Lipids
13 Sep Praluent Plus Statins Reduce LDL In High Risk Cardiovascular Patients
MedicalResearch.com Interview with: [caption id="attachment_36944" align="alignleft" width="107"]
Dr. Edelberg[/caption]
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.
12 Sep Positive Emotions Predict Health Lipid Profiles In Western, But Not Eastern Cultures
MedicalResearch.com Interview with: [caption id="attachment_36941" align="alignleft" width="132"]
Jiah Yoo[/caption]
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.
03 Sep Hyperlipidemia Linked To Lower Breast Cancer Mortality, Perhaps Due To Statin Therapy
MedicalResearch.com Interview with: [caption id="attachment_36729" align="alignleft" width="167"]
Dr. Potluri[/caption]
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.
28 Aug PCSK 9 Inhibitors May Be Cost Effective For Subset of High Risk Patients, If Price is Right
MedicalResearch.com Interview with: [caption id="attachment_25325" align="alignleft" width="160"]
Dr. Gregg Fonarow[/caption]
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.
28 Aug Familial Hypercholesterolemia: “Junk” RNA May Facilitate Gene Therapy
MedicalResearch.com Interview with: [caption id="attachment_36672" align="alignleft" width="200"]
Dr. Sallam[/caption]
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.
07 Aug Even After Rebates, Use of PCSK9 Inhibitor Would Still Cost Over $5 Million To Prevent One Stroke
MedicalResearch.com Interview with: [caption id="attachment_36336" align="alignleft" width="132"]
Dr. Hernandez[/caption]
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.
22 Jun PCSK9 Inhibitor Praluent Added to Statins Improved Lipid Profile in Diabetes
MedicalResearch.com Interview with: [caption id="attachment_35536" align="alignleft" width="131"]
Dr. Henry[/caption]
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.
19 Jun Adding Praluent (Alirocumab) To Statins Reduces LDL in High Cardiovascular Risk Diabetics
Posted at 20:19h
in AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Lipids, Merck
MedicalResearch.com Interview with:
[caption id="attachment_35424" align="alignleft" width="200"]
Dr. Lawrence Leiter[/caption]
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.
12 Jun Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World.
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 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”.
13 May Improving Statin Adherence Would Reduce Need For Expensive PCSK9 Inhibitors
Posted at 01:15h
in AHA Journals, Author Interviews, Baylor College of Medicine Houston, Heart Disease, Lipids
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.
13 Apr Fewer Heart Attacks and Strokes After Trans-Fat Restriction Laws in New York
MedicalResearch.com Interview with: [caption id="attachment_33863" align="alignleft" width="200"]
Dr. Eric Brandt[/caption]
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%.
16 Mar Older Women Face Greater Risk of Diabetes From Statins
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.02 Mar Many Eligible Groups Not Receiving Recommended Statin Therapy
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.13 Feb PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol
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.30 Jan Treatment With Liraglutide (Victoza) Reduces Fat Around the Heart
Posted at 16:21h
in Author Interviews, Diabetes, Endocrinology, Heart Disease, Lipids, Pharmacology, Weight Research
MedicalResearch.com Interview with:
[caption id="attachment_31502" align="alignleft" width="130"]
Dr. Gianluca Iacobellis[/caption]
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.
21 Jan Statins Linked to Reduced Risk of Venous Thromboembolism
MedicalResearch.com Interview with: [caption id="attachment_31414" align="alignleft" width="133"]
Dr. Setor Kunutsor[/caption]
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.
21 Jan Meta-analysis of Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk
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.29 Dec Some Type 2 Diabetics May Benefit From Adding Fenofibrate To Statins
MedicalResearch.com Interview with: [caption id="attachment_30835" align="alignleft" width="170"]
Dr. Marshall B. Elam[/caption]
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.
25 Dec Familial Hypercholesterolemia Diagnosed Through EHR and Genetics Data
Posted at 21:04h
in Author Interviews, Electronic Records, Genetic Research, Heart Disease, Lipids, Science
MedicalResearch.com Interview with:
[caption id="attachment_30763" align="alignleft" width="133"]
Dr. Michael Murray[/caption]
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.
16 Dec PCSK9 Inhibitor Praluent Substantially Reduced LDL-C Cholesterol
MedicalResearch.com Interview with: [caption id="attachment_30566" align="alignleft" width="100"]
Dr. Eli Roth[/caption]
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.
13 Dec Byproduct of Sweet Potato Waste Offers Clue To Lipid Metabolism
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.04 Dec High Intensity Statins Increase For High Risk Atherosclerotic Patients, But Lagging in Women and Minorities
MedicalResearch.com Interview with: [caption id="attachment_30181" align="alignleft" width="166"]
Dr. Fatima Rodriguez[/caption]
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.
02 Dec Americans Continue To Have Better Lipid Profiles
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.01 Dec Cardioprotective Effect of PCSK9 Inhibitors Should Outweigh Potential Harm of Diabetes Risk
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.14 Nov Phase1 Trial Supports PCSK9-Inhibitor Inclisiran For Reducing LDL Cholesterol
MedicalResearch.com Interview with: [caption id="attachment_29622" align="alignleft" width="133"]
Dr. Kevin Fitzgerald[/caption]
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.
09 Nov Hypertriglyceridemia Markedly Increases Risk of Acute Pancreatitis
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.26 Oct Balancing Omega 6 to Omega 3 To Prevent and Manage Obesity
MedicalResearch.com Interview with: [caption id="attachment_29227" align="alignleft" width="130"]
Dr. Artemis P. Simopoulos[/caption]
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.
28 Sep Statins Reduce Inflammation As Well As LDL
MedicalResearch.com Interview with: [caption id="attachment_28426" align="alignleft" width="200"]
Dr. Johan Frostegård[/caption]
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.
23 Aug Systematic Review Finds PCSK9 Inhibitors Reduce LDL-C and Are Well Tolerated
MedicalResearch.com Interview with: [caption id="attachment_27256" align="alignleft" width="133"]
Dr. Gouni Gerthold[/caption]
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.