Author Interviews, Heart Disease, JACC, Statins / 17.05.2022

MedicalResearch.com Interview with: Dr. Raffaele Bugiardini, UNIBO Professor & MD Clinical cardiologist Full Professor of Cardiology at the University of Bologna MedicalResearch.com:  What is the background for this study?  Response: Questions about the evidence base for primary prevention with statins continue to emerge from many quarters. It has been argued that prior estimates of statin effects were mainly based on information from both individuals with and without pre-existing cardiovascular disease, which may overestimate the true benefits of statins. Some investigators attempted to quantify the impact of statins on outcomes of women versus men and reported significantly different effect estimates. Others have questioned the benefits of statins in adults 76 years and older as this age group was poorly represented in the randomized trials for primary prevention of cardiovascular disease. There is little or no information on concomitant preventive medications in prior work. Thus, how large is the incremental benefit of statin, added to other standard preventive interventions? and is cholesterol a reliable surrogate endpoint to guide prevention of cardiovascular disease? (more…)
Author Interviews, COVID -19 Coronavirus, Statins / 22.10.2021

MedicalResearch.com Interview with: Rita Bergqvis Department of Global Public Health Karolinska Institutet Stockholm, Sweden MedicalResearch.com: What is the background for this study? Response: There is a theoretical background for the discussion regarding statins in relation to COVID. Hyperinflammation and hypercoagulability have been identified as central to the development of severe COVID and COVID related complications. Hence, drugs that modulate the host immune response and inhibit thrombosis and vascular dysfunction have received a lot of attention. Statins are known to have pleiotropic effects; apart from their cholesterol lowering properties they are thought to modulate immune system processes and decrease the risk of thrombotic events. Previous observational studies on statins and COVID had some major methodological limitations and showed varying results. (more…)
Author Interviews, Diabetes, Statins / 04.10.2021

MedicalResearch.com Interview with: Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Data & Population Science, University of Texas Southwestern, Dallas, TX MedicalResearch.com: What is the background for this study? Response: Several scientific societies guidelines recommend Statins prescription to patients with diabetes aged 40 to 75 with LDL-cholesterol ≥70 mg/dL to prevent cardiovascular diseases from occurring. Statins have been shown to lower the risk of cardiovascular diseases. However, prior research has shown statins to be associated with increased insulin resistance. But doctors do not routinely measure “insulin resistance” for their patients, rather, it is done on research and academic circles only but not in everyday life. Increased insulin resistance may result in less controlled diabetes and/or escalation of anti-diabetes medications. (more…)
Author Interviews, COVID -19 Coronavirus, Heart Disease, Nature, Statins / 27.02.2021

MedicalResearch.com Interview with: Aakriti Gupta MD MS Fellow, Interventional Cardiology Columbia University Irving Medical Center NewYork-Presbyterian Hospital  MedicalResearch.com: What is the background for this study? Response: While taking care of patients with COVID-19 last spring and summer at the height of the pandemic, we observed that patients who got very sick and required hospitalization had high rates of hyperinflammation with elevated CRP levels, and thromboembolic phenomena. As cardiologists who frequently prescribe statins for hyperlipidemia, they were a class of drugs that came naturally to mind for their anti-inflammatory, anticoagulant and immunomodulatory properties in addition to their cholesterol lowering properties. As such, we decided to look at the association of statin use with in-hospital mortality in patients who are hospitalized with COVID-19. (more…)
Author Interviews, Cost of Health Care, CT Scanning, Heart Disease, JACC, Statins / 14.01.2021

MedicalResearch.com Interview with: Prasanna Venkataraman MBBS Thomas H. Marwick MBBS, PhD Baker Heart and Diabetes Research Institute Monash University, Melbourne Melbourne, Australia   MedicalResearch.com: What is the background for this study?
  • Coronary artery calcium score (CAC) quantifies coronary calcium as determined by computed tomography and is a good surrogate marker for overall coronary plaque burden. It can help to reclassify patients at intermediate risk – many of whom are actually at low risk and can be reassured. Conversely, the finding of coronary calcium can also motivate patients (and their clinicians) to more aggressively control their cardiovascular risk factors. This is particularly problematic in those with a family history of premature coronary artery disease, where standard risk prediction tools are less accurate. However, CT CAC does not routinely attract third party payer support limiting its access and utilisation.
  • We screened 1084 participants who have a family history of premature coronary disease and a 10-year Pooled cohort Equation (PCE) cardiovascular risk >2% with CAC. We then assessed the cost-effectiveness of commencing statins in those with any coronary calcium compared to a strategy of no CAC testing and commencing statins if their PCE risk was ≥7.5% consistent with current guidelines. 
(more…)
Author Interviews, COVID -19 Coronavirus, Lipids, Statins, UCSD / 26.09.2020

MedicalResearch.com Interview with: Lori B. Daniels, MD, MAS, FACC, FAHA Professor of Medicine Director, Cardiovascular Intensive Care Unit UCSD Division of Cardiovascular Medicine Sulpizio Cardiovascular Center La Jolla, CA 92037-7411  MedicalResearch.com: What is the background for this study? Response: The purpose of our study was to investigate whether there is an association between the use of statin medications and COVID-19 morbidity and mortality among patients hospitalized for COVID-19. Our study investigated all patients hospitalized for treatment of COVID at a major US academic medical center during the study period. We studied patients who were hospitalized with COVID-19, and compared those who had been taking statins for at least 30 days prior to admission, with those not on statins.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Heart Disease, Race/Ethnic Diversity, Statins / 14.05.2020

MedicalResearch.com Interview with: Dr. Ankur Pandya, PhD Assistant Professor of Health Decision Science Department of Health Policy and Management Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? Response: The 2013 ACC-AHA cholesterol treatment guidelines greatly expanded statin medication eligibility for individuals between the ages of 40-75 years without known cardiovascular disease, and there was some concern that African Americans at "intermediate risk" per those guidelines could be (arguably) overtreated with statins. The 2018 ACC-AHA guidelines included coronary artery calcium assessment for individuals at intermediate cardiovascular disease risk; those with a "zero" calcium score and no other risk factors would now change the eligibility (from indicated statin to not indicated). (more…)
Author Interviews, Genetic Research, Heart Disease, Lipids, NEJM, Statins / 13.03.2019

MedicalResearch.com Interview with: Brian A Ference, MD, MPhil, MSc, FACC, FESC Professor and Director of Research in Translational Therapeutics Executive Director, Centre for Naturally Randomized Trials Strangeways Research Laboratory University of Cambridge Cambridge, UK MedicalResearch.com: What is the background for this study? Response: Bempedoic acid is a novel therapy currently in development that lowers LDL-C by inhibiting ATP-citrate lyase, an enzyme in the same cholesterol biosynthesis pathway as HMG-CoA reductase (the target of stains).  However, whether lowering LDL-C by inhibiting ATP-citrate lyase will reduce the risk of cardiovascular events to the same extent as lowering LDL-C by inhibiting HMG-CoA reductase with a statin is unknown. We conducted a “naturally randomized trial” using Mendelian randomization in more than 650,000 participants who experienced more than 100,000 cardiovascular events to evaluate the potential clinical benefit of lowering LDL-C by inhibiting ATP-citrate lyase as compared to lowering LDL-C by inhibiting HMG-CoA reductase. (more…)
Author Interviews, Heart Disease, Imperial College, Lipids, NEJM, Statins / 13.03.2019

MedicalResearch.com Interview with: Prof. Kosh Ray, MB ChB, MD, MPhil Faculty of Medicine, School of Public Health Chair in Public Health (Clinical) Imperial College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Bempedoic acid is the first in class of a new therapy for lowering LDL cholesterol. This is the largest and longest study to date with this therapy and involved about 2200 pts with patients with either established cardiovascular disease or familial hypercholestrolaemia and in whom LDL was > 70mg/dl or 1.8 mmol/L despite maximally tolerated statins. %0% were on high intensity statins and the majority of the rest on moderate intensity. The aim was to show long term safety 1 year and efficacy at 24 weeks and at 1 year.  (more…)
Author Interviews, Diabetes, Statins / 08.03.2019

MedicalResearch.com Interview with: Fariba Ahmadizar, PharmD, MSc, PhD Department of Epidemiology Erasmus University Medical Centre Rotterdam, the Netherlands MedicalResearch.com: What is the background for this study? Response: Several observational studies and trials have already reported an increased risk of incident type 2 diabetes in subjects treated with statins; however, most of them lack details, meaning that there were limited studies on the association of statin use with glycemic traits. Studies on this association underestimated type 2 diabetes incident cases due to including either questionnaire-based data, short follow-up time or lack of a direct comparison between different statin types, dosages and duration of use with respect to diabetes-related outcomes. (more…)
ALS, Author Interviews, Statins / 15.02.2019

MedicalResearch.com Interview with: Alastair J. Noyce MD, PhD Preventive Neurology Unit, Wolfson Institute of Preventive Medicine Queen Mary University of London, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology, London UK MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Amyotrophic lateral sclerosis (ALS) or motor neurone disease (MND) is a relentlessly progressive disorder that affects nerves which supply muscles. Over time the nerves die, leading to limb weakness, speech and swallowing problems, and ultimately breathing problems. Patients die on average 3-5 after diagnosis. There is no cure and the underlying disease processes are only understood in part. In this study, we adopted a large-scale approach to exploring causal risk factors for ALS. Causality is important because it implies that if one could modify or induce a change in a risk factor, one would observe a change in the risk of ALS. Observational studies struggle to prove causality definitely. Associations in observational studies can arise because: 1) the risk factor truly changes risk of ALS; or 2) something about ALS changes one’s exposure to the risk factor; or 3) the presence of another factor, which may or may not be known, can induce an association between a risk factor and ALS. Unless scenario 1 represents the truth, then changing the risk factor will not have any effect on risk of ALS. We used a proxy-based approach, known as Mendelian randomisation, to assess hundreds of possible risk factors for ALS for evidence of causality. What emerged from this was a very clear signal linking LDL cholesterol to risk of ALS. (more…)
Author Interviews, JAMA, Rheumatology, Statins / 31.07.2018

MedicalResearch.com Interview with: Dr Gillian E. Caughey PhD Senior Research Fellow | School of Medicine Discipline of Pharmacology THE UNIVERSITY OF ADELAIDE Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: Statins are one of the most commonly prescribed medications worldwide.  Muscular adverse effects (myalgia and myopathy) are well recognised adverse effects and symptoms resolve with cessation of statins. Idiopathic inflammatory myositis (IIM) is a heterogeneous group of autoimmune myopathies that may also be associated with statin use. IIM does not resolve with cessation of statin therapy, requires treatment with immunosuppressive agents and is a severe, debilitating condition. To date, there have been no epidemiological studies examining exposure to statins and the association of histologically confirmed IIM. In our case control study of 221 cases o fIdiopathic inflammatory myositis, there was an almost 2-fold increased likelihood of statin exposure in patients with IIM compared with controls (adjusted odds ratio, 1.79; 95%CI, 1.23-2.60). After observing a significant association of statin exposure with IIM, we conducted a sensitivity analysis where we excluded those patients with necrotizing myositis as recent studies have reported this type of IIM to be associated with statin use and the presence of autoantibodies against HMG-CoA reductase. Exclusion of these specific cases from the analysis did not change our study findings and an increased risk of Idiopathic inflammatory myositis with statin exposure remained (adjusted OR, 1.92; 95% CI, 1.29-2.86).  This suggest the potential association of all types of Idiopathic inflammatory myositis with statin exposure. (more…)
Author Interviews, Heart Disease, Lipids, Statins / 14.06.2018

MedicalResearch.com Interview with: Fatima Rodriguez, MD, MPH Division of Cardiovascular Medicine Stanford University Stanford, CA 94305-5406, MedicalResearch.com: What is the background for this study? What are the main findings? Response: Individuals with LDL-cholesterol levels above 190mg/dL are often underdiagnosed and undertreated, yet remain at high-risk of cardiovascular disease. In a national sample of veterans, we identified over 60,000 patients who met criteria for uncontrolled, severe hypercholesterolemia based on an index LDL-C value ≥190mg/dL. We found that only half of these high-risk patients are being treated with statins, and less than 10% are on high-intensity statin therapy as recommended by the 2013 ACC/AHA guidelines. We also found that both older and younger patients were less likely to be treated with statins. Women were less likely to be treated with statins, whereas minority groups and those with a diagnosis of hypertension were more likely to be treated. Disparities in use of statins were also noted by geographic region and hospital teaching status. (more…)
Author Interviews, Duke, Heart Disease, JAMA, Lipids, Race/Ethnic Diversity, Statins / 14.06.2018

MedicalResearch.com Interview with: Michael G. Nanna, MD Fellow, Division of Cardiology Duke University Medical Center Durham, NC MedicalResearch.com: What is the background for this study? Response: We know that African Americans are at higher risk for cardiovascular disease than white patients. We also know that African American individuals have been less likely to receive statin therapy compared to white individuals in the past. However, the reasons underlying these racial differences in statin treatment are poorly understood. We set out to determine if African American individuals in contemporary practice are treated less aggressively than whites and, if so, we wanted to investigate potential reasons why this might be the case. (more…)
Author Interviews, Heart Disease, Statins / 07.10.2015

Giancarlo Marenzi, M.D. Centro Cardiologico Monzino Milan, ItalyMedicalResearch.com Interview with: Giancarlo Marenzi, M.D. Centro Cardiologico Monzino Milan, Italy  Medical Research: What is the background for this study? What are the main findings? Dr. Marenzi: Pre-treatment with statins in patients with stable angina or non-ST-elevation acute coronary syndromes undergoing elective or urgent percutaneous coronary intervention (PCI) has been shown to reduce myocardial injury and to improve clinical outcomes. Conversely, data on a cardio-protective effect of statin pre-treatment in ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI are more controversial. In this prospective study, we evaluated infarct size and myocardial salvage by cardiac magnetic resonance imaging in a consecutive cohort of 230 STEMI patients undergoing primary PCI, comparing patients on chronic statin with those without. Patients on chronic statin therapy showed an almost 40% lower enzymatic (troponin I) peak value, when compared to patients without. In parallel, a 32% smaller infarct size and a 24% higher myocardial salvage were found in the statin group, as compared to those without. In the entire population, no significant association was found between infarct size and LDL-cholesterol levels at hospital admission. (more…)
Author Interviews, Geriatrics, JAMA, Statins / 24.08.2015

Michael Johansen MD MS Assistant Professor - Clinical Dept of Family Medicine The Ohio State UniversityMedicalResearch.com Interview with: Michael Johansen MD MS Assistant Professor - Clinical Dept of Family Medicine The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Johansen: -Over the last 15 years there has been increasing emphasis placed on the use of statins to decrease people's risk of heart attacks and strokes. Individuals with known heart disease are recommended to be on statins. However, there is no convincing evidence that elderly individuals (>79 years of age) without heart disease benefit from statins. Therefore, we investigated how use patterns of statins has changed over the last ~14 years. We identified a dramatic increase in statin use in the very elderly during the time of the study. As of 2012, around 1/3 of very elderly individuals without heart disease took a statin during that year. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Statins / 14.07.2015

Dr. Ankur Pandya Ph.D. Assistant Professor of Health Decision Science Department of Health Policy and Management Harvard T.H. Chan School of Public Health Boston, MA MedicalResearch.com Interview with: Dr. Ankur Pandya Ph.D. Assistant Professor of Health Decision Science Department of Health Policy and Management Harvard T.H. Chan School of Public Health Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Pandya: The American College of Cardiology and the American Heart Association (ACC-AHA) cholesterol treatment guidelines were controversial when first released in November 2013, with some concerns that healthy adults would be over-treated with statins. We found that the current 10-year ASCVD risk threshold (≥7.5%) used in the ACC-AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (incremental cost-effectiveness ratio of $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0%) or $150,000/QALY (≥3.0%). (more…)
Author Interviews, Heart Disease, Statins / 01.07.2015

dr-duk-woo-park.pngMedicalResearch.com Interview with: Duk-Woo Park, MD, PhD. Professor, Division of Cardiology Asan Medical Center, University of Ulsan College of Medicine Seoul, Korea Medical Research: What is the background for this study? What are the main findings? Response: The applicability and potential clinical effects of the 2013 ACC/AHA cholesterol guidelines on major cardiovascular outcomes in the “real-world” population remains uncertain and also should also be evaluated in multiple groups of various ethnic backgrounds. We determined the proportions of adult persons eligible for statin therapy by changes of 2013 ACC/AHA cholesterol guidelines using a nationally representative sample from an Asian country (South Korea) and also we evaluated the potential clinical effects of this cholesterol guideline on future cardiovascular outcomes using an external validation cohort from the Korean National Health Examination. Similar to findings from the United States and the European cohort, our study showed that the 2013 ACC/AHA guidelines would substantially increase the number of adults who would be potentially eligible for statin therapy in Korean population. In addition, the 2013 ACC/AHA guidelines would have identified more cases with higher events of cardiovascular disease (CVD) for statin treatment than the ATP-III guidelines. (more…)
Author Interviews, BMJ, Geriatrics, Lipids, Statins, Stroke / 19.05.2015

Christophe Tzourio, MD, PhD Professor of Epidemiology University of BordeauxMedicalResearch.com Interview with: Christophe Tzourio, MD, PhD Professor of Epidemiology University of Bordeaux Medical Research: What is the background for this study? What are the main findings? Dr. Tzourio: The efficacy of lipid-lowering drugs (LLD) - which include statins and fibrates - to reduce the risk of coronary events and stroke has already been demonstrated in randomized trials. However, these trials were performed on highly selected patients, usually of middle-age (50-70 yrs) and with a history of cardiovascular disease or a high vascular profile. There is therefore currently no indication on the benefit of these drugs in elderly individuals of the general population without a past-history of cardiovascular disease and guidelines do not recommend the use of lipid-lowering drugs in elderly individuals without clinical atherosclerotic disease. As there are not randomized trials in non-selected individuals in this age category, observational population-based cohorts are therefore the only alternative to study the impact of lipid-lowering drugs on the risk of cardiovascular diseases in the elderly. We analyzed data from the Three-City study, a community-based cohort in 7484 elderly individuals (mean age 74 years), followed-up during 9 years, without known history of vascular disease at baseline. We observed a one third decrease in the risk of stroke in lipid lowering drug users (hazard ratio 0.66, 0.49 to 0.90) compared with non-users. Reduction in stroke risk was similar for the statin and fibrate groups. No protective effect was seen on the risk of coronary heart disease. (more…)
Author Interviews, Diabetes, General Medicine, Statins, UT Southwestern / 08.05.2015

Ishak Mansi, MD Staff Internist, VA North Texas Health System.   Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TXMedicalResearch.com Interview with: Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Mansi:  Statin use is associated with increased incidence of diabetes, and possibly increased body weight, and less exercise capacity. Data on the long-term effects of these associations in healthy adults are very limited. Additionally, the effects of these associations on diabetic complications have not been adequately studied. Dr. Mansi at VA North Texas Health System, Dallas and Professor of Medicine and Clinical Sciences at the University of Texas Southwestern, Dallas, TX and his colleagues found that among generally healthy individuals, statin-users in comparison to non-users had a higher odds of being diagnosed with new onset diabetes, diabetes with complications, and overweight/obesity. The researchers examined the records of tens of thousands of Tricare beneficiaries, during the period from 10/1/2003 to 3/1/2012. After excluding patients who had at baseline a preexisting cardiovascular diseases or severe chronic diseases that may be life-limiting (including diabetes mellitus), they identified a cohort of 25,970 patients as “healthy cohort”. They, further, matched 3,351 statins-users and 3,351 nonusers on several baseline characteristics to ensure comparability. There are 3 main important findings for our study:
  1. Statin use was associated with significantly higher risk of new onset diabetes even in a very healthy population. Whereas the risk of diabetes with statins is known, it was thought that this may be due to the overall multiple risks of statin-users (that caused them to receive statins as a therapy).
  2. Statin use was associated with very high risk of diabetes complications in this healthy population: this was never shown before.
  3. Statin use is associated with higher risk of obesity: this also is widely unknown. However, few studies have noted this (one study using patient survey noted this, another study using Mendelian randomization showed it, and post-hoc analysis of a clinical trial showed that statin user gained more weight). Our study, which used a different methodology (retrospective cohort study) add another piece of evidence. Obesity is at endemic level in the US and treatment options are limited.
High-intensity statins was associated with greater risks of all outcomes. This article is published in the Journal of General Internal Medicine (JGIM). JGIM is the official journal of the Society of General Internal Medicine. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Lipids, Statins / 11.03.2015

Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine AmsterdamMedicalResearch.com Interview with: Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine Amsterdam Medical Research: What is the background for this study? What are the main findings? Response: Statins are associated with an increased risk for type 2 diabetes mellitus (DM). The exact mechanism for this adverse event is largely unknown, although the upregulation of the low-density lipoprotein receptor (LDLR) has been suggested to play a role. In familial hypercholesterolemia (FH) the uptake of LDL-cholesterol via the LDLR is decreased due to a genetic defect. We found that the prevalence of type 2 DM is 50% lower in relative terms in patients with familial hypercholesterolemia. Moreover, there was a dose-response relationship: the more severe the genetic defect that causes familial hypercholesterolemia, the lower the prevalence of type 2 DM. (more…)
Author Interviews, Depression, Heart Disease, Statins / 07.03.2015

Heidi May, Ph.D., M.S.P.H. Cardiovascular Epidemiologist Intermountain Medical Center Heart Institute Salt Lake CityMedicalResearch.com Interview with: Heidi May, Ph.D., M.S.P.H. Cardiovascular Epidemiologist Intermountain Medical Center Heart Institute Salt Lake City   Medical Research: What is the background for this study? What are the main findings? Dr. Heidi May: Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Statin therapy is known to reduce the risk of cardiovascular disease incidence through the reduction of blood cholesterol levels and through its pleiotropic cardioprotective properties. Depression is a risk factor for cardiovascular disease. It has been recommended that antidepressant medications should be considered first-line treatment for depression of any severity. We hypothesized that taking both statins and antidepressants would reduce cardiovascular risk more than either medication alone. However, we did not find this. Instead we found that the effectiveness of antidepressants and statin therapy to reduce death and incident cardiovascular disease at 3 years varied by the severity of depressive symptoms. Among those with none to mild depressive symptoms, statin use, with or without antidepressant therapy, was associated with a decrease in risk, but among those with moderate to severe depression, antidepressant use was associated with a decrease in risk. The combination of antidepressant and statin use did not result in a greater risk reduction in either depressive symptom category. (more…)
Author Interviews, PNAS, Statins / 04.03.2015

Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UKMedicalResearch.com Interview with: Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Munro: Statins are blockbuster drugs that inhibit the key enzyme in cholesterol synthesis: 3-beta-hydroxymethylglutaryl CoA reductase (HMG-CoA reductase), which catalyzes the rate-limiting step in the biosynthesis of cholesterol. As a consequence, statin drugs reduce levels of low-density lipoprotein (LDL-) cholesterol, are effective against hypercholesterolemia and reduce the risk of atherosclerosis and heart attack. One of the major statin drugs is pravastatin, which is derived from a fungal natural product called compactin. The process of conversion of compactin into pravastatin involves the use of an oxygen-inserting enzyme called a cytochrome P450 (or P450), which catalyzes the hydroxylation of compactin to form pravastatin. In order to produce a more cost-efficient and streamlined route to pravastatin production, our teams from the University of Manchester (UK) and DSM (Delft, The Netherlands) developed a single-step process for pravastatin production. This process involved harnessing the productive efficiency of an industrial strain of the beta-lactam (penicillin-type) antibiotic producing fungus Penicillium chrysogenum. The beta-lactam antibiotic genes were deleted from this organism, and replaced by those encoding for compactin biosynthesis (transferred from a different Penicillium species). This led to high level production of compactin, but also to substantial formation of a partially degraded (deacylated) form. To get around this problem and in order to further improve compactin production, the enzyme responsible for the deacylation (an esterase) was identified and the gene encoding this activity was deleted from the production strain. The final stages of development of the novel, one-step pravastatin production process involved the identification of a suitable P450 enzyme that could catalyze the required hydroxylation of compactin. A bacterial P450 was identified that catalyzed hydroxylation at the correct position on the compactin molecule. However, the stereoselectivity of the reaction was in favour of the incorrect isomer – forming predominantly epi-pravastatin over the desired pravastatin. This was addressed by mutagenesis of the P450 – ultimately leading to a variant (named P450Prava) that hydroxylated compactin with the required stereoselectivity to make pravastatin in large amounts. Determination of the structure of P450Prava in both the substrate-free and compactin-bound forms revealed the conformational changes that underpinned the conversion of the P450 enzyme to a pravastatin synthase. The expression of P450Prava in a compactin-producing strain of P. chrysogenum enabled pravastatin production at over 6 g/L in a fed-batch fermentation process, facilitating an efficient, single-step route to high yield generation of pravastatin. (more…)
Author Interviews, Heart Disease, JACC, Statins / 20.01.2015

Dr. Robert S. Rosenson, MD Professor, Cardiology Icahn School of Medicine at Mount Sinai Cardiovascular Institute New York, New York 10029MedicalResearch.com Interview with: Dr. Robert S. Rosenson, MD Professor, Cardiology Icahn School of Medicine at Mount Sinai Cardiovascular Institute New York, New York 10029 Medical Research: What is the background for this study? What are the main findings? Dr. Rosenson: High intensity statin therapy is evidence-based and guideline directed for patients with acute coronary syndromes.  In a 5 percent random sample of Medicare patients, we investigated the utilization of high vs low-moderate dosage statin in older adjusts who were admitted with an acute myocardial infarction of severe myocardial ischemia requiring hospitalization for a revascularization procedure (PCI or CABG). We report that only 27 percent of hospitalized patients received high-intensity statin therapy based on their first outpatient fill for a statin medication.  The most important determinant for the utilization of statin therapy is the dosage of the statin previously prescribed as an outpatient.  When patients were started on a high-intensity statin, the continued use diminished in the ensuing year (more…)
Author Interviews, Rheumatology, Statins / 12.01.2015

Dr Geeske Peeters Postdoctoral Research Fellow School of Public Health The University of Queensland AustraliaMedicalResearch.com Interview with: Dr Geeske Peeters Postdoctoral Research Fellow School of Public Health The University of Queensland Australia Medical Research: What is the background for this study? What are the main findings? Dr. Peeters: The hypothesis we set out to investigate was that statin use is associated with reduced joint pain/stiffness and consequently improved physical functioning and quality of life. This hypothesis was based on findings from previous studies suggesting that statin use may prevent the development of radiographic osteoarthritis. However, in contrast with this hypothesis, results from this large study did not demonstrate an association between statin use and reduced onset of joint pain or stiffness. Moreover, statin use did seem to be associated with an increased risk of functional limitations and poorer self-reported health, especially in the middle-aged women. (more…)
Author Interviews, Heart Disease, Statins / 26.12.2014

Beth Taylor, PhD Director of Exercise Physiology Research Department of Preventive Cardiology Hartford Hospital Hartford, CT 06102MedicalResearch.com Interview with: Beth Taylor, PhD Director of Exercise Physiology Research Department of Preventive Cardiology Hartford Hospital Hartford, CT 06102 Medical Research: What is the background for this study? Dr. Taylor:  Statins reduce incidence of cardiac events, and thus are extremely effective drugs. However, they may cause muscle side effects such as pain, weakness and soreness (i.e., statin myalgia) in up to 10% of patients. One potential mechanism underlying statin myalgia may be the depletion of Coenzyme Q10, a mitochondrial transport element used in energy production, as statin therapy produces a 30-50% reduction in intramuscular Coenzyme Q10. Seven previous studies to date have produced conflicting results, yet CoQ10 supplementation is used by many patients and recommended by many clinicians despite the absence of definitive results. The purpose of the present study was to assess the effect of CoQ10 on muscle pain, muscle strength and aerobic performance in confirmed myalgics (i.e., patients who tested positive for  myalgia during a randomized, double-blinded cross-over trial of statin therapy vs. placebo to confirm myalgia prior to CoQ10 treatment). Medical Research: What are the main findings? Dr. Taylor:  The first main finding was that after our randomized double-blind cross-over run-in phase, only 35.8% of patients experienced myalgia on simvastatin and did not experience it on placebo, what we term true or confirmed statin myalgia, and 17.5% of patients had no symptoms on simvastatin or placebo which could have been because the dose we selected was too low.  However, 29.2% experienced pain on placebo but not on simvastatin and 17.5% experienced pain on both simvastatin and placebo during the confirmation phase. Secondly, we found that Coenzyme Q10 supplementation had no effect on the incidence and severity of myalgia, time to onset of pain, muscle strength, or aerobic performance.  Serum levels of CoQ10 went up, suggesting dosing worked, and LDL-C went down similarly in both groups, suggesting the statin was not compromised. Therefore we did not find an observable effect of CoQ10 on any muscle outcome. Finally, there were no reductions from baseline in muscle strength or aerobic performance when statins were combined with placebo in our verified statin myalgics. This is notable because while there have been observational reports of decreased muscle strength and aerobic performance in statin myalgics, there have been few rigorous assessments of muscle strength and aerobic performance with statins and myalgia. In our previous study, the The Effect of STatins On Skeletal Muscle Performance (STOMP) trial , we randomized healthy, statin-naïve patients to atorvastatin 80 mg daily or placebo for 6 months, confirming myalgia via a challenge-dechallenge protocol. In that study, we also found no significant differences in the two groups  in muscle and exercise performance, and thus the present results confirm those findings. (more…)
Author Interviews, Ophthalmology, Statins / 02.12.2014

B. John Mancini, MD, FRCPC, FACP, FACC Professor of Medicine; University of British Columbia; Department of Medicine, Division of Cardiology; Research Director, Division of Cardiology; Director, Cardiovascular Imaging Research Core Laboratory (CIRCL); President, Vancouver Hospital Medical, Dental and Allied Staff; Staff Cardiologist, VH Cardiology Clinics and Cardiac Computed Tomographic Angiography Program; Staff Cardiologist, St. Paul's Hospital Healthy Heart/Prevention Clinic.MedicalResearch.com Interview with: B. John Mancini, MD, FRCPC, FACP, FACC Professor of Medicine; University of British Columbia; Department of Medicine, Division of Cardiology; Research Director, Division of Cardiology; Director, Cardiovascular Imaging Research Core Laboratory (CIRCL); President, Vancouver Hospital Medical, Dental and Allied Staff; Staff Cardiologist, VH Cardiology Clinics and Cardiac Computed Tomographic Angiography Program; Staff Cardiologist, St. Paul's Hospital Healthy Heart/Prevention Clinic. MedicalResearch: What are the main findings of this study? Dr. Mancini: The main findings are that we found evidence of a relationship between statin use and the need for cataract surgery. The unique nature of the study is that it looked for the association in two distinctly different populations (a Canadian database and a separate, American database) and found a consistent association in both populations. (more…)
Author Interviews, General Medicine, JAMA, Statins / 18.11.2014

Dr. Mike Miedema MD, MPH Minneapolis Heart InstituteMedicalResearch.com Interview with: Dr. Mike Miedema MD, MPH Minneapolis Heart Institute Medical Research: What is the background for this study? What are the main findings? Dr. Miedema: " Released in November 2013, the ACC/AHA guidelines for the treatment of blood cholesterol attempt to target individuals that are most likely to benefit from cholesterol-lowering statin therapy. These guidelines are a significant change from prior guidelines that relied heavily on levels of bad cholesterol to determine who to treat. Instead, the new guidelines recommend focusing statin therapy on the individuals that are at the highest risk for heart attack and stroke, even if their cholesterol levels are within normal limits. In addition to recommending statin therapy for individuals with known cardiovascular disease, diabetes, or markedly elevated cholesterol levels, they also recommend statin therapy for individuals without these conditions but with an elevated estimated risk of a heart attack or stroke in the next 10-year based on a risk calculator that factors in an individual’s age, gender, race, and risk factors. Patients with an estimated 10-year risk > 7.5% are recommended to consider statin therapy. While I believe the scientific evidence supports this “risk-based” approach, one potential concern is that the risk-calculator relies heavily on age to determine an individual’s risk, so we wanted to examine the implications for these guidelines in an older sample of adults." (more…)
Author Interviews, OBGYNE, Statins / 14.11.2014

Mostafa Borahay, MD, FACOG Assistant Professor, Director of Simulation Education Department of Obstetrics and Gynecology University of Texas Medical BranchMedicalResearch.com Interview with: Mostafa Borahay, MD, FACOG Assistant Professor, Director of Simulation Education Department of Obstetrics and Gynecology University of Texas Medical BranchCo-director of Minimally Invasive Gynecologic Surgery University of Texas Medical Branch Medical Research: What is the background for this study? What are the main findings? Dr. Borahay: Uterine fibroids are the most common type of tumor in the female reproductive system, accounting for half of the 600,000 hysterectomies done annually in the U.S. Their estimated annual cost is up to $34 billion in the U.S. alone. Despite this, the exact cause of these tumors is not well understood, as there are several genetic, familial and hormonal abnormalities linked with their development. Even more, we currently don’t have a satisfactory medical treatment for these tumors. Our team investigated the impact of simvastatin on human uterine fibroid cell growth. Statins, such as simvastatin, are commonly prescribed to lower high cholesterol levels. Statins work by blocking an early step in cholesterol production. Beyond these well-known cholesterol-lowering abilities, statins also combat certain tumors. Statins have previously been shown to have anti-tumor effects on breast, ovarian, prostate, colon, leukemia and lung cancers. However, the effect of statins on uterine fibroids was unknown. We found that simvastatin impedes the growth of uterine fibroid tumor cells. We also studied the way simvastatin works to suppress these tumors. Simvastatin was shown to inhibit ERK phosphorylation, which is a critical step in the molecular pathway that prompts the growth of new cells. In addition, simvastatin stops the progression of tumor cells that have already begun to grow and induces calcium-dependent cell death mechanisms in fibroid tumor cells. Therefore, we identified a novel pathway by which simvastatin induces the death of uterine fibroid tumor cells. (more…)
Author Interviews, Diabetes, Lipids, Statins / 22.09.2014

Prof. Moses Elisaf Professor of Internal Medicine University of Ioannina, GreeceMedicalResearch.com Interview with: Prof. Moses Elisaf Professor of Internal Medicine University of Ioannina, Greece Medical Research: What are the main findings of the study? Dr. Elisaf: We evaluated the effects of rosuvastatin in two groups of hyperlipidemic patients: one group had impaired fasting glucose (IFG) while the second group had normal fasting glucose. After study end, both groups had similar changes in their lipidemic profile. However, patients with IFG had a significant greater decrease in the cholesterol concentration of the more atherogenic small dense low-density lipoprotein (sdLDL) particles (-65.7%) compared with controls (-38.5%). Moreover, a greater increase in the mean LDL particle size was observed in the impaired fasting glucose group (+1.5% vs +0.4%). In addition, redistribution from the more atherogenic sdLDL to large buoyant LDL (lbLDL) subfractions was observed in the IFG group. (more…)