Beneficial Effects Of Statins Research Articles

Pleiotrophic effect of statins (3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors)

The development of statins improved the therapy of hypercholesterolemia and atherosclerotic disease tremendously. The beneficial effects of statins were clearly demonstrated in large scale primary and secondary prevention studies. In addition to the reduction of plasma cholesterol, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase also results in the depletion of intermediates of cholesterol biosynthesis that are important for cellular integrity. The so called pleiotrophic effects of statins and probably also their adverse events can be attributed to the inhibition of synthesis of these intermediates. The review article describes the pathogenesis of atherosclerosis, the pharmacokinetic and pharmacodynamik of statins, and their pleiotrophic effects concerning endothelial function, LDL (low density lipoprotein) oxidation, macrophages, smooth muscle cell proliferation, atherosclerotic plaque, platelets, thrombosis, proinflammatory factors, haemorheology, hypertension, venous thrombosis, bone metabolism, stroke, and the possible influence on the prevention of Alzheimer's disease.

Effect of Intraperitoneally Injection of Different Doses of Lovastatin on Pain and Inflammatory Response Induced by Formalin in Mice

Problem statement: The 3-Hydroxy-3-Methyl Glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have been unequivocally shown to reduce cardiovascular morbidity and mortality. T heir lipid-lowering actions are by reversible and compet itive inhibition of the enzyme HMG-CoA reductase, a precursor of cholesterol. It has been suggested tha t statins appear to have therapeutic benefits in di seases that are unrelated to elevated serum cholesterol levels, such as pain and inflammatory. The aim of this stu dy was to determination the effect of intraperitoneally in jection of different doses of lovastatin on pain an d inflammatory response induced by formalin in mice. Approach: Mice were divided into 9 groups randomly: the first group received saline normal (i p) (saline group); the second group received Carboxymethylcellulose (CMC) 0.5% (ip) (vehicle group) and the next groups received respectively different doses of lovastatin (1, 5, 10, 20, 40, 80 and 100 mg kg daily -1 ) for 4 days (ip) before formalin test. After intrapawly injection of formalin, the time of hind paw biting and licking time measured in 5 min interval for an hour. Results: Results showed that formalin induces biphasic pain response (the first phase: 0-5 min and the second phase 15-40 min after inject ion). Intraperitoneal injection of lovastatin showe d significant (p<0.05) decrease of pain responses in the first and the second phase in a dose dependentl y manner. Conclusion: According to our results, lovastatin has analgesic and anti-inflammatory effects on mice. Nevertheless, new studies must be carried out in order to determine the beneficial effects of st atins in treatment of pain and inflammatory.

Anticonvulsant Effect of Pitavastatin in Mice Induced by Pentylenetetrazole

Problem statement: The 3-Hydroxy-3-Methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have been unequivocally shown to reduce cardiovascular morbidity and mortality by their lipid-lowering actions. It has been suggested that statins appear to have therapeutic benefits in diseases that are unrelated to elevated serum cholesterol levels. The aim of this study was to evaluation the effect of intraperitoneally injection of different doses of pitavastatin on PTZ-induced seizure threshold in mice. Approach: Mice were divided into 9 groups randomly: the first group received saline normal (ip) (control group); the second group received Carboxymethylcellulose (CMC) 0.5% (ip) (vehicle group) and the next groups received respectively different doses of pitavastatin (1, 5, 10, 20, 40, 80 and 100 mg kg daily-1) for 4 days (ip) before determination of seizure threshold induced by PTZ. Results: Results showed that PTZ-induced seizure threshold in control mice was 35.48±1.39 mg kg-1. Intraperitoneal injection of pitavastatin showed significant (p<0.05) increase of PTZ-induced seizure threshold in a dose dependently manner. Conclusion: According to our results, pitavastatin has anticonvulsant effects on mice. Nevertheless, new studies must be carried out in order to determine the beneficial effects of statins in treatment of epilepsy.

Protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of nitric oxide formation in aged and ovariectomized rats

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been used as a cholesterol-lowering drug to treat hyperlipidemia clinically. In recent years, accumulating evidence indicates the possible beneficial effect of statins on osteoporosis. The aim of present study was to investigate whether protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of nitric oxide (NO) formation in aged and ovariectomized rats. The aged and ovariectomized rats were used as two models of osteoporosis for evaluation of the effect of simvastatin. It was found that simvastatin abated oxidative stress, increased NO production, subsequently attenuating osteoporosis in two models. In the in vitro studies, the protective effects against H2O2-induced cell injury were examined in the MG-63 human osteoblastic cells. It was found that simvastatin ameliorated H2O2-induced cell loss and cell apoptosis and increased alkaline phosphatase (ALP) activity in osteoblastic cells. Simvastatin abated oxidative stress through enhancing catalase, heme oxygenase 1 (HO-1), and superoxide dismutase (SOD) activity and suppressing NADPH oxidase activity. In addition, simvastatin raised nitric oxide synthase (NOS) activity and eNOS expression at basal condition; inhibited NOS activity and iNOS expression when treated with H2O2. In conclusion, protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of NO formation in aged and ovariectomized rats.

The beneficial effect of statins on renal anemia in hemodialysis patients: Another point of view

The beneficial effect of statins on renal anemia in hemodialysis patients: Another point of view

Statin therapy is associated with superior clinical outcomes after endovascular treatment of critical limb ischemia

The aim of this study was to determine if statin therapy improves clinical outcomes after endovascular intervention in patients with critical limb ischemia (CLI). A retrospective review of all patients undergoing endovascular treatment for CLI was performed. Two groups were created according to whether they were receiving statin therapy at the time of intervention. Demographics, lesion morphology, overall mortality, primary and secondary patency, and limb salvage were compared between these groups. Analysis was performed using multivariate regression and Kaplan-Meier analysis. Between 2004 and 2009, 646 patients, 319 receiving statin therapy and 327 without, underwent an endovascular intervention for CLI. The statin group had significantly higher rates of diabetes mellitus, coronary artery disease, congestive heart failure, previous myocardial infarction, and coronary artery bypass grafting (P < .05). The two groups had similar lesion length, location, lesion type, TransAtlantic Inter-Society Consensus (TASC) classification, and primary procedure. At 24 months, the statin-treated group had higher rates of primary patency (43% vs 33%; P = .007), secondary patency (66% vs 51%; P = .001), limb salvage (83% vs 62%; P = .001), and overall survival (77% vs 62%; P = .038). Statin therapy was also independently associated with improved limb salvage by multivariate regression analysis (hazard ratio, 2.55; P < .001). Patients who were receiving statin therapy when they underwent interventions to treat CLI had significantly improved overall survival, primary and secondary patency, and limb salvage rates. Our findings suggest that statins should be part of the periprocedural treatment regimen and support further investigation into the beneficial effects of statins in patients undergoing endovascular treatment of CLI.

Neutral effects of statins to prevent atrial fibrillation recurrences after catheter ablation of atrial fibrillation: Should we bury upstream therapy for secondary prevention of atrial fibrillation?

r a w h a o Statins have been introduced to inhibit the main enzyme of cholesterol synthesis 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA-reductase) to lower low-density lipoprotein cholesterol levels. In addition, anti-inflammatory (pleiotropic) effects at the vascular endothelium have been appreciated to reduce inflammatory responses in the vessel wall. Thereby, statins have become a cornerstone of therapy in patients with coronary artery disease. Recently, the molecular biology of fibrillating atrial tissue has been elucidated. Experimental studies have demonstrated hat atrial fibrillation (AF) stimulates Rac1-dependent pathays, nicotinamide adenine dinucleotide phosphate-oxidase NADPH) activity, and oxidative stress in atrial tissue. As a onsequence, fibrotic processes are induced and prothromotic adhesion molecules are upregulated at the atrial endoardium. Interestingly, all these AF-induced processes have the potential to be influenced by statins. Thus, statins appear as a well-tolerated therapeutic approach to prevent or treat AF. In particular, during open heart surgery, which is characterized by the presence of inflammatory responses, statins should have protective effects in the atrial myocardium. In accordance with this assumption, several studies have shown beneficial effects of statins for the primary prevention of postoperative AF. Similar to an open heart procedure, the application of radiofrequency energy ablation has been shown to induce an inflammatory response in the atria. Extensive ablation can ause a temporary release of inflammatory cytokines and nvasion of inflammatory cells. Thereby, in the early phase fter extensive radiofrequency energy ablation an arrhythogenic milieu is created. This phenomenon has forced the lectrophysiologist to induce a blanking period after the adiofrequency energy ablation of AF before the true benefit

Simvastatin protects osteoblast against H2O2-induced oxidative damage via inhibiting the upregulation of Nox4

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been used clinically as a cholesterol-lowering drug to treat hyperlipidemia. In recent years, accumulating evidence indicates the possible beneficial effect of statins on osteoporosis. However, the underlying molecular mechanism remains to be elucidated. In the present study, we investigated the therapeutic effects of simvastatin on cell viability, apoptosis, and alkaline phosphatase activity in murine osteoblastic MC3T3-E1 cells treated by hydrogen peroxide (H(2)O(2), 100 μM). It was shown that simvastatin suppressed H(2)O(2)-induced oxidative stress and attenuated H(2)O(2)-induced cell injury including increasing osteoblastic viability, inhibiting apoptosis, and promoting differentiation. Then, we examined the effects of simvastatin (10(-7) M) on Nox1, Nox2, and Nox4 expressions in osteoblastic cells treated by H(2)O(2) (100 μM). We found that in MC3T3-E1 cells, H(2)O(2)-induced upregulation of Nox4 expression was inhibited by simvastatin, which was restored by farnesyl pyrophosphate (5 μM) as well as geranylgeranyl pyrophosphate (5 μM). RNAi approach was used to reduce Nox4 protein levels in osteoblastic cells to explore its biological effects against H(2)O(2)-induced oxidative damage. When Nox4 expression was reduced in osteoblastic cells, H(2)O(2)-induced cell injury was attenuated markedly. We concluded that simvastatin protected osteoblast against H(2)O(2)-induced oxidative damage, at least in part, via inhibiting the upregulation of Nox4.

In Vivo Cardioprotection by Pitavastatin From Ischemic-reperfusion Injury Through Suppression of IKK/NF-κB and Upregulation of pAkt–e-NOS

Recent studies have uncovered the beneficial effects of statin in cardiovascular diseases; however, the role of pitavastatin in ischemia-reperfusion (IR)-induced apoptosis and myocardial damage is not established. Therefore, in this study, we aim to investigate whether pitavastatin treatment attenuates myocardial IR injury via regulating oxidative stress, inflammation, apoptosis, and phosphorylated protein kinase B (pAkt) endothelial nitric oxide synthase (e-NOS) pathways. After the 14-day treatment with pitavastatin (0.16-0.64 mg·kg·d, po) or saline, rats were subjected to 45 minutes of ischemia by occluding the left anterior descending coronary artery and to 60 minutes of reperfusion to induce myocardial damage. Pitavastatin at a dose of 0.32 and 0.64 mg/kg significantly improved cardiac function as evidenced by the normalization of the mean arterial pressure, heart rate, ±LVdP/dtmax, and left ventricular end-diastolic pressure as compared with the IR control. Additionally, pitavastatin dose-dependently normalized myocardial antioxidants, lactate dehydrogenase, and thiobarbituric acid reactive substances along with decreased serum tumor necrosis factor-α level and creatine kinase isoenzyme-MB activity. Furthermore, pitavastatin enhanced pAkt, (p) e-NOS, Bcl-2, and suppressed IκB kinase/nuclear factor-kappa B, nitrotyrosine (NO inactivation product), Bax, and capases-3 protein expression in the heart. Morphological assessments of the IR-challenged myocardium showed that 0.32 and 0.64 mg/kg of pitavastatin decrease myocardial necrosis and inflammatory changes. Thus, pitavastatin reduced IR-induced infarction and dysfunction via the augmentation of endogenous antioxidant, suppression of IκB kinase/nuclear factor-kappa B, activation of pAkt-e-NOS, and/or decreased NO inactivation and apoptosis.

Statins for prevention of diabetic-related blindness: a new treatment option?

Diabetic retinopathy (DR), the most feared complication of diabetes, compromises vision and quality of life of approximately 50 million people worldwide, with its prevalence projected to double by 2025 [101]. DR, the leading cause of blindness in working-age adults in the USA, is characterized by early neurodegeneration, glial activation and vascular injury, which includes breakdown of the blood–retina barrier (BRB) and acellular capillary formation that eventually leads to retinal neo-vascularization and blindness (reviewed in [1]). Interestingly, early clinical trials including the Hoorn study, the Early Treatment Diabetic Retinopathy Study (ETDRS), and the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) [2–4] indicated that elevated serum lipids, including total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol, were associated with the presence of hard exudates and increased risk of DR. These results suggested that lipid-lowering therapies might be beneficial in the reduction of hard exudates and the associated vision loss in patients with DR. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that lower total and LDL-cholesterol in diabetic patients with or without cardiovascular disease. They inhibit the generation of mevalonate, a precursor of cholesterol, and inhibit isoprenoid synthesis. The beneficial effects of statins may extend beyond their cholesterol-lowering effects, to so-called pleiotropic effects, which include improving endothelial function, attenuating vascular and myocardial remodeling, inhibiting vascular inflammation and oxidation, and stabilizing atherosclerotic plaques. Statins’ pleiotropic effects are mainly attributed to blocking the isoprenylation of small GTPase proteins such as Rac-1, Rho and Cdc42 (reviewed in [5]). Although statins have reported benefits in diabetic microvascular diseases, their efficacy for DR has not been thoroughly investigated [6–8].

Squalene Synthase Inhibitor Lapaquistat Acetate

Elevated serum cholesterol level is an important risk factor for cardiovascular disease,1 and cholesterol lowering by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins has been shown to reduce cardiovascular events.2 The reduction in cardiovascular risks with statin therapy, whether for primary or secondary prevention, correlates almost linearly with the reduction in serum cholesterol levels.3 Indeed, for every 30 mg/dL decrease in low-density lipoprotein-cholesterol (LDL-C), there is a concomitant 30% decrease in cardiovascular events.2 For patients presenting with acute coronary syndrome,4 or in patients with stable coronary artery disease,5 intensive lipid-lowering therapy provides even greater clinical benefits, implying that the lower the LDL-C, the better the outcome is, especially for high-risk patients. Because most of the US adult population with coronary heart disease has serum LDL-C levels between 135 and 145 mg/dL,6 to achieve an Adult Treatment Panel III/National Cholesterol Education Panel guideline for LDL-C target goal of <100 mg/dL with an optional goal of <70 mg/dL, most high-risk patients with coronary heart disease will likely require at least a 40% to 50% reduction in LDL-C.2 Article see p 1974 Depending on the dose used, most statins can reduce serum cholesterol by 30% to 58%.7 This is compared with bile acid sequestrants or intestinal cholesterol absorption inhibitors, which tend to lower serum cholesterol by only 15% to 18%. Thus, it is not surprising that statins have emerged as the principal cholesterol-lowering therapy for patients at risk for cardiovascular disease. However, most statins, with the exception of the more potent statins, such as atorvastatin and rosuvastatin, will require near-maximum dosages to achieve a 40% to 50% LDL-C reduction. This is because the majority of statins' LDL-C–lowering efficacy occurs at the starting dose with only a modest 4% to 6% further LDL-C reduction with …

Simvastatin Prevents Skeletal Metastasis of Breast Cancer by an Antagonistic Interplay between p53 and CD44

Substantial data from clinical trials and epidemiological studies show promising results for use of statins in many cancers, including mammary carcinoma. Breast tumor primarily metastasizes to bone to form osteolytic lesions, causing severe pain and pathological fracture. Here, we report that simvastatin acts as an inhibitor of osteolysis in a mouse model of breast cancer skeletal metastasis of human mammary cancer cell MDA-MB-231, which expresses the mutant p53R280K. Simvastatin and lovastatin attenuated migration and invasion of MDA-MB-231 and BT-20 breast tumor cells in culture. Acquisition of phenotype to express the cancer stem cell marker, CD44, leads to invasive potential of the tumor cells. Interestingly, statins significantly decreased the expression of CD44 protein via a transcriptional mechanism. shRNA-mediated down-regulation of CD44 markedly reduced the migration and invasion of breast cancer cells in culture. We identified that in the MDA-MB-231 cells, simvastatin elevated the levels of mutated p53R280K, which was remarkably active as a transcription factor. shRNA-derived inhibition of mutant p53R280K augmented the expression of CD44, leading to increased migration and invasion. Finally, we demonstrate an inverse correlation between expression of p53 and CD44 in the tumors of mice that received simvastatin. Our results reveal a unique function of statins, which foster enhanced expression of mutant p53R280K to prevent breast cancer cell metastasis to bone.

Generic Statins in Cardiovascular Medicine

Cardiovascular disease is the leading cause of death and disability in Europe. Several large, population-based trials and their meta-analyses have shown the beneficial effects of statins in reducing mortality and cardiovascular morbidity both primary and secondary prevention. Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brandname drugs may be clinically superior to generic drugs. The aim of our study was to review the efficacy of generic statin therapy in both primary and secondary vascular prevention. Treatment with generic statins seem to be safe and quite effective. Lipid parameters should be monitorized, there are class effects in the lipid lowering potency of different drugs. Based on comparism trials, worsening lipid profile was associated with unfavourable outcome. From an economic point of view, society could gain a lot from substituting statin therapy, especially from therapeutic substitution. Moreover, prescribing generic or preferred medications within a therapeutic class seemed to be associated with improvements in adherence to therapy.

The effect of atorvastatin on mRNA levels of inflammatory genes expression in human peripheral blood lymphocytes by DNA microarray

Accumulating evidence indicates that beneficial effects of statins on inflammatory processes besides their lowering-lipid activities, statins are thought to exert anti-inflammatory effects via direct inhibition of inflammatory genes expression. Little comprehensive analysis has been made of gene-expression changes after statin therapy. In this study, to search novel genes after treatment by atorvastatin (one of the most potent statins), we performed a DNA microarray analysis by using normal human peripheral blood lymphocytes (PBL). Analysis of gene expression by DNA microarray showed that 180 genes were downregulated 3-fold changes by atorvastatin therapy compared with controls, changes in the expression of 11 inflammatory genes, confirmed by real-time RT-PCR. The results showed that atorvastatin significantly decreased the expression of six cytokines (IL-6, IL-8, IL-1, PAI-1, TGF-β1, TGF-β2) and five chemokines (CCL2, CCL7, CCL13, CCL18, CXCL1). Our results showed the marked changes in these cytokine and chemokine expression in human PBL by atorvastatin therapy. It seemed that these data were useful as a reference database of inflammatory gene changes, some of which may be new biomarkers follow atorvastatin treatment.

Can statins slow the process of vascular calcification? Possibilities of lipid-lowering therapy and pleiotropic effect by statin treatment

Widespread vascular calcification is a ubiquitous feature of aging and is prevalent in association with several atherosclerotic diseases. HMG-CoA reductase inhibitors (statins) have been shown to exert protective potentials against cardiovascular diseases via the lipid-lowering and/or their independent pleiotropic effects. Recently, statins have been extensively investigated as potential therapeutic agents capable of slowing the progression of vascular and valvular calcification. However, accumulating recent evidences show that there are conflicting data regarding beneficial effects of statins on progression of cardiovascular calcification. In particular, regarding coronary artery calcification, which is shown to can predict coronary events, it still remains unclear and controversial. To address the positioning of statins as therapeutic strategy for cardiovascular calcification more clearly, clinical studies by intensive therapy using statins throughout long-term period is indispensable in near future. In addition, future investigation about the detailed molecular mechanisms how statins affect calcification process in vascular cells is necessary.

The role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in modern rheumatology

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase commonly known as statins are widely used for treating hypercholesterolemia. However, there is much evidence to suggest that statins may have other properties in addition to their cholesterol-lowering effect. In particular, statins may neutralize post-translational prenylation of vitally important regulatory small GTPases, which are involved in several processes such as tissue fibrosis, cell maturation, apoptosis, immune cell maturation, and immune response. The beneficial effect of statins has been reported in animal and in vitro models as well as in some clinical studies. As they have an acceptable safety profile, statins may be considered, in selected cases, as a valuable concomitant therapy in the treatment of rheumatic and autoimmune disorders.

Perioperative statin therapy reduces mortality in normolipidemic patients undergoing cardiac surgery

Statins might have pleiotropic effects, independent of their ability to reduce lipid levels. Recent data have suggested that statins improve early survival and cardiovascular outcomes after coronary artery bypass graft surgery. The effectiveness of statin therapy in normolipidemic cardiac surgery patients is as yet unclear. We evaluated 3056 consecutive patients who had undergone cardiac surgery between April 2004 and April 2009. Perioperative statin therapy was defined as continued treatment both before (≥ 6 months) and after the index surgery (included as a discharge medication). Hyperlipidemia (HL) was defined as a total cholesterol level greater than 200 mg/dL within 6 months before surgery. Four groups were analyzed: (1) statin-untreated normolipidemic (NL-, n=1052); (2) statin-treated normolipidemic (NL+, n=206); (3) statin-untreated hyperlipidemic (HL-, n=638); and (4) statin-treated hyperlipidemic (HL+, n=1160) patients. Adjusted hazard ratios accounted for the known preoperative cardiac risk factors. Mortality was ascertained by retrospective database review and the Social Security Death Index. The mean follow-up was 2.2 years. The crude rate of 30-day mortality was 3.0% (32/1052), 0% (0/206), 8.0% (51/638), and 0.7% (8/1160) for the NL-, NL+, HL-, and HL+ groups, respectively. The overall all-cause crude mortality rate was 9.6% (101/1052), 3.9% (8/206), 17.2% (110/638), and 6.5% (75/1160) for the NL-, NL+, HL-, and HL+ groups, respectively. Statin therapy for NL patients undergoing cardiac surgery independently reduced the overall all-cause mortality (adjusted hazard ratio, 0.34; 95% confidence interval, 0.16-0.71; P=.004). Perioperative statin therapy was associated with reduced mid-term mortality for patients undergoing cardiac surgery, irrespective of their baseline lipid status. This clinical evidence suggests that the beneficial effects of statins might extend beyond their lipid-lowering ability.

Atorvastatin treatment affects atrial ion currents and their tachycardia-induced remodeling in rabbits

Aims Atrial fibrillation (AF) leads to electrical atrial remodeling including alterations of various ion channels early after arrhythmia onset. The beneficial effects of statins in AF treatment due to their influence on oxidative stress and inflammation are discussed. Our hypothesis was that statins might also alter atrial ion currents and their early tachycardia-induced remodeling. Main methods Effects of an atorvastatin treatment (7 days) on atrial ion currents and their tachycardia-induced alterations were studied in a rabbit model of tachycardia-induced electrical remodeling (rapid atrial pacing (600 min) for 24 and 120 h). Ion currents (L-type calcium channel [I Ca,L], transient outward current [I to]) were measured using whole cell patch clamp method and were compared with previous experiments in untreated but also tachypaced animals. Key findings Atorvastatin treatment alone decreased I Ca,L similar to rapid atrial pacing alone, currents were also further reduced by additional atrial tachypacing. I to and its pacing-induced down-regulation after 24 h were not influenced by atorvastatin treatment. However, I to was still reduced after 120 h in atorvastatin-treated animals and did not return to control values as expected. Significance The present study establishes that an atorvastatin treatment can affect atrial ion currents and their tachycardia-induced remodeling in a rabbit model. These results show that—amongst other positive effects on oxidative stress and inflammation—the impact of statins on ion currents and their tachycardia-induced alterations might also play a role in “upstream” treatment of AF with HMG-CoA reductase inhibitors.

Persistence with statins and onset of rheumatoid arthritis: a population-based cohort study.

The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA. The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins. A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 person-years) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of <20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52-0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81-0.88) compared to nonadherent patients. The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up.

Effects of Statin Therapy on Inflammatory Markers in Chronic Heart Failure: A Meta-analysis of Randomized Controlled Trials

Inflammation is thought to be important in mediating the progression of chronic heart failure (CHF). Whether beneficial effects on inflammation can be achieved by statins in patients with CHF remains uncertain. This meta-analysis was conducted to determine the role of statin therapy in inflammation markers in CHF patients. Pubmed, MEDLINE, EMBASE, and EBM Reviews databases were searched for randomized controlled trials comparing statin treatment with non-statin treatment in CHF patients. Two reviews independently assessed studies and extracted data. Standardized mean differences (SMD) were calculated using random effects models. Ten studies with 6052 patients were included. Pooled analysis showed that statin therapy was associated with significant decrease in high-sensitivity C-reactive protein (SMD = -0.74, 95% CI -1.16 to -0.32; p = 0.0005) and soluble vascular cell adhesion molecule-1 (SMD = -0.49, 95% CI -0.91 to -0.08; p = 0.02). However, the beneficial effects of statin were not shown regarding interleukin-6 (SMD = -0.85, 95% CI -2.09 to 0.38; p = 0.18) and tumor necrosis factor-α (SMD = -0.13, 95% CI -0.50 to 0.25; p = 0.51). Sources of heterogeneity were not found by meta-regression analyses, whereas subgroup analyses showed that difference in age, etiology, baseline left ventricular ejection fraction, type of statins and follow-up duration might influence the effects of statins. Statin may partially suppress inflammatory markers in patients with CHF; moreover, this beneficial effect may be associated with different types of statins, treatment intervals and characteristics of patients.