Statins Reduce Research Articles

(370) - Statins Reduce Inflammation, Oxidative Stress and Endothelial Cell Activation in a Model of Venous Congestion in Systolic Heart Failure Patients

(370) - Statins Reduce Inflammation, Oxidative Stress and Endothelial Cell Activation in a Model of Venous Congestion in Systolic Heart Failure Patients

Aspirin and Statins Reduce the Risk of Stroke in Women with Endometriosis (S3.002)

<h3>Objective:</h3> To determine (1) the risk of stroke in women with endometriosis and (2) the effect of aspirin and statins on that risk. <h3>Background:</h3> Endometriosis is an inflammatory chronic gynecologic condition that affects approximately 10% of reproductive aged women. Previous research suggests that endometriosis increases stroke risk, but the role of medications known to prevent stroke in modifying this risk is uncertain. <h3>Design/Methods:</h3> We retrospectively analyzed data from the California Teachers Study, a large prospective cohort of female teachers followed continuously since 1995, excluding those with prior stroke or heart attack. This analyses’ exposure was self-reported history of endometriosis, and the outcome was hospitalization for any stroke (ischemic stroke, intracerebral and subarachnoid hemorrhage). Study covariates were self-reported use of aspirin and statin, race-ethnicity, hysterectomy, and vascular risk factors: hypertension, diabetes mellitus, obesity, migraine, current or prior tobacco use, malignancy, and oral contraceptive use. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for stroke by age among women with and without history of endometriosis after adjustment for demographics and vascular risk factors. We examined association of aspirin and statin use with stroke among women with endometriosis. <h3>Results:</h3> Of 121,993 women, 13,938 (11.4%) reported a history of endometriosis. Women with endometriosis had slightly higher rates of vascular risk factors than women without endometriosis. Adjusted risk of stroke in the endometriosis group was higher than in the non-endometriosis group (HR 1.20, CI 1.09–1.28). Stroke occurred at a younger age among women with endometriosis (77.9 vs 80.2, p&lt;0.01). Within the endometriosis group, stroke risk in users of aspirin (HR 0.80, CI 0.69–0.92) or statins (HR 0.74, CI 0.62–0.88) was lower than that of non-users. <h3>Conclusions:</h3> In a large cohort study, history of endometriosis was associated with increased stroke risk and, among women with endometriosis, aspirin and statin use decreased this risk. <b>Disclosure:</b> Dr. Seitz has stock in Baxter International Inc. (&lt;0.0003% ownership), Bristol-Myers Squibb Company (&lt;0.0001%), Colgate-Palmolive Company (&lt;0.0002%), CVS Health Corporation (&lt;0.0002%), Johnson &amp; Johnson (&lt;0.00004%), Eli Lilly and Company (&lt;0.00005%), Proctor &amp; Gamble Company (&lt;0.00005%), UnitedHealth Group Incorporated (&lt;0.00002%), Walgreen Boots Alliance, Inc. (&lt;0.0002%), White Mountains Insurance (&lt;0.002%). Ms. Bull has stock in United Bank. Ms. Bull has received research support from Weill Cornell Medical College. Dr. Parikh has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for cases of neurological illness. The institution of Dr. Parikh has received research support from Leon Levy Foundation. The institution of Dr. Parikh has received research support from Florence Gould Foundation. The institution of Dr. Parikh has received research support from NY State Empire Clinical Research Investigator Program. The institution of Dr. Parikh has received research support from NIA. The institution of Dr. Parikh has received research support from Medtronic. Dr. Navi has nothing to disclose. Dr. Merkler has received personal compensation in the range of $0-$499 for serving as a Consultant for GLG. Dr. Merkler has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Neurohospitalist. Dr. Merkler has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for n/a. The institution of Dr. Merkler has received research support from AHA. The institution of Dr. Merkler has received research support from Weill Cornell Medical College. Dr. Kamel has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Kamel has received personal compensation in the range of $50,000-$99,999 for serving as a Endpoint adjudication committee with Boehringer-Ingelheim. The institution of Dr. Liberman has received research support from NIH.

Influence of rosuvastatin on apolipoproteins and coagulation factor levels: Results from the STAtin Reduce Thrombophilia trial

BackgroundThe STAtins Reduce Thrombophilia trial showed that, in patients with prior venous thrombosis, rosuvastatin decreased various coagulation factor levels. ObjectivesHere, we investigated the hypothesis that statins decrease coagulation factor levels through shared mechanisms of synthesis or regulatory pathways with apolipoproteins. MethodsWe measured the levels of apolipoprotein (Apo)A-I, A-II, A-IV, (a), B-100, B-total, C-I, C-II, C-III, and E in patients (n = 126) randomized to 28 days of rosuvastatin use. We assessed the association between apolipoproteins and coagulation factors at baseline using linear regression. The mean difference in apolipoprotein levels between baseline and after 28 days of rosuvastatin use was determined through linear regression, adjusting for age, sex, and body mass index. Coagulation factors were added to this model to determine if the lowering of apolipoproteins by rosuvastatin was linked with coagulation factor levels. ResultsAt baseline, levels of all apolipoproteins, except Apo(a), were positively associated with FVII, FIX, and FXI. Apolipoproteins levels, except for ApoA-I, A-IV, and Apo(a), were decreased after 28 days of rosuvastatin. ApoB-100 showed the largest mean decrease of -0.43 g/L (95% CI = −0.46 to −0.40). The decrease in ApoC-I and C-III levels was associated with a decrease in FVII, whereas the decrease in apoA-II, B-100, and B-total was associated with a decrease in FXI. The decrease in apolipoproteins was neither associated with FVIII or vWF decrease nor with endogenous thrombin potential changes. ConclusionsRosuvastatin decreases the level of several apolipoproteins, but this decrease was associated only with a decrease in FVII and XI and not with FVIII/vWF.

Rosuvastatin treatment decreases plasma procoagulant phospholipid activity after a VTE: A randomized controlled trial

BackgroundVenous thromboembolism (VTE) is a frequent cardiovascular disease with severe complications, including recurrence and death. There is a great need for alternative prophylactic treatment options as anticoagulation is accompanied by increased bleeding risk. Statins are reported to reduce the risk of incident and recurrent VTE, but the mechanisms are elusive. Procoagulant phospholipids (PPL), and phosphatidylserine in particular, are crucial for efficient coagulation activation, but no studies have investigated the effect of statin treatment on plasma PPL activity. ObjectivesTo investigate the impact of rosuvastatin treatment on plasma PPL activity and levels of extracellular vesicles (EVs). Patients/MethodsPatients with a history of VTE (≥18 years) allowed to stop anticoagulant treatment were randomized to either 20 mg/day of rosuvastatin treatment or no treatment for 28 days in the Statins Reduce Thrombophilia (NCT01613794) trial. Plasma samples were collected at baseline and study end. PPL activity was measured in samples from 245 participants using a factor Xa‐dependent clotting assay and EV levels by flow cytometry. ResultsRosuvastatin treatment yielded an overall 22% (95% confidence interval [CI] −38.2 to −5.8) reduction in PPL activity, and 37% (95% CI −62.9 to −11.2) reduction in PPL activity in participants with a history of pulmonary embolism. The effect of rosuvastatin on plasma PPL activity was not explained by changes in total cholesterol nor change in levels of total‐ or platelet‐derived EVs. ConclusionsRosuvastatin treatment caused a substantial decrease in plasma PPL activity, suggesting that a PPL‐dependent attenuation of coagulation activation may contribute to a reduced VTE risk following statin treatment.

Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study.

Simple SummaryStatins are medicines used to treat patients with high lipid levels (hyperlipidemia). Studies have reported that patients undergoing statin therapy are at reduced risk of developing liver cancer. In this study, we compared the risk of developing liver cancer among hyperlipidemic patients with and without statin therapy in three patient groups classified by renal function: normal renal function (NRF) group, chronic kidney disease (CKD) not requiring dialysis, and dialysis-dependent end stage of real disease (ESRD). Our results showed that the risk of developing liver cancer increased progressively from NRF group to CKD and ESRD groups, but was lower for patients receiving statins treatment than non-treated patients. We also found that the statin therapy effectiveness was better in patients taking hydrophilic statins than in those taking lipophilic statins, and in patients taking statin-ezetimibe combination than in those taking statin alone, particularly in the NRF group. Ezetimibe is also an effective option of treating hyperlipidemia.Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999–2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant.

Statins Reduce Intratumor Cholesterol Affecting Adrenocortical Cancer Growth.

Mitotane causes hypercholesterolemia in patients with adrenocortical carcinoma (ACC). We suppose that cholesterol increases within the tumor and can be used to activate proliferative pathways. In this study, we used statins to decrease intratumor cholesterol and investigated the effects on ACC growth related to estrogen receptor α (ERα) action at the nuclear and mitochondrial levels. We first used microarray to investigate mitotane effect on genes involved in cholesterol homeostasis and evaluated their relationship with patients' survival in ACC TCGA. We then blocked cholesterol synthesis with simvastatin and determined the effects on H295R cell proliferation, estradiol production, and ERα activity in vitro and in xenograft tumors. We found that mitotane increases intratumor cholesterol content and expression of genes involved in cholesterol homeostasis, among them INSIG, whose expression affects patients' survival. Treatment of H295R cells with simvastatin to block cholesterol synthesis decreased cellular cholesterol content, and this affected cell viability. Simvastatin reduced estradiol production and decreased nuclear and mitochondrial ERα function. A mitochondrial target of ERα, the respiratory complex IV (COXIV), was reduced after simvastatin treatment, which profoundly affected mitochondrial respiration activating apoptosis. Additionally, simvastatin reduced tumor volume and weight of grafted H295R cells, intratumor cholesterol content, Ki-67 and ERα, COXIV expression and activity and increase terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Collectively, these data demonstrate that a reduction in intratumor cholesterol content prevents estradiol production and inhibits mitochondrial respiratory chain-inducing apoptosis in ACC cells. Inhibition of mitochondrial respiration by simvastatin represents a novel strategy to counteract ACC growth.

Statins Reduce Mortality in Multiple Myeloma: A Population-Based US Study

BackgroundWe studied the effect of statins on mortality in a nationally representative sample of patients with multiple myeloma, and explored the benefit of statins in a subgroup of patients treated with novel agents. MethodsPatients diagnosed with multiple myeloma between 2007 and 2013 were identified in the SEER-Medicare database using International Classification of Diseases (ICD)-03 codes. ICD-9 and Healthcare Common Procedure Coding System codes were used to identify comorbidities and treatments. We assessed the association of statins with mortality in patients with multiple myeloma using multivariate Cox proportional hazards regression analysis. For subanalysis, we used the same statistical technique to investigate the effect of statins on mortality in myeloma patients treated with novel agents. ResultsA total of 5922 patients were diagnosed with multiple myeloma within the study period. Use of statins was associated with 21% reduction in risk of death (adjusted hazard ratio [aHR] 0.79; 95% confidence interval [CI] 0.74-0.84) among all patients with multiple myeloma. Among the patents treated with novel agents (n = 3603), statins reduced mortality by 10% (aHR = 0.90, 95% CI 0.83-0.98). ConclusionsUse of statins is likely associated with lower mortality in patients with multiple myeloma.

Abstract #781083: Statins Reduce Incident Hip Fractures Among Chinese People with Type 2 Diabetes: The Effect of Cumulative Daily Defined Dose

Abstract #781083: Statins Reduce Incident Hip Fractures Among Chinese People with Type 2 Diabetes: The Effect of Cumulative Daily Defined Dose

Rosuvastatin use increases plasma fibrinolytic potential: a randomised clinical trial.

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor‐1 (PAI‐1) and thrombin‐activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non‐rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8·75 min (95% CI −13·8 to −3·72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (−0·05 U/ml; 95% CI −0·07 to −0·02 and −4·77%; 95% CI −6·81 to −2·73, respectively). PAI‐1 levels did not change and fibrinogen levels were 0·17 g/l (95% CI 0·04–0·29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non‐statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.

Statins Reduce Epicardial Adipose Tissue Attenuation Independent of Lipid Lowering: A Potential Pleiotropic Effect.

BackgroundHigh epicardial adipose tissue (EAT) attenuation (Hounsfield units [HUs]) on computed tomography is considered a marker of inflammation and is associated with an increased risk of cardiovascular events. Statins reduce the volume of EAT, but it is unknown whether they affect EAT HUs.Methods and ResultsWe reviewed the chest computed tomographic scans of 420 postmenopausal women randomized to either 80 mg of atorvastatin or 40 mg of pravastatin daily and rescanned after 1 year to measure change in coronary artery calcium score. EAT HUs were measured near the proximal right coronary artery and remote from any area of coronary artery calcium. Computed tomographic images were also queried for subcutaneous adipose tissue (SubQ) attenuation (HUs) change over time. The mean patients’ age was 65±6 years. The baseline EAT HU value was higher than the SubQ HU value (−89.4±24.0 HU versus −123.3±30.4 HU; P<0.001). The EAT HU value decreased significantly in the entire cohort (−5.4±29.7 HU [−6% change]; P<0.001), but equally in the patients given atorvastatin and pravastatin (−6.35+31 HU and −4.55+28 HU; P=0.55). EAT HU change was not associated with change in total cholesterol, low‐density lipoprotein cholesterol, coronary artery calcium, and EAT volume (all P=not significant). Change in high‐density lipoprotein cholesterol was marginally associated with EAT HU change (P=0.07). Statin treatment did not induce a change in SubQ HUs.ConclusionsStatins induced a decrease in EAT HUs over time, independent of intensity of low‐density lipoprotein cholesterol lowering. The positive effect on EAT and the neutral effect on SubQ suggest that statins induced a decrease in metabolic activity in EAT by reduction in cellularity, vascularity, or inflammation. The clinical significance of the observed change in EAT HUs remains to be demonstrated.

Statins Reduce Major Vascular Events in All Age Groups

According to this study: Statin therapy significantly reduces the risk of major vascular events in all age groups, but the proportional reductions in risk decreased slightly with increasing age.

Statins Reduce Cellular Respiration and Induce De‐differentiation of Myofibroblasts

BackgroundFibroblast to myofibroblast trans‐differentiation with altered bioenergetics precedes cardiac fibrosis (CF). Promotion of de‐differentiation could mitigate CF‐related pathologies; however, no specific remedial therapeutics for CF is clearly defined. Therefore, we determined whether statins, a hypolipidemic class of drugs commonly prescribed in patients at risk of heart failure (HF), can alter cellular bioenergetics and de‐differentiate myofibroblasts.MethodsPrimary cultures of differentiated human ventricular fibroblasts (hVFs) were randomly subjected to in vitro statin treatment (n = 3–6). Differentiation status was determined by α‐smooth muscle actin (α‐SMA) expression while cellular respiration was measured by Seahorse Extracellular Flux Analyzer XF‐96, as oxygen consumption rate (OCR) at baseline and following application of each well with mitochondrial modulators: Oligomycin (1 μg/ml), FCCP (0.1 μM) and antimycin A (1 μg/ml), normalized to total protein. Data were analyzed by either unpaired t test or one‐Way Analysis of Variance.ResultsIn vitro treatment of already differentiated myofibroblasts for 72 hours with both lipophilic (atorvastatin, simvastatin) and hydrophilic (rosuvastatin) statins concentration – dependently reduced α‐SMA/α‐β‐tubulin expression, normalized to % maximal differentiation. The respective IC50 values were 729 ± 13 nM (atorvastatin), 3.6 ± 1 μM (rosuvastatin) and 185 ± 13 nM (simvastatin); n = 3 per concentration of each statin. Basal OCR was significantly decreased in the simvastatin‐treated hVFs vs the differentiated control hVFs (TGF) (0.144 ± 0.026 vs. 0.278 ± 0.104, p = 0.002). Simvastatin reduced the ATP‐linked (0.083 ± 0.018 vs. 0.160 ± 0.059, p = 0.01), the proton leak‐linked (0.017 ± 0.008 vs. 0.074 ± 0.041, p = 0.01) and the maximal (0.250 ± 0.031 vs. 0.501 ± 0.142, p&lt;0.001) OCR, but did not significantly affect spare capacity or non‐mitochondrial OCR. The inhibitory effect of simvastatin on the mitochondrial OCR was reversed by geranylgeranyl pyrophosphate (GGPP, 20 μM ) which significantly increased the basal (0.193 ± 0.053, p = 0.020), the spare‐capacity (0.233 ± 0.091, p = 0.008), and the maximal (0.377 ± 0.131, p = 0.003) OCR, without any change in the non‐mitochondrial OCR. The simvastatin treatment of the differentiated hVFs in vitro reduced ECAR after addition of FCCP (0.066 ± 0.011 vs. 0.093 ± 0.010, p&lt;0.001) and AA (0.056 ± 0.014 vs. 0.097 ± 0.008, p&lt;0.001). GGPP reversed ECAR to a similar level as control differentiated hVFs (FCCP: 0.081 ± 0.015, p = 0.005; AA: 0.080 ± 0.014, p = 0.018). Both atorvastatin (100 nM, 300 nM) and rosuvastatin (300 nM, 1 μM) also increased the ADP/ATP ratio in these cells, confirming the pan‐statin effect of decreased bioenergetics during de‐differentiation. Therefore, statins altered hVF bioenergetics and de‐differentiated the myofibroblasts which involved GGPP‐sensitive mechanisms, reduced cellular respiration with potential activation of KATP channels, as GGPP supplementation or KATP‐channel inhibition by glibenclamide countered the de‐differentiation.ConclusionStatin induced de‐differentiation of myofibroblasts via GGPP‐sensitive signaling, lowered bioenergetics, and KATP channels.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Statins Reduce Abdominal Aortic Aneurysm Growth, Rupture, and Perioperative Mortality: A Systemic Review and Meta-Analysis

This study is a retrospective review of Cochrane CENTRAL database, MEDLINE, and Embase through June 15, 2018. Analysis of 22 studies involving 80,428 patients with abdominal aortic aneurysms (AAAs) revealed that statin use is associated with a mean AAA growth rate reduction of 0.82 mm/y (P = .001), lower rupture risk (P < .0001), and lower 30-day mortality after elective AAA repair (P = .005). The crude rupture rate was 34% for statin patients and 47% for control patients. The crude 30-day mortality rate was 1.8% for the statin group and 2.6% for the control group. The largest effect was in patients who underwent open AAA repair as opposed to endovascular aneurysm repair. Statin use may be associated with reduction in AAA growth, rupture, and perioperative mortality after elective AAA repair.

Statins Reduce Thoracic Aortic Aneurysm Growth in Marfan Syndrome Mice via Inhibition of the Ras-Induced ERK (Extracellular Signal-Regulated Kinase) Signaling Pathway.

BackgroundStatins reduce aneurysm growth in mouse models of Marfan syndrome, although the mechanism is unknown. In addition to reducing cholesterol, statins block farnesylation and geranylgeranylation, which participate in membrane‐bound G‐protein signaling, including Ras. We dissected the prenylation pathway to define the effect of statins on aneurysm reduction.Methods and Results Fbn1 C1039G/+ mice were treated with (1) pravastatin (HMG‐CoA [3‐hydroxy‐3‐methylglutaryl coenzyme A] reductase inhibitor), (2) manumycin A (MA; FPT inhibitor), (3) perillyl alcohol (GGPT1 and ‐2 inhibitor), or (4) vehicle control from age 4 to 8 weeks and euthanized at 12 weeks. Histological characterization was performed. Protein analysis was completed on aortic specimens to measure ERK (extracellular signal‐regulated kinase) signaling. In vitro Fbn1 C1039G/+ aortic smooth muscle cells were utilized to measure Ras‐dependent ERK signaling and MMP (matrix metalloproteinase) activity. Pravastatin and MA significantly reduced aneurysm growth compared with vehicle control (n=8 per group). In contrast, PA did not significantly decrease aneurysm size. Histology illustrated reduced elastin breakdown in MA‐treated mice compared with vehicle control (n=5 per group). Although elevated in control Marfan mice, both phosphorylated c‐Raf and phosphorylated ERK1/2 were significantly reduced in MA‐treated mice (4–5 per group). In vitro smooth muscle cell studies confirmed phosphorylated cRaf and phosphorylated ERK1/2 signaling was elevated in Fbn1 C1039G/+ smooth muscle cells (n=5 per group). Fbn1 C1039G/+ smooth muscle cell Ras‐dependent ERK signaling and MMP activity were reduced following MA treatment (n=5 per group). Corroborating in vitro findings, MMP activity was also decreased in pravastatin‐treated mice.ConclusionsAneurysm reduction in Fbn1 C1039G/+ mice following pravastatin and MA treatment was associated with a decrease in Ras‐dependent ERK signaling. MMP activity can be reduced by diminishing Ras signaling.

Statins Reduce the Development of Complications in Patients With Asymptomatic Gallstone Disease: A Propensity Matched Analysis

Introduction: In a time to event analysis, we previously demonstrated an association between statin use and a decreased frequency of gallstone-related complications in patients with asymptomatic gallstone disease. The aim of this study is to use propensity matching, a more robust form of analysis, to evaluate the efficacy of statins in reducing specific gallstone associated complications. Methods: Patients with asymptomatic gallstones diagnosed on CT or ultrasound reports between 1996 - 2016 were identified using a validated natural language algorithm. Patients with at least one completed prescription for statin were propensity matched (one-to-one with non-replacement) to patients not on statins based on 30 variables: demographic information, comorbidities, features of gallstones at the time of initial imaging, other medication use, and years to event or last follow up. Quality of propensity matching was assessed using t-test. Occurrence of gallstone complications of chronic cholecystitis (includes right upper quadrant pain), acute cholecystitis, gallstone pancreatitis, choledocholithiasis or cholangitis, gallbladder cancer or cholangiocarcinoma, and procedural interventions for these complications were compared in patients with and without statin use. Results: N=22,800 patients were propensity matched to 7,493 patients each in the statin and non-statin groups (Figure 1). T-test analysis yielded no significant differences between the groups based on any matched variables. As noted on Table 1, patients on statins had significantly reduced rates of any complication (No statins, 16.1% versus statin, 11.3%; P= versus 6.1%; P versus 2.5%; P=0.003), and gallstone pancreatitis (2.6% versus 1.8%; P=0.001). No significant differences were noted based on statin use for choledocholithiasis or cholangitis (2.5% versus 2.3%; P=0.368), gallbladder cancer or cholangiocarcinoma (0.5% versus 0.4%; P=0.377), surgery or percutaneous drainage for above indications (3.6% versus 3.1%; P=0.069).86_A Figure 1. One-to-one propensity matching was performed to match patients using statins to patients without statin use based on 30 variables. This figure shows propensity scores of the two matched groups along those excluded from the analysis.Conclusion: In this well-matched propensity analysis of a large cohort, statin use was associated with a 30% reduced incidence of subsequent cholecystitis (acute or chronic) and gallstone pancreatitis in patients diagnosed with asymptomatic cholelithiasis. Given the relative safety of statin medications, use of these medications may be considered in patients with asymptomatic gallstone disease at high risk for the development of symptomatic gallstone disease. A randomized control trial is needed to confirm these findings.86_B Figure 2. Differences in occurrence of gallstone complications in patients with and without statins.

Statins Reduce Abdominal Aortic Aneurysm Growth, Rupture, and Perioperative Mortality: A Systematic Review and Meta-Analysis.

BackgroundThere are no recognized pharmacological treatments for abdominal aortic aneurysms (AAA), although statins are suggested to be beneficial. We sought to summarize the literature regarding the effects of statins on human AAA growth, rupture, and 30‐day mortality.Methods and ResultsWe conducted a systematic review and meta‐analysis of randomized and observational studies using the Cochrane CENTRAL database, MEDLINE, and EMBASE up to June 15, 2018. Review, abstraction, and quality assessment were conducted by 2 independent reviewers, and a third author resolved discrepancies. Pooled mean differences and odds ratios with 95% confidence intervals were calculated using random effects models. Heterogeneity was quantified using the I2 statistic, and publication bias was assessed using funnel plots. Our search yielded 911 articles. One case‐control and 21 cohort studies involving 80 428 patients were included. The risk of bias was low to moderate. Statin use was associated with a mean AAA growth rate reduction of 0.82 mm/y (95% confidence interval 0.33, 1.32, P=0.001, I2=86%). Statins were also associated with a lower rupture risk (odds ratio 0.63, 95% confidence interval 0.51, 0.78, P<0.0001, I2=27%), and preoperative statin use was associated with a lower 30‐day mortality following elective AAA repair (odds ratio 0.55, 95% confidence interval 0.36, 0.83, P=0.005, I2=57%).ConclusionsStatin therapy may be associated with reduction in AAA progression, rupture, and lower rates of perioperative mortality following elective AAA repair. These data argue for widespread statin use in AAA patients.Clinical Trial Registration URL: http://www.crd.york.ac.uk. Unique identifier: CRD42017056480.

Corrigendum: Statins Reduce the Risk of Cirrhosis and Its Decompensation in Chronic Hepatitis B Patients: A Nationwide Cohort Study.

This corrects the article DOI: 10.1038/ajg.2017.494.

Statins Reduce the Risk of Cirrhosis and its Decompensation in CHB Patients?

Statins Reduce the Risk of Cirrhosis and its Decompensation in CHB Patients?

Statins Reduce Lipopolysaccharide-Induced Cytokine and Inflammatory Mediator Release in an In Vitro Model of Microglial-Like Cells.

The anti-inflammatory effects of statins (HMG-CoA reductase inhibitors) within the cardiovascular system are well-established; however, their neuroinflammatory potential is unclear. It is currently unknown whether statins' neurological effects are lipid-dependent or due to pleiotropic mechanisms. Therefore, the assumption that all statin compounds will have the same effect within the central nervous system is potentially inappropriate, with no studies to date having compared all statins in a single model. Thus, the aim of this study was to compare the effects of the six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) within a single in vitro model of neuroinflammation. To achieve this, PMA-differentiated THP-1 cells were used as surrogate microglial cells, and LPS was used to induce inflammatory conditions. Here, we show that pretreatment with all statins was able to significantly reduce LPS-induced interleukin (IL)-1β and tumour necrosis factor (TNF)-α release, as well as decrease LPS-induced prostaglandin E2 (PGE2). Similarly, global reactive oxygen species (ROS) and nitric oxide (NO) production were decreased following pretreatment with all statins. Based on these findings, it is suggested that more complex cellular models should be considered to further compare individual statin compounds, including translation into in vivo models of acute and/or chronic neuroinflammation.

Do Statins Reduce Flu Vaccine Effectiveness

Because statins have anti-inflammatory effects in addition to cholesterol-lowering properties, researchers have begun to probe the possible effects of statins on infection. Now, Wisconsin researchers have retrospectively analyzed data from a large population-based registry on patients who presented with acute respiratory symptoms at an outpatient clinic from 2004 to 2015 to determine whether chronic statin use affects flu vaccine efficacy. Of 3285 patients (age, ≥45 years), 63% had received seasonal …