Treatment Of Lipid Disorders Research Articles

ANGPTL3 as a target for treating lipid disorders in type 2 diabetes patients

Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder, and cardiovascular disease (CVD) is a significant cause of mortality and morbidity in diabetic individuals. In addition to hyperglycemia, lipid abnormalities associated with T2DM play a crucial role in the development of CVD complications. Diabetic dyslipidemia is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL) particles, reduced high-density lipoprotein (HDL) cholesterol, and impaired HDL function. Angiopoietin protein-like 3 (ANGPTL3) is a liver-derived protein that plays a crucial role in regulating plasma lipoprotein metabolism by inhibiting lipoprotein lipase and influencing lipid levels. Inhibiting ANGPTL3 has shown promising effects in promoting HDL-mediated cholesterol reverse transport and reducing the levels of TG-rich lipoproteins and LDL cholesterol. Here, we explore the potential of ANGPTL3 as a therapeutic target for lipid management in T2DM patients.

The pharmacokinetics of single-dose oral atorvastatin and its metabolites support therapeutic use in cockatiels (Nymphicus hollandicus).

To evaluate the plasma concentrations and determine the pharmacokinetic parameters of atorvastatin and its primary active metabolites (para- and orthohydroxyatorvastatin) after administration of a single oral dose in cockatiels (Nymphicus hollandicus). 14 adult cockatiels (7 male, 7 female) around 2 years of age. A compounded oral suspension of atorvastatin 10 mg/mL made with an oral suspending agent and an oral sweetener was administered via oral gavage at 20 mg/kg to each bird. Blood samples were collected at 7 different time points from 0.5 to 24 hours postadministration in a balanced incomplete block design with 3 blood samples per bird and 6 replicates per time point. Plasma concentrations of atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental analysis. The estimated time to maximum concentration (tmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 3 hours for each. The estimated maximum plasma concentration (Cmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 152.6, 172.4, and 68.8 ng/mL, respectively. The terminal half-lives were 4, 6.8, and 4.6 hours, respectively. These results support the therapeutic use of atorvastatin at the dose evaluated in this species based on human pharmacokinetic data. A starting dose of 20 mg/kg PO every 12 to 24 hours could be used to treat lipid disorders in cockatiels pending more data on multidose use and hypolipidemic efficacy.

Laminaria japonica Aresch-Derived Fucoidan Ameliorates Hyperlipidemia by Upregulating LXRs and Suppressing SREBPs.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and hyperlipidemia is one major inducing factor of CVD. It is worthy to note that fucoidans are reported to have hypolipidemic activity with species specificity; however, the underlying mechanisms of action are far from clarification. This study is aimed at investigating the plasma lipid-lowering mechanisms of the fucoidan from L. japonica Aresch by detecting the levels of hepatic genes that are involved in lipid metabolism. Our results demonstrated that the fucoidan F3 significantly lowered total cholesterol and triglyceride in C57BL/6J mice fed a high-fat diet. In the mouse liver, fucoidan F3 intervention significantly increased the gene expression of peroxisome proliferator-activated receptor (PPAR) α, liver X receptor (LXR) α and β, and ATP-binding cassette transporter (ABC) G1 and G8 and decreased the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, cholesterol 7 alpha-hydroxylase A1, and sterol regulatory element-binding protein (SREBP) 1c and SREBP-2. These results demonstrated that the antihyperlipidemic effects of fucoidan F3 are related to its activation of PPARα and LXR/ABC signaling pathways and inactivation of SREBPs. In conclusion, fucoidan F3 may be explored as a potential compound for prevention or treatment of lipid disorders.

Position paper of the Polish Expert Group on the use of pitavastatin in the treatment of lipid disorders in Poland endorsed by the Polish Lipid Association.

Lipid disorders, primarily hypercholesterolemia, are the most common cardiovascular (CV) risk factor in Poland (this applies even 3/4 of people). The low-density lipoprotein cholesterol (LDL-C) serum level is the basic lipid parameter that should be measured to determine CV risk and determines the aim and target of lipid-lowering treatment (LLT). Lipid-lowering treatment improves cardiovascular prognosis and prolongs life in both primary and secondary cardiovascular prevention. Despite the availability of effective lipid-lowering drugs and solid data on their beneficial effects, the level of LDL-C control is highly insufficient. This is related, among other things, to physician inertia and patients' fear of side effects. The development of lipidology has made drugs available with a good safety profile and enabling personalisation of therapy. Pitavastatin, the third most potent lipid-lowering statin, is characterised by a lower risk of muscle complications and new cases of diabetes due to its being metabolised differently. Thus, pitavastatin is a very good therapeutic option in patients at high risk of diabetes or with existing diabetes, and in patients at cardiovascular risk. This expert opinion paper attempts at recommendation on the place and possibility of using pitavastatin in the treatment of lipid disorders.

Abstract 14777: Effectiveness of Virtual vs Face-to-Face Medical Nutrition Therapy in Patients With Hyperlipidemia

Introduction: Medical nutrition therapy provided by registered dietician nutritionists (RDNs) is an effective therapy for treating lipid disorders. There has been a shift in practice for patients to receive nutrition counseling virtually rather than in-person. Hypothesis: We evaluated whether virtual nutrition visits are as effective as face-to-face (F2F) visits at reducing lipid levels. Methods: We performed an observational study of patients seen by a RDN as part of the University of Michigan Preventive Cardiology lipid management program from 3/31/2019 - 9/31/22. Lipid markers, including total cholesterol (TC), high-density lipoprotein (HDL), and triglycerides (TG) were collected prior to meeting with an RDN and a median of 33 days later. Low-density lipoprotein (LDL) was calculated using the Sampson equation (patients with TG >800 mg/dL were excluded). We used a paired T-test to evaluate the mean difference in lipid marker pre-post visit. Linear regression was used to compare the impact of virtual and F2F nutrition visits. Results: 192 patients were included (41 virtual visits and 151 F2F visits). After a single virtual or F2F visit with an RDN, TC, LDL, and non-HDL decreased (all p-values <0.05, Figure). HDL decreased for F2F visits only. Change in TG was not significant for either group. There were no significant differences between virtual and F2F for changes in mean pre-post visit for any lipid markers (TC p=0.37, LDL p=0.54, non-HDL p=0.29, HDL p=0.72, TG p=0.67). Conclusions: Both virtual and face-to-face RDN visits lead to overall improvement in lipid profiles at post-visit follow-up. Telehealth is an effective way for patients to receive nutrition counseling and may help to overcome barriers in access to treatment for hyperlipidemia.

Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension.

Hypertension characterized by an elevated blood pressure is a cardiovascular disease that afflicts greater than one in every three adults worldwide. Nuclear receptors are large superfamily of DNA-binding transcription factors that target genes to regulate metabolic and cardiovascular function. Drugs have been developed for nuclear receptors such as peroxisome proliferator-activated receptors (PPARα and PPARγ) and farnesoid X receptor (FXR). PPARα, PPARγ, and FXR agonists are used clinically to treat lipid disorders and metabolic diseases. Evidence from clinical studies and animal hypertension models have demonstrated that PPARα, PPARγ, and FXR agonism can lower blood pressure and decrease end organ damage which could be useful for the treatment of hypertension in patients with metabolic diseases. Unfortunately, PPAR and FXR agonists have unwanted clinical side effects. There have been recent developments to limit side effects for PPAR and FXR agonists. Combining PPAR and FXR agonism with soluble epoxide hydrolase (sEH) inhibition or Takeda G protein receptor 5 (TGR5) agonism has been demonstrated in preclinical studies to have actions that would decrease clinical side effects. In addition, these dual modulating drugs have been demonstrated in preclinical studies to have blood pressure lowering, anti-fibrotic, and anti-inflammatory actions. There is now an opportunity to thoroughly test these novel dual modulators in animal models of hypertension associated with metabolic diseases. In particular, these newly developed dual modulating PPAR and FXR drugs could be beneficial for the treatment of metabolic diseases, organ fibrosis, and hypertension.

Angiopoietin-like proteins inhibitors: New horizons in the treatment of atherogenic dyslipidemia and familial hypercholesterolemia.

Angiopoietin-like proteins (ANGPTL) are involved in the regulation of numerous physiological and biochemical processes. ANGPTL3, 4 and 8, which are involved in the regulation of lipoprotein metabolism, are particularly important. ANGPTL3, 4 and 8 have been shown to regulate triglyceride availability depending on the nutritional status of the body. In addition, a deficiency of these proteins has been found to cause hypolipidemia (reduction of all lipid fractions). Increases in ANGPTL3, 4 and 8 appear to be associated with cardiovascular risk. Animal studies indicate that the use of ANGPTL3 (evinacumab) inhibitors significantly reduces plasma total cholesterol, triglycerides and low-density lipoprotein concentrations. The use of evinacumab in clinical trials also led to the normalization of plasma lipid concentrations in patients with atherogenic dyslipidemia and homozygous familial hypercholesterolemia. The results of these studies indicate that evinacumab may in the future be used in the treatment of lipid disorders, especially those with hypertriglyceridemia.

Inclisiran-Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9.

Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve the target LDL-C. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has triggered intensive research on a new class of protein-based drugs. The protein PCSK9 is located mainly in hepatocytes and is involved in the metabolism of LDL-C. In the beginning, antibodies against the PCSK9 protein, such as evolocumab, were invented. The next step was inclisiran. Inclisiran is a small interfering RNA (siRNA) that inhibits the expression of PCSK9 by binding specifically to the mRNA precursor of PCSK9 protein and causing its degradation. It has been noticed in recent years that siRNA is a powerful tool for biomedical research and drug discovery. The purpose of this work is to summarize the molecular mechanisms, pharmacokinetics, pharmacodynamics of inclisiran and to review the latest research.

Polygenic risk scores for the diagnosis and management of dyslipidemia.

To review current progress in the use of polygenic risk scores for lipid traits and their use in the diagnosis and treatment of lipid disorders. Inherited lipid disorders, including those causing extremes of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides were initially identified as monogenic traits, in which a single rare variant with large effect size is responsible for the phenotype. More recently, a polygenic basis for many lipid traits has also been identified. Patients with polygenic dyslipidemia can be identified through the use of polygenic risk scores (PRSs), which collapse information from a handful to several million genetic variants into a single metric. PRSs for lipid traits may aid in the identification of the genetic basis for the lipid phenotype in individual patients, may provide additional information regarding the risk of cardiovascular disease, and could help in guiding therapeutic decision making.

The International Lipid Expert Panel (ILEP)—the role of ‘optimal’ collaboration in the effective diagnosis and treatment of lipid disorders

The International Lipid Expert Panel (ILEP)—the role of ‘optimal’ collaboration in the effective diagnosis and treatment of lipid disorders

Evinacumab — an ANGPTL3 inhibitor; a new drug in the treatment of lipid disorders. Review on the literature and clinical studies

Angiopoietin-like proteins (ANGPTL) are a family of several proteins, of which ANGPTL3, 4 and 8 are involved in lipid metabolism. These proteins, discovered relatively recently, regulate the availability of triglycerides for the heart, skeletal muscles and white and brown adipose tissue depending on the nutritional status of the body, thus contributing to the maintenance of energy homeostasis. ANGPTL3, 4 and 8 gene mutations are associated with a significant reduction in plasma lipid levels, which translates to a reduction in the risk of ischaemic heart disease and diabetes type 2. It was shown that blood levels of ANGPTL3, 4, 5 and 8 may change in various disease states, such as obesity or diabetes type 2, and thus may constitute biomarkers of the cardiovascular risk. Evinacumab, being a fully humanized anti-ANGPTL3 antibody, February, 11 th , 2021, as Evkeeza® preparation, has been registered by the US Food and Drug Administration for the treatment of homozygous familial hypercholesterolaemia. In clinical trials, evinacumab was characterized by a high lipid-lowering efficacy in patients with homozygous and heterozygous familial hypercholesterolaemia, as well as treatment-resistant hypercholesterolaemia and hypertriglyceridaemia. Another drug that reduces ANGPTL3 activity are antisense oligonucleotides targeting Angptl3 mRNA (ANGPTL3 ASO) which were also characterized by lipid lowering properties in clinical trials.

Comparative risk assessment for the development of cardiovascular diseases in the Hungarian general and Roma population

Cardiovascular diseases (CVDs) are the number one cause of death globally, and the early identification of high risk is crucial to prevent the disease and to reduce healthcare costs. Short life expectancy and increased mortality among the Roma are generally accepted (although not indeed proven by mortality analyses) which can be partially explained by the high prevalence of cardiovascular risk factors (CVRF) among them. This study aims to elaborate on the prevalence of the most important CVD risk factors, assess the estimation of a 10-year risk of development of fatal and nonfatal CVDs based on the most used risk assessment scoring models, and to compare the Hungarian general (HG) and Roma (HR) populations. In 2018 a complex health survey was accomplished on the HG (n = 380) and HR (n = 347) populations. The prevalence of CVRS was defined and 10-year cardiovascular risk was estimated for both study populations using the following systems: Framingham Risk Score for hard coronary heart disease (FRSCHD) and for cardiovascular disease (FRSCVD), Systematic COronary Risk Evaluation (SCORE), ACC/AHA Pooled Cohort Equations (PCE) and Revised Pooled Cohort Equations (RPCE). After the risk scores had been calculated, the populations were divided into risk categories and all subjects were classified. For all CVD risk estimation scores, the average of the estimated risk was higher among Roma compared to the HG independently of the gender. The proportion of high-risk group in the Hungarian Roma males population was on average 1.5–3 times higher than in the general one. Among Roma females, the average risk value was higher than in the HG one. The proportion of high-risk group in the Hungarian Roma females population was on average 2–3 times higher compared to the distribution of females in the general population. Our results show that both genders in the Hungarian Roma population have a significantly higher risk for a 10-year development of cardiovascular diseases and dying from them compared to the HG one. Therefore, cardiovascular interventions should be focusing not only on reducing smoking among Roma but on improving health literacy and service provision regarding prevention, early recognition, and treatment of lipid disorders and diabetes among them.

Limitations of current screening methods for lipid disorders in Korean adolescents and a proposal for an effective detection method: a nationwide, cross-sectional study.

PurposeTo determine the limitations of current screening methods for lipid disorders and to suggest a new method that is effective for use in Korean adolescents.MethodsData from the 6th Korea National Health and Nutrition Examination Survey (2013–2015) were analyzed. The diagnostic validity (sensitivity and specificity) of various cardiovascular risk factors currently used for lipid disorder screening was investigated, as was the diagnostic validity of non-HDL-cholesterol ≥145 mg/dL as a screening tool.ResultsThe prevalence of dyslipidemia and familial hypercholesterolemia (FH) among Korean adolescents was 20.4%±1.0% and 0.8%±0.3%, respectively. The current standard screening methods identified only 5.9%±1.4% and 30.3%±17.2% of the total number of dyslipidemia and FH cases, respectively. The diagnostic sensitivity and specificity of lipid profile analysis for dyslipidemia among obese adolescents were 19.5%±2.3% and 93.6%±0.8% and for FH were 30.3%±17.2% and 91.1%±0.8%, respectively. When adolescents with obesity, hypertension, or a family history of dyslipidemia or cardiocerebrovascular disease for over 3 generations were included in the screening, diagnostic sensitivity increased to 68.4%±2.8% for dyslipidemia and 83.5%±2.7% for FH. Universal screening of all adolescents based on non-HDL-cholesterol levels had sensitivities of 30.2%±2.7% and 100%, and specificities of 99.2%±0.3% and 94%±0.6% for dyslipidemia and FH, respectively.ConclusionsNew screening methods should be considered for early diagnosis and treatment of lipid disorders in Korean adolescents.

37-LB: GLP-2 Regulation of Dietary Fat Absorption and Intestinal Lipoprotein Production: The Role of the Enteric Nervous System via nNOS Signaling

Objective: Postprandial dyslipidemia, a condition commonly presented in individuals with type 2 diabetes (T2D), is characterized by the overproduction of triglyceride (TG)-rich lipoproteins (TRL). This results in excess atherogenic chylomicron (CM) remnants in circulation, significantly increasing the risk of cardiovascular disease (CVD). Using a Syrian golden hamster model, our laboratory has revealed that intestinal hormone glucagon-like peptide-2 (GLP-2) regulates dietary fat uptake and increases CM production in insulin-resistant states. However, the mechanisms by which GLP-2 enhances CM production remain unclear. Previous studies have implicated nitric oxide (NO) in the actions of GLP-2, demonstrating the requirement of NO in CM secretion. Therefore, this study investigated the role of neuronal NO synthase (nNOS)-mediated NO generation in lipid uptake and CM formation. Methods: nNOS-/- and C57BL/6 (WT) mice received an intraduodenal injection of olive oil, followed by an acute intraperitoneal (i.p.) injection of GLP-2 (0.25mg/kg; n=7) or vehicle (PBS; n=8). Blood samples were collected over a 2-hour period to assess postprandial lipid accumulation, and TRL fractions were isolated via ultracentrifugation. Immunoblotting was used to measure plasma apolipoprotein B48 (apoB48) protein expression. Results: While GLP-2-treated WT mice showed characteristic rises in postprandial TG and cholesterol in whole plasma and TRL fractions, the effect of GLP-2 in nNOS-/- mice was abolished. The effect of GLP-2 on postprandial plasma apoB48 protein expression was also abolished in nNOS-/- mice relative to GLP-2-treated WT mice. Conclusions: These findings demonstrate a novel mechanism in which nNOS-generated NO is crucial for GLP-2-mediated lipid absorption and CM production in the postprandial state. Understanding this pathway will provide insight for future therapeutic interventions to treat lipid disorders in T2D. Disclosure E.M. Grande: None. K. Adeli: None. Funding Canadian Institutes of Health Research

Adjuvant drug-assisted bone healing: Part III - Further strategies for local and systemic modulation.

In this third in a series of reviews on adjuvant drug-assisted bone healing, further approaches aiming at influencing the healing process are discussed. Local and systemic modulation of bone metabolism is pursued with use of a number of drugs with completely different indications, which are characterized by a pleiotropic spectrum of action. These include drugs used to treat lipid disorders (HMG-CoA reductase inhibitors), hypertension (ACE inhibitors), osteoporosis (bisphosphonates), cancer (proteasome inhibitors) and others. Potential applications to enhance bone healing are discussed.

Statin use and its potential therapeutic role in esophageal cancer: a systematic review and meta-analysis.

Purpose: Statins, known as inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductases, are designed to treat lipid disorders, especially hypercholesterolemia. Apart from their role in preventing heart diseases in patients with high cholesterol, recent evidence suggests that statins have anti-tumor properties. However, studies assessing the association between statin use and esophageal cancer survival outcomes have provided controversial results.Methods: We conducted a systematic review and meta-analysis focusing on studies evaluating associations between statin use and survival outcomes for esophageal cancer patients.Results: A total of five cohort studies comprising 24,576 patients were included. Statin use associated with improved overall survival (OS: HR 0.84, 95% CI, 0.75–0.94) and disease-free survival (DFS: HR 0.84, 95% CI, 0.75–0.96) of esophageal cancer patients. The improved survival outcomes were consistent in the esophageal adenocarcinoma subgroup and the esophageal squamous cell cancer subgroup.Conclusion: A potential therapeutic role of statins in esophageal cancer has been demonstrated in our study, however, the results should be interpreted cautiously and need further confirmation by future studies.

The fucoidan A3 from the seaweed Ascophyllum nodosum enhances RCT-related genes expression in hyperlipidemic C57BL/6J mice

Reverse cholesterol transport (RCT) has been demonstrated to reduce hyperlipidemia, and fucoidans are found to possess hypolipidemic effect. This study was designed to investigate the lipid-lowering effect of the fucoidan from the brown seaweed A. nodosum and whether it improves RCT-related genes expression in C57 BL/6J mice. Our results indicated that fucoidan A3 (100 mg/kg/day) intervention significantly reduced plasma total cholesterol (~23.2%), triglyceride (~48.7%) and fat pad index. This fucoidan significantly increased the mRNA expression of low-density lipoprotein receptor (LDLR), scavenger receptor B type 1 (SR-B1), cholesterol 7 alpha-hydroxylase A1 (CYP7A1), liver X receptor (LXR) β, ATP-binding cassette transporter (ABC) A1 and sterol regulatory element-binding protein (SREBP) 1c, and decreased the expression of peroxisome proliferator-activated receptor (PPAR) γ, however, it had no effect on the expression of proprotein convertase subtilisin/kexin type 9, PPARα, LXRα, SREBP-2, ABCG1, ABCG8 and Niemann-Pick C1-like 1. These results demonstrated that this fucoidan improved lipid transfer from plasma to the liver by activating SR-B1 and LDLR, and up-regulated lipid metabolism by activating LXRβ, ABCA1 and CYP7A1. In conclusion, this fucoidan lowers lipid by enhancing RCT-related genes expression, and it can be explored as a potential candidate for prevention or treatment of lipid disorders.

Czy nie-HDL cholesterol lepiej niż cholesterol frakcji LDL odzwierciedla ryzyko sercowo-naczyniowe?

The concentration of lipids and lipoproteins in plasma is essential in the treatment of lipid disorders. The routine lipid panel includes total cholesterol, triglycerides, cholesterol of low-density lipoprotein (LDL-C) and cholesterol of high- -density lipoprotein (HDL-C). The latest guidelines of the European Society of Cardiology (valid until 2020) indicate that besides many players in the lipid arena (apolipoprotein, concentration and size of LDL particles) another parameter, non-HDL-cholesterol (non-HDL-C), is very important. This parameter, being easily available for routine clinical use, has been highlighted as a key secondary goal of therapy in patients with cardiometabolic risk. Non-HDL-C is a superior parameter to LDL-C, especially the one estimated using Friedewald formula for prediction of cardiovascular events, because non-HDL-C is an integrated complex of all lipoprotein particles containing apolipoprotein B, i.e.: LDL, very low-density lipoproteins, intermediate-density lipoproteins, chylomicrons, remnants and Lp(a). Crucially, it can be calculated directly from the values of routine lipid panels, without additional cost. In our opinion, non-HDL-C should be presented in all routine lipid profiles conducted by diagnostic laboratories. We also propose a new presentation of the results of routine lipid panel, which allows a significant change in treatment goals, taking into account the hierarchy of values of individual concentrations of lipoprotein fractions and how they are interpreted in the management of dyslipidaemia for optimal prevention of atherosclerosis and cardiovascular diseases.

NEW BIOTECHNOLOGICAL TREATMENTS FOR LIPID DISORDERS.

Disorders of lipid and lipoprotein metabolism play a central role in the pathogenesis of atherosclerotic cardiovascular diseases (CVDs). Despite the widespread use of efficacious lipid-modifying therapies, the residual risk of CVD remains unacceptably high. The purpose of this manuscript is to review the application of new technologies in the treatment of lipid disorders. New therapies work mostly at the gene expression level and are, therefore, different from traditional small-molecule drugs that work mainly by inhibiting already synthesized proteins. We will briefly lay out the function of the gene products targeted by the new agents. Then, we will organize our review of new biotechnological treatments by the molecular approach, namely: monoclonal antibodies, antisense oligonucleotides, small-interfering RNAs, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9)-based genome editing. The paper concludes with the description of the current clinical studies and the perspectives for the use of these agents. (REV INVEST CLIN. 2018;70:244-54).

Statins and Colorectal Cancer - A Systematic Review.

Statins act by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase and are an important drug class in the treatment of lipid disorders. They lower cholesterol levels and modulate cardiovascular disease risk in both primary and secondary prevention. In addition, some studies have shown that statins may have an effect on colorectal cancer development and treatment. Our objective is to summarize published studies on the effect of statins on colorectal carcinogenesis. A systematic review of the PubMed and Cochrane databases was performed to identify studies published between April 2010 and April 2018 that investigated the association between statin use and colorectal cancer incidence, mortality, and treatment. Overall, 126 articles were identified with our search strategy. Based on the eligibility criteria, 69 studies were excluded from the review process. In vitro and animal studies have shown a potential chemopreventive effect of statins and their efficacy in adjuvant therapy of colorectal cancer. The anticarcinogenic effect on cancer risk in human studies was heterogeneous. Some studies reported better overall and cancer specific survival rates in patients using statins before and during colorectal cancer treatment. Statins also show a potential role in chemoprevention of colorectal cancer in patients with inflammatory bowel disease. Accumulating evidence suggests that statins may have a role in colorectal cancer prevention and treatment. Further studies are necessary to define the associations between individual statin characteristics, their doses and colorectal cancer.