0.32], p<0.0001). These benefits were confirmed in all subgroups according to the propensity score, and at multivariate analysis (adjusted R(2) [95% CI]=0.24 [0.12-0.47], p<0.0001). CONCLUSIONS: Statin therapy at discharge was associated with a significant reduction in 1-year mortality after primary angioplasty for STEMI. Therefore, the use of statins is highly recommended in these patients.

Aged↗
PubMed2006

Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment.

While statin treatment may transiently mobilize endothelial progenitor cells (EPCs), the dose-dependent effects of a continuous statin therapy on EPCs in patients with chronic coronary artery disease (CAD) have not been analyzed. In 209 patients with angiographically documented CAD, 144 of which received 10-40 mg/day of statins for >8 weeks, the EPC number was determined by flow cytometry directly (CD34(+)/KDR(+), n=58) and after in vitro-culture (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled Ac-LDL (DiI-Ac-LDL(+))/lectin(+), n=209). EPC function was assessed by the formation of colony forming units (CFUs). Univariate analysis revealed that the dose of continuous statin therapy inversely correlated with the EPC number. Treatment with 40 mg/day significantly reduced EPC counts. Multivariate analysis unveiled the statin dose and extent of CAD as independent predictors of reduced EPC numbers. Conversely, obesity predicted increased counts, while CFU development was not detectable in all patients and augmented in females and smokers but not in statin-treated patients. Compared with matched controls, statin-treated patients showed significantly reduced absolute and relative EPC counts. In a prospective analysis, initiation of statin therapy significantly diminished the number of circulating and isolated EPCs after 3 but not after 1 month(s). Thus, the statin dose during chronic and continuous treatment independently predicts reduced numbers of circulating as well as isolated EPCs in patients with CAD.

Antigens, CD34↗
PubMed2005

Effect of statins on the proteasomal activity in mammalian endothelial and vascular smooth muscle cells.

Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins, effectively prevent cardiovascular events. In addition to their lipid lowering properties, a variety of pleiotropic effects on cardiovascular cells were demonstrated in vitro and in vivo. It has been hypothized that statins deploy a part of their effects by targeting the proteasome. Statin-induced effects remarkably overlap with effects obtained by inhibition of the proteasome in endothelial and vascular smooth muscle cells (e.g., endothelial nitric oxide synthase (eNOS)-upregulation, attenuation of nuclear factor kappa B (NF-kappaB) activation, inhibition of proliferation). We therefore examined, whether statins modulate the proteasomal activity of vascular cells. We studied the effect of simvastatin, atorvastatin, and pravastatin as well as of the proteasome inhibitor clasto-lactacystin on morphology, proliferation, viability, and proteasomal activity in two mammalian endothelial cell lines (CPAE and Ea.hy962), and in primary vascular smooth muscle cells (VSMCs). Both statins and lactacystin induced comparable morphological changes and attenuated proliferation of calf pulmonary artery cell line (CPAE). Whereas the statin-induced effects were reversed by mevalonic acid, however, the lactacystin-induced alterations were not influenced by mevalonic acid. As expected, lactacystin caused a significant loss of proteasomal activity measured in the extract of treated CPAE cells, whereas the extracts of statin-treated CPAEs exhibited unchanged activities. This result was also confirmed in Ea.hy926 cells and in primary rat VSMCs. We show here, that even high doses of statins do not modulate the activities of purified human 20S proteasomes. We conclude that the similar biological effects of statins and proteasome inhibitors in vascular cells are not due to a common inhibitory mechanism of action on the proteasome.

Animals↗
PubMed2005

Oxidized low density lipoproteins, statin therapy and severity of coronary artery disease.

BACKGROUND: The impact of statin therapy on the association between circulating levels of oxidized low density lipoproteins (OxLDL) and severity of coronary artery disease (CAD) has not been studied. METHODS: OxLDLs were measured in 687 patients with angiographically proven CAD (320 patients, 46.6% on statin therapy and 367 patients, 53.4% not on statin therapy on admission) using the Mercodia Oxidized LDL Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Patients on statin therapy had lower levels of OxLDL (median [interquartile range]; 63.9 U/L [53.9; 79.8] versus 72.3 U/L [58.4; 86.1], P<0.001) and C-reactive protein (3.0 mg/L [1.2; 6.6] versus 4.0 mg/L [1.7; 13.1], P<0.001) than patients not on statins. Multivariable analysis showed that statin therapy was an independent predictor of lower levels of OxLDL (P=0.0001). In univariate analysis, OxLDL level did not differ significantly among the patients with 1-, 2-or 3-vessel disease (70.5 U/L [57.5; 85.6], 66.3 U/L [53.8; 82.6] and 68.2 U/L [57.0; 83.4], respectively, P=0.26). Multivariable logistic regression analysis showed that OxLDL was an independent correlate of angiographic severity of CAD (P=0.04) and that there was an interaction (P=0.038) between statins and OxLDL in that the increased levels of OxLDL were associated with more extensive CAD. CONCLUSION: Patients with CAD who receive statins have lower levels of OxLDL and an attenuation of the relationship between circulating levels of OxLDL and CAD severity compared with patients who do not receive statins.

Aged↗
PubMed2006

Study on the conversion of three natural statins from lactone forms to their corresponding hydroxy acid forms and their determination in Pu-Erh tea.

Conversions of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, from lactone forms to their corresponding hydroxy acid form in 0.1 N NaOH or 0.05 N KOH (prepared with 25, 50, 75, 90% acetonitrile or methanol in water or 100% water) were evaluated. Results showed that lactone form statins could be transformed almost completely only in alkaline solutions prepared with 25 or 50% acetonitrile. In all methanolic alkaline solutions, lactone form statins could also be converted entirely, nevertheless, they would be further transformed to the methyl ester of the hydroxy acid form and the transformation increased as methanol rises. When lactone and hydroxy acid forms of statins were in methanol, ethyl acetate, 70% acetonitrile in water (with 0.5% acetic acid or no) for 0-48 h at room temperature or in 100 degrees C water for 0-2 h, lactone form statins were converted to their corresponding hydroxy acids, which were raised as time extends and the highest conversions of them were about 35% in 100 degrees C water and 70% acetonitrile, slightly transformed for lactone form statins in 70% acetonitrile (with 0.5% acetic acid) after 8 h, and the other treatments for all statins showed no significant changes. Interferences would be reduced efficiently when statins were extracted from Pu-Erh tea with methanol, ethyl acetate or 100 degrees C water followed by purifying through a C18 solid-phase extraction cartridge. Lovastatin was the only statin found in Pu-Erh tea and the highest content of it was found under ethyl acetate extraction. In ethyl acetate and methanol extracts, lovastatin existed merely as lactone form. The lowest content of lovastatin was found in the 100 degrees C water extract of Pu-Erh tea, however, both of lactone and hydroxy acid forms were found to exist in the extract.

Chemical Fractionation↗