Hydrophilic Statins Research Articles

Association of lipid-lowering agent use and dry eye disease: A nationwide matched case-control study in Taiwan, 2002-2016.

The purpose of this study is to evaluate the association between lipid-lowering agent use and the risks of diagnosed dry eye disease (DED). This retrospective, case-control study included 780 786 patients who received lipid-lowering agents in 2002-2016, of which 17 409 were newly diagnosed with DED during a ≥2-year follow-up period. These patients were matched 1:4 with control participants for age, sex, and comorbidities. Separate odds ratios (OR) were calculated for DED and each of statin and fibrate use. Statin users had significantly higher odds of DED (adjusted OR=1.12; 95% confidence interval (CI)=1.08-1.16, p < 0.0001) than nonusers. Fibrate users did not show higher odds of DED than nonusers (adjusted OR=1.04; 95% CI=0.99-1.10, p=0.125). The lipophilic statin users did not show higher odds of DED compared with the hydrophilic statin users (adjusted OR=0.99, 95% CI=0.93-1.06, p=0.729). Among statin users, the odds of DED did not differ significantly between patients receiving statin therapy for >180 days vs. ≤90 days or patients receiving statin therapy for 91-180 days vs. ≤90 days (adjusted OR=1.00, p=0.922; adjusted OR=0.94, p=0.541, respectively). The odds of DED were not statistically different among patients receiving low-intensity, moderate-intensity, and high-intensity of statin therapy. Patients receiving statin therapy had a higher DED risk than patients not receiving statin therapy. The type of statin, the duration, and the intensity of statin use were not significantly associated with DED risks. Further studies are required to identify the relevant factors related to DED risks with statin.

Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study.

Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures. We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. We used data from the E3N cohort study of French women (follow-up, 2004-2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins-PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54-79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR]=0.87, 95% confidence interval [CI]=0.67-1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR=0.70, 95% CI=0.51-0.98), with a dose-response relation for the mean daily dose (P-linear trend=0.02). There was no association for hydrophilic statins. Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose-response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Role of rosuvastatin in bone metabolism of ovariectomized adult rats

The study was planned to explore the influence of one type of hydrophilic statins (rosuvastatin) on the level of serum osteocalcin, N-telopeptide of type 1 collagen (NTx), calcium, and phosphorus. In addition to calcium, phosphorus, and magnesium in femur bone ash of female ovariectomized rats. Thirty female rats aged 2.5-3 months were divided as follows, sham group, ovariectomized (ovx) group as a model of osteoporosis, and (ovx) group treated with 20mg /kg of rosuvastatin for 60 days. Blood samples were collected after 30 and 60 days of the experiment for biochemical analysis. Besides, after 60 days of the treatment, right femur bones were excised and ashed to estimate calcium, phosphorus, and magnesium. The results showed a significant elevation in serum osteocalcin, (NTx), calcium, and phosphorus, in addition to elevation in osteoclasts number and deceased osteoblasts and thickness of trabecular bone in the (ovx) group compared to the sham, while treatment with rosuvastatin caused a significant reduction in osteocalcin, (NTx), calcium and phosphorus after 60 days. Also, the results revealed a significant reduction in the percentage of (Ca, P and Mg) content in bone ash of the (ovx) group compared to the sham group. However, rosuvastatin treatment led to a significant elevation in the percentage of calcium and inorganic phosphate in bone ash and increased the thickness of trabecular bone and development in osteocytes compared with ovariectomized rats. The conclusion of the present study, rosuvastatin has a positive effect on the bone of ovariectomized rats.

Statin use improves the prognosis of ovarian cancer: An updated and comprehensive meta-analysis.

Statins are lipid-lowering agents that have also been found to have anticancer effects. The relationship between statin use and clinical outcomes in ovarian cancer (OC) remains controversial, as previous assessments of the relationship between statin use and OC prognosis have yielded inconsistent results. Therefore, a comprehensive meta-analysis was performed in the present study to investigate this association. Studies were systematically retrieved by searching the PubMed, Embase and Cochrane Library databases, and consulting reference lists of the related studies. The search timeframe was from database creation to September 1, 2022. Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to assess the association. In the present meta-analysis, 16 studies with 37,660 patients with OC were included, of which 11,296 patients had been prescribed statins. The results showed that statin use markedly improved the overall survival time (OS; HR, 0.79; 95% CI, 0.73-0.85; P<0.00001) and OC-specific survival time (HR, 0.84; 95% CI, 0.80-0.89; P<0.00001), especially the OS time in patients with serous OC (HR, 0.81; 95% CI, 0.74-0.89; P<0.0001) and endometrioid OC (HR, 0.80; 95% CI, 0.66-0.98; P=0.03). In addition, survival rate was higher in patients who used statins after OC diagnosis (HR, 0.79; 95% CI, 0.73-0.85; P<0.00001). However, there was no statistically significant association between statin use and the prognosis of mucinous and clear cell OC. The results suggested that statin use markedly improved the OS in patients with OC, including in those with serous and endometrioid OC. Statins were also found to improve the prognosis of patients of both Asian and non-Asian ethnicities. In addition, both lipophilic and hydrophilic statins improved the survival in patients with OC, especially in patients using statins after OC diagnosis. However, the effect may vary depending on the statin type, duration of use and cancer type, and more well-designed studies are needed to further evaluate this.

Abstract 14966: Mechanisms of Protection From Radiation-Induced Endothelial Injury by Statins

Introduction: The incidental use of statins during radiation therapy has been associated with a decreased risk of long-term atherosclerotic cardiovascular (CV) disease. However, the mechanisms by which statins protect the vasculature from irradiation injury remain poorly understood. Hypothesis: Establish the mechanisms by which lipophilic and hydrophilic statins preserve endothelial function after irradiation. Methods: Cultured human coronary and umbilical vein endothelial cells irradiated with 4 Gy and mice on day 1 and 10 after head and neck irradiation with 12 Gy were assessed for endothelial dysfunction, nitric oxide and reactive oxidative stress production and various mitochondrial phenotypes. Results: Pretreatment of mice with pravastatin or atorvastatin prevented the loss of endothelium-dependent relaxation on day 1 and 10 after head and neck irradiation. Both statins inhibit the loss of nitric oxide, and the increase in cytosolic reactive oxidative stress in endothelial cells. However, only pravastatin blocked mitochondrial superoxide production, mitochondrial DNA damage and loss of electron complex activity. In contrast to atorvastatin, pravastatin also significantly reduced the expression of inflammatory markers TNF-α, NFκB p65 and p50 after irradiation. Conclusions: Our findings provide mechanistic underpinnings for the vasoprotective effects of statins after irradiation. While lipo- and hydrophilic statins shield from endothelial dysfunction after irradiation, pravastatin also prevents mitochondrial injury and decreases an inflammatory response by actions in mitochondria. A correlation with clinical studies is necessary to determine whether hydrophilic statins, such as pravastatin reduce the risk of CV disease after irradiation in humans to a greater extent than lipophilic statins.

Association of venous thromboembolism between hydrophilic and lipophilic statin users among diabetic subjects: Erratum.

Association of venous thromboembolism between hydrophilic and lipophilic statin users among diabetic subjects: Erratum.

Association of venous thromboembolism between hydrophilic and lipophilic statin users among diabetic subjects.

This retrospective analysis aimed to compare the risk of venous thromboembolism (VTE) between patients with diabetes mellitus who received hydrophilic statin treatment to those who receive lipophilic statin. There were 6639 patients receiving hydrophilic statin therapy and 10,854 patients receiving lipophilic statin therapy in the study. The hazard ratios and 95% confidence intervals for VTE were estimated using univariate and multivariate Cox proportional hazards models when the study cohorts were compared. Among all patients, the incidence rate of VTE was 4.27 per 1000 person-years in the control cohort, 4.18 per 1000 person-years in the hydrophilic statin use cohort, and 3.91 per 1000 person-years in the lipophilic statin use cohort. After adjusting for age, sex, and comorbidities, the risk of VTE in the hydrophilic statin use cohort was 0.90 (0.72, 1.12) lower than that in the control cohort, the risk of VTE in the lipophilic statin use cohort was 0.87 (0.72, 1.05) lower than that in the control cohort, and the risk of VTE in the lipophilic statin use cohort was 0.97 (0.78, 1.21) lower than that in the hydrophilic statin use cohort. However, all were not statistically significant. Our result showed that there was no significant difference among the study cohorts regarding the outcome of VTE.

Detection of statin-induced rhabdomyolysis and muscular related adverse events through data mining technique

Background and objectiveRhabdomyolysis (RM) is a life-threatening adverse drug reaction in which statins are the one commonly related to RM. The study aimed to explore the association between statin used and RM or other muscular related adverse events. In addition, drug interaction with statins were also assessed.MethodsAll extracted prescriptions were grouped as lipophilic and hydrophilic statins. RM outcome was identified by electronically screening and later ascertaining by chart review. The study proposed 4 models, i.e., logistic regression (LR), Bayesian network (BN), random forests (RF), and extreme gradient boosting (XGBoost). Features were selected using multiple processes, i.e., bootstrapping, expert opinions, and univariate analysis.ResultsA total of 939 patients who used statins were identified consisting 15, 9, and 19 per 10,000 persons for overall outcome prevalence, using statin alone, and co-administrations, respectively. Common statins were simvastatin, atorvastatin, and rosuvastatin. The proposed models had high sensitivity, i.e., 0.85, 0.90, 0.95 and 0.95 for LR, BN, RF, and XGBoost, respectively. The area under the receiver operating characteristic was significantly higher in LR than BN, i.e., 0.80 (0.79, 0.81) and 0.73 (0.72, 0.74), but a little lower than the RF [0.817 (95% CI 0.811, 0.824)] and XGBoost [0.819 (95% CI 0.812, 0.825)]. The LR model indicated that a combination of high-dose lipophilic statin, clarithromycin, and antifungals was 16.22 (1.78, 148.23) times higher odds of RM than taking high-dose lipophilic statin alone.ConclusionsThe study suggested that statin uses may have drug interactions with others including clarithromycin and antifungal drugs in inducing RM. A prospective evaluation of the model should be further assessed with well planned data monitoring. Applying LR in hospital system might be useful in warning drug interaction during prescribing.

In Vitro Evidence of Statins' Protective Role against COVID-19 Hallmarks.

Despite the progressions in COVID-19 understanding, the optimization of patient-specific therapies remains a challenge. Statins, the most widely prescribed lipid-lowering drugs, received considerable attention due to their pleiotropic effects, encompassing lipid metabolism control and immunomodulatory and anti-thrombotic effects. In COVID-19 patients, statins improve clinical outcomes, reducing Intensive Care Unit admission, the onset of ARDS, and in-hospital death. However, the safety of statins in COVID-19 patients has been debated, mainly for statins’ ability to induce the expression of the ACE2 receptor, the main entry route of SARS-CoV-2. Unfortunately, the dynamic of statins’ mechanism in COVID-19 disease and prevention remains elusive. Using different in vitro models expressing different levels of ACE2 receptor, we investigated the role of lipophilic and hydrophilic statins on ACE2 receptor expression and subcellular localization. We demonstrated that the statin-mediated increase of ACE2 receptor expression does not necessarily coincide with its localization in lipid rafts domains, particularly after treatments with the lipophilic atorvastatin that disrupt lipid rafts’ integrity. Through a proteomic array, we analyzed the cytokine patterns demonstrating that statins inhibit the release of cytokines and factors involved in mild to severe COVID-19 cases. The results obtained provide additional information to dissect the mechanism underlying the protective effects of statin use in COVID-19.

Statin Prescription Patterns and Associations with Subclinical Inflammation.

Background and Objectives: Statins have been extensively utilised in atherosclerotic cardiovascular disease (ASCVD) prevention and can inhibit inflammation. However, the association between statin therapy, subclinical inflammation and associated health outcomes is poorly understood in the primary care setting. Materials and Methods: Primary care electronic health record (EHR) data from the electronic Practice-Based Research Network (ePBRN) from 2012–2019 was used to assess statin usage and adherence in South-Western Sydney (SWS), Australia. Independent determinants of elevated C-reactive protein (CRP) were determined. The relationship between baseline CRP levels and hospitalisation rates at 12 months was investigated. Results: The prevalence of lipid-lowering medications was 14.0% in all adults and 44.6% in the elderly (≥65 years). The prevalence increased from 2012 to 2019 despite a drop in statin use between 2013–2015. A total of 55% of individuals had good adherence (>80%). Hydrophilic statin use and higher intensity statin therapy were associated with elevated CRP levels. However, elevated CRP levels were not associated with all-cause or ASCVD hospitalisations after adjusting for confounders. Conclusions: The prevalence and adherence patterns associated with lipid-lowering medications highlighted the elevated ASCVD-related burden in the SWS population, especially when compared with the Australian general population. Patients in SWS may benefit from enhanced screening protocols, targeted health literacy and promotion campaigns, and timely incorporation of evidence into ASCVD clinical guidelines. This study, which used EHR data, did not support the use of CRP as an independent marker of future short-term hospitalisations.

Effect of Pravastatin and Simvastatin on the Reduction of Cytochrome C.

Statins are used to treat hypercholesterolemia, with several pleiotropic effects. Alongside their positive effects (for example, decreasing blood pressure), they can also bring about negative effects/symptoms (such as myopathy). Their main mechanism of action is inducing apoptosis, the key step being the release of cytochrome c from the mitochondria. This can be facilitated by oxidative stress, through which glutathione is oxidized. In this research, glutathione was used as a respiratory substrate to measure the mitochondrial oxygen consumption of rat liver with an O2 electrode. The reduction of cytochrome c was monitored photometrically. Hydrophilic (pravastatin) and lipophilic (simvastatin) statins were used for the measurements. Pravastatin reduces the reduction of cytochrome c and the oxygen consumption of the mitochondria, while simvastatin, on the other hand, increases the reduction of cytochrome c and the mitochondrial oxygen consumption. The results make it seem probable that statins influence the mitochondrial oxygen consumption through cytochrome c. Simvastatin could enhance the oxidizing capacity of free cytochrome c, thereby increasing oxidative stress and thus facilitating apoptosis. The observed effects could further the understanding of the mechanism of action of statins and thereby aid in constructing optimal statin therapy for every patient.

Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature.

Lipophilic but not hydrophilic statins have been shown to be associated with reduced risk for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. We investigated differential actions of lipophilic and hydrophilic statins and their ability to modulate a clinical prognostic liver signature (PLS) predicting HCC risk in patients with liver disease. Hepatitis C virus (HCV)–infected Huh7.5.1 cells, recently developed as a model to screen HCC chemopreventive agents, were treated with lipophilic statins (atorvastatin and simvastatin) and hydrophilic statins (rosuvastatin and pravastatin), and then analyzed by RNA sequencing and PLS. Lipophilic statins, particularly atorvastatin, more significantly suppressed the HCV‐induced high‐risk pattern of PLS and genes in YAP and AKT pathway implicated in fibrogenesis and carcinogenesis, compared with the hydrophilic statins. While atorvastatin inhibited YAP activation through the mevalonate pathway, the distinctive AKT inhibition of atorvastatin was mediated by stabilizing truncated retinoid X receptor alpha, which has been known to enhance AKT activation, representing a target for HCC chemoprevention. In addition, atorvastatin modulated the high‐risk PLS in an in vitro model of nonalcoholic fatty liver disease (NAFLD). Conclusion: Atorvastatin distinctively inhibits YAP and AKT activation, which are biologically implicated in HCC development, and attenuates a high‐risk PLS in an in vitro model of HCV infection and NAFLD. These findings suggest that atorvastatin is the most potent statin to reduce HCC risk in patients with viral and metabolic liver diseases.

Statins associate with lower risk of biliary tract cancers: A systematic review and meta-analysis.

Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs. PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random-effects model. Eight observational studies (3 cohort and 5 case-control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0-71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51-0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38-0.94) and GBC was 0.78 (95% CI: 0.68-0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66-1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69-0.88) and 0.70 (95% CI: 0.61-0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non-steroidal anti-inflammatory drugs (aRR: 0.80, 95% CI: 0.72-0.89) and metformin (aRR: 0.80, 95% CI: 0.72-0.90). Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC.

Hydrophilic Versus Lipophilic Statin Treatments in Patients With Renal Impairment After Acute Myocardial Infarction.

BackgroundHydrophilic and lipophilic statins have similar efficacies in treating coronary artery disease. However, specific factors relevant to renal impairment and different arterial pathogeneses could modify the clinical effects of statin lipophilicity, and create differences in protective effects between statin types in patients with renal impairment.Methods and ResultsA total of 2062 patients with acute myocardial infarction with an estimated glomerular filtration rate <60 mL/min per 1.73 m2 were enrolled from the Korea Acute Myocardial Infarction Registry between November 2011 and December 2015. The primary end point was a composite of 2‐year major adverse cardiac and cerebrovascular events (MACEs) after acute myocardial infarction occurrence. MACEs were defined as all‐cause death, recurrent myocardial infarction, revascularization, and stroke. Propensity‐score matching and Cox proportional hazards regression were performed. A total of 529 patients treated with hydrophilic statins were matched to 529 patients treated with lipophilic statins. There was no difference in the statin equivalent dose between the 2 statin groups. The cumulative event rate of MACEs, all‐cause mortality, and recurrent myocardial infarction were significantly lower in patients treated with hydrophilic statins in the propensity‐score matched population (all P<0.05). In the multivariable Cox regression analysis, patients treated with hydrophilic statins had a lower risk for composite MACEs (hazard ratio [HR], 0.70 [95% CI, 0.55–0.90]), all‐cause mortality (HR, 0.67 [95% CI, 0.49–0.93]), and recurrent myocardial infarction (HR, 0.40 [95% CI, 0.21–0.73]), but not for revascularization and ischemic stroke.ConclusionsHydrophilic statin treatment was associated with lower risk of MACEs and all‐cause mortality than lipophilic statin in a propensity‐score matched observational cohort of patients with renal impairment following acute myocardial infarction.

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008-2018.

Background Despite early goal-directed therapy, sepsis mortality remains high. Statins exhibit pleiotropic effects. Objective We sought to compare mortality outcomes among statin users versus nonusers who were hospitalized with sepsis. Methods Retrospective cohort study of patients (age ≥18 years) during 1/1/2008–9/30/2018. Mortality was compared between statin users and nonusers and within statin users (hydrophilic versus lipophilic, fungal versus synthetic derivation, and individual statins head-to-head). Multivariable Cox regression models were used to estimate hazard ratios (HR) for 30-day and 90-day mortality. Inverse probability treatment weighting (IPTW) analysis was performed to account for indication bias. Results Among 128,161 sepsis patients, 34,088 (26.6%) were prescribed statin drugs prior to admission. Statin users compared to nonusers had a 30-day and 90-day mortality HR (95% CI) of 0.80 (0.77–0.83) and 0.79 (0.77–0.81), respectively. Synthetic derived statin users compared to fungal derived users had a 30- and 90-day mortality HR (95% CI) of 0.86 (0.81–0.91) and 0.85 (0.81–0.89), respectively. Hydrophilic statin users compared to lipophilic users had a 30-day and 90-day mortality HR (95% CI) of 0.90 (0.81–1.01) and 0.86 (0.78–0.94), respectively. Compared to simvastatin, 30-day mortality HRs (95% CI) were 0.85 (0.66–1.10), 0.87 (0.82–0.92), 0.87 (0.76–0.98), and 1.22 (1.10–1.36) for rosuvastatin, atorvastatin, pravastatin, and lovastatin, respectively. Conclusion Statin use was associated with lower mortality in patients hospitalized with sepsis. Hydrophilic and synthetic statins were associated with better outcomes than lipophilic and fungal-based preparations.

Parkinson's Disease Progression and Statins: Hydrophobicity Matters.

Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson's disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance. Investigate a potential effect of statins on PD progression. Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participating in the PD Biomarker Program (PDBP, 2012-2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) of patients in the "on" drug state. R2* values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions. Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2* (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= -7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2* did not reach statistical significance (β= 2.5, p = 0.24). This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.

Incident Rheumatoid Arthritis Following Statin Use: From the View of a National Cohort Study in Korea.

Safety issues regarding the potential risk of statins and incident rheumatoid arthritis (RA) have been raised, but the existing data are largely based on Caucasian populations, and continue to have biases and require further validation in Asian populations. Here, we aimed to verify the risk of RA depending on the duration of previous statin use and statin types using a large-scale, nationwide database. This study enrolled 3149 patients with RA and 12,596 matched non-RA participants from the national health insurance database (2002–2015), and investigated their statin prescription histories for two years before the index date. Propensity score overlap-weighted logistic regression was applied after adjusting for multiple covariates. The prior use of any statins and, specifically, the long-term use of lipophilic statins (>365 days) were related to a lower likelihood of developing RA ((odds ratio (OR) = 0.73; 95% confidence intervals (CI) = 0.63–0.85, p < 0.001) and (OR = 0.71; 95% CI = 0.61–0.84, p < 0.001), respectively). Subgroup analyses supported these preventive effects on RA in those with dyslipidemia, independent of sex, age, smoking, alcohol use, hypertension, and hyperglycemia. Hydrophilic statin use or short-term use showed no such associations. Our study suggests that prior statin use, especially long-term lipophilic statin use, appears to confer preventive benefits against RA.

The Influence of Prior Statin Use on the Prevalence and Exacerbation of Chronic Obstructive Pulmonary Disease in an Adult Population.

BackgroundStatins have anti-inflammatory and antioxidant properties, and previous studies have reported the positive effects of statins on chronic obstructive pulmonary disease (COPD) outcomes. However, the effects of statins on the development and acute exacerbations of COPD remain unclear. Therefore, this study aimed to assess the relation between statin use and COPD occurrence in all participants and the link between statin use and COPD acute exacerbations in participants with COPD.MethodsThis case-control study comprised 26,875 COPD participants and 107,500 control participants who were 1:4 matched from the Korean National Health Insurance Service-Health Screening Cohort. Conditional logistic regression was used to evaluate the probability of COPD occurrence associated with previous statin use. In addition, unconditional logistic regression was employed to assess the risk of exacerbations related to statin use among COPD participants. These relations were estimated in subgroup analysis according to statin type (lipophilic vs. hydrophilic).ResultsThe association between previous statin use and the occurrence of COPD did not reach statistical significance in the overall population (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI] = 0.93–1.00, P = 0.059). However, statin use decreased the probability of exacerbations in participants with COPD (aOR = 0.79, 95% CI = 0.74–0.85, P < 0.001). Lipophilic statins decreased the probability of exacerbations, whereas hydrophilic statins were not associated with a decreased likelihood of exacerbations (aOR = 0.78, 95% CI = 0.72–0.84, P < 0.001 for lipophilic statins; aOR = 0.89, 95% CI = 0.78–1.02, P = 0.102 for hydrophilic statins).DiscussionStatin use was not associated with the occurrence of COPD in the adult population. However, statin use was associated with a reduced probability of exacerbations in participants with COPD, with a greater risk reduction with lipophilic statin use.

Effect of concomitant statin treatment in postmenopausal patients with hormone receptor-positive early-stage breast cancer receiving adjuvant denosumab or placebo: a post hoc analysis of ABCSG-18

BackgroundStatins are cholesterol-lowering drugs prescribed for the prevention and treatment of cardiovascular disease. Moreover, statins may possess anticancer properties and interact with receptor activator of nuclear factor κB ligand expression. We aimed at evaluating a hypothetical synergistic effect of statins with denosumab in early-stage breast cancer (BC) patients from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 18.Patients and methodsABCSG-18 (NCT00556374) is a prospective, randomized, double-blind, phase III study; postmenopausal patients with hormone receptor-positive BC receiving a nonsteroidal aromatase inhibitor were randomly assigned to denosumab or placebo. In this post hoc analysis, we investigated the effects of concomitant statin therapy on recurrence risk (RR) of BC, fracture risk and bone mineral density (BMD).ResultsIn the study population (n = 3420), statin therapy (n = 824) was associated with worse disease-free survival (DFS) [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.04-1.75; P = 0.023]. While no significant effect of lipophilic statins (n = 710) on RR was observed (HR 1.30, 95% CI 0.99-1.72; P = 0.062), patients on hydrophilic statins (n = 87) had worse DFS compared with patients not receiving any statins (HR 2.00, 95% CI 1.09-3.66; P = 0.026). This finding was mainly driven by the effect of hydrophilic statins on DFS in the denosumab arm (HR 2.63, 95% CI 1.21-5.68; P = 0.014). However, this effect subsided after correction for confounders in the sensitivity analysis. No association between statin use and fracture risk or osteoporosis was observed.ConclusionAccording to this analysis, hydrophilic statins showed a detrimental effect on DFS in the main model, which was attenuated after correction for confounders. Our data need to be interpreted with caution due to their retrospective nature and the low number of patients receiving hydrophilic statins.