Beneficial Effects Of Statins Research Articles

Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials.

Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, I2 = 68.5%). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL-6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL-6. However, statins reduced serum levels of TNF-α in patients with kidney disease.

Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study

The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association between statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC. A nationwide cohort study was performed with data from the National Health Insurance Service Database in Korea. Among 65,101 HCC patients who underwent hepatic resection between January 2002 and December 2017, we included 21,470 patients. For validation, a hospital-based cohort of 3366 patients with very early or early-stage HCC who received curative-intent hepatic resection between January 2010 and December 2018 was analyzed. Recurrence-free survival (RFS) and overall survival (OS) was compared between statin users and non-users. Among the nationwide cohort of 21,470 patients, 2399 (11.2%) used statins and 19,071 (88.8%) did not. Among the hospital cohort of 3366 patients, 363 (10.8%) used statins and 3003 (89.2%) did not. In the propensity score-matched nationwide cohort, statin users had better RFS (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.56-0.64; P<0.001) and OS (HR, 0.49; 95% CI, 0.45-0.53; P<0.001), with a duration-response relationship. In the propensity score-matched validation hospital cohort, statin treatment was significantly associated with better RFS (HR, 0.73; 95% CI, 0.59-0.90; P=0.003) and OS (HR, 0.48; 95% CI, 0.32-0.72; P<0.001). The beneficial effects of statins were more prominent in non-cirrhotics, tumors sized ≥3cm, tumors with microscopic vascular invasion, or early HCC recurrence (<2 years after resection). Statin use was associated with a better prognosis in a population-based cohort of patients with HCC after hepatic resection, which was further validated in a large hospital-based cohort. Asan Institute for Life Sciences and Corporate Relations; Korean Association for the Study of the Liver.

Differential Pharmacokinetic Interplay of Atorvastatin on Lacosamide and Levetiracetam on Experimental Convulsions in Mice.

The beneficial effects of statins, other than their hypocholesterolemia role, have been well documented, however, their use as an adjuvant drug with other antiseizure drugs, in the treatment of epilepsy is poorly understood. This study aimed to investigate the symbiotic effect of ATOR along with either lacosamide (LACO) or levetiracetam (LEVE) on experimentally induced epilepsy (Maximal electro-shock-MES or pentylenetetrazol- PTZ) in mice models. Conventional elevated-maze (EPM) and rotarod methods were performed to observe the behavioral effects. In both the animal models, we found that co-administration of ATOR along with LACO showed a significant reduction in hind-limb extension (HLE) and clonic convulsion (CC) responses, respectively, but not in the ATOR+LEVE treated group. Intriguingly, comparable Straub tail response and myoclonic convulsion as the diazepam (DIA) group were observed only in the ATOR+LACO treated group. Moreover, a significant muscle-grip strength was observed in both groups. Also, pharmacokinetic analysis has indicated that the mean plasma concentration of ATOR peaked at 2ndhr in the presence of LACO but marginally peaked in the presence of LEVE. An Insilico study has revealed that ATOR has a higher binding affinity toward neuronal sodium channels. This study has demonstrated that the plasma concentration of ATOR was potentiated in the presence of LACO, but not in the presence of LEVE and it has provided significant protection against both the electro and chemo-convulsive models in mice. This could be due to the symbiotic pharmacokinetic interplay of ATOR with LACO, and possibly, this interplay may interfere with sodium channel conductance.

Statins as preventive therapy for anthracycline cardiotoxicity: a meta-analysis of randomized controlled trials

BackgroundCardiotoxicity occurs in 5–20% of cancer patients who receive anthracyclines. The aim of this study was to pool all the randomized controlled trials (RCTs) investigating the cardio-protective role of statins in patients treated with anthracyclines. MethodsPubMed and Scopus electronic databases were scanned for eligible studies up to May 3rd, 2023. A total of 5 RCTs with 808 patients were included. Efficacy endpoints were the rate of anthracycline-mediated cardiotoxicity, the incidence of hospitalization for heart failure (HF), left ventricular ejection fraction (LVEF) value after anthracycline treatment, and ∆LVEF calculated as the difference in LVEF before and after anthracycline therapy. Safety endpoints [i.e., the incidence of muscle pain and serious adverse events (SAE)] were also assessed. ResultsOn pooled analysis, the statin-treated group had a lower incidence of cardiotoxicity compared to the placebo group [risk ratio (RR) 0.52, 95% confidence Interval (CI) 0.33–0.83, P = 0.01; I2 = 0%], as well as higher mean LVEF [Mean difference (MD) 1.88, 95% CI 0.66–3.1, P < 0.01; I2 = 57.3%)] and a more favorable ∆LVEF during follow-up (MD 2.38, 95% CI -0.03 – +4.79, P = 0.05; I2 = 99%), despite no significant difference in terms of hospitalization for HF and rate of adverse events. Of note, severe heterogeneity affected the analyses for both LVEF and ΔLVEF. ConclusionsThe current meta-analysis of all RCTs conducted so far shows an overall beneficial effect of statins on the risk of anthracyclines-induced cardiotoxicity and LVEF preservation. No difference was observed in the rate of HF hospitalization. More powered RCTs are needed to fully investigate the impact of statins on prognosis in patients receiving anthracyclines therapy.

Beneficial Effect of Statins in Chronic Kidney Disease

Beneficial Effect of Statins in Chronic Kidney Disease

Beneficial effects of statins on adropin level in patients with arterial hypertension

Introduction. Adropin is a new secretory hormone that takes part in the regulation of energy homeostasis. Hormone is known to have positive effects on endothelial cell proliferation and prevention of atherosclerosis, and low adropin level may be a risk factor and potential predictor of atherosclerosis. Arterial hypertension (AH), which remains one of the most common somatic pathologies among middle-aged and older people, plays an important role in predicting cardiovascular morbidity and mortality. A number of medications that are used as antihypertensive therapy contribute to an increase in the content of adropin. At the same time there are not enough studies on the effect of statins on the content of adropin.&#x0D; Aim of the study.To investigate the effects of statins on adropin level in patients with AH.&#x0D; Material and methods. 70 patients with hypertension aged 62,1 ± 9,9 years were examined. They were divided into 2 groups: 1 group – patients with AH, overweight and obesity who did not take statins (n=40); group 2 – persons with AH, overweight and obesity who took statins (n=30). All individuals underwent determination of basic indicators of biochemical blood analysis, lipid profile (total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), atherogenicity ratio). The level of adropin was determined by enzyme immunoassay (Finetest Elisa Kit) in blood serum.&#x0D; Results. Systolic blood pressure (BP) was significantly higher in group 1 individuals (p&lt;0.05), while diastolic BP remained unchanged (p&gt;0.05). Among patients who took statins, a significantly lower level of TC, LDL, atherogenicity ratio (p&lt;0.01), HDL (p&lt;0.05) was found, while the level of TG remained unchanged.&#x0D; Taking statins and achieving the target level of LDL improves the prognosis of patients with cardiovascular pathology, as evidenced by a significant increase in the content of adropin in blood serum in patients of the 2nd group. In women who took statins, a direct correlation was found between the level of adropin and HDL (r=0.609; p&lt;0.05).&#x0D; Conclusions. Taking statins is associated with significantly higher levels of adropin in patients with AH compared to individuals who did not take these drugs. A direct correlation was noted between the level of adropin and HDL in women who took statins. Statins effectively reduce atherogenic fractions of cholesterol and help to increase the concentration of adropin in blood serum.

Cardiotoxicity as a Possible Side Effect of Statins.

According to current views, statins have a wide range of beneficial effects (lipid and non-lipid) on the cardiovascular system, so they are one of the most commonly used drugs for the prevention and management of patients with cardiovascular diseases. However, it is important to note that information about many beneficial effects of statins is contradictory. In addition, a number of side effects of statins, in particular, myotoxicity, hepatotoxicity, diabetogenic property, etc., may limit the possibility of using statins or even force doctors to cancel these drugs. Also, some concerns are caused by recent studies reporting cardiotoxicity of statins and increased serum concentrations of biomarkers of myocardial damage (highly sensitive cardiac troponins (hs-cTns)) in patients taking statins. This article discusses in detail the possible mechanisms of cardiotoxicity of statins and outlines the directions for further research in this area.

Beneficial Effects of Statins on Seizures Independent of Their Lipid-Lowering Effect: A Narrative Review.

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin's mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders.

Statins and the Risk of Gastric Cancer: A Systematic Review and Meta-Analysis.

Previous epidemiological studies have reported that the use of statins is associated with a decreased risk of gastric cancer, although the beneficial effects of statins on the reduction of gastric cancer remain unclear. Therefore, we conducted a systematic review and meta-analysis to investigate the association between the use of statins and the risk of gastric cancer. Electronic databases such as PubMed, EMBASE, Scopus, and Web of Science were searched between 1 January 2000 and 31 August 2022. Two authors used predefined selection criteria to independently screen all titles, abstracts, and potential full texts. Observational studies (cohort and case-control) or randomized control trials that assessed the association between statins and gastric cancer were included in the primary and secondary analyses. The pooled effect sizes were calculated using the random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed to conduct this study. The total sample size across the 20 included studies was 11,870,553. The use of statins was associated with a reduced risk of gastric cancer (RRadjusted: 0.72; 95%CI: 0.64−0.81, p < 0.001). However, the effect size of statin use on the risk of gastric cancer was lower in Asian studies compared to Western studies (RRAsian: 0.62; 95%CI: 0.53−0.73 vs. RRwestern: 0.88; 95%CI: 0.79−0.99). These findings suggest that the use of statins is associated with a reduced risk of gastric cancer. This reverse association was even stronger among Asian people than Western individuals.

Statins as Repurposed Drugs in Gynecological Cancer: A Review.

Discovering new drugs is an expensive and time-consuming process, including target identification, bioavailability, pharmacokinetic (PK) tests, pharmacodynamic (PD) tests, toxicity profiles, recommended dosage test, and observation of the side effects, etc. Repurposed drugs could bypass some steps, starting from phase II trials, and shorten the processes. Statins, also known as HMG-CoA inhibitors (HMGCR), are commonly used to manage and prevent various cardiovascular diseases and have been shown to improve the morbidity and mortality of patients. In addition to the inhibitory effects on the production of cholesterol, the beneficial effects of statins on the prognosis and risk of various cancers are also shown. Statins not only inhibited cell proliferation, metastasis, and chemoresistance but affected the tumor microenvironment (TME). Thus, statins have great potential to be repurposed in oncology. Hence, we review the meta-analysis, cohort, and case-control studies of statins in gynecological cancers, and elucidate how statins regulate cell proliferation, apoptosis, tumor growth, and metastasis. Although the results in gynecological cancers remain controversial and the effects of different statins in different histotypes of gynecological cancers and TME are needed to elucidate further, statins are excellent candidates and worthy of being repurposed drugs in treating gynecological cancers.

*Effects of Icosapent Ethyl on Plasma Ceramides and Coronary Plaque Progression in EVAPORATE trial

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synops Despite the beneficial effects of statins on progression of coronary atherosclerosis, significant cardiovascular (CV) risk persists in patients with residual hypertriglyceridemia. REDUCE-IT demonstrated that Icosapent ethyl (IPE) added to statins significantly reduced adverse CV outcomes in these patients. The EVAPORATE trial showed a significant reduction in coronary plaque progression in the IPE arm, offering mechanistic insights to the CV benefits of IPE. Circulating ceramide (CER) levels and CER ratios are important predictors of coronary plaque instability, progression, and adverse CV risk. Objective/Purpose We sought to compare the effect of IPE vs placebo on ceramide scores and ratios in participants enrolled in EVAPORATE trial. We further assessed correlations between CER levels and changes in coronary plaque burden and characteristics. Methods EVAPORATE is a randomized, placebo-controlled trial, using CCTA to evaluate the effects of IPE as an adjunct to statins on coronary plaque progression in a cohort with elevated triglycerides, over 18 months. A total of 63 participants from the EVAPORATE trial were included. Changes in serum levels of CER species, ratios, and scores were compared between patients receiving IPE vs placebo. Spearman's correlation was used to examine association of ceramide scores and changes in coronary plaque volumes. Results CER ratios and scores were similar between the groups at baseline. In the IPE group, the CER score was 4.27 (SD 3.02) at baseline and was 4.00 (SD 3.05) at follow-up (p=0.55). At 18 month follow-up, there was a significant increase in CER ratios, CER 16:0/24:0 and CER 18:0/24:0, in the placebo group (p=0.0018; p=0.0076, respectively), compared to no significant change in the IPE group (p=0.85; p=0.37, respectively). Changes in CER score did not correlate with changes in total plaque volumes in either group (IPE (r=0.326), placebo (r=-0.295) (p>0.05). Conclusions There were significant differences in the CER ratios in the IPE arm vs placebo arm in the EVAPORATE trial, as well as a trend to lowered CER score in the IPE group. Future studies are warranted to further characterize correlations of IPE and CER. Nothing to disclose.

Statins reduce mortality of patients with myelodysplastic syndromes.

e19063 Background: Statins can inhibit cholesterol synthesis through inhibition of mevalonic acid synthesis, and reduce prenylation of proteins involved in tumor growth. Their anti-neoplastic potential has been explored for many malignancies (e.g., multiple myeloma) with improvement in progression free- and overall- survival. Preclinical data support anti-neoplastic activity of statins for myeloid malignancies. In this study, we examined the effect of statins on mortality of patients with myelodysplastic syndromes (MDS) in this nationwide retrospective cohort study. Methods: We identified patients diagnosed with MDS through ICD-O-03 codes in the SEER-Medicare database between 2007 and 2017. Statins users were required to have at least one claim for a statin prescription within 6 months prior to MDS diagnosis. Propensity score matching was done to identify non-statin users with a similar cardiovascular risk profile. We analyzed the effect of statins on mortality (from any cause) in a Cox proportional hazards model that adjusted for demographics, SEER-Medicare MDS Risk Score ( SMMRS comprises of age, comorbidities, MDS histological subtype, cytopenias, transfusion-dependence and hospital admissions), treatments for lower risk MDS (growth factors or lenalidomide), and higher risk MDS (hypomethylating agents/stem cell transplant). Results: Our cohort of 6878 MDS patients (3439 statin users and 3439 non-statin users) had a median age of 80 years at diagnosis, and most were Caucasians. Non-statin users were more likely to have higher risk MDS (by SMMRS) at diagnosis. Statins users had a 33% {95% Confidence Interval (CI) 25%-40%; p &lt;.001} lower risk of death than non-statin users. The beneficial effect of statins on mortality diminished over time (Table). Sub-group analysis (data not shown) showed a significant reduction in mortality with statin use in both patients with lower risk {low or intermediate-1 risk: Adjusted hazards ratio (aHR) 0.72; 95% CI 0.58-0.90; p = 0.003)} and higher risk {intermediate-2 or high-risk: aHR 0.67; 95% CI 0.59-0.76; p &lt; 0.001)} MDS (categorized by SMMRS). Conclusions: Use of statins at time of MDS diagnosis is associated with reduced mortality among these patients. The beneficial effect of statins on death from cardiovascular events and myeloid malignancy should be further explored in clinical trials enrolling MDS patients.[Table: see text]

Statins are associated with a large reduction in all-cause mortality in women from a cardiac outpatient population

ObjectivesUncertainty about the benefit of (high-intensity) statins for women remains due to under-representation of women in primary prevention trials and scarcity of sex-stratified data. This study evaluates the sex-specific relation...

Monotherapy versus combination therapy of statin and renin-angiotensin system inhibitor in ST-segment elevation myocardial infarction.

BackgroundThe beneficial effects of statin and renin–angiotensin system inhibitor (RASI) are well-known. In this retrospective cohort study, 2-year clinical outcomes were compared between monotherapy and combination therapy with statin and RASI in ST-segment elevation myocardial infarction (STEMI) patients after stent implantation.MethodsA total of 17,414 STEMI patients were enrolled and divided into the three groups (group A: 2448 patients, statin alone; group B: 2431 patients, RASI alone; and group C: 12,535 patients, both statin and RASI). The principal clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction, and any repeat revascularization.ResultsAfter adjustment, the cumulative incidences of MACEs in group A (adjusted hazard ratio [aHR] 1.337; 95% confidence interval [CI] 1.064–1.679; p = 0.013) and in group B (aHR 1.375; 95% CI 1.149–1.646; p = 0.001) were significantly higher than in group C. The cumulative incidence of all-cause death in group A was significantly higher than that in group C (aHR 1.539; 95% CI 1.014–2.336; p = 0.043). The cumulative incidences of any repeat revascularization (aHR 1.317; 95% CI 1.031–1.681; p = 0.028), target lesion vascularization, and target vessel vascularization in group B were significantly higher than in group C.ConclusionsA statin and RASI combination therapy significantly reduced the cumulative incidence of MACEs compared with a monotherapy of these drugs. Moreover, the combination therapy showed a reduced all-cause death rate compared with statin monotherapy, and a decreased repeat revascularization rate compared with RASI monotherapy.

Statins enhance the chemosensitivity of R-CHOP in diffuse large B-cell lymphoma

The beneficial effect of statins on the anti-lymphoma activity of the rituximab-based chemotherapy regimen is controversial. Here, we retrospectively reviewed patients with naïve-treated advanced diffuse large B-cell lymphoma (DLBCL) receiving frontline R-CHOP, and for whom data regarding differential statins use was available at the time of initiation of treatment. We observe that patients treated with statins and R-CHOP experienced a significantly higher CR rate as compared to those who received R-CHOP only. We further show that patients receiving medium or high intensity statins and R-CHOP experienced a significantly higher CR as compared to those treated with R-CHOP. Six-year progression free survival was higher for patients who received medium or higher intensity statins as compared to low or no statins. The potential contribution of cholesterol pathway in doxorubicin sensitivity was supported by in vitro/in vivo studies. Our study suggests that targeting cholesterol-using lovastatin could be a therapeutic strategy to enhance responses to R-CHOP in DLBCL patients.

Stratification Analysis of Statin Effect on Major Adverse Cardiac Events After Percutaneous Coronary Intervention in Patients on Hemodialysis.

The statin use in patients on hemodialysis remains controversial, and no beneficial effects of statin on the reduction of adverse cardiovascular events have been reported in these patients. This study used stratification analysis to examine the clinical factors in patients on hemodialysis who could benefit from statin for secondary prevention. This prospective multicenter study included 234 consecutive patients on hemodialysis with coronary artery disease who underwent successful reperfusion therapy with percutaneous coronary intervention. The patients were followed up for up to 3 years or until the occurrence of major adverse cardiac events (MACEs; defined as a composite of all-cause death and nonfatal myocardial infarction). Inverse probability of treatment weighting adjustment was used to remove the selection bias. During the median follow-up period of 30 months, MACEs occurred in 55 patients. Patients with MACEs had significantly lower statin therapy (P < 0.001). Multivariable Cox proportional hazards analysis showed that the patients on statins had a significantly reduced rate of MACE occurrence [adjusted hazard ratio 0.30 (0.11-0.81), P = 0.02]. The stratification analysis of outcomes according to the presence of clinical factors showed that beneficial effects of statin were associated with man, elderly, lower body mass index, lower abdominal circumference, hypertension, diabetes, higher C-reactive protein, symptomatic heart failure, lower left ventricular function, nonacute coronary syndrome, and shorter stent length. Statin was effective for the prevention of MACEs in patients on hemodialysis who underwent percutaneous coronary intervention. We identified specific clinical factors affecting statin effectiveness for secondary prevention.

The protective role of statins in COVID-19 patients: a retrospective observational study

BackgroundTo evaluate and determine the protective role of statins in COVID-19 patients.MethodsThis is a retrospective cohort study conducted across five hospitals in India. Patients diagnosed with COVID-19 and hospitalized with existing and valid medical documentation were included.ResultsThis study comprised 3252 COVID-19 patients, of whom 1048 (32.2%) were on statins, with 52.4% being males. The comorbidity prevalence of hypertension was 75%, followed by diabetes 62.51% and coronary artery disease being 47.5%. At the time of hospitalization, statin users had a higher incidence of dyspnea, cough, and fatigue (95.8, 93.3, and 92.7%). The laboratory results revealed a lower mean of WBC count (7.8 × 103/μL), D-dimer (2.4 μg/mL), and C-reactive protein (103 mg/L) among statin users. They also had lower mortality rates (17.1%), a lesser requirement for mechanical ventilation (20%), and hemodialysis (5.4%).ConclusionThis observation study elaborates on the beneficial effects of statins in COVID-19 patients. However, the inferences from this study should be viewed with caution due to the impending effect of confounding factors on its statistical results.

Abstract P259: Cardiovascular Pharmacotherapy And Covid-19

COVID-19 illness is associated with cardiovascular vulnerabilities at all stages pre-infection, acute phase and subsequent chronic phase. The major cardiometabolic drivers identified to have epidemiological and mechanistic associations with COVID-19 are abnormal adiposity, dysglycaemia, dyslipidaemia, and hypertension. Recent findings demonstrate that cardiovascular risk reduction interventions may have short-term benefits on COVID-19 risk and outcomes. Our aim was to investigate the effect of cardiovascular pharmacotherapy on SARS-CoV-2 infection. Demographic data, cardiovascular disease and other comorbidities, prescription data, discharge outcomes, RT-PCR tests, and investigations were obtained through record linkage for all patients admitted between 01/04/2020 and 31/05/2020 to NHS Greater Glasgow &amp; Clyde hospitals. The relationship between cardiovascular pharmacotherapy (antihypertensives and statins) and SARS-CoV-2 infection was analysed using multivariable logistic regression models. From 218,472 patient records available in Glasgow SafeHaven. 3,610 patients had confirmed COVID-19 based on clinical criteria or a positive RT-PCR test) and 18,050 propensity matched controls were selected. The average age was 62 years, 55% (1,985 of 3,610) females, 43% (1,552 of 3,610) resided in the most deprived areas (SIMD:1). There were 46% (1,660 of 3,610) on antihypertensive therapy and 35% (1,264 of 3,610) were on statin therapy. The risk of SARS-CoV-2 infection was greater in those with cancer, pulmonary or renal disease in the multivariable logistic regression model. Those on antihypertensive or statin therapy had an 11% (O.R.[95% CI]: 0.89 [0.82-0.97], p=0.007) and 9% (0.91 [0.83-0.99], p=0.03) lower risk of SARS-CoV-2 infection, respectively. The protective effect of statins and antihypertensive drugs were apparent only in those on both drug therapies (0.82 [0.74-0.92], p=0.001). Prior treatment with statins and antihypertensive drugs are associated with a lower risk of SARS-CoV-2 infection. The observed beneficial effect of statins and antihypertensives therapy warrants further investigation to address critical gaps in knowledge in prevention, treatment and long term follow up of patients with COVID-19.

A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins.

Background: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. Methods: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. Results: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. Conclusions: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

Post-Diagnostic Statin Use Reduces Mortality in South Korean Patients with Dyslipidemia and Gastrointestinal Cancer.

Background: Statins play a role in lowering serum cholesterol and are known to have pleiotropic effects in a variety of diseases, including cancer. Despite the beneficial effects of statins in dyslipidemia patients, the treatment rate for dyslipidemia in Korea remains low, and evidence supporting the continued use of statins is lacking. The purpose of this study was to evaluate the effect of continued statin use and dosage on patient mortality after diagnosis of dyslipidemia and gastrointestinal (GI) cancer. Methods: We used data from the National Health Insurance Sampling (NHIS) cohort to evaluate patients diagnosed with dyslipidemia from 2002 to 2015. A total of 901 GI cancer patients with dyslipidemia and 62,727 non-cancer dyslipidemia patients were included in the study. During the study period, each patient’s medication possession ratio (MPR) after diagnosis was evaluated as a measure of continued statin use. Statin dosage was measured based on a defined daily dose (DDD). Finally, we used Cox-proportional hazard ratios to identify associations between the continual use of statins and mortality in patients with dyslipidemia and GI cancer. Results: In our study, mortality decreased with increasing MPR and reached significance in MPRs exceeding 50% for GI cancer patients and 75% for dyslipidemia patients compared to patients that did not use statins. Moreover, patients with high MPRs had significantly reduced 5-year mortality compared to non-users, and cause-specific mortality analyses revealed that high MPR was associated with decreased colorectal cancer death. We did not find a significant dose–response relationship between statins and mortality. Conclusion: Our findings suggest that continued statin use after diagnosis is associated with reduced patient mortality. Altogether, these results support the continued use of statins in dyslipidemia patients with and without GI cancer and highlight the importance of patient education by healthcare providers.