Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 25.04.2019

MedicalResearch.com Interview with: Florian Kronenberg, MD Division of Genetic Epidemiology Department of Medical Genetics, Molecular and Clinical Pharmacology Medical University of Innsbruck, Innsbruck, Austria MedicalResearch.com: What is the background for this study? Response: Lp(a) is one of the most prevalent lipoprotein risk factors for cardiovascular disease. Roughly 20% of the general Caucasian population have concentrations above 50 mg/dL and the 10% with the highest concentrations have a 2 to 3-fold increased risk for myocardial infarction. There is strong evidence from genetic studies that high Lp(a) concentrations are causally related to cardiovascular outcomes. Until recently there was no drug available which lowers Lp(a) without any effects on other lipoproteins. This has recently changed by the development of drugs that block the production of Lp(a) in an impressive way. These drugs have to be studied in randomized controlled trials whether they not only lower Lp(a) concentrations but also cardiovascular outcomes. For the planning of such studies it is crucial to estimate the amount of Lp(a) lowering required to show a clinical benefit. (more…)
Author Interviews, Brigham & Women's - Harvard, Lipids, Stroke / 16.04.2019

MedicalResearch.com Interview with: Pamela M. Rist, ScD Assistant Professor of Medicine, Harvard Medical School Brigham and Women's Hospital, Division of Preventive Medicine Boston, MA 02215  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although hypercholesterolemia is a risk factor for ischemic stroke, some prior studies have observed an inverse association between total and low-density lipoprotein (LDL) cholesterol and risk of hemorrhagic stroke.  However, many studies were not able to study this association specifically among women. Our main result was very low levels of low-density lipoprotein (LDL) cholesterol or low levels of triglycerides were associated with an increased risk of hemorrhagic stroke among women. (more…)
Author Interviews, Heart Disease, JAMA, Lipids / 02.04.2019

MedicalResearch.com Interview with: Victor Wenze Zhong, Ph.D. Postdoctoral fellow Department of Preventive Medicine Feinberg School of Medicine Northwestern University Chicago, IL 60611  MedicalResearch.com: What is the background for this study? Response: Dietary cholesterol is a common nutrient in human diet. Eggs, specially egg yolks, are the single richest source of dietary cholesterol among all commonly consumed foods. The associations between dietary cholesterol consumption and cardiovascular disease and mortality remain controversial despite decades of research. Eating less than 300 mg of dietary cholesterol per day was the guideline recommendation before 2015. However, the most recent 2015-2020 Dietary Guidelines for Americans no longer include a daily consumption limit for dietary cholesterol and recommend weekly egg consumption as part of the healthy US-style eating pattern. Whether these recommendations are appropriate have been intensely debated. (more…)
Accidents & Violence, Author Interviews, Heart Disease, Inflammation, JACC, Lipids / 18.03.2019

MedicalResearch.com Interview with: Dr. George Dangas MD PhD Professor of Medicine, Cardiology Mount Sinai Health System MedicalResearch.com: What is the background for this study? Response: Widespread use of statins targeted to decrease levels of low density lipoprotein cholesterol (LDL-C) below 70mg/dL are recommended by guidelines. However, residual cholesterol risk may only be one part of the residual risk equation. Indeed, Biological inflammation has long been known as a pathophysiological mechanism of atherosclerosis and the recent CANTOS trial opened new therapeutic perspective by demonstrating that inflammation modulation via selective interleukin-1β inhibition could result in improved diagnosis in patients with coronary artery disease. However, the prevalence and impact of a residual inflammatory biological syndrome in patients with controlled cholesterol risk is unclear. (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…)
Annals Internal Medicine, Author Interviews, Beth Israel Deaconess, Cost of Health Care, Heart Disease, Lipids / 02.01.2019

MedicalResearch.com Interview with: Dhruv S. Kazi, MD, MSc, MS Associate Director Richard A. and Susan F. Smith Center for Outcomes Research Boston MA 02215 Associate Director Cardiac Critical Care Unit Beth Israel Deaconess Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY Outcomes trial found that addition of alirocumab to statin therapy reduces the incidence of a composite of cardiovascular death, myocardial infarction, and stroke among patients with a recent history of a myocardial infarction and elevated low-density lipoprotein cholesterol. We modeled the cost-effectiveness of alirocumab and found that, at the March 2018 price of the drug, it would not be cost-effective (either relative to statin alone or statin + ezetimibe) for this indication. We found that a large price-reduction would be required to meet the cost-effectiveness threshold of $100,000 per quality-adjusted life year. Shortly after the preliminary findings of this study were released, both manufacturers of PCSK9 inhibitors announced large price reductions in order to improve access to these drugs. (more…)
Annals Internal Medicine, Author Interviews, Lipids, Pharmacology / 04.12.2018

MedicalResearch.com Interview with: Prof. Dr. Milo Puhan Epidemiology, Biostatistics and Prevention Institute University of Zurich MedicalResearch.com: What is the background for this study? What are the main findings? Response: The use of statins for primary cardiovascular prevention is controversial and there is a debate at what risks statins provide more benefits than harms. Current guidelines recommend statins if the 10 year risk for cardiovascular events is above 7.5 to 10% and they do not distinguish between men and women, different age groups and different statins. We found in our study that the benefits of statins exceeds the harms if the 10 year risk for cardiovascular events is above 14% for middle aged mean (40-44 years) but even higher for older age groups, and women. In addition, the benefit harm balance varies substantially between different statins with atorvastatin providing the best benefit harm balance. (more…)
Author Interviews, Dermatology, Lipids / 04.12.2018

MedicalResearch.com Interview with: Wendy Bollag, PhD, FAHA Professor of Physiology VA Research Career Scientist Augusta University, Georgia MedicalResearch.com: What is the background for this study? Response: We have previously shown that the lipid (fat) phosphatidylglycerol (PG) is able to inhibit rapidly growing keratinocytes (skin cells) and promote their maturation. We also found that PG can suppress skin inflammation. Since the common skin disease psoriasis is characterized by inflammation and excessive growth and abnormal maturation of skin cells, we believed that PG might be useful as a treatment. However, the mechanism of its anti-inflammatory effect was unknown. PG in the lung has been found to inhibit inflammation induced by microbes or their components, which work by activating the innate immune system via binding to proteins called toll-like receptors (TLRs); however, psoriasis is not considered to be an infectious disease. We hypothesized that PG would also inhibit inflammation induced by anti-microbial peptides that activate TLRs. Anti-microbial peptides, produced normally by the skin to protect against infection, are known to be excessively up-regulated in psoriatic skin.  (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Lipids / 20.09.2018

MedicalResearch.com Interview with: Luca A. Lotta, MD, PhD Senior Clinical Investigator MRC Epidemiology Unit University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings?
  • Drugs that enhance the breakdown of circulating triglycerides by activating lipoprotein lipase (LPL) are in pre-clinical or early-clinical development.
  • It is not known if these drugs will reduce heart attacks or diabetes risk when added to the current first line therapies (statins and other cholesterol-lowering agents).
  • Studying this would require large randomised controlled trials, which are expensive (millions of GBPs) and time-consuming (years).
  • Human genetic data can be used to provide supportive evidence of whether this therapy is likely to be effective by “simulating” a randomised controlled trial.
  • Our study used naturally occurring genetic variants in the general population (study of ~400,000 people) to address this.
  • Individuals with naturally-lower cholesterol due to their genetic makeup were used as model for cholesterol-lowering therapies (eg. Statins).
  • Individuals with naturally-lower triglycerides due to genetic variants in the LPL gene were used as model for these new triglyceride-lowering therapies.
  • We studied the risk of heart attacks and type 2 diabetes in people in different groups.
(more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Lipids / 03.08.2018

MedicalResearch.com Interview with: Marc S. Sabatine, MD, MPH Chairman | TIMI Study Group Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine Brigham and Women's Hospital Professor of Medicine | Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease. The initial statin trials studied patients with high levels of LDL-C, and showed a benefit by lowering LDL-C. We and others did studies in patients with so-called “average” levels of LDL-C (120-130 mg/dL), and also showed clinical benefit with lowering. (more…)
AHA Journals, Author Interviews, Heart Disease, Lipids, Menopause, University of Pennsylvania, Women's Heart Health / 19.07.2018

MedicalResearch.com Interview with: Samar R. El Khoudary, Ph.D., M.P.H. BPharm, FAHA Associate Professor Department of Epidemiology University of Pittsburgh Graduate School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background for this study is based on the current measurements used to determine cardiovascular disease risk in postmenopausal women. Higher levels of HDL “good cholesterol” as measured by the widely available clinical test, HDL-Cholesterol, may not always be indicative of a lower risk of cardiovascular disease in postmenopausal women. HDL is a family of particles found in the blood that vary in sizes, cholesterol contents and function. HDL particles can become dysfunctional under certain conditions such as chronic inflammation. HDL has traditionally been measured as the total cholesterol carried by the HDL particles, known as HDL cholesterol. HDL cholesterol, however, does not necessarily reflect the overall concentration, the uneven distribution, or the content and function of HDL particles. We looked at 1,138 women aged 45 through 84 enrolled across the U.S. in the Multi-Ethnic Study of Atherosclerosis (MESA), a medical research study sponsored by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). MESA began in 1999 and is still following participants today. We assessed two specific measurements of HDL: the number and size of the HDL particles and total cholesterol carried by HDL particles. Our study also looked at how age when women transitioned into post menopause, and the amount of time since transitioning, may impact the expected cardio-protective associations of HDL measures. Our study points out that the traditional measure of the good cholesterol, HDL cholesterol, fails to portray an accurate depiction of heart disease risk for postmenopausal women. We reported a harmful association between higher HDL cholesterol and atherosclerosis risk that was most evident in women with older age at menopause and who were greater than, or equal to, 10 years into post menopause. In contrast to HDL cholesterol, a higher concentration of total HDL particles was associated with lower risk of atherosclerosis. Additionally, having a high number of small HDL particles was found beneficial for postmenopausal women. These findings persist irrespective of age and how long it has been since women became postmenopausal. On the other hand, large HDL particles are linked to an increased risk of cardiovascular disease close to menopause. Women are subject to a variety of physiological changes in their sex hormones, lipids, body fat deposition and vascular health as they transition through menopause. We are hypothesizing that the decrease of estrogen, a cardio-protective sex hormone, along with other metabolic changes, can trigger chronic inflammation over time, which may alter the quality of HDL particles. Future studies should test this hypothesis. The study findings indicate that measuring size and number of HDL particles can better reflect the well-known cardio-protective features of the good cholesterol in postmenopausal women. (more…)
Author Interviews, Heart Disease, JAMA, Lipids / 21.06.2018

MedicalResearch.com Interview with: Dr. Stephen Burgess PhD Programme Leader at the Medical Research Council Biostatistics Unit University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: Lipoprotein(a) is a lipoprotein subclass, and an important biomarker for coronary heart disease. As a clinical biomarker, it has a similar story to LDL-cholesterol (“bad” cholesterol), in that it is thought to be a causal risk factor for coronary heart disease, and so is a potential target for drug development. However, while drugs that lower LDL-cholesterol, such as statins, have been successful in reducing coronary heart disease risk, drugs that lower lipoprotein(a) have not as yet been successful. New drugs are currently in development that specifically target lipoprotein(a) and can lower lipoprotein(a) concentrations by 80-90%. We performed this study to investigate whether these drugs are likely to be successful in reducing coronary heart disease risk. We compared individuals with naturally-occurring genetic variants that predispose them to a higher or lower lifetime concentration of lipoprotein(a) as a way of mimicking a randomized controlled trial. This approach has previously been undertaken for other biomarkers, including LDL-cholesterol. We found that having 10mg/dL lower genetically-predicted concentration of lipoprotein(a) was associated with a 5.8% reduction in coronary heart disease risk. However, associations between genetically-predicted LDL-cholesterol and coronary heart disease risk are quantitatively much stronger than the proportional effect of LDL-cholesterol lowering on coronary heart disease risk as estimated by statin trials. This is because differences in genetic variants reflect lifelong changes in LDL-cholesterol, whereas statin trials only lower LDL-cholesterol for a few years. Hence, using the ratio between the genetic and trial estimates for LDL-cholesterol, we estimate that lowering lipoprotein(a) by 10mg/dL in a short-term clinical trial would only reduce coronary heart disease risk by 2.7%. To obtain the same reduction in coronary heart disease risk of around 20% as observed in statin trials, lipoprotein(a) would have to be lowered by around 100mg/dL. This explains why previous trials of less specific and less potent lipoprotein(a)-lowering drugs have failed to demonstrate benefit. (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…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids, Vanderbilt / 18.05.2018

MedicalResearch.com Interview with: Wei-Qi Wei, MD, PhD Assistant Professor Department of Biomedical Informatics Vanderbilt University Nashville, TN 37203 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study was motived by the clinical observation that some patients develop coronary heart disease events despite taking statins, one of our most effective drugs to reduce cardiovascular risk. We collected data within the eMERGE network of people taking statins and monitored them for development of coronary heart disease events over time.  We  conducted a genome-wide association study of those with events compared to those without events. Our results showed that single nucleotide polymorphisms (SNPs) on the LPA gene were associated with a significantly increased risk of coronary heart disease events. Individuals with the variant were 50% more likely to have an event. More importantly, even among patients who achieved ideal on-treatment LDL cholesterol levels (<70 mg/dL), the association remained statistically significant. We then did a phenome-wide association study to see if other diseases or conditions were associated with these LPAvariants. The major associated conditions were all cardiovascular. This sort of study can highlight potential other indications for a drug targeting this pathway and suggest potential adverse events that might be experienced from targeting this pathway. Clearly, more and larger studies will be needed to truly understand the potential risks and benefits of a future drug targeting this pathway.  (more…)
Author Interviews, Heart Disease, JAMA, Lipids / 17.04.2018

MedicalResearch.com Interview with: Dr. Jennifer Robinson, MD MPH Professor, Departments of Epidemiology & Medicine Director, Prevention Intervention Center Department of Epidemiology University of Iowa MedicalResearch.com: What is the background for this study? Response: Compared to previous placebo-controlled statin trials, the FOURIER trial where all patients were on high or moderate intensity statin, had no reduction in cardiovascular or total mortality and the reduction in cardiovascular events was less than expected.  However, other PCSK9 inhibitor trials performed in populations with higher baseline low density lipoprotein cholesterol (LDL-C) had cardiovascular risk reductions similar to that in the statin trails. (more…)
Author Interviews, Infections, Lipids / 11.04.2018

MedicalResearch.com Interview with: Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital, Denmark  MedicalResearch.com: What is the background for this study? Response: For decades research into the role and function of high-density lipoprotein (HDL) has revolved around the believe that HDL protects against atherosclerotic cardiovascular disease. However, results from large genetic studies and from large randomized clinical trials with HDL cholesterol elevating drugs have all indicated that there is no causal association between HDL cholesterol and risk of atherosclerotic cardiovascular disease. Given the hitherto strong focus on cardiovascular disease, little is known about the possible role of HDL in other aspects of human health and disease. Preclinical evidence has indicated that HDL might be of importance for normal function of the immune system and susceptibility to infectious disease, but it had never previously been investigated if levels of HDL cholesterol is associated with the risk of infectious disease in individuals from the general population. In the present study we tested this hypothesis in more than 100.000 Danes from the population at large. (more…)
Annals Internal Medicine, Author Interviews, Heart Disease, Lipids / 14.01.2018

MedicalResearch.com Interview with: Børge G. Nordestgaard, MD, DMSc Department of Clinical Biochemistry Herlev and Gentofte Hospital, Copenhagen University Hospital Herlev, Denmark MedicalResearch.com: What is the background for this study? Response: Five major organizations recently published guidelines for using statins to prevent atherosclerotic cardiovascular disease  -- the American College of Cardiology/American Heart Association (ACC/AHA) in 2013, the United Kingdom’s National Institute for Health and Care Excellence (NICE) in 2014, and in 2016 the Canadian Cardiovascular Society (CCS), the US Preventive Services Task Force (USPSTF), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS). We applied these five guidelines to a contemporary study cohort of 45,750 40-75 year olds from the Copenhagen General Population Study. (more…)
Author Interviews, BMJ, Lipids, Nutrition, Pediatrics, Weight Research / 15.12.2017

MedicalResearch.com Interview with: Dr. Angela S Donin Population Health Research Institute, St George’s University of London, London, UK  MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are increasing numbers of takeaway outlets, particularly in deprived neighbourhoods. This is driving an increase in consumption of takeaway meals, which previous evidence has shown is linked to higher risks of heart disease, type 2 diabetes and obesity. Little is known about the dietary and health impact of high consumption of takeaway foods in children. This research found children who regularly ate takeaway meals had higher body fat and cholesterol compared to children who rarely ate take away meals, they also had overall poorer diet quality. (more…)
Author Interviews, Heart Disease, Lipids, Sanofi / 29.11.2017

MedicalResearch.com Interview with: Dr. Jay Edelberg MD, PhD VP Head of CV Development and Head Global CV Medical Affairs Sanofi  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with heterozygous familial hypercholesterolemia (HeFH) are often not able to achieve their target low-density lipoprotein cholesterol (LDL-C) levels, and some may require lipoprotein apheresis (LA) to lower their “bad cholesterol.” Apheresis is a procedure similar to kidney dialysis, where bad cholesterol is mechanically removed from the blood. It is an invasive, expensive, and time-consuming treatment for patients, as well as physicians. The Phase III ESCAPE clinical study looked at the potential effect of LA on total Praluent, free and total PCSK9 concentrations, as well as the combined pharmacodynamics effect of total Praluent on LDL-C-lowering. Praluent levels remained unaffected by apheresis, and Praluent consistently suppressed free PCSK9 levels in patients with HeFH, regardless of LA treatment. This analysis further confirms clinical ESCAPE data that Praluent can be used in conjunction with LA and may reduce or potentially eliminate the need for LA in some patients. (more…)
Author Interviews, Lipids, Sanofi / 29.11.2017

MedicalResearch.com Interview with: Dr. Jay Edelberg MD, PhD VP Head of CV Development and Head Global CV Medical Affairs Sanofi MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clinical trials of lipid-lowering therapies (LLTs), including statins, often report variations in treatment response regarding effects on low density-lipoprotein cholesterol (LDL-C) levels, although LDL-C reductions are fairly consistent between trials. Praluent is generally well tolerated, however hyporesponsiveness exists in few patients. Potential causes for variation in patient responsiveness to Praluent include lack of receipt of active study drug, changes in concurrent LLTs, inaccurate or unrepresentative baseline lipid levels, concurrent acute-phase illness, and biological nonresponsiveness. This analysis evaluated patients pooled from 10 ODYSSEY trials to assess characteristics of patients with hyporesponsiveness to Praluent, defined as <15% LDL-C reduction from baseline at all analyzed time points. Overall, only 1% of patients (n=33) had <15% LDL-C reduction at all time points. Prolonged hyporesponsiveness to Praluent was rarely associated with Praluent antidrug antibodies. Of the 33 patients with <15% LDL-C reduction at all study timepoints, 27 had undetectable or missing alirocumab levels, absence of pharmacokinetics analyses, or early treatment discontinuation. (more…)
Author Interviews, Brigham & Women's - Harvard, Lipids / 19.11.2017

MedicalResearch.com Interview with: Gokhan S. Hotamisligil MD PhD J.S. Simmons Professor of Genetics and Metabolism Chair, Department of Genetics and Complex Diseases Department of Genetics and Complex Diseases Department of Nutrition Harvard Stem Cell Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cholesterol is often considered a ‘bad’ nutrient, as it has been strongly linked to a cluster of metabolic diseases. In reality however, cholesterol is absolutely vital for the health of all animal cells, serves as an essential building block for all membranes and precursor for essential molecules.  It usually only becomes toxic when cells are exposed to high levels or free forms of cholesterol or when it is stored in excess. The reasons why cholesterol over-accumulates or causes excessive damage in cells of some people is not entirely clear, as cells are normally should be able to remove such excesses, and there remains key mechanistic gaps in our understanding of how cells control the molecular process of sensing excess cholesterol, engage ways of removal and launch countermeasures to defend their integrity. Filling this gap may reveal a new path toward alleviating the burden of cholesterol-related diseases. To this end, we identified a new signal pathway mediated by a protein called Nrf1, which enables cells to know when to remove cholesterol, thereby preventing excess cholesterol storage. We show that Nrf1 directly senses cholesterol in a strategic subcellular compartment called the endoplasmic reticulum and coordinates an adaptive and defensive responses that protects the cells and promotes the removal of cellular cholesterol. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 15.11.2017

MedicalResearch.com Interview with: Hao Yu Chen, MSc Department of Medicine McGill University Montreal, Quebec, Canada Senior author: George Thanassoulis, MD, MSc MedicalResearch.com: What is the background for this study? Response: Aortic stenosis, a narrowing of the main valve of the heart, is the most common type of valve disease in the US. Present in more than 2.5 million individuals in North America, aortic stenosis can lead to heart failure and death. However, there is little known about the causes of aortic stenosis and how it should be treated. Previously, we have demonstrated that variants of the gene LPA are associated with the development of aortic stenosis. A better understanding of how this region contributes to aortic stenosis could identify higher-risk individuals and inform the development of new medical therapies for aortic stenosis.  (more…)
AHA Journals, Author Interviews, Gender Differences, Lipids, Menopause / 06.11.2017

MedicalResearch.com Interview with: Marija Glisic Epidemiology, Erasmus MC  MedicalResearch.com: What is the background for this study? Response: Carotid atherosclerosis is one of most important risk factors for developing stroke. Carotid atherosclerotic plaques characterized by lipid core presence and intraplaque haemorrhage are considered to be unstable, and therefore more prone to rupture and lead to consequent stroke. Sex differences have been observed in carotid plaque composition as well as in stroke incidence. Sex hormones, particularly estrogen and testosterone actions are suggested to underlie the observed sex differences in atherosclerosis. Experimental evidence suggests a direct action of estradiol and testosterone on the vascular system, affecting various mechanisms that may impact plaque composition and subsequently stroke risk. (more…)
Author Interviews, Diabetes, Lipids, NEJM / 01.11.2017

MedicalResearch.com Interview with: M. Loredana Marcovecchio, M.D. Clinical Scientist and Professor David Dunger M.D. Director of Research Professor of Paediatrics University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: The efficacy and safety of ACE Inhibitors and statins in adolescents have been shown in the context of hypertension and familial hypercholesterolemia, respectively. However, there is a lack of data on the long-term use of these drugs in those with type 1 diabetes and, in particular, there is no clear indication for their use in patients with increased albumin excretion. The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) was a multi-centre, international study, set up by investigators in the UK, Australia and Canada to explore if drugs already used to lower blood pressure (ACE inhibitors) and cholesterol levels (Statins) in adults with diabetes could reduce the risk of kidney, eye and cardiovascular disease in adolescents with Type 1 diabetes. Neither ACE inhibitors nor statins significantly reduced the albumin-creatinine ratio during the 2-4 year trial period. However, some of the secondary outcomes suggest that the drugs may have important benefits. Treatment with the ACE inhibitor resulted in a 43% reduction in the rates of progression to microalbuminuria, which was not statistically significant, but it could have important clinical implications. Preventing even intermittent cases of microalbuminuria is known to reduce the future risk of kidney and cardiovascular complications. Statin therapy led to reduced levels of lipid levels, which could reduce long-term risk for cardiovascular complications. These findings could translate into long-term benefits, but follow-up of this unique cohort will be essential. The essential biological samples and data provided by the participants will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes. (more…)
Author Interviews, Columbia, Heart Disease, Lipids / 13.09.2017

MedicalResearch.com Interview with: Dr. Jay Edelberg MD, PhD VP Head of Cardiovascular Development and Head Global Cardiovascular Medical Affairs Sanofi  MedicalResearch.com: What should readers take away from the data that Sanofi and Regeneron is presenting at ESC Congress 2017?    Response: This year at European Society of Cardiology (ESC,) we are pleased to present analyses that further demonstrate additional efficacy and tolerability of Praluent (alirocumab). While statins remain the first-line treatment, Praluent has shown a consistent benefit as an additional therapy to high-intensity statins in patients with clinical atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH), allowing many patients to achieve low-density lipoprotein (LDL) cholesterol levels previously considered unattainable in this patient population. Our data further emphasize the need for additional cholesterol-lowering options in these high cardiovascular (CV) risk patient populations, including individuals living with diabetes.   (more…)
Author Interviews, Lipids, Psychological Science / 12.09.2017

MedicalResearch.com Interview with: Jiah Yoo Ph.D. Student in Social Psychology University of Wisconsin-Madison Madison, WI 53706  MedicalResearch.com: What is the background for this study? Response: A growing number of studies have shown that positive emotions predict better physical health. However, a caveat of these findings is that most studies have been conducted with Western samples. As cultural psychologists, we have learned that European American cultural contexts are particular in that positive emotions are highly valued and emphasized. For example, in East Asian cultures, it is a commonly shared view that positive emotions have some dark sides such as that they are fleeting, may attract unnecessary attention from others, and can be a distraction from focusing on important tasks. Given the cultural differences in emotions, we thought it would be important to test whether the established link between positive emotion and enhanced physical health are relevant to other cultural contexts, such as those in East Asia. We focused on blood lipids profiles, one of the major risk factors for heart diseases, as objective measures of health. Because of the global prevalence of coronary artery diseases, blood lipids are considered important indices of biological health in many Western and East Asian countries. In addition, blood lipids are largely influenced by lifestyles and behavioral factors so we further tested the role of various health behaviors (i.e., dietary habits, body mass index, smoking, alcohol consumption) in the lipids-emotion link in different cultures. (more…)
Author Interviews, Heart Disease, Lipids / 03.09.2017

MedicalResearch.com Interview with: Dr Rahul Potluri Senior author and founder of the ACALM Study Unit Aston Medical School Aston University Birmingham, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: The links between hyperlipidaemia and cancer has been exciting scientists in recent years.  We have previously shown an association with breast cancer and hyperlipidaemia using a cross-sectional dataset in 2014. In 2016 we showed that in patients with the four main cancers in the UK (namely Breast, Lung, Colon and Prostate) that the presence of hyperlipidaemia improved the long term mortality and prognosis of these patients.  In this study utilising a big data, longitudinal study methodology, we looked at 16043 healthy women above the age of 40 with hyperlipidaemia and compared these to an age and gender matched control sample of 16043 healthy women without high cholesterol. We then followed up these patients and found that subsequent breast cancer rates in the women with hyperlipidaemia were 45% lower. Subsequent mortality in those patients who developed breast cancer was also 40% lower in the hyperlipidaemia group compared to the non-hyperlipidaemia controlled sample. (more…)
Author Interviews, Heart Disease, JAMA, Lipids, UCLA / 28.08.2017

MedicalResearch.com Interview with: Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of Cardiovascular Medicine and Science Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief of Clinical Cardiology, UCLA Division of Cardiology Co-Director, UCLA Preventative Cardiology Program David Geffen School of Medicine at UCLA Los Angeles, CA  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study identifies the clinical and economic consequences of treating a population of patients with established atherosclerotic cardiovascular disease (ASCVD ) at high-risk of cardiovascular (CV) events and defines the cost-effectiveness of the PCSK-9 inhibitor evolocumab under various clinical scenarios. The analysis is based on the clinical outcomes from the Repatha Outcomes Study (FOURIER) in patients with established atherosclerotic cardiovascular disease (ASCVD), such as those who have already had a heart attack or stroke who require additional therapy. This is the first cost-effectiveness assessment of evolocumab using a model based on a high-quality outcomes trial, combined with U.S. clinical practice data. The analysis identifies the types of high-risk patients for whom this therapy is both clinically beneficial and cost-effective. This study utilized cost-effectiveness and value thresholds employed by the World Health Organization and the American College of Cardiology/American Heart Association. Evolocumab was found to exceed generally accepted cost-effectiveness thresholds at current list price. However, this medication could be a cost-effective treatment for patients with established ASCVD in the U.S. when the net price is at or below $9,669 per year. (more…)