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…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids, UCLA / 28.08.2017

MedicalResearch.com Interview with: Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease. In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases. Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments. (more…)
Author Interviews, Cost of Health Care, JAMA, Lipids, University of Pittsburgh / 07.08.2017

MedicalResearch.com Interview with: Inmaculada Hernandez, PharmD, PhD Assistant Professor of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh, PA 1526 MedicalResearch.com: What is the background for this study? Response: A few months ago, the results of the FOURIER trial were published. This trial was the first one to evaluate the efficacy of PCSK9 inhibitors in the prevention of cardiovascular events, since the approval of these agents was based on trials that evaluated their efficacy in reducing levels of LDL-C. The results of the FOURIER trial did not meet the expectations generated by prior studies that had simulated how much the risk of cardiovascular events should decrease based on the observed reduction in LDL-C levels. A few hours after the publication of the results of the FOURIER trial, Amgen (evolocumab´s manufacturer) announced that it would be willing to engage in contracts where the cost of evolocumab would be refunded for those patients who suffer a heart attack or a stroke while using the drug. (more…)
Abuse and Neglect, Boehringer Ingelheim, Diabetes, Endocrinology, Lipids / 22.06.2017

MedicalResearch.com Interview with: Robert R. Henry, M.D. Professor of Medicine Member of the ODYSSEY DM Steering Committee and Director of the Center for Metabolic Research VA San Diego Healthcare System MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY DM-DYSLIPIDEMIA trial was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 patients with type 2 diabetes with mixed dyslipidemia at high cardiovascular (CV) risk, not adequately controlled with maximally tolerated dose (MTD) statins. The primary endpoint was percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24. In ODYSSEY DM-DYSLIPIDEMIA, Praluent 75 mg was added to MTD statins, with dose adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose. Results from the ODYSSEY DM-DYSLIPIDEMIA study found that Praluent added to MTD statins showed significant reduction in non-HDL-C and other lipid parameters compared to those on usual care. Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was -32.5 percent (p<0.0001). Praluent in combination with MTD statins reduced LDL-C by 43 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001). Treatment with Praluent also improved the overall lipid profile. There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Furthermore, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk. (more…)
AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Lipids, Merck / 19.06.2017

MedicalResearch.com Interview with: Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24. Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose. Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified. There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk. (more…)
Author Interviews, Biomarkers, Heart Disease, Lipids / 12.06.2017

MedicalResearch.com Interview with: Amane Harada, PhD Senior Researcher Central Research Laboratories, Sysmex Corporation Kobe, Japan Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of Medicine Kobe, Japan  MedicalResearch.com: What is the background for this study? Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions. Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease. However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical. To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”. (more…)
AHA Journals, Author Interviews, Baylor College of Medicine Houston, Heart Disease, Lipids / 13.05.2017

MedicalResearch.com Interview with: Julia M. Akeroyd, MPH Center for Innovations in Quality, Effectiveness, and Safety (IQuESt) Michael E. DeBakey Veteran Affairs Medical Center Salim S Virani, MBBS, Ph.D. Baylor College of Medicine MedicalResearch.com: What is the background for this study? Response: In the recently published Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, treatment with evolocumab resulted in a 15% relative (1.5% absolute) risk reduction of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) at a median follow-up of 2.2 years. Given the high cost of evolocumab, there is a need to identify what proportion of ASCVD patients would qualify for evolocumab based on FOURIER entry criteria and how eligibility would change if maximal doses of evidence-based lipid lowering therapies were required. (more…)
Author Interviews, Heart Disease, JAMA, Lipids, Nutrition, Stroke, Yale / 13.04.2017

MedicalResearch.com Interview with: Eric J. Brandt, MD Yale University Cardiovascular Disease Fellow MedicalResearch.com: What is the background for this study? What are the main findings? Response: From previous studies we know that industrial trans fatty acid (trans fat) consumption is linked to elevated risk for cardiovascular disease. Even small amounts of consumption can be deleterious to cardiovascular health. In New York state, there were 11 counties that restricted the use of trans fatty acids in eateries. We compared hospitalization for heart attacks and stroke from 2002 through 2013 in counties that did and did not have restrictions. Our study found that when comparing populations within New York state that restricted the use of trans fat, compared to those that did not, there was an associated additional decline beyond temporal trends for heart attacks and stroke events combined by 6.2%. (more…)
Author Interviews, Diabetes, Gender Differences, Lipids / 16.03.2017

MedicalResearch.com Interview with: Dr Mark Jones, Senior Lecturer Faculty of Medicine and Biomedical Sciences, School of Public Health The University of Queensland MedicalResearch.com: What is the background for this study? Response: Multiple clinical trials have shown statins reduce LDL cholesterol, cardiovascular events, and all-cause mortality. However statins are also associated with adverse events, including type 2 diabetes. There have been very few older women included in statin trials hence effects of the drug in this population are somewhat uncertain. Also, more generally, results from clinical trials may not translate well into clinical practice. (more…)
Author Interviews, Heart Disease, JAMA, Lipids / 02.03.2017

MedicalResearch.com Interview with: Dr. Yashashwi Pokharel MD, MSCR Department of Cardiovascular Research Saint Luke’s Mid-America Heart Institute Kansas City, Missouri and Salim S. Virani, MD PhD, FACC, FAHA Associate Professor, Section of Cardiovascular Research Associate Director for Research, Cardiology Fellowship Training Program Baylor College of Medicine Investigator, Health Policy, Quality and Informatics Program Michael E. DeBakey Veterans Affairs Medical Center HSR&D Center of Innovation Staff Cardiologist, Michael E. DeBakey Veterans Affairs Medical Center Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unlike the previous cholesterol management guideline that recommended use of either statin and non-statin therapy to achieve low density lipoprotein cholesterol (LDL-C) target, the 2013 American College of Cardiology/American Heart Association cholesterol management guideline made a major paradigm shift by recommending statin focused treatment in 4 specific patient groups and replaced LDL-C target with fixed statin intensity treatment (moderate to high intensity statin therapy). With this change, it was speculated that a large number of patients would be eligible for statin treatment (in one study, up to 11.1% additional patients were expected to be eligible for statin therapy). Our study provided the real world trends in the use of statin and non-statin lipid lowering therapy (LLT) from a national sample of cardiology practices in 1.1 million patients 14 months before and 14 months after the release of the 2013 guideline. We found a modest, but significant increasing trend in the use of statin therapy in only 1 of the 4 patient groups eligible for statin therapy (i.e., 4.3% increase in the use of moderate to high intensity statin therapy in patients with established atherosclerotic cardiovascular disease). We did not find any significant change in non-statin LLT use. Importantly, about a third to half of patients in statin eligible groups were not receiving moderate to high intensity statin therapy even after the publication of the 2013 guideline. (more…)
AHA Journals, Author Interviews, Columbia, Heart Disease, Immunotherapy, Lipids / 13.02.2017

MedicalResearch.com Interview with: Henry N. Ginsberg, MD Irving Institute for Clinical and Translational Research Columbia University Columbia College of Physicians and Surgeons New York, NY MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism. This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition. (more…)
Author Interviews, Diabetes, Endocrinology, Heart Disease, Lipids, Pharmacology, Weight Research / 30.01.2017

MedicalResearch.com Interview with: Gianluca Iacobellis MD PhD Professor of Clinical Medicine Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Miami, FL MedicalResearch.com: What is the background for this study? What are the main findings? Response: We know that epicardial fat, the visceral fat of the heart, is associated with coronary artery disease, diabetes and obesity. My studies have shown that epicardial fat can be easily measured with non invasive imaging procedures. Remarkably, epicardial fat has recently emerged as therapeutic target responding to medications targeting the fat. Liraglutide, a GLP-1 analog has shown to provide modest weight loss and beneficial cardiovascular effects beyond its glucose lowering action. So , we sought to evaluate the effects of liraglutide on epicardial fat. (more…)
Author Interviews, Lancet, Lipids, Thromboembolism / 21.01.2017

MedicalResearch.com Interview with: Setor Kunutsor BSc MD MPhil(cantab) PhD(cantab) Research Fellow/Epidemiologist Musculoskeletal Research Unit University of Bristol School of Clinical Sciences Southmead Hospital MedicalResearch.com: What is the background for this study? Response: Statins are well established for the prevention of cardiovascular disease and this is based on their ability to lower levels of circulating lipids in the blood. However, statins are also known to have pleotropic effects and these include potential protective effects on multiple disease conditions. Based on their anti-inflammatory and antithrombotic properties, there have been suggestions that statins may prevent venous thromboembolism (VTE) (which comprises of pulmonary embolism and deep vein thrombosis). The evidence is however uncertain. Several studies utilizing both observational cohort and randomized controlled designs have been conducted to evaluate whether statin therapy or use is associated with a reduction in the incidence of VTE, but the results have been inconclusive. In a recent review that was published in 2012, Rahimi and colleagues pooled the results of several randomized controlled trials (RCTs), but found no significant reduction in the risk of VTE with statin therapy [REF]. Given the publication of new studies since this study was published and the existing uncertain evidence on the effect of statins on VTE, we decided it was time to bring all the evidence together and evaluate if statin therapy really did have a protective effect on the risk of venous thromboembolism. (more…)
Author Interviews, Heart Disease, Lipids, Omega-3 Fatty Acids / 21.01.2017

MedicalResearch.com Interview with: Dominik D Alexander, PhD, MSPH Principal Epidemiologist EpidStat Institute Ann Arbor, MI Seattle, WA MedicalResearch.com: What is the background for this study? What are the main findings? Response: In recent years, the body of scientific literature on n-3 LCPUFA (EPA/DHA) intake and coronary heart disease (CHD) risk has exploded with mixed results. It was only logical to conduct a comprehensive meta-analysis of randomized controlled trials (RCTs) to estimate the effect of EPA+DHA on CHD, and to conduct a comprehensive meta-analysis of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Lipids / 29.12.2016

MedicalResearch.com Interview with: Marshall B. Elam PhD MD Professor Pharmacology and Medicine (Cardiovascular Diseases) University of Tennessee Health Sciences Center Memphis MedicalResearch.com: What is the background for this study? What are the main findings? Response: This manuscript presents the findings of extended follow up of patients with Type 2 Diabetes who were treated with fenofibrate, a member of a group of triglyceride lowering medications known as fibrates or PPAR alpha agonists, as part of the Action to Control Cardiovascular Risk in T2DM (ACCORD) study. ACCORD was designed to test the effect of intensive treatment of cardiovascular risk factors including blood glucose, blood pressure and lipids on risk of heart attack, stroke and cardiac death in patients with Type 2 Diabetes. The lipid arm of ACCORD tested the hypothesis that adding fenofibrate to statin therapy would further reduce risk of these cardiovascular events. (more…)
Author Interviews, Electronic Records, Genetic Research, Heart Disease, Lipids, Science / 25.12.2016

MedicalResearch.com Interview with: Michael F. Murray MD Geisinger Health System Danville, PA 17822 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The DiscovEHR cohort was formed as a result of a research collaboration between Geisinger Health System and Regeneron Pharmaceuticals. There are over 50,000 patient participants in the cohort who have volunteered to have their de-identified genomic sequence data linked to their de-identified EHR data for research purposes. We report in this paper findings around the identification of 229 individuals (1:256) with pathogenic or likely pathogenic variants in one of the three genes (LDLR, APOB, PCSK9) associated with Familial Hypercholesterolemia (FH). The study found that these individuals are unlikely to carry a diagnosis of FH and are at risk for early coronary artery disease. (more…)
AHA Journals, Author Interviews, Lipids, Pharmacology / 16.12.2016

MedicalResearch.com Interview with: Dr. Eli M. Roth MD, FACC President, Medical Director Sterling Research Group Cincinnati, OH MedicalResearch.com: What is the background for this study? What are the main findings? Response: At this year’s AHA 2016, we presented a pharmacodynamics analysis of ODYSSEY CHOICE I, which evaluated the effects of Praluent 300 mg administered every four weeks (Q4W) for 24 weeks in hypercholesterolemia patients at moderate to very high cardiovascular risk who were on maximally tolerated statin or no statin and/or other lipid-lowering therapies. The pharmacodynamic analysis of CHOICE I in patients on statins supports the use of Praluent 300 mg Q4W as an alternative starting dose for patients who prefer a Q4W dosing regimen and demonstrates the value of LDL-C based dosing interval adjustment. The findings from this analysis were consistent with prior ODYSSEY Phase 3 studies, showing that Praluent substantially reduced circulating free PCSK9 concentration, resulting in significant LDL-C reductions. Additionally, Praluent was generally well tolerated. (more…)
Author Interviews, Lipids, Nutrition, Weight Research / 13.12.2016

MedicalResearch.com Interview with: Dr. Koji Ishiguro National Agriculture and Food Research Organization Japan MedicalResearch.com: What is the background for this study? Response: -Sweet potato (Ipomoea batatas L.) roots are not only used for human consumption, they are used to make starch materials, processed foods, and distilled spirits in Japan. Starch use accounts for about 15% (131,500 tons) of total sweet potato production. Starch residues are discharged during starch production and are mainly used in animal feed and compost. Large amounts of the wastewater, which can cause serious environmental problems, are discarded after clarification. Investigation into the uses of the by-products of the sweet potato starch industry would benefit both the environment and industry. (more…)
Author Interviews, Heart Disease, Lipids, Stanford / 04.12.2016

MedicalResearch.com Interview with: Fatima Rodriguez, MD, MPH Division of Cardiovascular Medicine and Cardiovascular Institute Stanford University Stanford, CA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The 2013 ACC/AHA cholesterol management guidelines emphasized that high-risk patients with atherosclerotic disease should be on high-intensity statins. We sought to determine how these guidelines are being adopted at the Veterans Affairs (VA) Health System and to identify treatment gaps. Our main findings were that the use of high-intensity statins increased from 23 to 35% following the guideline release for these high-risk patients. However, high-intensity statin use was lowest in Hispanics and Native Americans. Women, older adults, and patients with peripheral arterial and cerebrovascular disease were also less likely to undergo statin intensification after the release of the guideline. We also noted geographic and institutional differences across VA hospitals in rates of high-intensity statin use for secondary prevention. (more…)
Author Interviews, CDC, JAMA, Lipids, Nutrition / 02.12.2016

MedicalResearch.com Interview with: Asher Rosinger, PHD, MPH Epidemic Intelligence Service Officer, Centers for Disease Control and Prevention Division of Health and Examination Nutrition Examination Surveys, Analysis Branch National Center for Health Statistic MedicalResearch.com: What is the background for this study? Response: Total cholesterol, triglycerides, and low-density lipoprotein (LDL) levels are linked to coronary heart disease and cardiovascular events. Between 1999 and 2010, total cholesterol, triglycerides, and LDL levels declined among U.S. adults. We used new data from the 2011-2014 nationally representative National Health and Nutrition Examination Survey (NHANES) to determine if earlier trends continued. (more…)
Author Interviews, Genetic Research, Lipids, NEJM / 01.12.2016

MedicalResearch.com Interview with: Brian A. Ference, M.D Division of Cardiovascular Medicine Wayne State University School of Medicine Detroit, MI MedicalResearch.com: What are the main findings? Response: Lifelong exposure to modestly lower plasma LDL-C levels caused by rare loss-of-function mutations in the PCSK9 gene is associated with a substantially lower lifetime risk of developing cardiovascular disease. This discovery motivated the development of monoclonal antibodies directed against PCSK9 which have now been shown to reduce plasma LDL-C levels by 50-60%. The cardiovascular medicine community is early anticipating the results of two large cardiovascular outcome trials that will determine if lowering LDL-C levels by inhibiting PCSK9 will reduce the risk of cardiovascular events. Because monoclonal antibodies and other therapies directed against PCSK9 are designed to recapitulate the phenotype of PCSK9 loss-of-function mutations, we reasoned that it may be possible to anticipate the efficacy and safety results of the ongoing cardiovascular outcome studies by more precisely characterizing the effect of genetic variants in the PCSK9 gene on the risk of both cardiovascular events and new onset diabetes. To do this, we a constructed genetic score consisting of multiple independently inherited variants in the PCK9 gene to create an instrument that mimics the effect of PCSK9 inhibitors. We then compared the effect of genetic variants that mimic the effect of PCSK9 inhibitors with the effect of genetic variants in the HMGCR gene that mimic the effect of statins to make inferences about the likely effect of PCSK9 inhibitors on the risk of cardiovascular events and new onset diabetes as compared to treatment with a statin. (more…)
Author Interviews, Heart Disease, Lipids, NEJM, Pharmacology / 14.11.2016

MedicalResearch.com Interview with: Kevin Fitzgerald, Ph.D. Alnylam Pharmaceuticals Cambridge, MA 02142 MedicalResearch.com: What is the background for this study? Response: Inclisiran (ALN-PCSsc) is a subcutaneously administered RNAi therapeutic targeting PCSK9 in development for the treatment of hypercholesterolemia. The Phase 1 trial of inclisiran was conducted in the U.K. as a randomized, single-blind, placebo controlled, single ascending-and multi-dose, subcutaneous dose-escalation study in 69 volunteer subjects with elevated baseline LDL-C (≥ 100 mg/dL). The primary objective of the study was to evaluate the safety, side effect profile, and pharmacodynamics effects of inclisiran. (more…)
Author Interviews, Gastrointestinal Disease, JAMA, Lipids / 09.11.2016

MedicalResearch.com Interview with: Borge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry, Herlev and Gentofte Hospital Copenhagen University Hospital Herlev, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Acute pancreatitis is an inflammatory disorder of the pancreas with gallstones and high-alcohol consumption as leading risk factors, while mild-to-moderately increased plasma triglycerides hitherto has been overlooked. We surprisingly found that the risk of developing acute pancreatitis was increased already from triglycerides of 175 mg/dL (2 mmol/L) and above. When triglycerides were above 443mg/dL (5mmol/L) the risk was increased a massive 9-fold. Interestingly, this risk was higher than the corresponding 3.4-fold higher risk for myocardial infarction. (more…)
Author Interviews, BMJ, Lipids, Nutrition, Omega-3 Fatty Acids, Weight Research / 26.10.2016

MedicalResearch.com Interview with: Artemis P. Simopoulos, M.D. FACN President, The Center for Genetics Nutrition and Health Washington, DC 20016 MedicalResearch.com: What is the background for this study? What are the main findings? Response: I have written extensively on the evolutionary aspects of diet, the diet of Crete prior to 1960 in which I pointed to the misinterpretation of the data of the Seven Countries Study by Keys et al. A major characteristic of these diets is a balanced omega-6/omega-3 ratio. The recommendation to substitute saturated fats with omega-6 rich oils (sunflower, corn, soybean) increases inflammation and coronary heart disease. It has been shown in a number of studies that a high omega-6/omega-3 (20/1 instead of a balanced ratio) leads to an increase in white adipose tissue and prevents the formation of brown adipose tissue leading to obesity. The changes in the diet-high in omega-6 oils depletion of omega-3 and high fructose along with highly refined carbohydrates in processed foods and a sedentary lifestyle lead to obesity, diabetes, coronary heart disease and cancer. The scientific evidence from the FAT-1 mouse and recent cohort studies clearly show that the current dietary guidelines as the previous ones are not based on science that takes into consideration genetics, metabolism, the concept that a calorie is not a calorie. It is important to consider that nutrients influence the expression of genes, the omega-6 fatty acids are the most pro-inflammatory nutrients, and inflammation is at the base of all chronic non-communicable diseases. (more…)
AHA Journals, Author Interviews, Heart Disease, Lipids / 28.09.2016

MedicalResearch.com Interview with: Dr. Johan Frostegård MD PhD Professor of medicine Karolinska Institutet's Institute of Environmental Medicine and Consultant at Karolinska University Hospital's Emergency Clinic MedicalResearch.com: What is the background for this study? What are the main findings? Response: Statins are one of the worlds most sold medications, which has generated large profits, but also, in my opinion, helped many people. Still, side effects are much discussed after more than 2 decades of use, as exemplified by a current debate between Lancet and BMJ (the former has the opinion that side effects are not major issues, but the latter do not agree). Also the exact role of LDL (low density lipoprotein, also known as the ”bad cholesterol”) as a risk factor is discussed, and can vary, according to many researchers. LDL levels are important among middle aged persons, especially men, as a risk markers for cardiovascular disease, especially myocardial infarction. LDL is most likely less important as a risk factor in individuals above 60 years of age, and also among women – as compared to middle aged men. (more…)
Author Interviews, Lipids, Pharmacology / 23.08.2016

MedicalResearch.com Interview with: Prof. Dr. Ioana Gouni-Berthold MD Center for Endocrinology, Diabetes and Preventive Medicine (ZEDP) University of Cologne Cologne, Germany MedicalResearch.com: What is the background for this study? Response: In Europe, up to half of the population aged between 35 and 64 has hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C]), putting them at risk of heart disease. Despite increased treatment rates in recent years, many patients still do not receive adequate therapy, and heart disease remains the biggest cause of death in the USA and most European countries. Two drugs, alirocumab and evolocumab, have recently been approved for lowering LDL-C in patients with hypercholesterolaemia as an ‘add-on’ therapy to other lipid-lowering medication, or for use alone in patients unable to tolerate statins. These drugs have a unique mode of action– they inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that binds to LDL receptors and targets them for degradation. In the absence of PCSK9, the LDL receptor recycling is restored and the receptors are able to remove LDL from the blood. Both alirocumab and evolocumab have been tested in numerous patient populations in phase 3 trials; albeit evolocumab has an additional indication of homozygous familial hypercholesterolemia. We therefore felt that there was a need to collate the available data to assess the efficacy and safety of each agent. We chose reduction in LDL-C as our outcome of interest, because this was the primary endpoint of the pivotal clinical trials. (more…)
Author Interviews, Heart Disease, JAMA, Lipids, Nutrition, Omega-3 Fatty Acids / 18.08.2016

MedicalResearch.com Interview with: David Iggman, MD, PhD Unit for Clinical Nutrition and Metabolism Department of Public Health and Caring Sciences Uppsala University, Uppsala Center for Clinical Research Dalarna Falun, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is some controversy regarding which dietary fats are preferable and in what amounts, not least regarding the polyunsaturated fats. It is also challenging to adequately assess peoples intakes of dietary fats. The main findings of this study was that among fatty acids in the body (reflecting the intake during the last year or so), linoleic acid (omega-6) was associated with lower mortality in 71-year-old men with 15 years follow-up. (more…)
Author Interviews, JAMA, Lipids / 16.08.2016

MedicalResearch.com Interview with: Dr. David Grossman M.D., M.P.H. Vice chair of the U.S. Preventive Services Task Force and Professor at the University of Washington Schools of Public Health and Medicine MedicalResearch.com: What is the background for this recommendation? Response: The Task Force recognizes the importance of cardiovascular health for young people. Children and adolescents with high cholesterol are more likely to become adults with high cholesterol, and high cholesterol in adulthood can lead to serious health outcomes such as heart attacks and strokes. However, when the Task Force reviewed evidence for cholesterol screening in children and adolescents without any signs or symptoms, we found that there is not enough evidence to recommend for or against screening. In the face of unclear evidence, the Task Force is calling on the research community to prioritize studies on screening and treatment of lipid disorders in children and teens to help us all learn more about the impact that screening at an early age may have on the cardiovascular health of adults. (more…)
Author Interviews, Heart Disease, Lipids / 14.08.2016

MedicalResearch.com Interview with: Ziyad Al-Aly, MD, FASN Assistant Professor of Medicine Washington University School of Medicine Co-Director, Clinical Epidemiology Center Associate Chief of Staff for Research and Education Veterans Affairs Saint Louis Health Care System MedicalResearch.com: What is the background for this study? What are the main findings? Response: I think the most important, and novel finding is that elevated levels of HDL-cholesterol (which is thought of as the good cholesterol) are associated with increased risk of death. Previously it was thought that high HDL (increased good cholesterol) is a good thing. We used Big Data approach (over 16 million person-years; 1.7 million people followed for over 9 years) to evaluate the relationship between HDL-Cholesterol (the good cholesterol) and risk of death. We found that low HDL is associated with increased risk of death (which is expected and consistent with prior knowledge). The novel and unexpected finding is the observation that high HDL-Cholesterol is also associated with increased risk of death. The relationship between HDL-Cholesterol levels and risk of death is a U-shaped curve where risk is increased at both ends of the HDL-C values spectrum (at both low and high end); Too low and too high is associated with higher risk of death. The findings may explain why clinical trials aimed at increasing HDL-Cholesterol levels failed to show improvement of clinical outcomes. This finding was not expected, and has not been reported previously in large epidemiologic studies such as Framingham Heart Study and others. The Framingham Heart study and others significantly advanced our understanding of the relationship between cholesterol parameters (including HDL-Cholesterol) and clinical outcomes. However, these studies are limited in that the number of patients in these cohorts was several thousands which is relatively small compared to what a Big Data approach (millions of patients) enables us to see. Big Data approach allows a more nuanced (a more detailed) examination of the relationship between HDL and risk of death across the full spectrum of HDL levels. (more…)