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Aims: To investigate the occurrence of myopathy with oral glucose-lowering drugs (OGLDs) and statins, with a focus on dipeptidyl peptidase-4 inhibitors (DPP4-is). Methods: The FDA adverse event reporting system (FAERS) was queried (2004–2016) to compare the proportion of adverse events with OGLDs, alone and in combination with statins, using the reporting odds ratio (ROR) with relevant 95% confidence interval (95%Cl), adjusted for sex, age and concomitant presence of other OGLDs/lipid-lowering drugs. Drug–drug interaction is claimed whenever the frequency of an event is enhanced by combination treatment. Consistency/robustness of findings was tested by applying additive/multiplicative models and accounting for competition bias (i.e., adverse events previously known to be associated with OGLDs were removed). Results: Over a 13-year period, we retrieved 142,888 cases of myopathy. The use of DPP4-is alone was not associated with higher reporting of myopathy (no. of cases = 4898; adjusted ROR = 1.00; 95%CI = 0.96–1.04), with the notable exclusion of vildagliptin (262; 1.64; 1.42–1.88). No increased occurrence emerged when used in combination with statins, with consistent findings from additive/multiplicative models for all DPP4-is. Likewise, no increased reporting was found for other OGLDs (28,964; 0.64; 0.62–0.67); data on the interaction with statins were consistent/robust across analyses only for sulfonylureas (the interaction is likely and biologically plausible) and sodium glucose cotransporter-2 inhibitors. Conclusions: Real-world FAERS data do not raise concern for muscular toxicity with DPP4-is in combination with statins, making a drug interaction very unlikely.

Background Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37–0.72; p p 50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p Conclusions Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted.

Background: Statin treatment is often associated with poor adherence, which may be due to the onset of adverse drug reactions (ADRs). We investigated on potential risk factors related to preventable cases of statin-induced ADRs and to the discontinuation of statin therapy. Methods: We performed a study using the database of Italian spontaneous reporting. The target population for the preventability assessment was all patients with suspected statin-induced ADRs deriving from Campania Region (a territory of Southern Italy) between 2012 and 2017. Additionally, a local sentinel surveillance site involving General Practitioners was selected to countercheck in routine clinical practice the role of ADRs for statin discontinuation. Results: In total, 34 of 655 (5.19%) regional cases were preventable and among detected risk factors 90.0% was related to healthcare professionals’ practices and 10.0% to patient behaviour. In 81.4% (533/655) of cases, statin therapy was discontinued due to ADRs, mainly classified as not serious and associated with a positive prognosis. These results were also confirmed in the active sentinel site. Conclusions: Our findings suggest an inappropriate use of statins among the identified preventable cases and a potential inappropriate statin discontinuation due to ADRs. These factors may be useful for targeting interventions to improve statin adherence.

Background and aims Meta-analyses of randomized control trials investigating the association between incident diabetes and statin use showed an increased risk of new-onset diabetes (NOD) from 9% to 13% associated with statins. However, short follow-up period, unpowered sample size, and lack of pre-specified diagnostic criteria for diabetes detection could be responsible of an underestimation of this risk. We conducted a meta-analysis of published observational studies to evaluate the association between statins use and risk of NOD. Methods and results PubMed, EMBASE and MEDLINE databases were searched from inception to June 30, 2016 for cohort and case–control studies with risk of NOD in users vs nonusers, on ≥1000 subjects followed-up for ≥1 year. Two review authors assessed study eligibility and risk of bias and undertook data extraction independently. Pooled estimates were calculated by a random-effects model and between-study heterogeneity was tested and measured by I 2 index. Furthermore, stratified analyses and the evaluation of publication bias were performed. Finally, the meta-analysis included 20 studies, 18 cohort and 2 case–control studies. Overall, NOD risk was higher in statin users than nonusers (RR 1.44; 95% CI 1.31–1.58). High between-study heterogeneity (I 2 = 97%) was found. Estimates for all single statins showed a class effect, from rosuvastatin (RR 1.61; 1.30–1.98) to simvastatin (RR 1.38; 1.19–1.61). Conclusions The present meta-analysis confirms and reinforces the evidence of a diabetogenic effect by statins utilization. These observations confirm the need of a rigorous monitoring of patients taking statins, in particular pre-diabetic patients or patients presenting with established risk factors for diabetes.

Despite encouraging progresses achieved in the management of viral diseases, efficient strategies to counteract infections are still required. The current global challenge highlighted the need to develop a rapid and cost-effective strategy to counteract the SARS-CoV-2 pandemic. Lipid metabolism plays a crucial role in viral infections. Viruses can use the host lipid machinery to support their life cycle and to impair the host immune response. The altered expression of mevalonate pathway-related genes, induced by several viruses, assures survival and spread in host tissue. In some infections, statins, HMG-CoA-reductase inhibitors, reduce cholesterol in the plasma membrane of permissive cells resulting in lower viral titers and failure to internalize the virus. Statins can also counteract viral infections through their immunomodulatory, anti-inflammatory and anti-thrombotic effects. Beyond statins, interfering with the mevalonate pathway could have an adjuvant effect in therapies aimed at mitigating endothelial dysfunction and deregulated inflammation in viral infection. In this review we depicted the historical and current evidence highlighting how lipid homeostasis and mevalonate pathway targeting represents a valid approach to rapidly neutralize viruses, focusing our attention to their potential use as effective targets to hinder SARS-CoV-2 morbidity and mortality. Pros and cons of statins and Mevalonate-pathway inhibitors have been also dissected.

Background and Aim Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with high cardiovascular risk. Management of dyslipidaemia plays a pivotal role in the prevention of CV events and statins have proved to be safe in these patients. However, in everyday clinical practice statin prescription is sometimes limited because of the concern of physicians about side-effects. The aim of the study was to investigate if the presence of NAFLD affects the prescription of lipid-lowering treatment in a large series of patients with cardio-metabolic disorders. Methods and Results Cardiovascular risk and LDL-C targets were defined according to ESC/EAS Guidelines in 605 consecutive adult subjects referred for screening of suspected metabolic diseases. Liver steatosis was assessed by ultrasound Hamaguchi criteria. In the whole cohort, 442 patients had indication for cholesterol-lowering treatment. Lack of statin prescription was present in 230 (52.0%) patients. Of these, 77 (33.5%) were very high-risk, 48 (20.8%) high-risk, and 105 (45.6%) moderate risk patients. Only 44% of the NAFLD patients with indication for statin treatment were on therapy. NAFLD patients on statin treatment had significantly lower ALT values as compared to those not on treatment (p Conclusions Our findings show that about 50% of patients with indication to statin treatment do not receive any cholesterol-lowering medication. Statin under-use was particularly high in subjects with NAFLD. Use of statin treatment should be encouraged in the context of NAFLD, as it may improve lipid profile and reduce the cardiovascular risk in this setting.

Objective Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. Methods We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case–control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. Results A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. Conclusions Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions.

The elderly population is increasing worldwide and shows an increasing prevalence of frailty. Frailty is recognized as an important factor for inappropriate drug prescribing in elderly patients. Appropriate drug prescription, either in terms of drug choice or in terms of drug dosage, is of paramount importance among the frail elderly patients, this requiring the need of a difficult balance between efficacy, safety and tolerability. Bacterial infections are quite frequent among the elderly, and use of antimicrobials may be associated with severe adverse events in this population, especially when in presence of co-medications and/or of co-morbidities. The aim of this paper is to argue about the most recent published evidences on how to prevent major adverse events whenever antimicrobials should be co-prescribed in frail elderly patients.

Statin therapy is generally well tolerated and very effective in the prevention and treatment of cardiovascular disease, regardless of cholesterol levels; however, it can be associated with various adverse events (myalgia, myopathy, rhabdomyolysis, and diabetes mellitus, among others). Patients frequently discontinue statin therapy without medical advice because of perceived side effects and consequently increase their risk for cardiovascular events. In patients with statin intolerance, it may be advisable to change the dose, switch to a different statin, or try an alternate-day regimen. If intolerance is associated with all statins—even at the lowest dose—non-statin drugs and certain nutraceuticals can be considered. This review focuses on the definition of statin intolerance and on the development of clinical and therapeutic strategies for its management, including emerging alternative therapies.

Background Patients with type 2 diabetes are at high risk for cardiovascular disease. Although hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Lipoprotein particle size and fraction changes are thought to contribute to such risks. The purpose of this study was to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid and docosahexaenoic acid, on lipoprotein particle size, concentration, and glycemic control in Japanese patients with type 2 diabetes and hypertriglyceridemia. Methods This was a multicenter, prospective, open-label, single arm study. We enrolled 14 patients with type 2 diabetes and hypertriglyceridemia treated with statins and dipeptidyl peptidase-4 inhibitors with glycated hemoglobin (HbA1c)

Background Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied. Methods We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications. Results We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78–0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78–0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission. Conclusions In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.

Background Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000-2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period. Background: Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods: A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000–2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results: The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion: Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period.

The YAP and TAZ mediators of the Hippo pathway (hereafter called YAP/TAZ) promote tissue proliferation and organ growth. However, how their biological properties intersect with cellular metabolism remains unexplained. Here, we show that YAP/TAZ activity is controlled by the SREBP/mevalonate pathway. Inhibition of the rate-limiting enzyme of this pathway (HMG-CoA reductase) by statins opposes YAP/TAZ nuclear localization and transcriptional responses. Mechanistically, the geranylgeranyl pyrophosphate produced by the mevalonate cascade is required for activation of Rho GTPases that, in turn, activate YAP/TAZ by inhibiting their phosphorylation and promoting their nuclear accumulation. The mevalonate-YAP/TAZ axis is required for proliferation and self-renewal of breast cancer cells. In Drosophila melanogaster, inhibition of mevalonate biosynthesis and geranylgeranylation blunts the eye overgrowth induced by Yorkie, the YAP/TAZ orthologue. In tumour cells, YAP/TAZ activation is promoted by increased levels of mevalonic acid produced by SREBP transcriptional activity, which is induced by its oncogenic cofactor mutant p53. These findings reveal an additional layer of YAP/TAZ regulation by metabolic cues.

A 62-year-old man presented to our neurology outpatient clinic with a 3-week history of progressive right wrist drop. He had been complaining of generalized asthenia, numbness, and tingling involving the soles of both feet for the last year. He had a history of chronic renal failure due to type 2 diabetes, for which he was on maintenance hemodialysis. He had hypertension and hyperlipidemia, treated respectively with propranolol and simvastatin. He denied smoking and alcohol abuse.

Background:The impact of statin use on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) remains controversial.Methods: We retrospectively evaluated 6842 patients who underwent RP for clinically localized prostate cancer (PC) between 2000 and 2011. Uni-and multivariable cox regression models addressed the association of statin use with BCR.Results:Overall, 2275 (33.3%) patients used statins. Statin users were older and had a higher rate of positive surgical margins than patients not using statins (P-values ≤0.05). Within a median follow-up of 25 months (interquartile range: 8-42 months), 778 (11.4%) patients experienced BCR. Actuarial estimate 5-years BCR-free survival was 82%±1 for patients without statin use and 84±1% for patients using statins (P=0.05); statin use was not associated with BCR (hazard ratio: 0.88, 95% confidence interval: 0.76-1.03, P=0.10) after adjusting for the effects of standard clinicopathologic features.Conclusions:In PC patients undergoing RP, statin use was not independently associated with lower risk of BCR. © 2013 Macmillan Publishers Limited All rights reserved.

Background Statin use is associated with a modest increase in the incidence of type 2 diabetes mellitus (DM) among the general population. However, HIV-infected patients have a higher risk of developing DM, and it is unclear whether statins have a diabetogenic effect in these patients. Therefore, we investigated the associations of statin use and exposure to antiretroviral drugs with type 2 DM onset in a cohort of HIV-infected patients. Methods This retrospective, controlled, cohort study identified HIV-1-infected patients who did not have DM and were not receiving statins at their antiretroviral treatment (ART) initiation. Follow-up was accrued from ART initiation to the earliest instance of a DM diagnosis, loss to follow-up, death, or last available visit. The incidence of DM was estimated according to statin use, which was adjusted for periods without statin treatment. The Fine-Gray competing risk model was used in the multivariate analysis to identify risk factors for developing DM. Results The analyses evaluated 6,195 patients followed for 9.8 years (interquartile range: 4.3–16.3 years). During 64,149 person-years of follow-up (PYFU), 235 patients developed DM (crude incidence: 3.66 [95%CI: 3.20–4.13] per 1,000 PYFU), and 917 (14%) patients used statins. After adjusting for potential confounders, statin use was associated with a non-significant increase in the risk of DM (AHR: 1.21, 95% CI: 0.71–2.07; P = 0.47). DM was more likely among patients who were ever treated with stavudine, and less likely among those ever treated using emtricitabine, tenofovir, abacavir, efavirenz, nevirapine, atazanavir or darunavir. Conclusions A higher risk of diabetes mellitus was not associated with statin treatment but with traditional risk factors and stavudine use while a reduced risk of DM was associated with the use of emtricitabine, tenofovir, abacavir, efavirenz, nevirapine, atazanavir or darunavir. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-2099-5) contains supplementary material, which is available to authorized users.

Background Several studies have shown a significant association between vitamin D deficiency and an increased risk of statin-related symptomatic myalgia in the general population, but there are no data among HIV-infected persons. Methods A retrospective, cohort study was conducted to assess the incidence of symptomatic myalgia and elevation in serum creatine kinase level among HIV-positive adults on combination antiretroviral therapy and treated with atorvastatin or rosuvastatin for at least 12 months between 2011 and 2015 in our outpatient unit. Results A total of 545 patients (mean age 53.4 years) were enrolled into the study. Atorvastatin was prescribed in 55.8% of patients and rosuvastatin in 44.2%. After a mean duration of statin therapy of 29 months, an isolated symptomatic myalgia was diagnosed in 42 patients (7.7%) and a myalgia associated with elevated creatine kinase level in 25 (4.6%). The mean concentration of 25-hydroxyvitamin D was significantly lower in patients with myalgia (19.4 ng/ml) and with creatine kinase elevation and myalgia (22.8 ng/ml) than in those without muscle toxicity (32.1 ng/ml; P = 0.017 and 0.024, respectively). In stratified multivariable-adjusted logistic regression models, there was a statistically significant association between vitamin D deficiency and occurrence of symptomatic myalgia (P = 0.009) or creatine kinase elevation and myalgia (P = 0.046). Other factors significantly associated with development of myalgia were duration of statin therapy more than 24 months, history of myalgia, and age older than 60 years. Discussion In our observational study, vitamin D deficiency was significantly associated with a statin-induced myalgia among HIV-infected patients on combination antiretroviral therapy, in conformity with data of the general population.

Statins were shown to have neuroprotective effects, with reduced vasospasm and delayed ischemic deficits in statin-treated patients after aneurysmal subarachnoid hemorrhage in two small, randomized, controlled clinical trials published in 2005. This review consolidated data from available published studies evaluating statin treatment for subarachnoid hemorrhage. A literature search was conducted to identify original research studies published through October 2010 testing immediate treatment with a statin in statin-naïve patients following aneurysmal SAH. Six randomized controlled clinical trials and four observational studies were identified. Despite inconsistent results among studies, a meta-analysis of randomized controlled data showed a significant reduction in delayed ischemic deficits with statins. Effect on vasospasm was more difficult to determine, due to differences in definitions used among studies. Interpretations from observational studies were limited by the use of relatively small sample sizes, historical controls, and treatment variability. © Springer Science+Business Media, LLC 2011.

Current available biomarkers cannot identify myocardial ischemia without necrosis. To overcome this issue and to increase diagnostic power, we evaluated the activation of the three MAPK pathways, ERK1/2, JNK and p38, in T lymphocytes of patients with acute coronary syndromes (ACS). We included sixty consecutive patients affected by either unstable angina (UA, N = 22), Non- ST-segment elevation MI (NSTEMI, N = 19) or ST-segment elevation MI (STEMI, N = 19). Two separate groups of patients were matched as controls: healthy subjects (CTRL, N = 20) and patients with stable coronary artery disease (CAD, N = 21). MAPK activation in T lymphocytes, measured by phospho-ERK1/2, phospho-JNK and phospho-p38 levels, was assessed by flow cytometry analysis which revealed significantly increased phosphorylated levels of ERK1/2 in patients with UA, compared to controls. In UA patients no significant changes were detected for phospho-JNK compared to both control groups. NSTEMI and STEMI groups showed a statistically significant increase in both phospho-ERK1/2 and phospho-JNK, compared to control groups. All ACS groups demonstrated significantly increased phosphorylation of p38 compared to CTRL, but not CAD. ROC curves showed that a cut-off value of 22.5 intensity of fluorescence for phospho-ERK1/2 was able to significantly discriminate UA patients from patients with stable angina with 78% sensitivity and 90% specificity. Therefore, a differential MAPK activation in T lymphocytes denotes patients with ACS. Indeed, patients with unstable angina are identified with high specificity by activated ERK1/2 and normal JNK levels. These data could represent a valuable new molecular signature to be used as specific biomarkers for the diagnosis of unstable angina within ACS. © 2011 Springer-Verlag.

Aims: The objective of the study is to determine the demographics and the in-hospital outcome of diabetic and non-diabetic patients treated with percutaneous coronary interventions (PCI) in Europe, to report the type of equipment and technology used for PCI procedures in diabetics and to clarify whether the treatment of diabetic patients complies with current European Society of Cardiology (ESC) guidelines. Methods and results: A total of 14,458 patients treated with PCI were enrolled from 29 member countries of the ESC between June 2005 and January 2006. Data were collected on patient characteristics and treatment, using new Cardiology Audit and Registration Data standards. In total, 3,603 patients (24.9%) were diabetic. Diabetics were older, more often female and had a higher body mass index than non-diabetics. Diabetics had higher rates of hypercholesterolaemia and hypertension, while current smokers were more frequent in the non-diabetics. Diabetics also had significantly higher rates of previous cardiovascular events. Clopidogrel was administered only in 48.1% of diabetic patients before PCI, while IIb/IIIa inhibitors were 22.9% during PCI. At discharge, there was a major adjustment of treatment with increases in the use of Beta-blocker (80.4%), angiotensin converting enzyme inhibitor (ACEI, 71.3%) and statins (89.8%) compared with on admission (Beta-blocker 60.9%, ACEI 55.0%, statin 63.1%). Inhospital mortality was higher in diabetics (1.8% vs 1.2%) although the in-hospital MACCE rate was not significantly different (3.6% vs 3.0%, p=0.09). Conclusions: Diabetic patients treated with PCI were older with more comorbidity. According to ESC guideline, the under-usage of clopidogrel, GP IIb/IIIa inhibitors should be improved. PCI is now taken as a good opportunity to adjust the use of appropriate medication. © Europa Edition. All rights reserved.

BACKGROUND: It is unclear whether patients age 65 years and over with a recent stroke or TIA benefit from statin treatment to a similar degree as younger patients. METHODS: The 4,731 patient cohort in the SPARCL study was divided into an elderly group (65 and over) and a younger group. The primary endpoint (fatal or nonfatal stroke) and secondary endpoints were analyzed, with calculation of the hazard ratio (HR) and p values from a Cox regression model. RESULTS: There were 2,249 patients in the elderly group and 2,482 in the younger group. The baseline LDL (133 mg/dL) and total cholesterol were comparable in the two groups. The elderly and younger groups had a 61.4 mg/dL and 58.7 mg/dL decrease in mean LDL during the trial. The primary endpoint was reduced by 26% in younger patients (HR 0.74, 0.57-0.96, p = 0.02) and by 10% in elderly subjects (HR 0.90, 0.73-1.11, p = 0.33). A test of heterogeneity for a treatment-age interaction was not significant (p = 0.52). The risk of stroke or TIA (HR 0.79, p = 0.01), major coronary events (HR 0.68, p = 0.035), any coronary heart disease event (HR 0.61, p = 0.0006), and revascularization procedures (HR 0.55, p = 0.0005) was reduced in the elderly group. CONCLUSIONS: There was no heterogeneity in the stroke reduction seen with atorvastatin in the elderly and younger groups. Cardiac events and revascularization procedures were also lower in both the elderly and younger subgroups treated with atorvastatin. These results support the use of atorvastatin in elderly patients with recent stroke or TIA.

Objectives: To investigate the use of statins and acetylsalicylic acid (ASA) in HIV people in clinical practice. Design: A multicenter, nationwide, prospective cohort study, including 1182 consecutive HIV patients was conducted. Methods: Statin and ASA prescription was evaluated in primary and secondary cardiovascular disease prevention, according to the European AIDS Clinical Society (EACS) guidelines. Results: Followed-up patients (998) were mostly males (70.9%) with a mean age at enrolment of 46.5years (SD 9.5). The mean time of follow-up was 3.3years (SD 0.8). At the last follow-up visit, statins would have been recommended for 31.2% and ASA for 16% by EACS guidelines. Conversely, only 15.6 and 7.6% of patients were on statin and ASA treatment, respectively; only 50.3% of patients treated with statins achieved recommended low-density lipoprotein cholesterol (LDL-c) levels. At the last follow-up visit, agreement between statin therapy and EACS recommendation was 0.58 (95% CI 0.52–0.63). The corresponding figure for ASA therapy was 0.50 (95% CI 0.42–0.58), whereas the agreement for ASA therapy in secondary prevention was 0.59 (95% CI 0.50–0.68). Conclusions: The prescription of statins and ASA in HIV-infected patients remains largely suboptimal, as only about 50% of patients requiring statins and ASA are properly treated. Higher attention on this relevant issue and further investigation are warranted in this at risk population.

The impact of low density lipoprotein (LDL) cholesterol levels on cardiovascular risk has been extensively studied. Statins have been demonstrated to significantly reduce LDL cholesterol levels, contributing to cardiovascular risk reduction particularly in patients with high cardiovascular risk. However, low adherence to statin therapy, often due to adverse effects, has raised the need for new pharmacological approaches to combine with statin therapy in order to reach the target levels of LDL cholesterol. Ezetimibe is a selective inhibitor of Niemann-Pick C1-like 1 (NPC1L1) protein that regulates the cholesterol uptake from the small intestine into the enterocytes. Ezetimibe has been demonstrated to significantly reduce LDL cholesterol levels in combination with statins and recent trials support its role in reducing the risk of cardiovascular events.

Statins have several pleiotropic effects, beyond cholesterol synthesis inhibition, including anti-inflammatory and antithrombotic properties.[1][1] They have been shown to reduce the rate of venous thromboembolism (VTE), but whether this beneficial effect is counterbalanced by an increased

Background Small studies have suggested that lipid-lowering strategies, and particularly statins, could influence blood pressure (BP) control. The aim of the present study was to evaluate the effect of different lipid-lowering strategies on BP control of subjects with hypercholesterolemia who were enrolled in the prospective, population-based, longitudinal Brisighella Heart Study. Methods A total of 1356 subjects with total cholesterol levels ≥239 mg/dL were randomly treated for 5 years (1988–1993) with 1 of these lipid-lowering regimens: low-fat diet, cholestyramine, gemfibrozil, or simvastatin. Participants were divided at baseline into 4 quartiles according to systolic BP level and examined for the percent change in systolic and diastolic BP during the 5 years of treatment. Results A significant decrease in BP was observed in the 2 upper quartiles of systolic BP (≥140 mm Hg) and was greater in subjects treated with cholesterol-lowering drugs who also had a greater reduction in plasma levels of low-density lipoprotein cholesterol. The BP decrease was greater in patients treated with statin drugs and, among those treated with antihypertensive drugs, in subjects in the fourth quartile. Conclusion The use of lipid-lowering measures could significantly improve BP control in subjects with both hypercholesterolemia and hypertension. The reduction in BP seems to be enhanced in subjects treated with statins.

Growing evidence indicates that overproduction of reactive oxygen species (ROS) plays a prominent role in the development of cardio- and cerebro-vascular diseases. Among the mechanisms identified to produce oxidative stress in the vascular wall, those mediated by membrane-bound NAD(P)H oxidases represent a major one. NAD(P)H oxidases are a family of enzymes that generate ROS both in phagocytic and non-phagocytic cell types. Vascular NAD(P)H oxidase contains the membrane-bound subunits Nox1, Nox2 (gp91phox), Nox4 and p22phox, the catalytic site of the oxidase, and the cytosolic components p47phox and p67phox. Rac1 (Ras-related C3 botulinum toxin substrate1) is a small GTPase essential for the assembly and activation of NADPH oxidase. Several molecular and cellular studies have reported the involvement of Rac1 in different cardiovascular pathologies, such as vascular smooth muscle proliferation, cardiomyocyte hypertrophy, endothelial cell shape change, atherosclerosis and endothelial dysfunction in hypertension. In addition, increased activation of NADPH oxidase by Rac1 has been reported in animals and humans after myocardial infarction and heart failure. The Rac1/NADPH pathway has also been found involved in different pathologies of the cerebral district, such as ischemic stroke, cognitive impairment, subaracnoid hemorrhage and neuronal oxidative damage typical of several neurodegenerative disorders. In addition, thrombotic events are an important step in the onset of cardio- and cerebrovascular diseases. Rac1 has been found involved also in platelet activation, inducing actin polymerization and lamellipodia formation, which are necessary steps for platelet aggregation. Taken together, the evidence candidates Rac1 as a new pharmacological target of cardiovascular and cerebrovascular diseases. Although the involvement of Rac1 in the beneficial pleiotropic effects of drugs such as statins is well known, and the onset of numerous side effects has raised concern for the management of some patient groups. Interestingly, a novel selective Rac1 inhibitor, NSC23766, has recently been introduced; its use has been reported mainly in the oncology field. Future studies are needed to extend its application to cardio- and cerebro-vascular diseases, and translate its use to humans.

Since contradictory findings have been reported on potential effects of statins in modulating the inflammatory response, we have analysed the biological activity of lovastatin both in vitro using the Raw 264.7 murine macrophagic cell line and in vivo using BALB/c mice. When added to Raw 264.7 cells in combination with lipopolysaccharide, lovastatin significantly potentiated the release of interleukin-1β, interleukin-6 and interleukin-12 with respect to lipopolysaccharide alone and showed an additive effect on the release of nitric oxide. Similarly, when lovastatin was intraperitoneally administrated to BALB/c mice, it did not induce any pro-inflammatory effect when used alone, but it significantly potentiated the pro-inflammatory activity of lipopolysaccharide, in terms of number of intraperitoneal cells and serum levels of serum amyloid A, interleukin-1β, interleukin-6 and interleukin-12. A potential clinical implication of our study is that lovastatin might exert a pro-inflammatory activity in subjects affected by inflammatory processes, with clinically evident or subclinical infections.

Purpose The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines advocate the use of statin treatment for prevention of cardiovascular disease. We aimed to assess the usefulness of coronary artery calcium (CAC) for stratifying potential candidates of statin use among asymptomatic Korean individuals. Materials and methods A total of 31375 subjects who underwent CAC scoring as part of a general health examination were enrolled in the current study. Statin eligibility was categorized as statin recommended (SR), considered (SC), and not recommended (SN) according to ACC/AHA guidelines. Cox regression analysis was employed to estimate hazard ratios (HR) with 95% confidential intervals (CI) after stratifying the subjects according to CAC scores of 0, 1-100, and >100. Number needed to treat (NNT) to prevent one mortality event during study follow up was calculated for each group. Results Mean age was 54.4±7.5 years, and 76.3% were male. During a 5-year median follow-up (interquartile range; 3-7), there were 251 (0.8%) deaths from all-causes. A CAC >100 was independently associated with mortality across each statin group after adjusting for cardiac risk factors (e.g., SR: HR, 1.60; 95% CI, 1.07-2.38; SC: HR, 2.98; 95% CI, 1.09-8.13, and SN: HR, 3.14; 95% CI, 1.08-9.17). Notably, patients with CAC >100 displayed a lower NNT in comparison to the absence of CAC or CAC 1-100 in SC and SN groups. Conclusion In Korean asymptomatic individuals, CAC scoring might prove useful for reclassifying patient eligibility for receiving statin therapy based on updated 2013 ACC/AHA guidelines.

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with ( n=368) and without ( n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least squares mean percent change from baseline and 95% confidence intervals in lipid efficacy parameters were calculated for the population and within subgroups. Treatment with ezetimibe/simvastatin was significantly more effective than rosuvastatin at lowering low-density lipoprotein cholesterol, total cholesterol, non- high-density lipoprotein cholesterol, and apolipoprotein B (all p

Background/Aims: The use of statins in patients with acute coronary syndrome (ACS) has increased, and reduced levels of low-density lipoprotein cholesterol (LDL-C) lead to lower coronary event rates. We studied the effect of lipid levels during statin treatment on prognosis in patients with ACS and percutaneous coronary intervention (PCI). Methods: Between January 2005 and May 2007, 325 ACS patients who underwent PCI and received statins were evaluated. We measured serum lipid levels at baseline and 4 weeks. The relationships between ontreatment levels of triglyceride (TG) and LDL-C and one-year major adverse cardiac events (MACE) were assessed. Results: At 4 weeks, the mean LDL-C level was 72.5±23.8 mg/dL and the mean TG was 123.2±62.8 mg/dL. MACE occurred in 41 cases (12.6%). Baseline serum lipid levels were similar between the patients with and those without MACE. However, the patients with MACE showed significantly higher TG level at 4 weeks (149.6±81.4 vs. 119.3±58.9 mg/dL, p=0.026) than those without. High on-treatment TG level (≥150 mg/dL) were associated with increased adverse events compared to lower TG level in a univariate analysis (hazard ratio [HR], 3.3; p

Background and Purpose— In SPARCL, treatment with atorvastatin 80 mg daily reduced stroke risk in patients with recent stroke or TIA and no known coronary heart disease by 16% versus placebo over 4.9 years of follow-up. The purpose of this secondary analysis was to determine whether men and women similarly benefited from randomization to statin treatment. Methods— The effect of sex on treatment-related reductions in stroke and other cardiovascular outcomes were analyzed with Cox regression modeling testing for sex by treatment interactions. Results— Women (n=1908) constituted 40% of the SPARCL study population. At baseline, men (n=2823) were younger (62.0±0.21versus 63.9±0.27 years), had lower systolic BPs (138.1±0.35 versus 139.5±0.47 mm Hg), higher diastolic BPs (82.2±0.20 versus 81.0±0.25 mm Hg), more frequently had a history of smoking (73% versus 38%), and had lower total cholesterol (207.0±0.54 versus 218.9±0.67 mg/dL) and LDL-C levels (132±0.45 versus 134±0.57 mg/dL) than women. Use of antithrombotics and antihypertensives were similar. After prespecified adjustment for region, entry event, time since event, and age, there were no sex by treatment interactions for the combined risk of nonfatal and fatal stroke (treatment Hazard Ratio, HR=0.84, 95% CI 0.68, 1.02 in men versus HR=0.84, 95% CI 0.63, 1.11 in women; treatment×sex interaction P =0.99), major cardiac events (HR=0.61, 95% CI 0.42, 0.87 in men versus HR=0.76, 95% CI 0.48, 1.21 in women; P =0.45), major cardiovascular events (HR=0.78, 95% CI 0.65, 0.93 in men versus HR=0.84, 95% CI 0.65, 1.07 in women; P =0.63), revascularization procedures (HR=0.50, 95% CI 0.37, 0.67 in men versus HR=0.76, 95% CI 0.46, 1.24 in women; P =0.17), or any CHD event (HR=0.54, 95% CI 0.41, 0.72 in men versus 0.67 95% CI 0.46, 0.98 in women; P =0.40). Conclusion— Stroke and other cardiovascular events are similarly reduced with atorvastatin 80 mg/d in men and women with recent stroke or TIA.

Preclinical studies suggest that HMG-CoA reductase inhibitors (statins) may attenuate organ dysfunction. We evaluated whether statins are associated with attenuation of lung injury and prevention of associated organ failure in patients with ALI/ARDS. From a database of patients with ALI/ARDS, we determined the presence and timing of statin administration. Main outcome measures were the development and progression of pulmonary and nonpulmonary organ failures as assessed by changes in PaO2/FiO(2) ratio and Sequential Organ Failure Assessment score (SOFA) between days 1 and 7 after the onset of ALI/ARDS. Secondary outcomes included ventilator free days, ICU and hospital mortality, and lengths of ICU and hospital stay. From 178 patients with ALI/ARDS, 45 (25%) received statin therapy. From day 1 to day 7, the statin group showed less improvement in their PaO2/FiO(2) ratio (27 vs. 55, P = 0.042). Ventilator free days (median 21 vs. 16 days, P = 0.158), development or progression of organ failures (median Delta SOFA 1 vs. 2, P = 0.275), ICU mortality (20% vs. 23%, P = 0.643), and hospital mortality (27 vs. 37%, P = 0.207) were not significantly different in the statin and non-statin groups. After adjustment for baseline characteristics and propensity for statin administration, there were no differences in ICU or hospital lengths of stay. In this retrospective cohort study, statin use was not associated with improved outcome in patients with ALI/ARDS. We were unable to find evidence for protection against pulmonary or nonpulmonary organ dysfunction.

Statins, the inhibitors of HMG-CoA reductase, are currently among the most commonly prescribed agents for the prevention of cardiovascular disease. It is well established that statins reduce cholesterol levels and prevent coronary heart disease. Moreover, evidence suggests that statins have additional properties such as endothelial protection via actions on the nitric oxide synthetase system as well as antioxidant, anti-inflammatory and antiplatelet effects. There is evidence that all these actions might have potential therapeutic implications not only in stroke, but also in various neurological disorders, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and primary brain tumors. In this review, we summarize the protective effects of statins on various neurological diseases. Currently available data suggest that statins are safe and effective in the treatment of these neurological disorders, although further experiments and new data are required. © 2008 Expert Reviews Ltd.

Objective: To evaluate how the presence and timing of statin therapy affect perioperative renal outcomes after major vascular surgery. Design: Retrospective cohort study. Setting: Surgical intensive care unit at a single academic medical center. Participants: Patients undergoing major vascular surgery between July 2004 and October 2005. Measurements and Main Results: The presence and timing of perioperative statin administration and the propensity for receiving such therapy were noted. Renal outcomes, lengths of stay, and mortality were reviewed. One hundred fifty-one procedures were performed. Eighty-nine patients (59%) received statin therapy. There was no evidence for renal protection with perioperative statin therapy (A creatinine 0.2 mg/dL v 0.2 mg/dL, p = 0.41; acute renal injury/acute renal failure 8% v 6%, p = 1.00; renal replacement therapy 3% v 3%, p = 1.00; all statin v no statin, respectively). With the possible exception of early reinstitution of statin therapy in chronic statin users, subgroup analyses failed to confirm an association between statin timing and prevention of postoperative renal dysfunction. Conclusions: In the present investigation, neither the presence nor timing of perioperative statin therapy was associated with improved renal outcomes in patients undergoing a range of major vascular procedures. A possible exception is early postoperative reinitiation of statin therapy in chronic statin users. The discrepant results of available literature preclude a definitive statement on the use of statin therapy as a means of preventing postoperative renal dysfunction. An adequately powered prospective trial is needed before advocating the routine use of statin therapy for perioperative renal protection. (C) 2008 Elsevier Inc. All rights reserved.

Recent evidence suggests a link between statins and telomere biology. Whether statin treatment may modulate telomerase activity and affect telomere erosion rate is unknown. We aimed at investigating the potential impact of statin therapy on peripheral blood mononuclear cells telomerase activity, its implication on LTL variability, and its association with telomere shortening rates along with aging. The cross-sectional study was conducted in 230 subjects (age range: 30-86 y) stratified according to statins treatment. LTL was measured by quantitative polymerase chain reaction and telomerase activity by a PCR-ELISA protocol. Subjects on statin treatment showed higher telomerase activity (P